Should I consider acute acalculous cholecystitis in my elderly ambulatory patient admitted with right upper quadrant pain?

Short answer: Yes! Although we usually associate acute acalculous cholecystitis (AAC) with critically ill patients (eg, with sepsis, trauma, shock, major burns) in ICUs, AAC is not as rare as we might think in ambulatory patients. In fact, a 7 year study of AAC involving multiple centers reported that AAC among outpatients was increasing in prevalence and accounted for 77% of all cases (1)!

 
Although the pathophysiology of ACC is not fully understood, bile stasis and ischemia of the gallbladder either due to microvascular or macrovascular pathology have been implicated as potential causes (2). One study found that 72% of outpatients who developed ACC had atherosclerotic disease associated with hypertension, coronary, peripheral or cerebral vascular disease, diabetes or congestive heart failure (1). Interestingly, in contrast to calculous cholecystitis, “multiple arterial occlusions” have been observed on pathological examination of the gallbladder in at least some patients with ACC and accordingly a name change to “acute ischemic cholecystitis” has been proposed (3).

 
AAC can also complicate acute mesenteric ischemia and may herald critical ischemia and mesenteric infarction (3). The fact that cystic artery is a terminal branch artery probably doesn’t help and leaves the gallbladder more vulnerable to ischemia when arterial blood flow is compromised irrespective of the cause (4).

 
Of course, besides vascular ischemia there are numerous other causes of ACC, including infectious (eg, viral hepatitis, cytomegalovirus, Epstein-Barr virus, Salmonella, brucellosis, malaria, Rickettsia and enteroviruses), as well as many non-infectious causes such as vasculitides and, more recently, check-point inhibitor toxicity (1,5-8).

 
Bonus Pearl: Did you know that in contrast to cholecystitis associated with gallstones (where females and 4th and 5th decade age groups predominate), ACC in ambulatory patients is generally more common among males and older age groups (mean age 65 y) (1)?

 

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References
1. Savoca PE, Longo WE, Zucker KA, et al. The increasing prevalence of acalculous cholecystitis in outpatients: Result of a 7-year study. Ann Surg 1990;211: 433-37. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1358029/pdf/annsurg00170-0061.pdf
2. Huffman JL, Schenker S. Acute acalculous cholecystitis: A review. Clin Gastroenterol Hepatol 2010;8:15-22. https://www.cghjournal.org/article/S1542-3565(09)00880-5/pdf
3. Hakala T, Nuutinene PJO, Ruokonen ET, et al. Microangiopathy in acute acalculous cholecystitis Br J Surg 1997;84:1249-52. https://bjssjournals.onlinelibrary.wiley.com/doi/abs/10.1046/j.1365-2168.1997.02775.x?sid=nlm%3Apubmed
4. Melo R, Pedro LM, Silvestre L, et al. Acute acalculous cholecystitis as a rare manifestation of chronic mesenteric ischemia. A case report. Int J Surg Case Rep 2016;25:207-11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4941110/
5. Aguilera-Alonso D, Median EVL, Del Rosal T, et al. Acalculous cholecystitis in a pediatric patient with Plasmodium falciparum infection: A case report and literature review. Ped Infect Dis J 2018;37: e43-e45. https://journals.lww.com/pidj/pages/articleviewer.aspx?year=2018&issue=02000&article=00020&type=Fulltext  
6. Kaya S, Eskazan AE, Ay N, et al. Acute acalculous cholecystitis due to viral hepatitis A. Case Rep Infect Dis 2013;Article ID 407182. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3784234/pdf/CRIM.ID2013-407182.pdf
7. Simoes AS, Marinhas A, Coelho P, et al. Acalculous acute cholecystitis during the course of an enteroviral infection. BMJ Case Rep 2013;12. https://casereports.bmj.com/content/12/4/e228306
8. Abu-Sbeih H, Tran CN, Ge PS, et al. Case series of cancer patients who developed cholecystitis related to immune checkpoint inhibitor treatment. J ImmunoTherapy of Cancer 2019;7:118. https://jitc.biomedcentral.com/articles/10.1186/s40425-019-0604-2

 

 

Should I consider acute acalculous cholecystitis in my elderly ambulatory patient admitted with right upper quadrant pain?

My patient with history of gastric bypass surgery now presents with right upper quadrant pain and gallstones. Is there a connection between gastric bypass surgery and gallstones?

An increased risk of new gallstones following gastric bypass surgery (GBS) has been reported by several studies (1-5).  More specifically, a study involving patients with baseline normal gallbladder ultrasound found that at 6 months following GBS 36% of patients developed gallstones and 13% developed sludge (4).  Similarly, a gallstone formation rate of 32% has been reported after GBS among patients who did not receive prophylactic treatment (5). 

New cholelithiasis following GBS may be largely attributed to rapid weight loss following this procedure, not the surgery itself or its related anatomical changes. Of interest, rapid weight loss, even by dieting, has been shown to increase the risk of gallstones (6).

However, overweight patients also have an increased risk of developing cholelithiasis at baseline, in part related to increased cholesterol secretion resulting in bile supersaturation with cholesterol (1).  Though weight loss may be expected to decrease this risk, rapid weight loss is thought to change the bile composition towards higher concentrations of calcium and cholesterol and increased production of gallbladder mucin, contributing to the pathogenicity of gallstone formation (5). 

