case studies - Gastrointestinal Endoscopy

J Benninger, T Rabenstein, M Farnbacher, et al.

17.

18.

19.

20.

therapy: enzymatic conversion into protoporphyrin. Photochem Photobiol 1998;67:150-4. Marti A, Jichlinski P, Lange N, Ballini J, Guillou L, Leisinger H, et al. Comparison of aminolevulinic acid and hexylester aminolevulinate induced protoporphyrin IX distribution in human bladder cancer. J Urol 2003;170:428-32. Lange N, Jichlinski P, Zellweger M, Forrer M, Marti A, Guillou L, et al. Photodetection of early human bladder cancer based on the fluorescence of 5-aminolaevulinic acid hexylester-induced protoporphyrin IX: a pilot study. Br J Cancer 1999;80:185-93. Jichlinski P, Marti A, Guillou L, Lange N, Wagnieres G, Leisinger H-J. First report of hexyl-ester aminolevulinic acid induced fluorescence cystoscopy in superficial bladder cancer. Eur Urol 2001;39(Suppl 5):139. Endlicher E, Ruemmele P, Hausmann F, Krieg R, Knuechel R, Rath H, et al. Protoporphyrin IX distribution following local application of 5-aminolevulinic acid and its esterified

CASE STUDIES Extracorporeal shockwave lithotripsy of gallstones in cystic duct remnants and Mirizzi syndrome Johannes Benninger, MD, Thomas Rabenstein, MD, Michael Farnbacher, MD, Jens Keppler, MD, Eckhart G. Hahn, MD, H. Thomas Schneider, MD Background: Although the efficacy of extracorporeal shockwave lithotripsy for treatment of bile duct calculi is established, there are few studies of the value of extracorporeal shockwave lithotripsy for cystic duct remnant stones and for Mirizzi syndrome. Methods: Patients who required extracorporeal shockwave lithotripsy for cystic duct stones were identified in a cohort of 239 patients with bile duct stones treated by extracorporeal shockwave lithotripsy between January 1989 and December 2001 at a single institution. The medical records of these patients were reviewed. Followup information was obtained by telephone contact. Observations: Six women (age range 19-85 years) underwent extracorporeal shockwave lithotripsy for cystic duct stones after failure of endoscopic treatment measures. Three of the patients presented with retained cystic duct remnant calculi (one also had Mirizzi syndrome

Received December 5, 2003. For revision March 10, 2004. Accepted April 9, 2004. Current affiliation: Department of Medicine I, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany. Reprint requests: Johannes Benninger, MD, Department of Medicine I, Friedrich-Alexander-University Erlangen-Nuremberg, Ulmenweg 18, D-91054 Erlangen, Germany. Copyright Ó 2004 by the American Society for Gastrointestinal Endoscopy 0016-5107/$30.00 PII: S0016-5107(04)01810-3 454

GASTROINTESTINAL ENDOSCOPY

Gallstones: ESWL in cystic duct remnants and Mirrizzi syndrome

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derivatives in the tissue layers of the normal rat colon. Br J Cancer 2001;85:1572-6. Hamilton SR, Aalton LA, editors. Pathology and genetics. Tumours of the digestive system, World Health Organization Classification of tumours. Lyon (France): IARC Press; 2000. Messmann H, Szeimies R, Bdumler W, Knuchel R, Zirngibl H, Scholmerich J, et al. Enhanced effectiveness of photodynamic therapy with laser light fractionation in patients with esophageal cancer. Endoscopy 1997;29:275-80. Krieg RC, Messmann H, Rauch J, Seeger S, Knuechel R. Metabolic characterization of tumor cell-specific protoporphyrin IX accumulation after exposure to 5-aminolevulinic acid in human colonic cells. Photochem Photobiol 2002;76: 518-25. Moan J, Ma L, Juzeniene A, Iani V, Juzenas P, Apricena F, et al. Pharmacology of protoporphyrin IX in nude mice after application of ALA and ALA esters. Int J Cancer 2003;103: 132-5.

type I), and 3 presented with Mirizzi syndrome type I. The stones were fragmented successfully by extracorporeal shockwave lithotripsy in all patients; the fragments were extracted endoscopically in 5 patients. Endoscopy plus extracorporeal shockwave lithotripsy was definitive treatment for all patients except one who subsequently underwent cholecystectomy. Conclusions: Gallstones in a cystic duct remnant and in Mirizzi syndrome can be successfully treated by extracorporeal shockwave lithotripsy in conjunction with endoscopic measures. Extracorporeal shockwave lithotripsy is especially useful when surgery is contraindicated.

