Postcholecystectomy Syndrome

Etiology

Early studies focused primarily on anatomic abnormalities identified at the time of exploratory surgery. An improved understanding of disorders/etiologies has grown with improvements in technology and imaging studies affecting the preoperative approach to these patients. Post-cholecystectomy syndrome may result from organic or functional diseases of the gastrointestinal tract and can be further classified based on the origin of symptoms[2][3][4]: 

• Most commonly, practitioners overlook extrabiliary disorders like reflux esophagitis, peptic ulcer disease, IBS, or pancreatitis as causes of post-cholecystectomy syndrome
• Primarily reported extrabiliary causes to include gastrointestinal causes like pancreatitis and its complications, pancreatic tumors, hepatitis, esophageal diseases, mesenteric ischemia, diverticulitis, and peptic ulcer disease
• However, biliary etiologies known to cause post-cholecystectomy syndrome include such as bile salt-induced diarrhea, retained calculi, bile leak, biliary strictures, cystic duct remnant, stenosis, and dyskinesia of the sphincter of Oddi
• Extra-intestinal causes like psychiatric and neurologic disorders, intercostal neuritis, wound neuroma, coronary artery disease, and unexplained pain syndromes can also cause symptoms consistent with post-cholecystectomy syndrome

Epidemiology

Approximately 500000 cholecystectomies were performed each year in the late 1990s in the United States; mostly laparoscopic. About 50000 or more cases of PCS occurred each year with at least 10% of patients developing PCS. The frequency of PCS varies widely in the literature with 5 to 30% of patients reported to have post-cholecystectomy syndrome. International incidence of post-cholecystectomy syndrome is almost identical to the United States. One study found that 65% of patients had no symptoms, 28% presented with mild symptoms, while only 2% had severe symptoms.[5] This study also found that the cause of post-cholecystectomy syndrome was by functional disorders in 26% of patients. Previous investigations attempted to evaluate the preoperative risk of cholecystectomy on the symptoms, but results were contradictory due to variations of the study design.[6] Although no preoperative risk stratification exists, certain factors make an individual more likely to develop PCS[7]:

• Urgent surgery presents a higher risk of developing PCS
• If cholelithiasis is present, 10-25% of patients develop PCS - if absent, approximately 30% develop PCS
• There is an exponential increase in the risk of developing PCS with increasing duration of preoperative symptoms
• About 20% of patients will develop PCS whether choledochotomy is performed or not

One study identified age and sex differences in the incidence of PCS with patients aged 20 to 29 years with an incidence of 43% while those aged 30 to 69 years had an incidence of 21 to 31% and a female-to-male incidence ratio of 1.8:1.[8]

Pathophysiology

The pathophysiology is related to alterations in bile flow suggested by the removal of the reservoir function of the gallbladder altering bile flow. Bile is thought to be the main trigger in patients with mild gastroduodenal symptoms or diarrhea. While our current knowledge about the pathophysiology of post-cholecystectomy syndrome has improved since the introduction of endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic sphincter of Oddi manometry (ESOM) in diagnostic circumstances, the pathophysiology is not yet fully understood. Post-cholecystectomy syndrome is thought to be caused by organic or functional disease of the gastrointestinal tract and can be further classified into patients with symptoms of non-biliary and biliary origin for systematic evaluation.

History and Physical

An accurate history and physical is essential towards guiding the workup towards diagnosing a patient with post-cholecystectomy syndrome as a wide range of symptoms may be noted. These symptoms often correlate with the gallbladder with 90% of patients presenting with colic, 75% presenting with pain, 38% with fever, 25% with jaundice, and about 35% with diarrhea or nausea.[8] The cause of PCS is identifiable in most patients. The workup varies based on the clinical presentation with a complete examination of the patient in an attempt to identify a specific etiology for the symptoms and exclude serious postcholecystectomy complications. Close attention is given to prior workup and diagnosis, surgical and pathologic findings, and any postoperative problems. Further workup is aimed at the most likely diagnosis while excluding other possible etiologies.

Evaluation

Initial post-cholecystectomy syndrome workup would usually include:

• Complete blood count (CBC) to eliminate infectious etiologies
• Complete metabolic panel (CMP), amylase, lipase, and prothrombin time (PT) to evaluate for possible hepatobiliary or pancreatic diseases
• A blood gas analysis if the patient is acutely toxic appearing

If the above are within reference ranges, repeating these studies when symptoms are present should be considered. Also, other laboratory studies may be indicated to rule out other etiologies including gamma-glutamyl transpeptidase (GGT), hepatitis panel, thyroid function, and cardiac enzymes.

