Cholangitis & Management of Choledocholithiasis

1. Cholangitis &Management of Choledocholithiasis Ruby Wang MS 3 Surg 300A 8/20/07

2. Content • Case • Cholangitis • Clinical manifestations • Diagnosis • Treatment • Diagnosis and management of choledocholithiasis • Pre-operative • Intra-operative • Post-operative

3. Case • HPI: • 86 yo lady p/w 3-4 episodes of RUQ/mid-epigastric abdominal pain over the last year, lasting generally several hours, accompanied by occasional emesis, anorexia, and sensation of shaking chills. • ROS: negative otherwise • PE: • VS: T 36.2, P98 , RR 18, BP 124/64 • Abdominal exam significant for RUQ TTP • Labs • AST 553, ALT 418. Alk Phos 466. Bilirubin 2.7 • WBC 30.3 • Imaging • Abdominal US: multiple gallstones, no pericholecystic fluid, no extrahepatic/intrahepatic/CBD dilatation

4. Introduction • Cholangitis is bacterial infection superimposed on biliary obstruction • First described by Jean-Martin Charcot in 1850s as a serious and life-threatening illness • Causes • Choledocholithiasis • Obstructive tumors • Pancreatic cancer • Cholangiocarcinoma • Ampullary cancer • Porta hepatis • Others • Strictures/stenosis • ERCP • Sclerosing cholangitis • AIDS • Ascaris lumbricoides

5. Epidemiology • Nationality • U.S: uncommon, and occurs in association with biliary obstruction and causes of bactibilia (s/p ERCP) • Internationally: • Oriental cholangiohepatitis endemic in SE Asia- recurrent pyogenic cholangitis with intrahepatic/extrahepatic stones in 70-80% • Gallstones highest in N European descent, Hispanic populations, Native Americans • Intestinal parasites common in Asia • Sex • Gallstones more common in women • M: F ratio equal in cholangitis • Age • Median age between 50-60 • Elderly patients more likely to progress from asymptomatic gallstones to cholangitis without colic

6. Pathogenesis • Normally, bile is sterile due to constant flush, bacteriostatic bile salts, secretory IgA, and biliary mucous; Sphincter of Oddi forms effective barrier to duodenal reflux and ascending infection • ERCP or biliary stent insertion can disrupt the Sphincter of Oddi barrier mechanism, causing pathogeneic bacteria to enter the sterile biliary system. • Obstruction from stone or tumor increases intrabiliary pressure • High pressure diminishes host antibacterial defense- IgA production, bile flow- causing immune dysfunction, increasing small bowel bacterial colonization. • Bacteria gain access to biliary tree by retrograde ascent • Biliary obstruction (stone or stricture) causes bactibilia • E Coli (25-50%) • Klebsiella (15-20%), • Enterobacter (5-10%) • High pressure pushes infection into biliary canaliculi, hepatic vein, and perihepatic lymphatics, favoring migration into systemic circulation- bacteremia (20-40%). Adam.about.com Gpnotebook.co.uk Pathology.med.edu

7. Clinical Manifestations Charcot’s Triad: Found in 50-70% of patients • RUQ pain (65%) • Fever (90%) • May be absent in elderly patients • Jaundice (60%) • Hypotension (30%) • Altered mental status (10%) Reynold’s Pentad: Additional History Pruitus, acholic stools PMH for gallstones, CBD stones, Recent ERCP, cholangiogram Additional Physical Tachycardia Mild hepatomegaly

8. Diagnosis: lab values • CBC • 79% of patients have WBC > 10,000, with mean of 13,600 • Septic patients may be neutropenic • Metabolic panel • Low calcium if pancreatitis • 88-100% have hyperbilirubinemia • 78% have increased alkaline phosphatase • AST and ALT are mildly elevated • Aminotransferase can reach 1000U/L- microabscess formation in the liver • GGT most sensitive marker of choledocholithiasis • Amylase/Lipase • Involvement of lower CBD may cause 3-4x elevated amylase • Blood cultures • 20-30% of blood cultures are positive

9. Diagnosis: first-line imaging Ultrasonography • Advantage: • Sensitive for intrahepatic/extrahepatic/CBD dilatation • CBD diameter > 6 mm on US associated with high prevalence of choledocholithaisis • Of cholangitis patients, dilated CBD found in 64%, • Rapid at bedside • Can image aorta, pancreas, liver • Identify complications: perforation, empyema, abscess • Disadvantage • Not useful for choledocholithiasis: • Of cholangitis patients, CBD stones observed in 13% • 10-20% falsely negative - normal U/S does not r/o cholangitis • acute obstruction when there is no time to dilate • Small stones in bile duct in 10-20% of cases CT • Advantages • CT cholangiograhy enhances CBD stones and increases detection of biliary pathology • Sensitivity for CBD stones is 95% • Can image other pathologies: ampullary tumors, pericholecystic fluid, liver abscess • Can visualize other pathologies- cholangitis: diverticuliits, pyelonephritis, mesenteric ischemia, ruptured appendix • Disadvantages • Sensitivity to contrast • Poor imaging of gallstones Med.virgina.edu Soto et al. J. Roenterology. 2000