Gallstone retention in a cystic duct remnant and Mirizzi syndrome are rare complications of gallstone disease. The incidence of Mirizzi syndrome in patients undergoing biliary surgery ranges from 0.7% to 1.4% and can be as high as 2.7% in highrisk populations such as native Americans.1,2 No data are available as to the frequency of retained cystic duct stones after cholecystectomy. Previously, the standard therapy for both of these complications was surgery, but the use of endoscopic therapy is increasing, including ancillary measures such as electrohydraulic lithotripsy (EHL) and extracorporeal shockwave lithotripsy (ESWL).3-13 This report describes our experience with ESWL for the treatment of cystic duct remnant stones and of Mirizzi syndrome in patients in whom endoscopic therapy alone was unsuccessful.

PATIENTS AND METHODS During a 13-year-period (January 1989 to December 2001), 239 patients with bile duct stones that were not extractable by endoscopic means, including mechanical lithotripsy, were treated by ESWL at our universityaffiliated referral center. Patients who required ESWL for VOLUME 60, NO. 3, 2004



Table 1. Characteristics, treatment, and outcome for patients with cystic-duct remnant stones and/or Mirizzi syndrome Age (y)

Clinical presentation

1

26

Abdominal pain, jaundice

2

19

3

19

Abdominal pain, jaundice Abdominal pain

4

64

5

6

Patient

ERCP

No. stones/ maximum diameter

ESWL sessions (n)

1/10 mm

4

1/11 mm

3

Total fragment extraction not possible Fragment extraction

Additional measures

3/7 mm

2

None

Abdominal pain

Cystic-duct remnant stone, Mirizzi syndrome Cystic-duct remnant stone Cystic-duct remnant stones Mirizzi syndrome

1/25 mm

2

Fragment extraction

70

Jaundice

Mirizzi syndrome

1/11 mm

1

85

Abdominal pain, jaundice

Mirizzi syndrome

3/25 mm

2

Fragment extraction, mechanical lithotripsy, open cholecystectomy Fragment extraction, mechanical lithotripsy

Outcome/follow-up Symptom-free, Mirizzi syndrome resolved/108 mo Symptom-free, stone-free/55 mo Symptom-free, stone-free/24 mo Symptom-free, stone-free/117 mo Symptom-free, stone-free/90 mo Symptom-free, stone-free/died of pancreatic cancer after 44 mo

ESWL, Extracorporeal shockwave lithotripsy.

cystic duct stones were identified by searching an endoscopy database. The medical records for these patients and the retrograde cholangiograms were reviewed retrospectively. Demographic information, presentation, clinical and cholangiographic findings, endoscopic and surgical treatment, and treatment of complications were recorded. Follow-up data were obtained by telephone contact with the patient. ESWL was performed by one of 4 experienced physicians using successive generations of piezoelectric lithotriptors (Piezolith 2501, Piezolith economy, Piezolith 3000; R. Wolf, Knittlingen, Germany). ESWL was carried out with the patient in the prone position, mainly under conscious sedation with pethidine and diazepam.14 Stones were localized mainly by US, occasionally with the addition of fluoroscopy. In all patients, either a biliary endoprosthesis or a nasobiliary tube was inserted; the latter allowed injection of contrast medium during ESWL for visualization of the stones. Either device also prevented biliary obstruction by stone fragments. Before ESWL, a sphincterotomy had been performed in all patients. After ESWL, residual stone fragments were removed endoscopically with a Dormia basket and/or an extraction balloon catheter, as necessary.

OBSERVATIONS Six women (mean age 47.2 years, range 19-85 years) underwent ESWL for cystic duct stones (Table 1). Three patients had retained stones in the cystic duct remnant after cholecystectomy; a diagnosis of Mirizzi syndrome was made in the other 3 patients. One of the patients with retained cystic duct stones also had Mirizzi syndrome. No patient presented with clinical evidence of acute inflammation. For VOLUME 60, NO. 3, 2004

