Original Article

Mirizzi syndrome: a diagnostic and operative challenge

C.Y. Chan K.H. Liau C.K. Ho S.P. Chew
Hepatobiliary Unit, Department of General Surgery, Clinical Staff Office 4B, Tan Tock Seng Hospital, Singapore 308433

Correspondence to: S.P. Chew, Hepatobiliary Unit, Department of General Surgery, Clinical Staff Office 4B, Tan Tock Seng Hospital, Singapore 308433 Email: chew_soo_ping@ttsh.com.sq

Introduction Materials and methods Results

Discussion Conclusion References

Keywords: Mirizzi syndrome, cholecystobiliary fistula, choledochoduodenostomy, hepaticojejunostomy, laparoscopic cholecystectomy Surg J R Coll Surg Edinb Irel., 1 October 2003, 273-278

Introduction: Mirizzi syndrome (MS) is an unusual complication of gallstone disease. The majority of cases are not identified pre-operatively, despite advances in imaging techniques. Materials and Methods: Eighteen cases of MS were treated between January 1997 and April 2002. The clinical presentation, modes of investigation, surgical management and outcome are retrospectively reviewed. Results: There were 13 female and 5 male patients, with a mean age of 60 years. Seven patients presented with the classical Charcot’s triad. Ultrasonography (US) was the first imaging investigation in 13 patients and computerised tomography (CT) in the other five cases. Eleven patients had a successful endoscopic retrograde cholangio-pancreatography (ERCP) carried out. Diagnosis of MS was arrived at in seven patients following pre-operative imagings. Overall, 11 patients had Type 1 and seven patients had Type 2 MS. In the group with Type 1 MS, nine patients underwent open cholecystectomy, of whom six had concomitant common bile duct (CBD) exploration for stones and one patient with biliary stenosis had a hepaticojejunostomy bypass. Laparoscopic cholecystectomy was attempted in two patients, with successful completion in one case. In the group with Type 2 MS, four fistulas were closed surgically, the other three had biliary bypass procedures. Conclusion: Mirizzi syndrome is an unusual condition that poses diagnostic and operative challenges to the surgeon. With a judicious approach during dissection and early recognition of its presence, bile duct injury can be avoided. Good outcome can be achieved with an appropriate surgical procedure

INTRODUCTION
Mirizzi syndrome (MS) was first described in 1948, and comprises of four components: parallel course of the cystic duct to the common hepatic duct (CHD); impaction of stones in the cystic duct or neck of the gallbladder; mechanical obstruction of the CHD by the stones or secondary inflammation and intermittent or constant jaundice and recurrent cholangitis (Figure 1 and 2).¹ Mirizzi syndrome occurs in about 1% of all patients with cholelithiasis. It often escapes detection due to its intermittent symptoms and the limitation of radiological imagings. In MS, the distorted biliary anatomy and marked scarring of the subhepatic space around Calot’s triangle, makes surgery difficult and with a significant risk of biliary complications, especially in undiagnosed or unsuspected cases.² Eighteen cases of MS were found when operative records of all cholecystectomies over a five-year period (January 1997 to April 2002) carried out in our department were reviewed. Patients’ demographics, clinical presentation, pre-operative investigations, operative management, and post-operative outcomes were analysed. Long-term outcome was correlated with the operative procedures employed.

MATERIALS AND METHODS
This is a retrospective analysis of the 18 patients who underwent operative management for MS at Tan Tock Seng Hospital in a consecutive period of five years from January 1997 to April 2002. Clinical data and operative findings were obtained from case records, and radiological films were reviewed. Clinical presentation, modes of investigation, management and subsequent progress are reported.