10. Diagnostic: MRCP and ERCP Magnetic resonance cholangiopancreatography (MRCP) • Advantage • Detects choledocholithiasis, neoplasms, strictures, biliary dilations • Sensitivity of 81-100%, specificity of 92-100% of choledocholithiasis • Minimally invasive- avoid invasive procedure in 50% of patients • Disadvantage: • cannot sample bile, test cytology, remove stone • Contraindications: pacemaker, implants, prosthetic valves • Indications • If cholangitis not severe, and risk of ERCP high, MRCP useful • If Charcot’s triad present, therapeutic ERCP with drainage should not be delayed. Endoscopic retrograde cholangiopancreatography (ERCP) • Gold standard for diagnosis of CBD stones, pancreatitis, tumors, sphincter of Oddi dysfunction • Advantage • Therapeutic option when CBD stone identified • Stone retrieval and sphincterotomy • Disadvantage • Complications: pancreatitis, cholangitis, perforation of duodenum or bile duct, bleeding • Diagnostic ERCP complication rate 1.38% , mortality rate 0.21%

11. Medical Treatment • Resucitate, Monitor, Stabilize if patient unstable • Consider cholangitis in all patients with sepsis • Antibiotics • Empiric broad-spectrum Abx after blood cultures drawn • Ampicillin (2g/4h IV) plus gentamicin (4-6mg/kg IV daily) • Carbapenems: gram negative, enterococcus, anaerobes • Levofloxacin (250-500mgIV qD) for impaired renal fxn. - 80% of patients can be managed conservatively 12-24 hrs Abx - If fail medical therapy, mortality rate 100% without surgical decompression: ERCP or open - Indication: persistent pain, hypotension, fever, mental confusion

12. Surgical treatment • Endoscopic biliary drainage • Endoscopic sphincterotomy with stone extraction and stent insertion • CBD stones removed in 90-95% of cases • Therapeutic mortality 4.7% and morbidity 10%, lower than surgical decompression • Surgery • Emergency surgery replaced by non-operative biliary drainage • Once acute cholangitis controlled, surgical exploration of CBD for difficult stone removal • Elective surgery: low M & M compared with emergency survey • If emergent surgery, choledochotomy carries lower M&M compared with cholecystectomy with CBD exploration

13. Our case… • Condition: • No acute distress, reasonably soft abdomen • ERCP attempted • Duct unable to cannulate due to presence of duodenum diverticulum at site of ampulla of Vater • Laparoscopic cholecystectomy planned • Dissection of triangle of Calot • Cystic duct and artery visualized and dissected • Cystic duct ductotomy • Insertion of cholangiogram catheter advanced and contrast bolused into cystic duct for IOC • Intraoperative cholangiogram • Several common duct filling defects consistent with stones • Decision to proceed with CBD exploration

14. Choledocholithiasis • Choledocholithiasis develops in 10-20% of patients with gallbladder disease • At least 3-10% of patients undergoing cholecystectomy will have CBD stones • Pre-op • Intra-op • Post-op

15. Pre-op diagnosis & management • Diagnosis: Clinical history and exam, LFTs, Abdominal U/S, CT, MRCP • High risk (>50%) of choledocholithiasis: • clinical jaundice, cholangitis, • CBD dilation or choledocholithiasis on ultrasound • Tbili > 3 mg/dL correlates to 50-70% of CBD stone • Moderate risk (10-50%): • h/o pancreatitis, jaundice correlates to CBD stone in 15% • elevated preop bili and AP, • multiple small gallstones on U/S • Low risk (<5%): • large gallstones on U/S • no h/o jaundice or pancreatitis, • normal LFTs • Treatment: • ERCP • Surgery

16. Intra-op diagnosis and management • Diagnosis:intraoperative cholangiography (IOC) • Cannulation of cystic duct, filling of L and R hepatic ducts, CBD and common hepatic duct diameter, presence or absence of filling defects. • Detect CBD stones • Potentially identify bile duct abnormalities, including iatrogenic injuries • Sensitivity 98%, specificity 94% • Morbidity and mortality low • Treatment • Open CBD exploration • Most surgeons prefer less invasive techniques • Laparoscopic CBD exploration • via choledochotomy: CBD dilatation > 6mm • via cystic duct (66-82.5%) • CBD clearance rate 97% • Morbidity rate 9.5% • Stones impacted at Sphincter of Oddi most difficult to extract • Intraoperative ERCP

