Cholangiocarcinoma - SUNY Downstate Medical CenterCholangiocarcinoma Anita Chiu, MD Brooklyn VA Hospital March 31, 2011 Case Presentation • 63 year old male Vietnam veteran • PMH:
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Cholangiocarcinoma Anita Chiu, MD Brooklyn VA Hospital March 31, 2011 www.downstatesurgery.org
• 63 year old male Vietnam veteran• PMH: obesity, HTN, DM2 (1999), CAD (3v disease),
ischemic cardiomyopathy, CHF with EF 18-25%, h/o MI (1999), hyperlipidemia, chronic liver disease (NASH/NAFLD), prostate cancer s/p EBRT, prior 40 pack yr smoking history
• Liver mass first found 3/2010 on CT• Inconclusive biopsy 4/2010 • Repeat biopsy 12/10• Plan for surgery after multidisciplinary
discussion• Cardiology optimization
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Presentation Notes
First seen on CT 3/22/10 – compared to CT 2009 5.2x3.5x2.0 hypodense lesion within dome of liver – on delayed postcontrast images there is partial filling (benign hemangioma vs malignancy) RIJ transjugular liver bx under US guidance 4/13 – focal nodular hyperplasia and microvesicular steatosis CT 11/22/10 – increased ill-defined right hepatic lesion with increased adjacent arterial enhancement concerning for neoplasm US guided liver bx 12/2/10 – stains + for CK 19 and CA 19-9 -> pancreas or cholangiocarcinoma CT C –upper abd cuts show stable liver lesion Cardiac clearance tests CT A/P 1/13/11 prior to surgery No MRI because of pacemaker
Case Presentation
• 30 lb weight loss in past 2-3 months• T 98.7 BP 125/69 HR 72 R18 228lbs• Gen: obese, NAD, A&Ox3• Chest: CTA b/l• CVS: systolic heart murmur, 2nd ICS• Abdomen: soft, no hepatosplenomegaly,
well healed lower midline scar• Ext: b/l pedal edema
1. RE: CT Scan 4 phase liver Oct 7 2008, 10:24 PM EDT | Post edited: Oct 7 2008, 10:24 PM EDT Hi,The four phases are pre contrast, arterial phase, portal venous phase, and delayed phase. Multiphase liver CT is used to detect and characterise liver lesions as different types of tumours enhance differently during each phase depending on whether they are hypervascular or hypovascular lesions.Precontrast liver scans are used to detect calcifications, visualise haemorrhage from trauma, and demonstrate hypervascular lesions which appear hypodense compared to the surrounding liver parenchyma.The arterial phase of scanning is performed approximately 30 seconds after the contrast injection is initiated and is most accurately detemined by using bolus tracking software (eg SmartPrep) to monitor the level of contrast enhancement in the aorta and automatically triggering the scan when it reaches a pre determined level of enhancement (eg 120HU). Hypervascular lesions enhance during the arterial phase and apper hyperdense. Arterial phase images are also used for pre operative evaluation of the arterial vasculature through the use of MIPs and 3D reconstructions.The portal venous phase is performed 70-90 seconds post contrast and hypovascular lesions appear hypodense and hypervascular lesions appear isodense (same density as surrounding liver).The delayed phase is performed 5-10 minutes post contrast and is used to further characterise lesions. Haemangiomas are slow to enhance and some HCC can appear hypodense due to rapid washout and CCC can appear hyperdense due to delayed washout. Reading 1/13/11 Hyperenhancement in segment 6 and 7 of liver adjacent to ill-defined heterogenous lesion in the right lower lobe (5.8x5.6x5.9) CBD not dilated Stable but prominent periportal/peripancreatic lymph nodes with portocaval lymph nodes measuring up to 1.3cm in short axis
extended right hepatectomy involving portions of 4a/4b, intraoperative ultrasound
• Liver without cirrhosis but consistent with NASH• Large firm mass involving middle hepatic vein,
segments 4/5/6/7/8 at hilum of liver, encroaching but not invading IVC
• IOUS – large tumor mass and 2 satellite lesions to right of middle hepatic vein (but extending on 4b)
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Presentation Notes