RESULTS

Demographics and Presentation (Table 1)
There were 13 female and 5 male patients, ranging in ages from 32 to 86 years with a mean age of 60. This represents 0.89% of 2033 patients treated for biliary lithiasis during the same period. Sixteen patients were admitted as emergencies and underwent surgery during the same admission. Two patients underwent elective operations. One had presented with cholangitis that resolved with antibiotic therapy. Radiologic workup, using US, ERCP and CT, had revealed stones in the CBD. Mirizzi syndrome was not apparent on all three imagings but an ovarian tumour was incidentally noted on the CT scan. Elective operation was performed after consultation with the gynaecologist. Findings during operation were of a Type 2 MS and a right ovarian fibroma. Cholecystectomy, removal of CBD stones and primary closure of the fistula, as well as hysterectomy and bilateral salphingo-oophorectomy were performed. The other patient had a history of a perforated duodenal ulcer. Abdominal CT at the time revealed a thick-walled gallbladder with gallstones. The patient continued to experience abdominal pain due to biliary colic after the ulcer had been healed. Laparoscopic cholecystectomy was performed and a Type 1 MS was noted during surgery.

All except one patient had complained of upper abdominal pain at the time of presentation; 13 patients had jaundice and 10 patients had fever. Seven patients had the classical Charcot’s triad. Ten patients had associated nausea and/or vomiting. None of the patients were previously diagnosed to have gallstones, and neither was there a history suggesting a long-standing problem of biliary disease prior to presentation.

Figure 1: ERCP cholangiogram showing dilated CHD and intra-hepatic ducts with normal CBD and filling defect at cystic duct/CBD junction - Mirizzi syndrome. (See schematic illustration below)

Figure 2: Sketch representation of Figure. 1 demonstrating Mirizzi syndrome

Diagnostic Investigations (Table 1)
Sixteen patients had biochemical evidence of hyperbilirubinaemia with a mean of 82 umol/L (range 32-162umol/ L), 15 had a raised alkaline phosphatase (ALP) with a mean of 518 U/L (range 114-1365U/L). Ultrasonography scan was the first imaging in 13 patients. Dilatation of the extra-hepatic bile duct was noted in 10 patients; in three the dilation could be traced to its beginning, at the level of the CHD, where the gallbladder stone was also noted, suggestive of MS. One patient underwent urgent operation without further imaging in view of non-resolving cholecystitis and the operative findings confirmed a Type 1 MS. In the other two patients, MS was confirmed on subsequent ERCP and at operation. Five patients had a CT of the abdomen carried out as an initial imaging. Dilatation of the extra-hepatic bile duct was noted in four patients, one of them had magnetic resonant cholangio-pancreatography (MRCP) as well. A CT scan and MRCP failed to detect MS in these patients. In 12 patients ERCP was attempted with successful bile duct canulation in 11 of the cases. Diagnosis of MS was made in six patients (all reported as Type 1); in the other five patients, ERCP revealed CBD stones only (Figure 3).

To summarise, the diagnosis of MS was made pre-operatively in 7 of 18 patients (39%); all were reported as having a Type 1. The sensitivities of ultrasonography and ERCP were 23% (3 out of 13 patients) and 55% (6 out of 11 patients), respectively; they were unable to discern between a Type 1 and Type 2 MS. Among the seven patients who had Type 2 MS, six had preoperative ERCP with the report of Type 1 MS in two patients and CBD stones in the other four cases.

Operative Details (Table 1)
Sixteen patients were operated upon during the same acute hospital admission and two had elective operations. Eleven patients had a Type 1 MS and seven had a Type 2 MS. Laparoscopic cholecystectomy was attempted in two patients (both were Type 1 MS). One was successful and the other needed open conversion due to dense inflammatory adhesions in Calot’s triangle. The other 16 patients underwent open surgery from the start. Of the remaining nine patients with a Type 1 MS - two had cholecystectomy and an intra-operative cholangiogram (IOC) (Figure 4). Six had cholecystectomy (2 subtotal) and CBD exploration and one had a cholecystectomy and a hepatico-jejunostomy bypass for a tight CHD stricture. Of the seven patients with Type 2 MS - four had subtotal cholecystectomy and closure of the cholecysto-choledochal fistula (primary closure in one and using a cuff of the remnant gallbladder in the other three); two had cholecystectomy and choledochoduodenostomy and one had cholecystectomy and hepaticojejunostomy.

