Mirizzi’s syndrome

Introduction

• Mirizzi’s syndrome is caused by an impacted gallstone in the cystic duct or the neck of the gallbladder that compresses the adjacent bile duct and results in complete or partial obstruction of the common hepatic bile duct.
  
• It is often not recognized preoperatively, which can lead to significant morbidity and biliary injury, particularly with laparoscopic surgery.

In 1905, Kehr first reported on external compression of the bile duct following stone impaction in the cystic duct. However, the syndrome was named after the Argentinian surgeon Pablo Mirizzi, who described in 1948 a hepatic duct obstruction due to cholelithiasis and cholecystitis as “syndrome del conducto hepatico”

Incidence

• In the largest series, including 17,000 patients undergoing open surgery for gallstone disease, 219 patients (1.3%) had Mirizzi’s syndrome and/or cholecystobiliary fistula.

• This figure may rise up to 2.7% in high-risk populations such as native American Indians.
  
• The recently published, largest series of 13,023 cases on laparoscopic cholecystectomy found Mirizzi’s syndrome and/or cholecystobiliary fistula in 0.3% of patients.
  
• Approximately 50 to 77% of all patients reported are women, probably reflecting the increased incidence of the gallstone disease in the female population.

A correlation was also noted between the stage of the disease and the mean age of patients.

• In patients with type A disease the mean age was 44 years while the mean age was 62 years in patients with type C compression.

Classification

McSherry et al. initially classified this syndrome into two types.

• Type I involves the external compression of the common hepatic duct due to a stone impacted in the neck of the gallbladder or the cystic duct.
  
• Type II refers to cholecystocholedochal fistula and stone migration into the common hepatic duct.

A further modification of this classification was suggested by Csendes et al., in which

• type II is an obstruction that involves less than one-third of the bile duct,
  
• type III is an obstruction involving up to two-thirds of the duct, and
  
• type IV is complete obstruction of the bile duct.

The third classification expanded the definition of the Mirizzi syndrome :

• Type I referred to a stone impacted in the cystic duct or gallbladder neck.
• Type II was characterized by a fistula of the common duct.
• Type III was defined by hepatic duct stenosis due to a stone at the confluence of the hepatic and cystic ducts.
• Type IV was characterized by hepatic duct stenosis as a complication of cholecystitis in the absence of calculi impacted in the cystic duct or gallbladder neck.

Pathophysiology

• Mirizzi’s syndrome may be caused by either a single large stone or multiple small stones impacted in the Hartmann’s pouch of the gallbladder or in the cystic duct.
• Anatomically, a long cystic duct parallel to the bile duct predisposes to the development of this syndrome.
• Recurrent cystic duct obstruction may lead to recurrent attacks of cholecystitis and may cause gallbladder dilatation, thickening, and inflammation.
  

Impaction of a large gallstone (or multiple small gallstones) in the Hartmann pouch or cystic duct results in the Mirizzi syndrome in 2 ways:

• (1) chronic and/or acute inflammatory changes lead to contraction of the gallbladder,
  • which then fuses with and causes secondary stenosis of the CHD,
    
  • there may present episodes of cholangitis which further increases inflammatory process,
• (2) large impacted stones lead to cholecystocholedochal fistula formation secondary to direct pressure necrosis of the adjacent duct walls.
  
• Increasingly, these phenomena are seen not as distinct and separate steps but as part of a continuum.
• This hypothesis is supported by the observation that in most cases the cholecystocholedochal fistula is occupied by a large impacted gallstone in the fistula tract.

Clinical signs

Mirizzi’s syndrome is typically seen in the setting of longstanding biliary symptoms.

• Obstructive jaundice is the key feature of Mirizzi’s syndrome and is frequently accompanied by pain and fever.
  
• This presentation often suggests acute cholangitis.
  
• Rarely, patients may be anicteric at presentation.

• Patients can also present with cholecystitis or pancreatitis.

Laboratory data are not specific, with hyperbilirubinemia as the most encountered laboratory abnormality. Elevated levels of alkaline phosphatase and transaminases are also common. Leukocytosis is a frequent presence in concomitant acute cholecystitis, pancreatitis, or cholangitis.

Diagnosis

• In clinical practice, the diagnosis is rarely made preoperatively.

The diagnostic approach usually begins with ultrasonography followed by cholangiography via direct cholangiography, endoscopic retrograde cholangiopancreatography, or magnetic resonance cholangiography.

Endoscopic retrograde cholangiopancreatography (ERCP) is the procedure of choice to establish the diagnosis and to classify the lesion.

• Mirizzi type A presents as an extrinsic compression of the common hepatic duct by a distended gallbladder with dilatation of the intrahepatic biliary tree.
  
• ERCP is also essential in determining the presence of a fistula preoperatively.
  
• Percutaneous transhepatic cholangiography (PTC) can provide similar information.
  
• However, ERCP can identify a low-lying cystic duct that may be missed by PTC.
• In addition, PTC may not visualize the distal common bile duct because of the obstruction in the hepatic duct.
  