therapeutic purposes, endoscopic sphincterotomy was performed in all patients. Retained stones in cystic duct remnant Case 1. A 26-year-old woman was admitted for cholecystectomy because of known gallstone disease. ERCP, performed to exclude bile duct stones, was complicated by post-ERCP pancreatitis and, subsequently, acute cholecystitis. At open cholecystectomy, there was substantial inflammation and also adhesions involving the duodenum, so that a ‘‘fundusfirst’’ dissection of the gallbladder was carried out. Intra-operative cholangiography did not demonstrate flow of the contrast medium through the cystic duct. Seven months later, the patient experienced abdominal pain, followed by jaundice and vomiting. Laboratory data were consistent with marked cholestasis: bilirubin, 108 lmol/L (normal: 2-19 lmol/L). CT and ERCP demonstrated a 10-mm-diameter calcified stone in the cystic duct remnant and corresponding high-grade compression of the bile duct at the location of the stone (post-cholecystectomy Mirizzi syndrome type I). The stone could not be extracted, and the patient was referred to our hospital for ESWL. Four lithotripsy sessions of the easily visualized stone were performed under US guidance. Endoscopic retrograde cholangiography (ERC) revealed at least 4 fragments that were not extractable endoscopically. The fragments appeared to be strongly adherent to the cystic duct wall. However, the compression of the bile duct was significantly reduced, as GASTROINTESTINAL ENDOSCOPY

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confirmed by normalization of the biochemical tests of liver function. Because the patient was asymptomatic, no further therapy appeared to be necessary. Nineteen months later, she again developed abdominal pain that persisted for a few days; there also was biochemical evidence of transient cholestasis. Based on CT and ERCP findings, this episode was interpreted as spontaneous passage of fragments from the cystic duct remnant. Case 2. In a 19-year-old woman with epigastric pain, US revealed a large gallbladder without stones and no dilatation of the bile ducts. Icterus subsequently developed, and ERCP demonstrated small bile duct stones that were removed endoscopically. However, complete obstruction of the cystic duct at its mid point led to laparoscopic cholecystectomy at which intra-operative cholangiography was not obtained. Two weeks later, the patient developed abdominal pain and jaundice: bilirubin, 86 lmol/L; gamma glutamyl transferase, 142 U/L (4-18 U/L); alkaline phosphatase, 450 U/L (70-150 U/L). ERC revealed an 11-mm-diameter stone in the common bile duct. During attempts at extraction, the stone was dislocated into the proximal cystic duct remnant, presumably where it had been located until cholecystectomy. It could not be removed from the cystic duct despite several attempts. A biliary endoprosthesis was inserted, and the patient was referred to our hospital for ESWL. After 3 ESWL sessions under US and radiologic guidance, ERCP revealed stone fragments in the common bile duct, which were extracted; the cystic duct remnant was stone free. After the second lithotripsy session, fever occurred in a pattern suggestive of sepsis and was attributed to acute cholangitis; the fever resolved with antibiotic therapy. Case 3. A 19-year-old woman with known hereditary spherocytosis underwent uncomplicated laparoscopic cholecystectomy (without cholangiography) because of symptoms caused by gallbladder stones and acute cholecystitis. Three days later, she again experienced abdominal pain without evidence of cholestasis. CT disclosed calcified stones suspected to be in the common bile duct. At ERCP, however, 3 stones of up to 7 mm in diameter were demonstrated in the cystic duct remnant; these could not be extracted with Dormia baskets. A double-pigtail catheter was inserted into the bile duct, and two sessions of ESWL were performed 1 week later. Follow-up ERC demonstrated spontaneous clearance of the fragments from the cystic duct remnant. Mirizzi syndrome Case 4. A 64-year-old woman, who presented with abdominal pain of 1 week’s duration, was referred 456



because of Mirizzi syndrome type I. Despite use of different baskets and even laser lithotripsy, it was impossible to extract a 25-mm stone lodged at the confluence of the cystic duct with the bile duct. ESWL was performed in two sessions under direct radiologic guidance by using contrast medium injected endoscopically. Follow-up ERC disclosed fragmentation of the large stone, with nearly complete spontaneous clearance of the fragments. Cholecystectomy was recommended, but the patient refused surgery. Case 5. A 70-year-old woman was referred because of painless jaundice and a shrunken gallbladder containing stones. At US, dilated intra- and extrahepatic bile ducts were noted, together with an 11-mm-diameter stone in the distal common bile duct. ERC, however, demonstrated a 15-mmdiameter stone in the distal cystic duct with partial obstruction of the hepatic duct, thereby making the diagnosis of Mirizzi syndrome type I. Endoscopic attempts at stone removal were unsuccessful. One ESWL session under radiologic and US guidance resulted in a good fragmentation, with particles that were amenable to endoscopic extraction. Because of mild pain and low-grade fever subsequent to ESWL, the patient underwent open cholecystectomy at which dense adhesions were found between the gallbladder and the liver and the colon, along with a small abscess between the gallbladder and the liver. Case 6. An 85-year-old woman with multiple comorbid conditions presented with abdominal pain and jaundice (bilirubin 109 lmol/L). ERC revealed two large cystic duct stones (18 mm and 22 mm) and one 25-mm-diameter stone at the neck of the gallbladder with compression of the common hepatic duct (Fig. 1A), findings compatible with a diagnosis of Mirizzi syndrome type I. Endoscopic insertion of a catheter into the common hepatic duct was not possible. A 7F nasobiliary drain was placed into the gallbladder for the purpose of ESWL. Two ESWL sessions performed under US and radiologic guidance resulted in good fragmentation of the stones (Fig. 1B). Subsequent ERC disclosed many stone fragments in the common bile and cystic ducts, and in the gallbladder. Some of these fragments were extracted, and a double-pigtail endoprosthesis was inserted into the common hepatic duct. Over the next several months, 4 further endoscopic sessions with ERC were performed. Almost all fragments initially lying in the gallbladder and cystic duct passed into the common duct. After additional mechanical lithotripsy and extraction of a large stone mass, the bile ducts and the gallbladder were stone free (Fig. 1C). Laboratory data normalized, and the patient became asymptomatic. VOLUME 60, NO. 3, 2004