IVF 8L, 1 pRBC; 2 FFP, 1 platelets, UOP 700 EBL 1400 Dx lap performed to rule out peritoneal carcinomatosis and cirrhosis Bilateral subcostal incision Hepatic colic flexure mobilized to begin IVC exposure Full Kocher to complete IVC exposure and access Morrison’s pouch Right lobe mobilized from diaphragmatic attachments and right HV exposed as well as origin of middle HV Suprahepatic IVC exposed IOUS performed R0 resection by extended right hepatectomy Retrograde cholecystectomy Identified right hepatic artery by palpation and then isolated and divided Lowered hilar plate to expose portal triad -> found node, sent off for frozen Dissected off right branch of portal vein and divided it Liver then dissected off IVC (no invasion) Right HV taken Resection followed line of demarcation by bovie along Cantlie’s line to spare blood supply to 4a (Habib used) Resection completed with CUSA in order to obtain a good margin, intermittent warm inflow occlusion for total 20 min Middle hepatic vein divided flush to IVC Hemostasis Left liver anchored to falciform to prevent torsion and ischemic changes to liver remnant 2 JPs placed Specimens: portal lymph node, extended right love of liver for frozen and permanent section with negative margins
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Pathology
• Pathologic Staging:• pT2bNxMx
• 12x15x10cm right hepatectomy specimen
• Moderately differentiated intrahepatic bile duct adenocarcinoma, tumor (9x6x6.5cm)
• Negative margins of resection (closest margin 1mm)
• Portal vein LN negative
Tubular structures with variable fibrous stroma
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Presentation Notes
Special stains – CK7 – useful to differentiate bile duct carcinoma vs metastases CK20 – differentiates between intra (+) and extrahepatic (-) cholangio Hep-par 1 and AFP – useful to dx liver cell carcinoma
Postoperative Course
• ICU POD#1-4 for cardiac monitoring• Transferred to floor on POD#5• Gradual but uneventful recovery• Discharged on POD#19• Seen in clinic on POD#20, POD#27• Medical oncology appointment 4/11/11
• Uncommon tumor • Incidence in US 1:100,000• Age 50 – 90 years old• Can occur anywhere in extrahepatic or
intrahepatic biliary tree
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The reported incidence of cholangiocarcinoma in the United States is 1 or 2 cases per 100,000 population. Incidence data from the American Cancer Society are difficult to interpret because intrahepatic bile duct cancers are included with primary liver cancers, whereas extrahepatic biliary cancers are in a separate category that includes gallbladder cancer. In the United States, an estimated 17,550 primary liver cancers will be diagnosed in 2005. Data from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) program suggest that about 15% of these (2600 cases) will be intrahepatic cholangiocarcinomas. About 7000 cases of extrahepatic bile duct cancer are diagnosed annually in the United States, two thirds of which are gallbladder cancers. Thus, 2000 to 3000 cases per year are extrahepatic cholangiocarcinomas.
At least two genetic disorders are associated with an increased risk for cholangiocarcinoma: the inherited “cancer family” syndrome termed Lynch syndrome II, and a rare inherited disorder called multiple biliary papillomatosis; the latter condition is characterized by multiple adenomatous polyps in the bile ducts, and repeated episodes of abdominal pain, jaundice, and acute cholangitis. Five percent of patients in a large Italian series developed cholangiocarcinoma between 11 and 18 years after a biliary-enteric anastomosis. The risk for bile duct cancer was higher after transduodenal sphincteroplasty and choledochoduodenostomy than after hepaticojejunostomy and was most strongly associated with recurrent episodes of cholangitis.
Location
Distal
Intrahepatic
Extrahepatic
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60 – 80% of cases at hepatic duct bifucation!!! Intrahepatic tumors are treated like hepatocellular carcinoma with hepatectomy, when possible. The perihilar tumors make up the largest group and are managed with resection of the bile duct, preferably with hepatic resection. Distal tumors are managed in a fashion similar to other periampullary malignancies with pancreatoduodenectomy.