Surgical Outcome (Table 1)
The main difficulty encountered during operation in these cases was the dense inflammatory adhesions in Calot’s triangle and the portal hepatis. Dissection had to be done with extreme care in order to avoid injuring the main bile duct. We found the fundus-first technique for cholecystectomy helpful in these situations. Subtotal cholecystectomy (leaving a small cuff of the gallbladder on the liver and the porta hepatis) was a safe procedure especially when dense adhesions made dissection near the CHD hazardous.

The mean follow-up period was 29 months (range 7 to 71 months). Outcomes following operation were generally good. There was no major procedure related complication. Following surgery, we monitor all patients with serial liver function tests (albumin, bilirubin, alkaline phosphatase and aspartate transferase). Check cholangiography is not routinely performed. A technetium-99 iminodiacetate (Tc99-IDA) scan, MRCP or ERCP will be done if the biochemical tests show a cholestatic profile or if patients report recurrent febrile episodes. Liver function tests had referred to normal in all patients and none had clinically significant 

febrile episodes that needed further investigations. One patient had recurrent abdominal pain two months following subtotal cholecystectomy for a Type 1 MS; ERCP showed a retained stone in the cystic duct remnant and this was successfully removed endoscopically. Two patients had post-operative pneumonia, one recovered and one died from overwhelming sepsis from pneumonia 31 days post-operation (overall operative mortality 5.6%).

Incidental cancer was noted in two patients. The first was a 69-year-old woman who underwent urgent cholecystectomy for a Type 1 MS and empyema of the gallbladder. Adenocarcinoma of the gallbladder was noted on histology. In view of her poor health and multiple co-morbidities, no further surgery was offered and she received external beam radiotherapy. She died from metastatic cancer 13 months later. The other patient was an 86-year-old woman who presented with obstructive jaundice; ERCP showed a Type 1 MS and this was confirmed during operation. Incidentally, a malignant stricture was noted at the hepatic duct confluence on IOC and biopsy confirmed cholangiocarcinoma. Cholecystectomy followed by palliative biliary stenting were performed instead of radical surgery. Histology of the gallbladder also showed incidental adenocarcinoma. She died from tumor progression eight months later.

P: upper abdominal pain; J: jaundice; F: fever; N/V: nausea and/or vomiting; U: ultrasound; CT: computed tomography; ERCP: endoscopic retrograde cholangiogram; MRC: magnetic resonance cholangiogram; +S/T: sub total; CBDE: common bile duct exploration; CD: choledochoduodenostomy; GB: gall bladder; HJ: hepaticojejunostomy; IOC: intra-operative cholangiogram; Pr: primary; LAP: laparoscopic; chole: cholecystectomy; #CA: carcinoma; H/O: history of

DISCUSSION
Mirizzi, the father of operative cholangiography, described the syndrome in 1948 detailing the following features - a cystic duct parallel to the CBD, gallstones impacted in the cystic duct or neck of the gallbladder causing obstruction of the CHD (Figure 1 and 2), recurrent cholangitis, and an alleged spasm of the circular muscle of the hepatic duct.1 It is now recognised that there is no significant muscle in the CHD. It is also postulated that a long parallel cystic duct or a low insertion of it into the CBD predispose to (MS).^2,3

However, this anatomic variant is often difficult to demonstrate because of severe inflammation in Calot’s triangle. Since then, the definition has evolved to include cases with a cholecysto-biliary fistula (Figure 4). Mirizzi syndrome is rare and is found in 0.7-1.1 percent of patients undergoing cholecystectomy.4

McSherry et al. (1982) proposed a classification of MS into Type 1 - with external compression of the CHD by a calculus impacted in the cystic duct (Figure 1 and 2), and Type 2 - where the calculus had eroded into the bile duct creating a cholecysto-choledochal fistula (Figure 4). When we applied this to our series of 18 patients - 11 had Type 1 MS and seven had Type 2 MS.5 Csendes et al. (1989), in a series of 219 patients, had further sub-classified McSherry Type 2 MS into type II to IV, according to increasing size of the fistula, relative to the diameter of the CBD. ⁶ Csendes et al. (1989) reported an older mean age of patients with type III and IV lesions, but this trend was not observed in our small series. 6 Seven of our patients presented with the Charcot’s triad of upper abdominal pain, jaundice and fever. Nausea and/or vomiting were common associated complaints.