Figure 1. A, Retrograde cholangiogram (case 6) showing two cystic duct stones (arrows), a large stone in neck of gallbladder (arrowhead), and dilatation (13 mm) of common hepatic duct (Mirizzi syndrome, type I). B, Retrograde cholangiogram obtained after two ESWL sessions, showing multiple stone fragments in common bile duct, cystic duct, and gallbladder. C, Retrograde cholangiogram obtained after 3 months and further endoscopic extraction of stones, showing complete clearance of stones from bile ducts. VOLUME 60, NO. 3, 2004


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DISCUSSION Since its introduction into gastroenterology by Sauerbruch et al.15 in 1986, ESWL has been shown to be efficacious for fragmentation of bile duct stones that are not extractable endoscopically by using balloon catheters and baskets.4,16 The results of ESWL in a small group of patients with retained cystic duct remnant stones or/and with Mirizzi syndrome treated in a single universityaffiliated referral center were reviewed retrospectively in the present study. Retained calculi in a cystic duct remnant could be the explanation for post-cholecystectomy pain.13 Retention of stones in a cystic duct remnant is a rare occurrence, which usually is difficult to diagnose, the best method being ERC.13 There are few data on the optimum management of cystic duct remnant stones. Formerly, open laparotomy with excision of the remnant was the treatment of choice.17,18 This approach is still used, especially if resection can be performed laparoscopically.19 During the last 2 decades, cases have been reported in which cystic duct remnant stones were treated endoscopically, either percutaneously after surgical cholecystostomy20 or via a retrogradetranspapillary approach.5,9,13 Beyer et al.5 noted that it was easy to extract multiple stones from the cystic duct remnant in their patient, but Kodali and Petersen9 encountered marked problems in removing calculi from two patients with post-cholecystectomy Mirizzi syndrome. In all 3 patients with retained cystic duct stones in the present series, it was impossible to extract the stones endoscopically by using balloons and baskets, particularly because of the position of the stones at the proximal end of the cystic duct remnant with consequent obstruction to the passage of the endoscopic accessories. ESWL fragmented the stones in all 3 cases. In two patients, the fragments passed spontaneously, whereas, in one patient with post-cholecystectomy Mirizzi syndrome, the fragments could not be removed with baskets or balloons. In the latter patient, the presumed reason for the failure to extract the fragments was adherence to the cystic duct because of severe inflammation, as documented at cholecystectomy. However, the bile duct obstruction and jaundice were resolved by ESWL in this patient. With the exception of fever, presumably caused by sepsis, in one patient 1 day after ESWL, there was no major side effect as a result of the stone fragmentation procedure in the present series. Thus, ESWL of cystic duct remnant stones proved to be safe. In principle, it should be possible to use laser lithotripsy under cholangioscopic guidance to fragment stones 458



