38
Gallbladder and Pancreas

Kirstie Jarrett, MD¹ and Andrew Tang, MD²

¹ Banner University Medical Center, Tucson, AZ, USA

² Banner University Medical Center, University of Arizona College of Medicine, Tucson, AZ, USA

Which of the following is true regarding the natural history of asymptomatic cholelithiasis?
1. Less than 10% of patients will develop complications requiring cholecystectomy during their lifetime.
2. 20–30% of patients will develop complications requiring cholecystectomy during their lifetime.
3. Cholecystectomy is indicated for asymptomatic gallstones > 1 cm in diameter.
4. It is common for patients to develop acute cholecystitis without any prior symptoms of biliary colic.
5. It is never appropriate to perform a prophylactic cholecystectomy for asymptomatic gallstones.
Cholelithiasis is extremely prevalent and affects approximately 10% of the United States population. Most patients never go on to develop symptoms that warrant surgical intervention. In fact, only about 30% of patients with asymptomatic gallstones will develop complications that require cholecystectomy during their lifetime. Further, it is quite rare for a patient to develop severe complications (cholecystitis, cholangitis, pancreatitis, gallbladder cancer) from gallstones if they have not previously had symptoms of biliary colic. For these reasons, the risks of prophylactic cholecystectomy do not outweigh the potential benefits for most patients.

That being said, some patients are at a higher risk of developing severe complications and so are likely to benefit from prophylactic cholecystectomy in the setting of asymptomatic cholelithiasis. This includes patients with large (>2 cm) gallstones, hemolytic anemias, porcelain gallbladder (calcified gallbladder wall), and/or a long common bile duct or pancreatic duct. These patients are more likely to benefit from prophylactic cholecystectomy to reduce risk of gallstone complications and/or gallbladder cancer.

Answer: B

Festi D, Reggiani ML, Attili AF, et al. Natural history of gallstone disease: expectant management or active treatment? Results from a population‐based cohort study. Journal of Gastroenterology and Hepatology. 2010; 25(4):719–24.

Lammert F, Gurusamy K, Ko CW, et al. Gallstones. Nature Reviews Disease Primers. 2016; 2:16024.
A 50‐year‐old woman with a history of biliary colic presents to the emergency department with right upper quadrant pain and subjective fever that started 6 hours ago. Heart rate is 115 bpm, blood pressure is 110/70 mmHg, and she is febrile to 39.3 °C. On exam, she has mild jaundice, scleral icterus, and severe tenderness in the right upper quadrant. Which of the following is true regarding this constellation of signs when used as a diagnostic tool for acute cholangitis?
1. <5% of patients with acute cholecystitis are falsely diagnosed with acute cholangitis based on these findings.
2. Low sensitivity, high specificity.
3. High sensitivity, low specificity.
4. >50% of patients with acute cholecystitis are falsely diagnosed with acute cholangitis based on these findings.
5. Of these symptoms, abdominal pain is the most specific for acute cholangitis.
The 2007 Tokyo Guidelines (TG07) outlined data from a large, systematic review that compared Charcot’s Triad (fever, right upper quadrant abdominal pain, jaundice) to the gold standard for diagnosis of cholangitis (purulent bile, clinical improvement after biliary drainage, and/or remission after antibiotic therapy alone). This review showed that Charcot’s Triad had excellent specificity for diagnosing acute cholangitis (95.9%), but lacked sensitivity (26.4%). Based on these findings, a new set of diagnostic criteria were proposed. These criteria were revised in the 2013 Tokyo Guidelines (TG13) and were found to have significantly improved sensitivity (91.8%) with comparable specificity (77.7%) to Charcot’s Triad.

These criteria are based on three categories: inflammation (leukocytosis/elevated inflammatory markers and/or fever/chills), cholestasis (elevated bilirubin and/or jaundice/icterus), and imaging findings (ductal dilatation and/or obstruction). Inflammation plus either cholestasis or imaging evidence qualifies as “suspected diagnosis,” while patients who fulfill criteria in all three of the categories qualify for a “confirmed diagnosis.” The TG13 diagnostic criteria also showed a lower false‐positive rate in patients who were ultimately diagnosed with acute cholecystitis (5.9%) compared to Charcot’s Triad (11.9%), presumably because the TG13 criteria excluded abdominal pain and prior history of biliary disease.