Radiographic studies should also be pursued with chest radiography to screen for pulmonary and mediastinal conditions. Abdominal films should also be obtained in most cases. An abdominal ultrasound is a quick, inexpensive and noninvasive method to evaluate the hepatobiliary system, pancreas, and surrounding areas. Common bile duct (CBD) dilation of up to 10mm is normal, while dilation exceeding 10mm, in most cases, is diagnostic of obstruction distally suggestive of retained stone, CBD stricture, or ampullary stenosis. Computed tomography (CT) can assist in identifying pancreatitis or complications from pancreatitis such as pseudocysts. Nuclear imaging such as a hepatobiliary iminodiacetic acid (HIDA) scan may demonstrate a biliary leak or help identify sphincter of Oddi dysfunction as a potential cause although differentiation between stenosis and dyskinesia is difficult. Endoscopic ultrasonography (EUS) is a valuable tool for determining which patients would require endoscopic retrograde cholangiopancreatography (ERCP); the use of EUS aided in reducing the number of patients who received ERCP by 50% and may be useful in identifying cystic remnant stones.[9] Esophagogastroduodenoscopy (EGD) allows direct visualization of the ampulla of Vater and evaluates the mucosa throughout from the esophagus to the duodenum for signs of disease. ERCP is considered the most helpful test for diagnosis of the postcholecystectomy syndrome as about half the patients with PCS have a biliary etiology for the disease. Therapeutic maneuvers including stone extraction, sphincter dilation, or sphincterotomy can be performed at the time of the ERCP. Percutaneous transhepatic cholangiography (PTC) or magnetic resonance cholangiopancreatography (MRCP) is an option for those patients who are unable to undergo ERCP.

Treatment / Management

Post-cholecystectomy syndrome is generally a temporary diagnosis as further workup establishes an organic or functional diagnosis. Upon determining the diagnosis, treatment should be guided by the specific diagnosis made and may include pharmacologic or procedural approaches.

Pharmacologic approach

The goal of pharmacotherapy is to prevent complications and reduce morbidity. The following approaches may be pursued in the management of patients with PCS[10]:

• Administration of bulking agents, antispasmodics, or sedatives may be beneficial in patients with irritable bowel syndrome
• Cholestyramine may be helpful for patients with diarrhea alone
• For patients with GERD or gastritis symptoms, antacids, histamine-2 blockers, or proton-pump inhibitors may provide relief from symptoms
• One study demonstrated that patients with dyspeptic symptoms correlated with the concentration of gastric bile salt - however, this has not been reproducible; these patients may benefit from bile acid binders such as cholestyramine.

Procedural approach

Procedural therapy should point towards the specific diagnosis, just like pharmacologic therapy[3][11]. Surgery is an option when there is a well established and identifiable etiology known to respond to operative intervention. ERCP is the most commonly pursued procedure as it can be both diagnostic and therapeutic. Rarely, no cause of PCS is identifiable on initial workup and ERCP. In these cases, that may also prove to be refractory to medical therapy; exploratory surgery may be necessary. If exploration is unrevealing, the patient may respond to sphincteroplasty. 

In cases of post-cholecystectomy syndrome resulting from remnant cystic duct lithiasis or Mirizzi syndrome, stone extraction by endoscopic therapy may be sufficient. However, surgical excision of the remnant cystic duct may be necessary in some cases to prevent future development of PCS[12].(B2)

Differential Diagnosis

As symptoms of post-cholecystectomy syndrome may originate from other organic diseases of the gastrointestinal tract, differential diagnosis can be difficult and often extensive. To identify an underlying organic disorder, a thorough history, physical examination, laboratory studies, abdominal imaging, and/or endoscopy may be useful, which will help identify or rule out either biliary or non-biliary etiologies of PCS.

Prognosis

The outcome and prognosis in post-cholecystectomy syndrome vary by the patients and conditions encountered including the procedures that may be performed. One study showed that 75% of patients demonstrated good relief of pain on long-term follow-up.[13] Follow-up care should be emphasized by the physician to ensure appropriate postoperative management.

Complications

Complications after undergoing cholecystectomy include the development of diarrhea or bloating due to alteration of biliary flow. There is also the possibility of having a cystic duct remnant that could potentially lead to stone formation and cause Mirizzi syndrome. In patients with stent placement during ERCP, it is crucial to ensure timely removal of the biliary stent within 3 to 6 months to prevent the development of occlusion, migration of the stent or cholangitis.