RECURRENT PYOGENIC CHOLANGITIS

RECURRENT PYOGENIC CHOLANGITIS Resident(s): Evan Raff, MD MHA Attending(s): Narasimham Dasika, MD Program/Dept(s): University of Michigan Health System, Department of Radiology

CHIEF COMPLAINT & HPI Chief Complaint and/or reason for consultation Itching, jaundice, fever, and abdominal pain for 1 week History of Present Illness 44-year-old Chinese woman with history of recurrent episodes of cholangitis who presents with one week history of increased systemic itching and yellowing in her eyes. She reports sharp midepigastric pain that lasted for about 30 minutes starting 1 day ago with subjective fevers, chills and sweats. She also reports dark urine, light colored stools and noticed her skin was yellow. She also has intermittent nausea without vomiting. Patient reports several year history of intermittent fevers and chills without abdominal pain, nausea or vomiting which began during pregnancy. Work up included several ERCPs with findings interpreted as primary sclerosing cholangitis.

RELEVANT HISTORY Past Medical History Multiple episodes of cholangitis. Reported history of parasitic infection in infancy. Past Surgical History None Family & Social History Born in China and moved to USA in the late 1970s. No tobacco or drug use, rare alcohol. Review of Systems Negative unless as stated above. Medications: None Allergies: NKDA

DIAGNOSTIC WORKUP Physical Exam T 98.4 BP 111/62 HR 96 RR 18 O2 sat 96% on RA General: Well-appearing, lying in bed, NAD Eyes: Mild scleral icterus GI/ABD: Soft, nondistended, mild tenderness to palpation in the RUQ/epigastric region w/o rebound/guarding, normoactive bowel sounds. Ext: No LE edema, all 4 extremities w/w/p

DIAGNOSTIC WORKUP Laboratory Data WBC 17.7, AST 74, ALT 118, Alk phos 830, Tbil 3.0. Non-Invasive Imaging Ultrasound: Intrahepatic ductal dilation filled with echogenic material suspected to be stones. MRCP: Severe stricturing of the central intrahepatic ducts and large intrahepatic stone burden. Transient periductal arterial hyperenhancement likely reflects cholangitis.

QUESTION SLIDE 1) Recommended first line imaging for patients with suspected recurrent pyogenic cholangitis: A: Contrast enhanced CT. B: Ultrasound. C: MRCP. D: ERCP.

CORRECT! CONTINUE WITH CASE 1) Recommended first line imaging investigation for patients with suspected recurrent pyogenic cholangitis: A: Contrast enhanced CT. Provides better spatial resolution than ultrasound, but with radiation. Similar ability to detect stones, pneumobilia and masses. Enhancement of biliary mucosa can indicate active cholangitis. B: Ultrasound. Quick and cost effective, ultrasound can demonstrate the general features of RPC including intrahepatic calculi (identified in up to 90% of patients), pneumobilia, ductal dilatation and related complications including hepatic masses (e.g., abscess, cholangiocarcinoma). (Heffernan et al., AJR 2009) C: MRCP. Expensive but with ability to characterize ducts proximal to an obstruction or tight stenosis better than ERCP. No risk of aggravating biliary sepsis. Improved sequence speed reduce motion artifacts. D: ERCP. Allows for stone removal, cytologic but has risk for aggravation/development of biliary sepsis. Previously the gold standard with high spatial resolution, MRCP is preferred for given noninvasive nature.

SORRY, THAT S INCORRECT! CONTINUE WITH CASE 1) Recommended first line imaging investigation for patients with suspected recurrent pyogenic cholangitis: A: Contrast enhanced CT. Provides better spatial resolution than ultrasound, but with radiation. Similar ability to detect stones, pneumobilia and masses. Enhancement of biliary mucosa can indicate active cholangitis. B: Ultrasound. Quick and cost effective, ultrasound can demonstrate the general features of RPC including intrahepatic calculi (identified in up to 90% of patients), pneumobilia, ductal dilatation and related complications including hepatic masses (e.g., abscess, cholangiocarcinoma). (Heffernan et al., AJR 2009) C: MRCP. Expensive but with ability to characterize ducts proximal to an obstruction or tight stenosis better than ERCP. No risk of aggravating biliary sepsis. Improved sequence speed reduce motion artifacts. D: ERCP. Allows for stone removal, cytologic but has risk for aggravation/development of biliary sepsis. Previously the gold standard with high spatial resolution, MRCP is preferred for given noninvasive nature.

ABDOMINAL US Abdominal US: Several shadowing echogenic foci (arrow) are present in the central biliary system compatible with intrahepatic biliary stone with diffuse biliary intrahepatic dilatation.

CT ABDOMEN PELVIS CT Abdomen Pelvis: Marked central intrahepatic biliary dilatation. Several foci of high attenuation are present compatible with stones (not seen on these images).

MRCP MRCP images demonstrate multifocal biliary strictures and dilatation with intrahepatic filling defects (arrow) compatible with stones. Volume rendered images (right) demonstrate diffuse intrahepatic biliary dilatation.