in the cystic duct,13 but ESWL is probably easier in such an anatomically difficult circumstance. Moreover, the lithotripsy systems used in the present series offered simultaneous US and radiologic visualization, which made it easy to localize the stones for ESWL; such systems have obvious advantages. Ultimately, however, the choice of treatment, whether ESWL or laser, will depend on availability and experience with the use of the different methods. Mirizzi syndrome is caused by impaction of a gallstone in the cystic duct or the neck of the gallbladder, with compression of the adjacent bile duct and consequent complete or partial obstruction of the common hepatic duct. Jaundice, pain, and fever are the most common symptoms.1 The classification of Mirizzi syndrome proposed by McSherry et al.,21 among others,22,23 is most commonly used: type I involves external compression of the common hepatic duct by a stone impacted in the cystic duct; type II occurs when a stone produces a cholecystocholedochal fistula and migrates into the common hepatic duct. ERC is the method of choice for the diagnosis of Mirizzi syndrome. Until 10 to 15 years ago, the therapy of choice for Mirizzi syndrome was surgery. To facilitate cholecystectomy, pre-operative ERC with placement of a nasobiliary drain is recommended.24 In the laparoscopic era, however, controversy developed as to whether cholecystectomy should be performed laparoscopically or as an open operation to reduce the possibility of iatrogenic bile duct injury, and a ‘‘fundus-first’’ technique was recommended as a method of reducing the rate of conversion to an open operation.25-28 With evolving experience and the development of ancillary methods, such as ESWL, EHL, and laser lithotripsy, it has become possible to treat patients with Mirizzi syndrome by using interventional endoscopic methods. Binmoeller et al.6 treated 14 patients with EHL under cholangioscopic guidance with one complication (bile leak); Tsuyuguchi et al.12 successfully treated 23 patients with type II Mirizzi syndrome by EHL (16 patients) or laser lithotripsy (7 patients). Sugiyama et al.11 successfully used ESWL in one case. England and Martin10 used the concept of multimodal therapy (mechanical lithotripsy, dissolution with methyl tertbutyl ether, stent insertion) in 5 patients. In all cases, including the 4 from the present series, no side effect of ESWL was encountered. ESWL is easy and comfortable for patients and requires administration of only low doses of sedative and analgesic drugs. Systems that offer dual localization (US and radiograph) facilitate visualization of the stone(s) and improve fragmentation efficacy, even in patients with the Mirizzi syndrome. VOLUME 60, NO. 3, 2004


In conclusion, ESWL, combined with appropriate therapeutic endoscopic interventions, is safe and effective for the treatment of cystic duct remnant stones and Mirizzi syndrome, especially when it is desirable to avoid surgical therapy. REFERENCES 1. Abou-Saif A, Al-Kawas FH. Complications of gallstone disease: Mirizzi syndrome, cholecystocholedochal fistula, and gallstone ileus. Am J Gastroenterol 2002;97:249-54. 2. Curet MJ, Rosendale DE, Congilosi S. Mirizzi syndrome in a native American population. Am J Surg 1994;168:616-21. 3. Cairns SR, Watson GN, Lees WR, Salmon PR. Percutaneous lithotripsy and endoprosthesis: a new treatment for obstructive jaundice in Mirizzi’s syndrome. BMJ 1987;295:1448. 4. Lee SH, Fache JS, Burhenne HJ. The value of extracorporeal shock-wave lithotripsy in the management of bile duct stones. Am J Roentgenol 1990;155:775-9. 5. Beyer KL, Marshall JB, Metzler MH, Elwing TJ. Endoscopic management of retained cystic duct stones. Am J Gastroenterol 1991;86:232-4. 6. Binmoeller KF, Thonke F, Soehendra N. Endoscopic treatment of Mirizzi’s syndrome. Gastrointest Endosc 1993;39: 532-6. 7. Vakil N, Sawyer R. Endoscopic drainage of the gallbladder in a septic variant of the Mirizzi syndrome. Gastrointest Endosc 1994;40:236-8. 8. Baron TH, Schroeder PL, Schwartzberg MS, Carabasi MH. Resolution of Mirizzi’s syndrome using endoscopic therapy. Gastrointest Endosc 1996;44:343-5. 9. Kodali VP, Petersen BT. Endoscopic therapy of postcholecystectomy Mirizzi syndrome. Gastrointest Endosc 1996;44: 86-90. 10. England RE, Martin DF. Endoscopic management of Mirizzi’s syndrome. Gut 1997;40:272-6. 11. Sugiyama M, Naka S, Nagashima Y, Kozawa K, Wada N, Kurosawa S, et al. Mirizzi syndrome successfully treated by extracorporeal shock wave lithotripsy following endoscopic sphincterotomy. Gastrointest Endosc 1997;46:361-3. 12. Tsuyuguchi T, Saisho H, Ishihara T, Yamaguchi T, Onuma EK. Long-term follow-up after treatment of Mirizzi syndrome by peroral cholangioscopy. Gastrointest Endosc 2000;52:639-44. 13. Walsh RM, Ponsky JL, Dumot J. Retained gallbladder/cystic duct remnant calculi as a cause of postcholecystectomy pain. Surg Endosc 2002;16:981-4.

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