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

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

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

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

Epidemiology Nationality Sex Age 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

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

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

Diagnosis: lab values CBC Metabolic panel Amylase/Lipase 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

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

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 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%

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

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

Our case… Condition: ERCP attempted 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

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 We know that she has elevated LFTs.

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

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

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

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

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

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

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

…our case Open procedure Cholecystectomy CBD exploration 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.