In light of these findings, some have recommended routine prophylactic cholecystectomy as part of the GBS (7,8),  while others have argued against it (9,10), largely due to different observed rates of post-GBS symptomatic gallstones requiring cholecystectomies in various studies. Of note, post-operative ursodiol (ursodeoxycholic acid) may also reduce the incidence of post-GBS cholelithiasis (5,11). 
References

1. Everhart JE. Contributions of obesity and weight loss to gallstone disease. Ann Intern Med 1993;119(10):1029–35. https://www.ncbi.nlm.nih.gov/pubmed/8214980
2. Wudel LJ, Wright JK, Debelak JP, Allos TM, Shyr Y, Chapman WC. Prevention of gallstone formation in morbidly obese patients undergoing rapid weight loss: Results of a randomized controlled pilot study. J Surg Res 2002;102(1):50–6. https://www.ncbi.nlm.nih.gov/pubmed/11792152
3. Manatsathit W, Leelasincharoen P, Al-Hamid H, Szpunar S, Hawasli A. The incidence of cholelithiasis after sleeve gastrectomy and its association with weight loss: A two-centre retrospective cohort study. Int J Surg [Internet] 2016;30:13–8. Available from: http://dx.doi.org/10.1016/j.ijsu.2016.03.060 https://www.ncbi.nlm.nih.gov/pubmed/27063855
4. Shiffman M, Sugerman H, Kellum J, Brewer W, Moore E. Gallstone formation after rapid weight loss: a prospective study in patients undergoing gastric bypass surgery for treatment of morbid obesity. Am J Gastroenterol 1991;(86):1000–5. https://www.ncbi.nlm.nih.gov/pubmed/1858735
5. Sugerman H, Brewer W, Shiffman M, et al. A Multicenter, Placebo-Controlled, Randomized, Double-Blind, Prospective Trial of Prophylactic Ursodiol for the Prevention of Gallstone Formation Rapid Weight Loss. Am Jourmal Surg 1995;169(January):91–7. https://www.ncbi.nlm.nih.gov/pubmed/7818005

6. de Oliverira CIB, Chaim EA, da Silva BB. Impact of rapid weight reduction on risk of cholelithiasis after bariatric surgery. Obesity Surgery 2003;13:625-8.
7. Tarantino I, Warschkow R, Steffen T, Bisang P, Schultes B, Thurnheer M. Is routine cholecystectomy justified in severely obese patients undergoing a laparoscopic Roux-en-Y gastric bypass procedure? A comparative cohort study. Obes Surg 2011;21(12):1870–8. https://reference.medscape.com/medline/abstract/21863228
8. Amstutz S, Michel JM, Kopp S, Egger B. Potential Benefits of Prophylactic Cholecystectomy in Patients Undergoing Bariatric Bypass Surgery. Obes Surg 2015;25(11):2054–60. https://link.springer.com/article/10.1007%2Fs11695-015-1650-6
9. Karadeniz M, Gorgun M, Kara C. The evaluation of gallstone formation in patients undergoing Roux-en -Y gastric bypass due to morbid obesity. Turkish J Surg 2014;30(2):76–9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4379817/
10. D’Hondt M, Sergeant G, Deylgat B, Devriendt D, Van Rooy F, Vansteenkiste F. Prophylactic Cholecystectomy, a Mandatory Step in Morbidly Obese Patients Undergoing Laparoscopic Roux-en-Y Gastric Bypass? J Gastrointest Surg 2011;15(9):1532–6. https://www.ncbi.nlm.nih.gov/pubmed/21751078
11. Miller K, Hell E, Lang B, Lengauer E. Gallstone Formation Prophylaxis after Gastric Restrictive Procedures for Weight Loss: A Randomized Double-Blind Placebo-Controlled Trial. Ann Surg 2003;238(5):697–702. https://www.ncbi.nlm.nih.gov/pubmed/14578732

Contributed by Kim Schaefer, Harvard medical student, Boston, MA. 

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My patient with history of gastric bypass surgery now presents with right upper quadrant pain and gallstones. Is there a connection between gastric bypass surgery and gallstones?

What is the clinical significance of “white bile” from my patient’s gallbladder drain?

“White bile” (WB) (Figure) is a clear sero-mucous secretion of gallbladder that is largely devoid of bilirubin and bile salts. It arises from glycoproteins that are normally secreted by the mucosal glands of the gallbladder infundibulum and neck, and is thought to shield the gallbladder wall from the lytic action of bile.

WB is observed in “hydrops” of gallbladder and is caused by absorption of bile by the gallbladder wall in the setting of persistent cystic duct obstruction1. It is commonly held that in persistent cystic duct obstruction, bile in the gallbladder is eventually absorbed into the lymphatics and blood vessels but that the gallbladder epithelium continues to produce clear sero-mucous secretions. In this setting, dilatation, perforation, and atrophy of the gallbladder lumen may also occur1-3.  Early cholecystostomy tube placement or cholecystectomy is often indicated1,3.

Common etiologies of persistent cystic duct blockage in adults include, stone impaction, cystic duct stenosis, tumors/polyps, and parasites (eg, ascariasis).

Figure: “White bile” drainage from a cholecystostomy drain of a patient with cholecystitis and persistent cystic duct blockage due to stones. The drainage was completely clear with mucous characteristics. 

whitebile

Reference:

  1. Schwartz, Seymour I, Brunicardi, F. Charles., eds. Schwartz’s Principles Of Surgery. New York : McGraw-Hill Medical, 2011.
  2. Ahmed A, Cheung RC, Keeffe EB. Management of gallstones and their complications. Am Fam Physician 2000; 61, 1673-1680.
  3. Lawrence S. Friedman, Mark Feldman. Sleisenger and Fordtran’s Gastrointestinal and Liver Disease 10th Edition. Philadelphia, PA: Elsevier, 2015.

Contributed by Alireza Sameie, Medical Student, Harvard Medical School

What is the clinical significance of “white bile” from my patient’s gallbladder drain?