CEA, CA19-9 (PSC) , combo of the two – basically there is no good tumor marker; for intrahepatic, unlike HCC, AFP will be normal Diagnosis of a cholangiocarcinoma can be challenging, particularly in patients with PSC. In such cases, mass lesions are infrequently identified on imaging, and patients often do not develop significant intrahepatic biliary dilatation. A high index of suspicion and multidisciplinary investigative procedures are needed. Most jaundiced patients undergo initial transabdominal ultrasound (US) to confirm biliary ductal dilatation, localize the site of the obstruction, and exclude gallstones [17]. The sequence of subsequent evaluation is slightly different for hilar as compared to distal lesions. For hilar lesions (intrahepatic ductal dilatation with normal caliber extrahepatic ducts), magnetic resonance cholangiopancreatography (MRCP) is emerging as the imaging technique of choice [18], while the use of invasive cholangiography, particularly ERCP, is diminishing. US - Intrahepatic cholangiocarcinomas appear as a mass lesion on US. Perihilar and extrahepatic cancers may not be detected, especially if small, but indirect signs (ductal dilatation throughout the obstructed liver segments) may point toward the diagnosis. An obstructing lesion is suggested by ductal dilatation (>6 mm in normal adults) in the absence of stones. Proximal lesions cause dilation of the intrahepatic ducts alone, while both intrahepatic and extrahepatic ducts are dilated with more distal lesions CT scan — Because of its widespread availability, CT is commonly obtained in patients with suspected biliary malignancy. It is useful for detecting intrahepatic tumors, the level of biliary obstruction, and the presence of liver atrophy. MRCP — Magnetic resonance cholangiopancreatography (MRCP) is a noninvasive technique for evaluating the intrahepatic and extrahepatic bile ducts and the pancreatic duct that is emerging as an excellent tool for the preoperative assessment of biliary tract cancers. Cholangiography — Cholangiography entails an injection of radiographic contrast material to opacify the bile ducts; it can be performed by endoscopic retrograde pancreatography (ERCP) or via a percutaneous approach Endoscopic ultrasound — For distal bile duct lesions, endoscopic ultrasound (EUS) can visualize the local extent of the primary tumor and the status of regional lymph nodes. PET scan — Positron emission tomography (PET scan) permits visualization of cholangiocarcinomas because of the high glucose uptake of bile duct epithelium. PET scans can detect nodular cholangiocarcinomas as small as 1 cm but is less helpful for infiltrating tumors [50-52]. Perhaps more important is the role of PET in identifying occult metastases [51-54]. In one series, PET led to a change in surgical management in 11 of 36 patients evaluated for cholangiocarcinoma because of detection of unsuspected metastases SUMMARY AND RECOMMENDATIONS — Making a definitive tissue diagnosis of cholangiocarcinoma preoperatively can be difficult. This is an important clinical issue since up to one-third of patients with symptoms and cholangiogram suggestive of a bile duct malignancy will have either benign fibrosing disease or another malignancy with metastases that obstruct the bile ducts. Preoperative evaluation typically includes right upper quadrant ultrasound, dynamic CT scan, MRCP (in centers with technical expertise in this procedure) and/or ERCP with brushing/biopsy. Tumor markers such as CA 19-9 can be useful in conjunction with biopsy or brushings to confirm the diagnosis. If a tissue diagnosis cannot be confirmed, ultrasound or CT-guided percutaneous biopsy should be considered. Even after extensive diagnostic work-up, many patients still require surgical exploration to confirm the diagnosis.
