Bile spillage and incidental gall bladder adenocarcinoma

The Editor-in-Chief of ‘Hepatobiliary Surgery and Nutrition’ invited me to write an editorial on the article entitled “Adverse outcomes after bile spillage in incidental gall bladder cancer” by Horkoff et al. which was published in the 2019 April issue of Annals of Surgery (1).

Gall bladder adenocarcinoma is a rare cancer which is most commonly discovered incidentally with the primary pre-operative impression of chronic cholecystitis. Increasing laparoscopic cholecystectomies as the gold standard procedure for resection of gall bladder, have caused more detection of incidental gall bladder cancers. Incidental gall bladder carcinoma is defined as carcinoma of gall bladder detected for the first time after cholecystectomy and accidentally found on histological examination of the gall bladder (2). The term incidental can be used just for cases which are operated with no knowledge about any malignancy before surgery. Radiological findings including ultrasonography and CT scan would also not add much information before surgery, especially in early stages of gall bladder cancer. Incidental gall bladder carcinoma has been reported in 0.20–3% of all cholecystectomies. Most of the above-mentioned incidental gall bladder carcinomas present with advanced disease and are not good candidates for curative surgeries (3,4).

In the patients with incidentally detected gall bladder cancers only 10% have resectable disease (1).

During the primary cholecystectomy for neoplastic and nonneoplastic gall bladders, risk of bile spillage either purposeful or accidental, is about 25% of preliminary surgeries (1).

Gall bladder emptying, and Bile spillage causes dissemination of cancer cells in 0.5% of the gall bladder surgeries. The leak can be from gall bladder, cystic duct or other parts of the biliary system (2).

To prevent unwanted and accidental bile spillage, surgeons should consider suspicious appearances of carcinoma such as irregular thickening of gall bladder wall, enlarged pericholecystic and hilar lymph-nodes, infiltration in the liver parenchyma, hard and shrunken gall bladder as well as polypoid lesions in the gall bladder (3,4).

Presence of suspicious findings should alert the surgeon not to attempt for primary resection and postpone the surgery to full workup by imaging studies such as magnetic resonance imaging (MRI) and computed tomography (CT) scan (1). In some centers, there is a high threshold of tissue biopsy for frozen section requesting upon the presence of thick-walled gall bladder, however it’s worthy to note that chronic long-standing cholecystitis with choledocholithiasis can cause significant increased gall bladder wall thickness as well (3). Also, frozen section cannot examine the whole tissue and entire lesion, so sometimes it’s difficult to distinguish cancer in situ from regenerative epithelial atypia by frozen section (5).

At any rate, incidental gall bladder cancers are surgical challenge for the surgeon to inform the patient, several days after cholecystectomy and to evaluate the patient for second revisional surgery (6,7).

Surgeons should be ready and prepared to manage a patient with incidentally detected gall bladder cancer. They should not forget about oncological main goals in the treatment of the cases with incidental gall bladder cancer. The surgeons should consider a two-stage approach (5,7).

Only T1a patients with clear margin and unbroken gallbladder can be treated with simple laparoscopy. Bile spillage is always a serious complication in these surgeries (8-10).

For patient’s stage T1b and above, an extended radical re-resection is highly recommended. It is because, patients with tumors staged higher than T1b might have residual disease including lymph node involvement, liver bed infiltration, and bile duct involvement (9-11). It should be mentioned that in some situations, re-operation after discovery of incidental gall bladder cancer is not possible because of patient’s unwillingness and advanced age (3).

Risk of bile spillage and port site metastasis is high, so an intact surgical specimen by using a plastic retrieval bag is advised by some authors to reduce the risks relapse (10). This is the reason for careful cholecystectomy avoiding any bile spillage, and the conversion from laparoscopic to open technique, when there is any suspicion or difficulty. This should not be considered as technical failure, and it is a decision for safer means to handle an unexpected situation to prevent declining the patients’ survival and surgical outcome (4). This is because, laparoscopic surgery for gall bladder cancer is still in the early phase of the learning curve, and more evidence is necessary before this procedure can be widely accepted as the procedure of choice for gall bladder cancers (9).

There are strong evidences shown that most important prognostic factors in gall bladder cancers are depth of invasion, extent of resection, and bile spillage (5).

