Introduction

Mirizzi syndrome is a rare condition caused by the obstruction of the common bile duct or common hepatic duct by external compression from multiple impacted gallstones or a single large impacted gallstone in Hartman's pouch. Presenting symptoms are similar to cholecystitis but may be confused with other obstructing conditions such as common bile duct stones and ascending cholangitis due to the presence of jaundice. Preoperative diagnosis is often difficult and usually missed. This syndrome is named after the Argentinean surgeon Pablo Luis Mirizzi. He was born in 1893 in Cordoba Argentina. Mirizzi graduated from the Medical Sciences School at the National University of Cordoba in 1915. His most well-known contribution to surgery is having performed the first intraoperative cholangiogram in 1931. The first published paper describing the syndrome which bears his name today was in 1940.[1]

Etiology

Gallstones are usually formed from bile that is in stasis. When bile is not fully emptied from the gallbladder, it can precipitate as sludge and subsequently turn into stones. Biliary obstruction may also lead to gallstones including bile duct strictures and cancers, such as pancreatic cancer. The most common cause of cholelithiasis is from the precipitation of cholesterol that subsequently forms into cholesterol stones. The second form of gallstones is pigmented gallstones which are the result of increased red blood cell destruction in the intravascular system causing increased concentrations of bilirubin which subsequently get stored in the bile. These stones are typically black. The third type of gallstones is mixed pigmented stones which are a combination of calcium substrates such as calcium carbonate or calcium phosphate, cholesterol and bile. The fourth type is made up primarily of calcium and usually found in patients with hypercalcemia. When multiple gallstones or a singular large gallstone get impacted in Hartman's pouch (the lower outpouching of the gallbladder), external compression of the common bile duct or the common hepatic duct can occur. The exact mechanism as to why this occurs is unknown, but it is felt to be related to a floppy Hartman's pouch containing a higher mass of stones such as with multiple stones or a single large impacted stone. This causes subsequent inflammation of the are which can also lead to fistula formation over time.[2]

Epidemiology

Epidemiology of gallstones must first be understood. Most gallstones are asymptomatic. In the United States, approximately 14 million men and 6 million women with an age range of 20 to 74 have gallstones. The prevalence increases as a person ages. Obesity increases the likelihood of gallstones, especially in women due to increases in the biliary secretion of cholesterol. On the other hand, patients with drastic weight loss or fasting have a higher chance of gallstones secondary to biliary stasis. Furthermore, there is also a hormonal association with gallstones. Estrogen has been shown to result in an increase in bile cholesterol as well as a decrease in gallbladder contractility. Women of reproductive age or on birth control medication that have estrogen have a 2-fold increase in gallstone formation compared to males. People with chronic illnesses such as diabetes also have an increase in gallstone formation as well as reduced gallbladder wall contractility due to neuropathy.

Mirizzi syndrome is relatively uncommon. Only 0.1% of patients with gallstones will develop this condition, and it has been found in 0.7% to 25% of patients who have undergone cholecystectomies. There may be an increase in occurrence in the older populations, but there has not been a predilection for either male or female patients who have gallstones. There also appears to be no prevalence for any particular ethnic population.[3]

Pathophysiology

Gallstones occur when substances in the bile reach their limits of solubility. As bile becomes concentrated in the gallbladder, it becomes supersaturated with these substances, which in time precipitate into small crystals. These crystals, in turn, become stuck in the gallbladder mucus, resulting in gallbladder sludge. Over time, these crystals grow and form large and/or multiple stones. These gallstones may cause symptoms of cholecystitis, but if they become embedded in a floppy Hartman's pouch, they can cause additional findings of jaundice. As this condition progresses, internal fistulas from the gallbladder into the common bile duct, common hepatic duct (CHD) and the duodenum can develop. A grading system has been developed to categorize the various stages of Mirizzi syndrome.

Type I: No Fistula Present

• Type IA: Presence of the cystic duct
• Type IB: Obliteration of the cystic duct

Types II to IV: Fistula Present

• Type II: Defect smaller than 33% of the CHD diameter
• Type III: Defect 33% to 66% of the CHD diameter
• Type IV: Defect larger than 66% of the CHD diameter[4]

Histopathology

Findings of acute or chronic cholecystitis can be found on histology. The gallbladder wall may be thickened to variable degrees, and there may be adhesions to the serosal surface. Smooth muscle hypertrophy, especially in prolonged chronic conditions, is present. Calcium bilirubinate or cholesterol stones are most often present and can vary in size from sand-like to filling the entire gallbladder lumen. They can be multiple or singular. The acalculous disease may reveal sludge or very viscous bile. These findings are usual precursors to gallstones and are formed from increased biliary salts or stasis. Normal appearing bile can also be present. Various species of bacteria can be found in 11% to 30% of the cases. Rokitansky-Aschoff sinuses are present 90% of the time in cholecystitis specimens. These are a herniation of intraluminal sinuses from increased pressures possibly associated with ducts of Luschka. The mucosa will exhibit varying degrees of inflammation.