17. Early years: Open CBD exploration & Introduction of endoscopic sphincterotomy • 1889, 1st CBD exploration by Ludwig Courvoisier, a Swiss surgeon • Kocherization of duodenum and short longitudinal choledochotomy • Stones removed with palpation, irrigation with flexible catheters, forceps, • Completion with T-tube drainage • For many years, this was the standard treatment for cholecystocholedocholithiasis • 1970s, endoscopic sphincterotomy (ES) • Gained wide acceptance as good, less invasive, effective alternative • In patients with CBD stones who have previously undergone cholecystectomy, ES is the method of choice

18. Open surgery vs Endoscopic sphincterotomy • In patients with intact gallbladders, ES or open choledochotomy? • Design: 237 patients with CBD stone and intact gallbladders, 66% managed with ES and rest with open choledochotomy • Results: No significant difference in morbidity and mortality rates • Lower incidence of retained stones after open choledochotomy • Conclusion: open surgery superior to ES in those with intact gallbladders • Miller et al. Ann Surg 1988; 207: 135-41 • Is ES followed by open CCY superior to open CCY+ CBDE? • Results: Initial stone clearance higher with open surgery (88% vs 65%, p< 0.05) • Conclusion: routine preoperative ES not indicated • Stain et al. Ann Surg 1991; 213: 627-34 • Cochraine database of systematic reviews • Design: 8 trials randomized 760 patients comparing ERCP with open surgical clearance • Results: Open surgery more successful in CBD stone clearance, associated with lower mortality • Conclusion: open bile duct surgery superior to ES • Cochrane database of systematic reviews 2007 • In patients with severe cholangitis, open or ES? • Study design: Randomized, prospsective trial of 82 patients with choledocholithiasis and severe toxic cholangitis managed endoscopically or with open choledochotomy • Results: In group managed initially with endoscopic drainage, need for ventilatory support (29% vs 63%) and mortality (33% vs 66%) significantly less • Conclusion: toxic cholangitis should managed with endoscopic sphincterotomy • Lai et al. J Engl J Med 1992; 326: 1582-6

19. Laparoscopic CBD Exploration • In 1989, laparoscopic removal of gallbladder replaced open surgery • In the past decade, laparoscopic CBD exploration (LCBDE) developed • Techniques • IOC define biliary anatomy: size and length of cystic duct, size of bile duct stones • Choledochotomy • If cystic duct < CBD stone, If CBD > 6mm • If stone located proximal to cystic duct-common bile duct junction • If stone impacted in bile duct or papilla • Transcystic approach • If CBD < 6mm in diameter • Cystic duct dissected close to junction with CBD, transverse incision made • Guidewire into CBd through cholangiogram catheter under fluoroscopy • Osotonic NaCl irrigate CBD to flush small stones through sphincter of Oddi • Unsuccessful in 10-20% of patients • Contraindications: pancreatitis, sphincter anomalies, • Results • High rate of lap CBD clearance: 73-100% • Similar success rates between transcystic and choledochotomy • Conversion to open 5.2-19.6% • Causes : multiple/impacted stones, bleeding, unclear anatomy,equipment failure • Length of hospital stay shorter in LCBDE than ES • Mortality and Morbidity • No difference between LCBDE and ES Cochrane database of systematic reviews 2007

20. Post-op Diagnosis and Management • T-tube cholangiography • T-tube placed following CBDE to diagnosis and manage retained stones • Retained CBD stones in 2-10% of patients after CBD exploration • If not obstruction, tube is clamped and left for 6 weeks. • Cholangiogram repeat after 6 wks • ERCP • Treatment of retained stones undetected or left behind

21. In summary • Non-surgical care first line • Goal: extract stone, but if not possible, drain bile to improve condition until definitive surgical intervention • ERCP: both diagnostic and therapeutic • Stones> 1cm - Sphincterotomy needed before extraction • Stones > 2cm: require lithotripsy or chemical dissolution • PTC • Surgical Care if endoscopy and IR drainage fail • Issues • Exploration of CBD • Fate of gallbladder • CBD exploration: laparoscopy first line • Transcystic: • Choledochotomy • CBD exploration: open • If laparoscopy has failed or contraindicated • T-tube cholangiogram 10-14 days posto • Open CBD is safe option, but limited to setting of concomitant open surgery

22. …our case • Open procedure • Due to previous failure of ERCP due to duodenum diverticulum • Incision joining epigastric port with subcostal inciion • Dis • Cholecystectomy • Gallbladder was dissected free from liver bed • Cystic artery/duct identified, ligated. • CBD exploration • 2 suture splaced in direction of common duct through anterior wall in the same longitudinal direction • Choledochotomy- extended in both proximal and distal directions of CBD • 4 CBD stones evacuated • Catheter advanced within CBD to perform sphincterotomy • T-tube placed within common bile duct.