Overall, the number of patients with incidental gall bladder cancer in the literature is not so high and clinical follow-up of these patients is not so long, so there is not a consensus or guideline for the management of incidental gall bladder cancer, however there is a theoretical concept of increased bile spillage and gall bladder cancer dissemination secondary to laparoscopic surgery and the post-operative incidental detection of gall bladder adenocarcinoma (9-15).

Acknowledgments

None.

Footnote

Conflicts of Interest: The author has no conflicts of interest to declare.

Ethical Statement: The author is 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.

References

1. Horkoff MJ, Ahmed Z, Xu Y, et al. Adverse Outcomes After Bile Spillage in Incidental Gallbladder Cancers: A Population-based Study. Ann Surg 2019. [Epub ahead of print]. [Crossref] [PubMed]
2. Geramizadeh B, Kashkooe A. Incidental Gall Bladder Adenocarcinoma in Cholecystectomy Specimens; A Single Center Experience and Review of the Literature. Middle East J Dig Dis 2018;10:249-53. [Crossref] [PubMed]
3. Antonakis P, Alexakis N, Mylonaki D, et al. Incidental finding of gallbladder carcinoma detected during or after laparoscopic cholecystectomy. Eur J Surg Oncol 2003;29:358-60. [Crossref] [PubMed]
4. Clemente G, Nuzzo G, De Rose AM, et al. Unexpected gallbladder cancer after laparoscopic cholecystectomy for acute cholecystitis: a worrisome picture. J Gastrointest Surg 2012;16:1462-8. [Crossref] [PubMed]
5. Tian YH, Ji X, Liu B, et al. Surgical treatment of incidental gallbladder cancer discovered during or following laparoscopic cholecystectomy. World J Surg 2015;39:746-52. [Crossref] [PubMed]
6. Waghmare RS, Kamat RN. Incidental Gall Bladder Carcinoma in Patients Undergoing Cholecystectomy: A Report of 7 Cases. J Assoc Physicians India 2014;62:793-6. [PubMed]
7. Kim JH, Kim WH, Kim JH, et al. Unsuspected gallbladder cancer diagnosed after laparoscopic cholecystectomy: focus on acute cholecystitis. World J Surg 2010;34:114-20. [Crossref] [PubMed]
8. Ahmad J, Mayne A, Zen Y, et al. Spilled gallstones during laparoscopic cholecystectomy. Ann R Coll Surg Engl 2014;96:e18-20. [Crossref] [PubMed]
9. Han HS, Yoon YS, Agarwal AK, et al. Laparoscopic Surgery for Gallbladder Cancer: An Expert Consensus Statement. Dig Surg 2019;36:1-6. [Crossref] [PubMed]
10. Pankaj K, Dubey V, Choudhuri AD. Patients Having Spillage of Bile and/or Gall Stone During Laparoscopic Cholecystectomy - Short Term Outcome. Available online: https://www.ijcmr.com/uploads/7/7/4/6/77464738/ijcmr_2099_v4.pdf
11. Rice DC, Memon MA, Jamison RL, et al. Long-term consequences of intraoperative spillage of bile and gallstones during laparoscopic cholecystectomy. J Gastrointest Surg 1997;1:85-90; discussion 90-1. [Crossref] [PubMed]
12. Yamaguchi J, Kaneoka Y, Maeda A, et al. Benefit of extended radical surgery for incidental gallbladder carcinoma. Surg Today 2016;46:453-9. [Crossref] [PubMed]
13. Yamashita S, Loyer E, Chun YS, et al. Laparoscopic Management of Gallbladder Cancer: A Stepwise Approach. Ann Surg Oncol 2016;23:892-3. [Crossref] [PubMed]
14. Patel K, Dajani K, Iype S, et al. Incidental non-benign gallbladder histopathology after cholecystectomy in an United Kingdom population: Need for routine histological analysis? World J Gastrointest Surg 2016;8:685-92. [Crossref] [PubMed]
15. Johnson RC, Fligelstone LJ, Wheeler MH, et al. Laparoscopic cholecystectomy: incidental carcinoma of the gallbladder with abdominal wall and axillary node metastasis. HPB Surg 1997;10:169-71. [Crossref] [PubMed]