Assessment of Resectability• Curative treatment only possible with
for negative margins with presence of hepatic lobar atrophy and hepatic ductal extension on imaging
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When a diagnosis of cholangiocarcinoma is confirmed at biopsy or is considered likely given a patient's clinical, laboratory, and radiologic findings, attention must be paid to the potential resectability of the lesion since surgery is the only means of attaining cure. The radiographic appearance of malignant biliary strictures is helpful in determining the feasibility of operative resection and in planning surgery. If questions remain as to the status of the portal vein and/or hepatic artery, many surgeons will request hepatic arteriography and portal venography to look for vascular invasion by the tumor. However, angiography is not needed in the majority of patients. Even with the enhanced diagnostic capability of newer radiologic studies such as MRCP and dynamic CT, unless there is clear evidence of metastatic disease, true resectability can often be determined only by operative evaluation. Radiologic Criteria to Suggest Unresectability of Cholangiocarcinoma Bilateral hepatic duct involvement up to secondary radicals Bilateral hepatic artery involvement Encasement of the portal vein proximal to its bifurcation Atrophy of one hepatic lobe with contralateral portal vein encasement Atrophy of one hepatic lobe with contralateral biliary radical involvement Distant metastasis Adapted from Anderson CD, Pinson CW, Berlin J, Chari RS: Diagnosis and treatment of cholangiocarcinoma. Oncologist 9:43-57, 2004.
Assessment of Resectability
• Imaging can help predict resectability• Even with enhanced diagnostic
technologies, true resectability can often be determined only by operative evaluation
• If unresectable, nonoperative palliation
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Traditional Criteria for Resectability
• Absence of retropancreatic and paraceliac nodal metastases or distant liver metastases
• Absence of invasion of the portal vein or main hepatic artery
• Absence of extrahepatic adjacent organ invasion
• Absence of disseminated disease
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Operative Approach
• Surgical exploration should be undertaken in good-risk patients without evidence of metastatic or unresectable disease
• Intraoperatively >50% of patients found to have peritoneal or hepatic metastases or locally unresectable disease
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Presentation Notes
Selective use of laparoscopy in patients with locally advanced but potentially resectable perihilar cholangiocarcinoma may avoid laparotomy in some patients with metastatic disease. In patients who are found to have extensive metastatic disease, the preoperatively placed biliary stents should be left in place. However, a cholecystectomy should be performed to avoid the risk of acute cholecystitis, which occurs in patients with long-term indwelling biliary stents. In patients with locally advanced unresectable perihilar tumors, several operative approaches are available for palliation, including a Roux-en-Y hepaticojejunostomy to segment III or V.
Distal Cholangiocarcinoma
• Treated with pancreatico-duodenectomy (Whipple)
• If unresectable –cholecystectomy and double bypass for palliation
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A pylorus-preserving operation is preferable and feasible in most patients, with 5-year survival rates averaging 15% to 25%, but can be as high as 54% in selected patients who undergo complete resection for node-negative disease. If resection is not possible owing to vascular encasement, cholecystectomy, Roux-en-Y hepaticojejunostomy proximal to the tumor, and a gastrojejunostomy to prevent gastric outlet obstruction should be performed. Lymph node involvement and depth of tumor invasion are important prognostic indicators No new data stratifying outcomes acccording to the new 2010 AJCC guidelines
Intrahepatic Cholangiocarcinoma
• Hepatic resection• Goal to achieve
negative resection margins
• Few data regarding benefits of lymphadenectomy
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Presentation Notes
Intrahepatic cholangiocarcinoma is treated by hepatic resection, and outcomes depend on disease stage (particularly the status of the lymph nodes) and the ability to achieve negative margins. There is a broad range of long-term outcomes in patients undergoing complete resection (3-year survival rates of 22%-66%). But lymph node involvement is an important prognostic factor Benefit of performing routing portal lymph node dissection should be weighed against risks such as CBD devascularization
Perihilar Cholangiocarcinoma
• Follows Bismuth classification• I, II: en bloc resection of extrahepatic bile
ducts, cholecystectomy with 5- to 10-mm bile duct margins, regional lymphadectomy, RNY hepaticojejunostomy, possible hepatic lobectomy
• III, IV: above, definitive partial hepatic resection