There is an increased risk of developing gallbladder cancer with Mirizzi's syndrome. The exact etiology is unclear but is felt to be due to persistent and recurrent irritation of the area and chronic biliary stasis. 5% to 28% of patients with Mirizzi syndrome were found to have gallbladder cancer after cholecystectomy. Virtually all diagnoses were made postoperatively with pathologic examination of the specimens.[5]

History and Physical

The presentation of Mirizzi syndrome is usually that of acute or chronic cholecystitis with the addition of jaundice. Patients with chronic cholecystitis usually present with dull right upper abdominal pain that radiates to the mid back or right scapular tip. It is usually associated with fatty food ingestion. Nausea and occasional vomiting also accompany complaints of increased bloating and flatulence. Often the symptoms occur in the evening. Prolonged less acute symptoms are usually present over weeks or months. Increased frequency and severeness of acute exacerbations (acute biliary colic) is usually seen in the presence of more prolonged chronic symptoms. The classic physical examination will demonstrate right upper abdominal pain with deep palpation (Murphy's sign). Patients are usually not acutely ill but are uncomfortable. Patients with advanced Mirizzi syndrome or of more severe acute cholecystitis may present with more pronounced symptoms and findings. Jaundice is usually present, and at times, significantly elevated bilirubin can be identified.[6]

Evaluation

The routine workup for cholecystitis should be initiated. The best test for diagnosing gallstones and subsequent acute cholecystitis is a right upper quadrant abdominal ultrasound. It is associated with a 90% specificity rate and depending on the ultrasound operator, can detect stones as small as 2 mm as well as sludge and gallbladder polyps. Ultrasound findings that point toward acute cholecystitis versus cholelithiasis include gallbladder wall thickening (greater than 3 mm), pericholecystic fluid and a positive sonographic Murphy's sign. Gallstones can also often be found on CT scans, and MRIs, however, these studies are not as sensitive for acute cholecystitis. Approximately 10% of gallstones may be found on routine plain films due to their high calcium content. Air in the biliary tree may also be detected on these radiographic studies if there is an enteric fistula present. If there is a suspected stone in the common bile duct based on ultrasound results, magnetic resonance cholangiopancreatography (MRCP) is the next step. If a common duct stone is identified on the MRCP, then the gold-standard test of an endoscopic retrograde cholangiopancreatogram (ERCP) should be performed by a gastroenterologist. A percutaneous transhepatic cholangiogram (PTHC) is also useful in diagnosing common bile duct stones if an ERCP is not possible. Usually, the diagnosis of Mirizzi syndrome is either mistaken for a simple common bile duct stone or is missed entirely on preoperative workup.[7]

Differential Diagnosis

Many other conditions can mimic gallbladder disease. Patients who present with acute biliary colic are often worked up for cardiac issues. Other common conditions with similar presenting symptoms are:[8]

• Peptic ulcer disease
• Irritable bowel disease
• Inflammatory bowel disease
• Gastroesophageal reflux disease
• Pulmonary embolism

The presence of jaundice in combination with the other presenting symptoms in Mirizzi syndrome is usually mistaken for other etiologies such as:

• Common bile duct stones
• Ascending cholangitis
• Biliary cancer
• Pancreatic tumors

Other medical conditions to consider, that may mimic Mirizzi syndrome include:

• Acute hepatitis
• Ischemic liver disease
• Drug-induced hepatitis

Prognosis

In patients without fistula formation, the surgical repair and outcome is usually favorable. Due to the distorted anatomy and high rate of conversion to open cholecystectomy for this disease; however, some sources recommend an open surgical approach for all patients affected by Mirizzi syndrome. The prognosis for patients with fistula formation involves prolonged treatment with T-tube placement through the small-moderate sized fistula or biliary diversion with a choledochoduodenostomy or a Roux-en-Y choledochojejunostomy for larger fistulas. Prolonged surgical and hospital course for the latter group of patients increases their risk of complications and increases the morbidity and mortality rate for these patients as well. Gallbladder cancer has been associated with Mirizzi syndrome as well, although this is thought to be due to prolonged inflammation leading to both diseases, rather than a result of Mirizzi syndrome itself.[10] In elderly patients with multiple comorbidities and high risk of surgical complications, nonoperative methods should be considered to minimize morbidity associated with the surgery.[11]

Complications

The most common complication of Mirizzi syndrome is cholecystobiliary or cholecysto-enteric fistula formation due to prolonged inflammation. Surgical complications with prolonged procedure time due to dense adhesions may also occur. These include bile duct injury and hemorrhage. Massive hemorrhage during dissection of the Calot triangle can occur in complex cases. Other complications of prolonged inflammation that can be seen in patients with Mirizzi syndrome include:

• Cutaneous fistula formation
• Secondary biliary cirrhosis
• Delayed onset biliary strictures[12]

Deterrence and Patient Education

Patient education on medical compliance, clinical follow-up and wound care is essential, especially in patients who required stent placement, biliary diversion, choledochoduodenostomy, or a Roux-en-Y choledochojejunostomy. Patients should be educated intensively on discharge and referred to wound care nursing if needed to prevent secondary infections and their associated complications. 

Pearls and Other Issues

Mirizzi syndrome often is not diagnosed preoperatively. Awareness of this condition with the knowledge of appropriate treatment is essential. The surgeon must also entertain the possibility of the presence of occult gallbladder cancer.

Enhancing Healthcare Team Outcomes

An interprofessional approach must be taken for this condition. Accurate diagnosis with an accurate evaluation of the extent of this disease must be concluded by all involved. The surgeon is the main specialist for diagnosis and treatment but familiarity and a high degree of suspicion of this condition must be present by the initially treating primary caregiver or emergency physician. Delay in making an adequate diagnosis and treatment could lead to the progression of this condition with increased patient morbidity and mortality.