• Finally, as discussed below, ERCP offers the opportunity to exercise a variety of therapeutic options including stone retrieval and stenting.

Ultrasonography generally reveals gallstones and a contracted gallbladder. Features suggestive of Mirizzi syndrome include :

• Dilatation of the biliary system above the level of the gallbladder neck.
• The presence of a stone impacted in the gallbladder neck.
• An abrupt change to a normal width of the common duct below the level of the stone.

The literature regarding the use of a CT scan for the diagnosis of Mirizzi’s syndrome is controversial.

• Some authors feel that CT does not provide any additional information beyond what can be obtained with ultrasonography; also, the presence of periductal inflammation can be misinterpreted as carcinoma of the gallbladder.
  
• Overall, CT may be helpful in excluding malignancies in the pancreas, the porta hepatis area, or the liver.

The differential diagnosis includes other causes of obstructive jaundice such as malignancies (e.g., cholangiocarcinoma, carcinoma of the gallbladder, or pancreatic cancer) and sclerosing cholangitis.

Treatment

Surgery remains the treatment of choice for Mirizzi’s syndrome.

• The choice of surgery is determined by whether a fistula into the bile duct is present.
  
• The common surgical approach is usually an incision in the gallbladder fundus and removal of the impacted stone.
  
• A gush of bile indicates a fistula, because the cystic duct is usually occluded.

A standardized surgical approach has been recommended based on the classification of the variants of Mirizzi syndrome:

• Type I — Cholecystectomy plus common bile duct exploration with T-tube placement. Exploration should be performed only if the CBD is easily exposed.

• Type II — Suture of the fistula with absorbable material or choledochoplasty with the remnant gallbladder.
  

• Type III — Choledochoplasty; suture of the fistula is not indicated.

• Type IV — Bilioenteric anastomosis is preferred since the entire wall of the common bile duct has been destroyed.

In any case, excellent drainage should be achieved.

A serious complication of the surgical approach is the ligation of the hepatic duct because a normal caliber hepatic duct may be mistaken for a dilated cystic duct that runs parallel to it.

Laparoscopic surgery —

• The Mirizzi syndrome presents a difficult challenge for laparoscopic surgery because the dense adhesions and edematous inflammatory tissue cause distortion of the normal anatomy and increase the risk for biliary injury.
  
• Thus, the use of laparoscopic surgery as the primary treatment of Mirizzi syndrome is controversial, although it appears to be feasible, especially for type I anatomy.
  
• It has been suggested that a prudent policy is to perform a dissection trial and convert to an open procedure if local conditions are not clear for an experienced laparoscopic surgeon.
• The largest series on Mirizzi’s syndrome identified during laparoscopic cholecystectomy reported a conversion rate of 71% for type A and 100% for type B/C.

Endoscopic therapy —

• The endoscopic treatment is not only for the evaluation, but also for the treatment of Mirizzi’s syndrome.
  
• Whether it is used as primary therapy or in addition to surgical treatment, ERCP is an attractive alternative and may be the only option for high-risk patients.
  
• In general, endoscopic management includes both biliary drainage and stone removal.
  
• Endoscopic sphincterotomy is generally recommended for stone extraction.
  
• Standard stone removal techniques are usually used and include baskets, balloons, and mechanical and electrohydraulic lithotripsy.
  
• The latter may be a valuable modality if standard techniques have failed.
  
• However, multiple treatment sessions may be required and leakage of contrast material from the cystic duct into the peritoneal cavity has been described after the fragmentation of large stones.

Further advances in the design of retrograde cholangioscopes may make this option more attractive in the future.

Association with cancer —

• The Mirizzi syndrome has been associated with a high frequency of gallbladder cancer.
  
• In one series of 1759 cholecystectomies, 18 cases of Mirizzi syndrome were identified; five (28 percent) had coincidental gallbladder carcinoma (versus only 2 percent in the patients without Mirizzi syndrome).
  
• An intraoperative frozen section of the gallbladder wall should be sampled.—in particular in the presence of markedly elevated CA 19-9 levels—to exclude carcinoma.

The patients with gallbladder carcinoma had a longer history of preexistent gallbladder disease (10.4 versus 6.8 years in those without carcinoma).

• The serum concentration of the tumor-associated antigen CA 19-9 was elevated in 12 of the 18 patients with Mirizzi syndrome but was significantly higher in those with malignancy (peaking at 1000 U/mL).

Although gallbladder carcinoma may be common in patients with Mirizzi syndrome, the latter disorder is unusual among patients with gallbladder carcinoma.

Mortality and morbidity

• In the largest series, Csendes reported no operative mortality (within 30 days of operation) in patients with type 1 disease, 2 to 12% with type 2, and 11% with type 3 disease.

Late mortality due to biliary disease was below 5% with any stages of the disease.

• The largest series of Mirizzi’s syndrome, which was found during intended laparosopic cholecystectomy, had no mortality for all types.

Postoperative morbidity includes mainly the development of

• external biliary fistula,
  
• bile peritonitis, and
  
• subphrenic abscess.
  
• The incidence of benign strictures of the bile duct occurs in 4 to 11% of patients.