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For perihilar cholangiocarcinomas, bile duct resection alone leads to high local recurrence rates due to early involvement of the confluence of the hepatic ducts and the caudate lobe branches. The addition of a modified hepatic resection has improved resectability rates. However, curative resections are still possible in less than half of patients, and most do not achieve long-term disease control. Surgical treatment depends on the Bismuth-Corlette classification (see Fig. 54-35). For type I and II lesions, the procedure is en bloc resection of the extrahepatic bile ducts and gallbladder with 5- to 10-mm bile duct margins, and regional lymphadenectomy with Roux-en-Y hepaticojejunostomy. In addition to the above operations, type II tumors may require hepatic lobectomy. Because type II and III lesions often involve the ducts of the caudate lobe, many surgeons recommend routine caudate lobectomy. Type III and IV tumors are amenable to potentially curative resection in centers with expertise in these procedures. Aggressive techniques such as hepatectomy and portal vein resection to achieve negative margins are now routine in specialized centers. Substantial progress has been made in curative resection for perihilar cholangiocarcinomas. At least some of this progress has been attributed to the routine use of partial hepatectomy. The rate of margin-negative resections is consistently more than 75% when partial hepatectomy (including resection of the caudate lobe) is added to the bile duct resection. This aggressive approach has resulted in 5-year survival rates above 50% in some series. However, these improvements have been accompanied by higher surgical mortality rates (8%-10% versus 2%-4%). The major prognostic factors are margin status and tumor stage. In addition to location, stage, and status of the resection margins, other factors influence outcome after resection. Major prog factors – margin status, vascular invasion, lymph node mets (2010 AJCC)
Bismuth Classification
Type I Type 2
Type 3a, b Type 4
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Presentation Notes
Bismuth classification of perihilar cholangiocarcinoma by anatomic extent. Type I tumors (upper, left) are confined to the common hepatic duct, and type II tumors (upper, right) involve the bifurcation without involvement of secondary intrahepatic ducts. Type IIIa and IIIb tumors (lower, left) extend into either the right or left secondary intrahepatic ducts, respectively. Type IV tumors (lower, right) involve the secondary intrahepatic ducts on both sides. Curative resections are still possible in fewer than ½ of patients Majority do not achieve long-term disease control
Staging
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Adjuvant Therapy
• Local relapse pattern most common after surgery– Subsequent bile duct obstruction– Liver failure– Recurrent sepsis
• Benefit of adjuvant therapy for patients with resected cholangiocarcinoma remains unproven but is frequently utilized
• Positive regional LN, carcinoma in situ at margins, positive margins with invasive disease– Fluoropyrimidine-based
chemoradiotherapy should be considered
Intrahepatic cholangiocarcinoma• No residual local disease
– No adjuvant therapy recommendations are made
• Positive margins– Reresection– Ablation– Fluoropyrimidine or
gemcitabine-based chemotherapy
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Presentation Notes
European Society of Medical Oncology – supportive care or palliative chemo and/or radiotherapy after a noncurative resection Consideration of postop chemoradiotherapy as option after complete surgical resection
Summary
• All patients with cholangiocarcinoma require individualized management
• Most patients will present with advanced disease only amenable to palliative procedures
• Resection is the only chance for cure
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References• AJCC (American Joint Committee on Cancer) Cancer Staging Manual, 7th ed. Edge, SB, Byrd,
DR, Compton, CC, et al (Eds), Springer, New York 2010. p. 219.• Allen Peter J, Fong Yuman, "Chapter 29. Benign and Malignant Primary Liver Neoplasms"
• Khan S et al. “Guidelines for the diagnosis and treatment of cholangiocarcinoma: consensus document.” Gut 2002;51:vi1-vi9 doi:10. 1136/gut.51.suppl_6v1.
• National Comprehensive Cancer Network (NCCN) guidelines www.nccn.org• Rajagopalan, V et al. Gallbladder and biliary tract carcinoma: A comprehensive update, Part 1.
Oncology (Williston Park) 2004; 18:889.• Townsend: Sabiston Textbook of Surgery, 18th edition. Chap 52. The Liver, “Primary Solid
• Welling, III Theodore H, "Chapter 14. Hepatectomy" (Chapter). Minter RM, Doherty GM: Current Procedures: Surgery: http://www.accesssurgery.com/content.aspx?aID=6562566.
• Whang Edward E, Zinner Michael J, "Chapter 35. Cancer of the Gallbladder and Bile Ducts" (Chapter). Zinner MJ, Ashley SW: Maingot's Abdominal Operations, 11th Edition: http://www.accesssurgery.com/content.aspx?aID=129969.