Answer: B

Kiriyama S, Takada T, Strasberg SM, et al.; Tokyo Guidelines Revision Committee. TG13 guidelines for diagnosis and severity grading of acute cholangitis. Journal of Hepato‐biliary‐pancreatic Sciences. 2013; 20(1):24–34.

Wada K, Takada T, Kawarada Y, et al. Diagnostic criteria and severity assessment of acute cholangitis: Tokyo guidelines. Journal of Hepato‐biliary‐pancreatic Surgery. 2007; 14(1):52–8.
Which of the following is false regarding pigmented gallstones?
1. They form when heme breakdown products become concentrated in the bile.
2. Black pigment stones predominantly occur in the gallbladder and not the biliary tree.
3. Brown pigment stones are associated with biliary dysmotility and stasis.
4. Dark pigmentation comes from the combination of calcium and cholesterol, as opposed to pure cholesterol stones which are lighter in color.
5. Biliary infection is a risk factor for brown stone formation.
Gallstone formation results when bile becomes concentrated, when stone components become supersaturated in the bile, and/or when gallbladder dysmotility/stasis is present. There are two major types of gallstones: cholesterol and pigment stones. Cholesterol stones are most commonly a combination of precipitated cholesterol and calcium, while pure cholesterol gallstones account for less than 10% of the gallstones identified in the United States. Risk factors for cholesterol stone formation include high‐estrogen states, parenteral nutrition, advanced age, and rapid weight loss.

Pigment stones are further subclassified into black and brown stones. Black stones are more common and are formed when bile becomes super‐saturated with bilirubin and its metabolic conjugates, all of which are formed in the breakdown of heme. As such, black stones are almost always associated with diseases that cause hyperbilirubinemia (i.e., hemoglobinopathies, hemolytic diseases, cirrhosis). Because the super‐saturated bile is further concentrated in the gallbladder, black stones form nearly exclusively in the gallbladder. Brown pigment stones are made up of bilirubin as well, but also have a significant cholesterol content which makes them lighter in color. Brown stones can form anywhere along the biliary tract and arise when there is biliary stasis and/or infection.

Answer: D

Jackson PG, Evans SRT (2017). Biliary System. In Townsend CM, Beauchamp RD, Evers BM, Mattox KL (Ed.). Sabiston Textbook of Surgery: The Biological Basis of Modern Surgical Practice (20th edition). Philadelphia, PA: Elsevier Saunders.

Lammert F, Gurusamy K, Ko CW, et al. Gallstones. Nature Reviews Disease Primers. 2016; 2:16024.

A 76‐year‐old man with COPD (baseline oxygen requirement of 2L) and heart failure with ejection fraction of 35% presents to the emergency department with clinical and radiographic evidence of acute cholecystitis. His blood pressure is 91/55 mmHg, heart rate is 118 bpm, and he is requiring 6 L via nasal cannula to maintain SpO2 in the high 80s. He is mildly confused. He is admitted to the ICU where appropriate antibiotics and resuscitative measures are initiated. By noon the following day, his hypotension worsens and pressors are started. Which of the following is the best plan to achieve source control in this patient?

Laparoscopic cholecystectomy within 72 hours of admission.
Continued antibiotics and supportive care, cholecystectomy as soon as the patient is optimized and deemed an acceptable surgical candidate.
Urgent percutaneous cholecystostomy tube placement, cholecystectomy as soon as the patient is optimized and deemed an acceptable surgical candidate.
Urgent percutaneous cholecystostomy tube placement, outpatient cholecystectomy only if cholangiogram at 3 weeks shows persistent blockage of the cystic duct.

This patient, who is a poor surgical candidate at baseline, meets criteria for grade III cholecystitis (Table 38.1) based on the 2013 and 2018 Tokyo Guidelines (TG13 and TG18). Per TG18, it is reasonable to try nonoperative management with IV antibiotics and supportive therapy first. The patient in this scenario did not respond and in fact worsened after this treatment. While there has been some debate as to the best step from this point, the general consensus is that source control and gallbladder decompression should be achieved via placement of a percutaneous cholecystostomy (PC) tube.