Abdominal US has a sensitivity of 23% in diagnosing MS in our series (3 out of 13 patients). This is in keeping with Csendes’ series, where US revealed bile duct dilatation in 81% of patients and raised suspicion of MS in 27%.6 Abdominal CT was the first imaging modality to be used in five patients in our series, but failed to detect MS in any of them. However, when compared with US scanning, CT had the added advantages of rapid capture time as well as better sensitivity and specificity in detecting intra-abdominal pathology. An incidental finding of a large ovarian tumor was noted on CT scans in one of our patients.

Some authors consider pre-operative diagnosis essential in avoiding CBD injuries.^4,7,8 Others have concluded that with a cautious intra-operative approach to periductal inflammation and judicious dissection, it is not necessary for successful management.^9,10 Additional imaging is often needed to obtain details of the biliary pathology because of lack of sensitivity of US and CT scans in discerning the underlying pathology. The most frequently used modality was ERCP and this was successfully completed in 11 of our patients. It had a sensitivity of 55% in detecting MS (6 out of 11 cases, all reported as Type 1). The possibility of stone retrieval and biliary stenting during ERCP is an added advantage in improving surgical outcome, and stenting also facilitates identification of the CBD during operative dissection.^7,11,12 However, ERCP is limited by failure to canulate the CBD in 5-10% of cases and suboptimal study from incomplete contrast filling of the ducts due to tight strictures or intraductal debris. Complications including sepsis and pancreatitis can occur after ERCP. When ERCP is unsuccessful or difficult, percutaneous transhepatic cholangiography (PTC) is a viable alternative.¹³

In MS, MRCP can be as good as ERCP in diagnosis and its ability to delineate details of biliary strictures and to detect a cholecystocholedochal fistula. In addition, T2 weighted sections can differentiate a neoplastic mass from an inflammatory one which US or CT scan may not be capable of.¹⁴ We prefer early ERCP when biliary sepsis is the dominant clinical issue and where a benefitial endoscopic therapeutic procedure can be instituted at the same time. By contrast, MRCP is used to corroborate the suspicion of malignancy after initial imaging with US or CT scans. It was performed in one of our patients who had bile duct dilatation seen on CT scan, but the final diagnosis of a Type 1 MS and carcinoma of the gallbladder was missed on MRCP.

The dense inflammatory adhesions in Calot’s triangle in MS, as well as the frequent aberrant biliary anatomy, pose a difficult challenge to the unsuspecting surgeon when dealing with a MS. Meticulous dissection and vigilance for a potential MS are essential in order to avoid inadvertent bile duct injury. We outline our surgical approach with reference to the literature.