ERCP ERCP image shows diffuse intrahepatic duct dilatation with multiple stones (arrow) and biliary sludge

DIAGNOSIS Recurrent pyogenic cholangitis (RPC) causing secondary sclerosing cholangitis Differential Diagnosis Primary sclerosing cholangitis Peribiliary cysts Hydatid disease Peripheral cholangiocarcinoma Caroli s disease AIDS cholangiopathy

QUESTION SLIDE 2) Complications of recurrent pyogenic cholangitis include A: Cholangiocarcinoma B: Biloma C: Portal vein thrombosis D: Cirrhosis E: All of the above

CORRECT! 2) Complications of recurrent pyogenic cholangitis include A: Cholangiocarcinoma B: Biloma C: Portal vein thrombosis D: Cirrhosis E: All of the above. Patients with severe RPC are at risk for all of the above. These complications should be monitored with serial imaging and cytology examinations. CONTINUE WITH CASE

SORRY, THAT S INCORRECT! 2) Complications of recurrent pyogenic cholangitis include A: Cholangiocarcinoma B: Biloma C: Portal vein thrombosis D: Cirrhosis E: All of the above. Patients with severe RPC are at risk for all of the above. These complications should be monitored with serial imaging and cytology examinations. CONTINUE WITH CASE

QUESTION SLIDE 3) Benefit of MRCP over ERCP in the evaluation of RPC includes: 1. Decreased risk of biliary sepsis 2. Improved spatial resolution 3. Allows for stone removal and cytological analysis 4. Ability to visualize ducts distal to central obstruction A: 2 and 3 B: 1 and 3 C: 1 and 4 D: 2 and 4

CORRECT! 3) Benefits of MRCP over ERCP in the evaluation of RPC include: A: 2 and 3 B: 1 and 3 C: 1 and 4. MRCP allows for improved visualization of ducts distal to obstructions but has a lower spatial resolution than ERCP. ERCP may be used for stone removal, analysis and cytology but results in increased risk for aggravation of bacteremia. D: 2 and 4 CONTINUE WITH CASE

SORRY, THAT S INCORRECT! 3) Benefits of MRCP over ERCP in the evaluation of RPC include: A: 2 and 3 B: 1 and 3 C: 1 and 4. MRCP allows for improved visualization of ducts distal to obstructions but has a lower spatial resolution than ERCP. ERCP may be used for stone removal, analysis and cytology but results in increased risk for aggravation of bacteremia. D: 2 and 4 CONTINUE WITH CASE

INTERVENTION Bilateral PTC tube placement for recurrent cholangitis with extensive intrahepatic stone burden. Biliary culture: Positive for Klebsiella, Enterococci and Pseduomonas. Dilatation of the bilateral PTC tract with placement of 20 Fr choledochoscope sheaths bilaterally. Choledochoscopy and biliary stone removal of extensive stone burden in the right and left intrahepatic ducts and exchange of PTC tubes.

INITIAL PTC PLACEMENT The biliary system was accessed under ultrasound guidance using a 22 gauge Chiba needle through which a wire was passed. Fluoroscopic images demonstrate moderate to severe bilateral central and intrahepatic ductal dilatation with associated central and intrahepatic biliary duct strictures. In addition, there are multiple filling defects seen throughout the bilateral biliary ducts, consistent with sludge, debris, and stones.

CHOLEDOCHOSCOPY (6 weeks post presentation) Fluoroscopic images show placement of bilateral Amplatz superstiff guidewires through existing biliary drainage tube tracts and dilatation of PTC tracts using two kissing 8 x 4 mm balloons. 20 Fr peel away sheaths were placed through which a 16.5 Fr choledochoscope was advanced into the right and left hepatic ducts.

CHOLEDOCHOSCOPY (6 weeks post presentation) Extensive right and left intrahepatic biliary calculi were seen involving almost all the segmental ducts including the common hepatic duct and CBD. Small casts and debris were removed by scope and Nitinol Zero tip 4 wire basket. Large CBD stone was fragmented using electrohydraulic lithotripsy. Bilateral 14Fr pigtail PTC tubes with additional sideholes were placed for additional external and internal drainage.

CLINICAL FOLLOW UP Patient has returned for multiple PTC exchanges with balloon clearance of CBD, right and left main hepatic ducts, and segmental/subsegmental ducts Labs: Stone analysis: calcium bilirubinate Repeat common bile duct/hepatic duct brushing cytology negative for malignant cells Course has been complicated by recurrent episodes of cholangitis with bile cultures positive for Klebsiella, Enterococci and Pseduomonas. Patient is maintained on outpatient oral antibiotics (augmentin, PCN, & Cipro). Given recurrent nature of disease, the patient was referred for surgical consultation for choledochojejunostomy

QUESTION SLIDE 4) Treatment option for localized lobar disease when atrophy has occurred includes: A: Segmental hepatic resection B: Orthotopic liver transplant C: Endoscopic intervention D: Biliary bypass