The next step is definitive treatment with cholecystectomy, though timing will depend on patient‐specific factors. In patients with grade III cholecystitis who do not have significant baseline comorbidities, cholecystectomy should be completed as soon as the patient is stabilized from a sepsis standpoint. This patient, however, will also need to be medically optimized from a cardiopulmonary standpoint. The patient may be discharged home with the PC tube in place if he is suitable for discharge but not for major surgery. If he is discharged with the PC tube in place, the tube may be removed once the patient is asymptomatic and a cholangiogram demonstrates a patent cystic duct. However, per the 2018 Tokyo Guidelines, the only definitive management for calculous cholecystitis is cholecystectomy when able.

Table 38.1 TG13/18 severity grading for acute cholecystitis.

Source: Reproduced from Yokoe et al. (2018); with permission from publisher John Wiley and Sons.

Grade III (severe) acute cholecystitis

“Grade III” acute cholecystitis is associated with dysfunction of any one of the following organs/systems:

Cardiovascular dysfunction: hypotension requiring treatment with dopamine ≥5 μg/kg per min, or any dose of norepinephrine
Neurological dysfunction: decreased level of consciousness
Respiratory dysfunction: PaO₂/FiO₂ ratio <300
Renal dysfunction: oliguria, creatinine >2.0 mg/dL
Hepatic dysfunction: PT‐MR >1.5
Hematological dysfunction: platelet count <l00 000/mm³

Grade II (moderate) acute cholecystitis

“Grade II” acute cholecystitis is associated with any one of the following conditions:

Elevated WBC count (>18 000/mm³)
Palpable tender mass in the right upper abdominal quadrant
Duration of complaints >72 h^a
Marked local inflammation (gangrenous cholecystitis, perichollecystic abscess, hepatic abscess, biliary peritonitis, emphysematous cholecystitis)

Grade I (mild) acute cholecystitis

“Grade I” acute cholecystitis does not meet the criteria of “Grade III” or “Grade II” acute cholecystitis. It can also he defined as acute cholecystitis in a healthy patient with no organ dysfunction and mild inflammatory changes in the gallbladder, making cholecystectomy a safe and low‐risk operative procedure

Answer: C

Dimou FM, Riall TS. Proper use of cholecystostomy tubes. Advances in Surgery. 2018; 52(1):57–71.

Okamoto K, Suzuki K, Takada T, et al. Tokyo Guidelines 2018: flowchart for the management of acute cholecystitis. Journal of Hepato‐biliary‐pancreatic Sciences. 2018; 25(1):55–72.

A 35‐year‐old woman with a history of obesity and biliary colic has been admitted to the trauma ICU for the last 5 days after a motor vehicle crash in which she sustained a femur fracture, pelvic fractures, and multiple left‐sided rib fractures with an associated large left pneumothorax. On hospital day six, the patient develops fever to 39.5 °C, significant right‐sided abdominal pain and right upper quadrant tenderness, jaundice with total bilirubin of 4 mg/dL, alkaline phosphatase of 300 U/L, mild transaminitis, and a white blood cell count of 20 000/μL. Imaging reveals choledocholithiasis. Which of the following antibiotic regimens would be inappropriate at this time?
1. Ciprofloxacin and vancomycin
2. Piperacillin/tazobactam and vancomycin
3. Meropenem and linezolid
4. Cefepime and linezolid
5. Cefepime and daptomycin
The most common organisms isolated from both community‐acquired and healthcare‐associated biliary infections include E. coli, Klebsiella species, Pseudomonas species, and Enterococcus species. This patient has been hospitalized for >48 hours prior to development of cholangitis, which by definition is a hospital‐associated biliary infection. According to the 2018 Tokyo Guidelines, vancomycin should be added for all hospital‐associated biliary infections due to the increased risk of multidrug‐resistant Enterococcus species. If the patient has a history of vancomycin‐resistant Enterococcus (VRE) infection, has a severe vancomycin allergy, has already failed vancomycin therapy, and/or there is a high local prevalence of VRE in the area, daptomycin or linezolid may be substituted for vancomycin. Piperacillin/tazobactam, meropenem, and cefepime‐based regimens with the addition of vancomycin (or other Enterococcus‐covering agent) would all be appropriate options. Ciprofloxacin‐based therapy, however, would not be appropriate for hospital‐associated or grade III community‐acquired cholangitis due to high fluoroquinolone resistance in Gram‐negative extended‐spectrum beta‐lactamase (ESBL) species.