Our surgical strategy aims at tackling the two difficult problems when faced with MS - firstly, the safe completion of the cholecystectomy without inflicting injury to the bile duct; secondly, the appropriate management of the cholecystocholedochal fistula. During cholecystectomy, the fundus first approach is favoured over the conventional Calot’s first dissection. In acute cholecystitis or when the gallbladder is distended and tense, decompressing it can facilitate dissection. A cholangiogram should be done at this point to confirm the diagnosis, to assess the location and size of the fistula, as well as to exclude the presence of stones or strictures in the bile duct. In a Type 1 MS, the minimum necessary surgery (a cholecystectomy) is adequate. In the absence of CBD stones on pre or per-operative cholangiogram, stones impacted in the cystic duct or the neck of the gallbladder are milked back into the gallbladder which is then removed and the cystic duct oversewn.^2,15 However, the cystic duct is frequently occluded and obscured by inflammatory changes in the region of Calot’s triangle. In these cases, a subtotal cholecystectomy, fundus first dissection and leaving the neck of the gallbladder behind,is a more prudent approach.⁴ Routine CBD exploration is not necessary unless stones are noted pre-operatively or on IOC.^6,16 Common bile duct exploration should be carried out only if the CBD is easily exposed, otherwise definitive management of CBD stones or stenosis should be left till the inflammatory process has resolved and the situation is reassessed.⁴ Bile duct stenosis generally resolves as inflammation subsides following cholecystectomy.^2,4,6 Surgical procedures for Type 2 MS depend on the severity of the fistula and any associated bile duct strictures. A small fistula may be closed primarily by interrupted stitches and a larger defect can be closed using a cuff of gallbladder remnant following subtotal cholecystectomy.⁶ Sandblom et al. (1975) described a technique using a well-vascularised flap from the gallbladder or cystic duct for the closure of a large defect.¹⁷ Siting of the T-tube following closure of the fistula remains contentious. While some advocate placement through the fistula opening, others suggest that the T-tube be placed through a separate choledochotomy distal to the fistula.^{4,6, 7,18} Baer et al. (1990) advocate routine biliary bypass of the choledochal fistula to the duodenum or jejunal loop.⁴ In a Csendes Type IV fistula, where there is complete section of the CHD and questionable vascularity of the CHD, Roux-en-Y hepaticojejunostomy is the procedure of choice.¹⁵ Among the seven patients with Type 2 MS in our series the overall outcomes were good, there was no incidence of bile leak or stricture formation, liver function tests returned to all patients and no patient required re-operation.

Although all the technical steps necessary in the management of MS are feasible laparoscopically the latter in MS is contentious.¹⁰ While Posta et al. (1995) and Rust et al (1991) considered MS a contraindication to laparoscopic surgery, others have reported success with the laparoscopic approach.^10,19-23 In addition, laparoscopic ultrasonography has been reported as an useful technique to facilitate this approach.²⁴ We attempted laparoscopic cholecystectomy in two patients with Type 1 MS and were successful in one case. We feel that with increasing expertise and careful patient selection, laparoscopic surgery can have a greater role in the management of MS.

Occasionally, tumours of the cystic duct and biliary tree may mimic MS.²⁵ Incidental cancers of the gall bladder and hepatic duct confluence were discovered in two patients with Type 1 MS. Some authors advocate routine frozen section to detect gallbladder cancer in young and fit patients where radical resection at the same operation can be considered.^4,26 In our centre, we routinely bisect the specimen for inspection but do not perform frozen section. We appreciate that it is difficult to differentiate gallbladder wall thickening and mucosal ulceration secondary to inflammation from that of a malignant process.

Surgical therapy in MS has a high morbidity and mortality rate, which in a large series is reported as 23% and 4%, respectively for type 2 MS.6 We report an overall procedure-related morbidity of 6%. Other than one case of a retained stone in the cystic duct remnant, there was no incidence of inadvertent bile duct injury, bile leak nor stricture formation. One patient (5.6%) died of pneumonia 31 days following cholecystectomy and biliary bypass for Type 2 MS %.

Figure 3: ERCP cholangiogram showing the presence of CBD stones obscuring the demonstration of the cholecysto-choledochal fistula - a common cause of missed diagnosis of Mirizzi syndrome

Figure 4: Intra-operative cholangiogram with Foley’s catheter at neck of gallbladder demonstrating a fistula - Mirizzi Type 2. Note absence of the cystic duct and direct apposition of the neck of the gallbladder to the CHD with filling of the biliary tree

CONCLUSION
Pre-operative diagnosis of MS, especially the Type 2, is often inconclusive despite advances in imaging techniques. A high index of suspicion must be maintained when operating on patients with gallstones presenting with a history of jaundice. With meticulous dissection at Calot’s triangle and hepatoduodenal ligament as well as adopting the fundus first approach to the gallbladder, iatrogenic injury and further damage to the bile duct can be avoided. Vigilance to the presence of MS and timely performance of IOC help in appreciating the full extent of the disease and, thus, selection of an appropriate surgical procedure. Good surgical outcome can be expected with this approach as demonstrated in this series of 18 patients.

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Copyright: 30 June 2003