CORRECT! 4) Treatment option which should be considered for localized RPC: A: Segmental hepatic resection. May be considered when calculi are isolated to the a single lobe generally after atrophy has occurred. This can reduce the risk for hepatic abscess formation and cholangiocarcinoma. B: Orthotopic liver transplant C: Endoscopic intervention D: Biliary bypass CONTINUE WITH CASE

SORRY, THAT S INCORRECT! 4) Treatment option which should be considered for localized RPC: A: Segmental hepatic resection. May be considered when calculi are isolated to the a single lobe generally after atrophy has occurred. This can reduce the risk for hepatic abscess formation and cholangiocarcinoma. B: Orthotopic liver transplant C: Endoscopic intervention D: Biliary bypass CONTINUE WITH CASE

SUMMARY & TEACHING POINTS Pathogenesis: Found almost exclusively in East and Southeast Asia where infection by parasitic helminths (Ascaris) or liver flukes (Clonorchis, Opisthorchis, and Metorchis) is common. Parasites induce biliary epithelial damage/fibrosis leading to stricturing and secondary infection by enteric bacteria (commonly E. coli, Klebsiella, Pseudomonas, and Proteus) Bacteria-produced gluconidases lead to pigment stone formation; low protein intake or abnormal phospholipid metabolism may reduce natural inhibition of glucoronidases. Presentation Fever, RUQ pain, leukocytosis, elevated alkaline phosphatase and bilirubin Incidence in Asia decreasing due to improved nutritional standards, but prevalence in the West increasing due to migration from endemic areas Recurrent episodes of cholangitis lead to secondary biliary sclerosis and eventually biliary cirrhosis and portal hypertension in later stages

SUMMARY & TEACHING POINTS Diagnosis: Combination of clinical, laboratory and imaging characteristics History of LFTs, stool O&P, serum ELISA, biliary cytology Initial evaluation by ultrasound, followed by ERCP/MRCP Treatment: Requires repeated multidisciplinary approach Antibiotic therapy for recurrent episodes; equivocal evidence for ursodial therapy Biliary drainage and stone removal via ERCP and PTC Surgical hepatico-jejunostomy or lobectomy for advanced or isolated left lobe disease Complications Liver abscess formation (20%) and risk for septic emboli Secondary biliary cirrhosis, portal vein thrombosis Biloma Cholangiocarcinoma (1.5-11%) and inflammatory pseudotumor

REFERENCES & FURTHER READING Afagh, A, et al: Radiologic findings in recurrent pyogenic cholangitis. The Journal of Emergency Medicine, Vol. 26, No. 3, pp. 343346, 2004 Al-Sukhni, W, et al: Recurrent Pyogenic Cholangitis with Hepatolithiasis The Role of Surgical Therapy in North America. J Gastrointest Surg 12:496 503, 2008 Cheung, MT, et al: Liver Resection for Intrahepatic Stones. Arch Surg.140:993-997, 2005 Harris, HW, et al: Recurrent Pyogenic Cholangitis. American Journal of Surgery. 176:35-37, 1998 Heffernan EJ et al: Recurrent pyogenic cholangitis: from imaging to intervention. AJR Am J Roentgenol. 192(1):W28-35, 2009 Jain M et al: MRCP findings in recurrent pyogenic cholangitis. Eur J Radiol. 66(1):79-83, 2008 Jeyarajah, DR: Recurrent Pyogenic Cholangitis Current Treatment Options in Gastroenterology. 7:91 98, 2004 Kim JH et al: CT findings of cholangiocarcinoma associated with recurrent pyogenic cholangitis. AJR Am J Roentgenol. 187(6):1571-7, 2006 Lee, KF et al: Outcome of surgical treatment for recurrent pyogenic cholangitis: a single-centre study. HPB 11, 75 80, 2009 Lee WJ et al: Radiologic spectrum of cholangiocarcinoma: emphasis on unusual manifestations and differential diagnoses. Radiographics. 21 Spec No:S97-S116, 2001 Lo CM et al: The changing epidemiology of recurrent pyogenic cholangitis. Hong Kong Med J. 3(3):302-304, 1997 Mori, T et al: Management of intrahepatic stones. Best Practice & Research Clinical Gastroenterology 20:6, 1117e1137, 2006 Nguyen, T et al: Recurrent Pyogenic Cholangitis. Dig Dis Sci (2010) 55:8 10 Park MS et al: Recurrent pyogenic cholangitis: comparison between MR cholangiography and direct cholangiography. Radiology. 220(3):677-82, 2001 Shoda, J et al: Molecular Pathogenesis of Hepatolithiasis A Type of Low Phospholipid-Associated Cholelithiasis. Frontiers in Bioscience 11, 669-675, 2006 Sperling RM et al: Recurrent pyogenic cholangitis in Asian immigrants to the United States: natural history and role of therapeutic ERCP. Dig Dis Sci. 42(4):865-71, 1997 Tsui WM et al: Hepatolithiasis and the syndrome of recurrent pyogenic cholangitis: clinical, radiologic, and pathologic features. Semin Liver Dis. 31(1):33-48, 2011