Answer: A

Gomi H, Solomkin JS, Schlossberg D, et al. Tokyo guidelines 2018: antimicrobial therapy for acute cholangitis and cholecystitis. Journal of Hepato‐biliary‐pancreatic Sciences. 2018; 25(1):3–16.
Which vessel is most commonly injured during laparoscopic cholecystectomy?
1. Proper hepatic artery
2. Left hepatic artery
3. Portal vein
4. Branches of the superior pancreaticoduodenal artery
5. Right hepatic artery
The right hepatic artery (RHA) is the most frequently injured vessel during laparoscopic cholecystectomy. This is likely related to its proximity to the common hepatic duct, which can be mistaken for an accessory duct or aberrant cystic duct during difficult dissections. Transection of the RHA typically results in brisk bleeding intraoperatively and may cause significant postoperative hemorrhage requiring reoperation or angioembolization. Occlusion of the RHA is often silent but can result in clinically relevant hepatic ischemia and/or abscess in about 10% of patients, some of whom go on to require partial hepatectomy.

Answer: E

Stewart L. Iatrogenic biliary injuries: identification, classification, and management. Surgical Clinics of North America. 2014; 94(2):297–310.

Strasberg SM, Helton WS. An analytical review of vasculobiliary injury in laparoscopic and open cholecystectomy. HPB (Oxford). 2011; 13(1):1–14.

A 32‐year‐old woman is currently admitted with grade II, community‐acquired, acute cholangitis with choledocholithiasis on ultrasound. She was started on appropriate antibiotic therapy when she was admitted last night and underwent urgent ERCP with successful removal of a large stone from the common bile duct. She is no longer febrile and has remained hemodynamically normal. She is scheduled for laparoscopic cholecystectomy tomorrow morning. What is the most appropriate duration of antibiotic therapy for this patient?

Four to 7 days after source control (ERCP).
Seven to 14 days after source control (ERCP).
Discontinue antibiotics now that the patient is afebrile and source control has been achieved.
Total 14‐day course of IV antibiotics to decrease the patient’s risk of infective endocarditis.
Continue antibiotics perioperatively, then discontinue after successful completion of cholecys‐ tectomy.

Per the 2018 Tokyo Guidelines, the appropriate treatment sequence for grade II (Table 38.2) acute cholangitis is: antibiotics and supportive care, urgent biliary drainage (ERCP vs. PTC), then subsequent definitive treatment of the cause of cholangitis (for this patient, cholecystectomy to decrease the risk of recurrent choledocholithiasis). Though source control has technically been achieved in this patient, continuation of antibiotics for an additional four to 7 days is recommended. It is also important to follow‐up on the results of this patient’s blood cultures. Gram‐positive bacteremia would necessitate a full 2 weeks of IV antibiotics to reduce her risk of infective endocarditis. While the majority of biliary flora are Gram‐negative, Enterococcus species are relatively common both in bile cultures and in blood cultures collected from cholangitis patients who developed bacteremia.

Table 38.2 TG13/18 severity grading for acute cholangitis.

Source: Reproduced from Kiriyama et al. (2018); with permission from publisher, John Wiley and Sons.

Grade III (severe) acute cholangitis

“Grade III” acute cholangitis is defined as acute cholangitis that is associated with the onset of dysfunction at least in any one of the following organs/systems:

Cardiovascular dysfunction: hypotension requiring dopamine ≥5 μg/kg per min, or any dose of norepinephrine
Neurological dysfunction: disturbance of consciousness
Respiratory dysfunction: PaO₂/FiO₂ ratio <300
Renal dysfunction: oliguria, serum creatinine >2.0 mg/dL
Hepatic dysfunction: PT‐INR >1.5
Hematological dysfunction: platelet count <l00 000/mm³