1. Hepatopancreatobiliary (HPB) Surgery, Department of Surgery
GI Symposium 2015: Advances in Hepatobiliary and Pancreatic Diseases Conference
February, 2015
Management of Liver Cysts
Sandeep Anantha, MD
HPB Surgery fellow
Hepatopancreatobiliary (HPB) Surgery, Department of Surgery
St. John Providence Healthcare System

2. Speaker Disclosures
Nothing to disclose

3. Contents Simple Cysts Polycystic Liver Disease
Biliary Cystadenoma and Biliary IPMN
Biliary Cystadenocarcinoma
Diagnosis
Treatment
Survival
Recurrence

4. Categories of Hepatobiliary Cysts
Congenital: simple cysts, polycystic disease, bile duct cysts (type IV,V), bile duct hamartomas
Neoplastic: hepatobiliary cystadenoma, biliary IPMN, cystadenoca, embryonal sarcoma, cystic variants of hepatic metastases

5. Congenital Simple Cysts
No communication with the biliary tract
5% of adults, most are < 3 cm
90% asymptomatic
2/3 female, age > 50 yrs
Typically solitary, but may be multifocal
Cyst lining: simple cuboidal epithelium
No septation, usually unilocular
Larger cysts can cause compression
US best modality
No septation unless two cysts are adjacent

6. Congenital Simple Cysts
Complications Symptoms
Intracystic bleeding
Imaging: US, MRI (T1 and T2)
Acute enlargement
Spontaneous rupture
Peritoneum, pleura
Compression
Bile ducts, portal vein, hepatic veins, IVC
Asymptomatic cysts: no need for routine surveillance, serial US studies show no appreciable changes over years
In women, typically > 50 yrs, cysts might enlarge rapidly and become symptomatic. If this occurs in men or younger female patients, consider an alternative diagnosis
Symptoms of intracystic bleeding, sudden severe pain, typically few days duration
T1 sequence MRI becomes hyperintense when bleeding occurs. Intracystic bleeding can change appearance of cyst. Confusion with biliary neoplasms or hydatid cysts when prior comparison studies are not available

7. Management of Symptomatic Simple Cysts
Laparoscopic deroofing (n=46)1
Hospital stay 1 day
Bile leak 4%
Bleeding, N.R.
Recurrence, symptomatic 4%
Open deroofing (n=24)1
Hospital stay 7 days
Complication rate 29%
Recurrence, symptomatic 5%
Perc drainage and sclerotherapy (n=129)2
EtOH or minocycline
Recurrence, symptomatic 5-20%
Single institution (Hospital Italiano, Buenos Aires), n=78
Deroofing: laparoscopic technique of partially excising the cyst wall with endoshears or simple cautery, and allowing fluid to drain freely into the peritoneum. If the cyst is covered by a thick layer of liver parenchyma, an endovascular stapler may be employed. Complications include bile leak and bleeding.
Others have added ablating the cyst epithelium with ABC or saline-linked electrocautery
1Mazza et al. JACS 2009; 209:733-9.
2Moorthy et al. Ann R Coll Surg 2001; 83:

8. Polycystic Liver Disease (PCLD)
GENETICS (autosomal dominant)
Associated with ADPKD
PKD1, polycystin-1, chr 16p (85%)
PKD2, polycystin-2, chr 4q (15%)
Isolated PCLD
PRKCSH, hepatocystin, chr 19p (40%)
SEC63
PATHOLOGY
Simple epithelium
Phenotypical and functional features of biliary epithelium
Secretory capacity
Retention of von Meyenburg complexes, ductal plate malformations
CLINICAL
Mostly asymptomatic
Massive hepatomegaly with abdominal protuberance and pain
Diaphragmatic, gastrointestinal compression
Malnutrition, poor QOL
Hepatic function preserved
PKD1, more renal cysts, larger renal cysts, and rapid progression to ESRD
Polycystin: alters cytosolic Ca signaling and cAMP levels
Both genes in isolated PCLD involved in protein secretion from the endoplasmic reticulum

9. Evaluate size, extent, and distribution of cysts
Management of PCLD
Asymptomatic
Symptomatic
Patient age
Symptom severity
Renal function
Stop estrogens
Stop estrogens
Evaluate size, extent, and distribution of cysts
Follow-up
Cyst related symptoms: pain from hepatomegaly, malnutrition, diaphragmatic compression producing dyspnea, infection, bleeding, and Budd Chiari manifestations.
Observation that cyst proliferation occurs under high estrogen states has led to general acceptance that estrogen therapy should be discontinued in patients with PCLD; however, little proof exists that this alters the natural course of PCLD.
Management of PCLD should involve a multi-disciplinary team in order to provide optimal patient selection for various surgical and non-surgical treatment options available for patients with PCLD. Patient selection should take into consideration the age of the patient, symptomatic severity, and the size, extent, and distribution of the cysts. Renal function and the pace towards progression to ESRD.
Non-surgical
Surgical
Somatostatin analogues
mTOR inhibitors
HA embolization
Sclerotherapy
Fenestration
Hepatectomy + fenest
Transplant

10. Surgical Treatment Options Classification of PCLD
Type
# Cysts
Cyst size
Total liver involvement I
< 10
Large (> 10 cm)
< 25% II
Multiple
Small, medium
25 – 50%
III
> 75%
Type I: laparoscopic cyst fenestration (superficial cysts in anterior segments)
Type II: open fenestration +/- partial hepatectomy
Type III: fenestration NOT indicated, hemi-hepatectomy usually difficult
A hand-full of classification systems have been developed over the years, but I will focus on two functional systems which can be applied to almost all patients with PCLD. Gigot aimed to characterize cysts based on size, number, and distribution. Patients with small number of large cysts, esp when predominantly situated in the anterior segments (III, IV, and V) are amenable to lap fenestration.
Type II PCLD is typically characterized by multiple medium and small cysts deep within the liver which are not amenable to laparoscopic fenestration. These patients may be approached with partial hepatectomy + open fenestration if the distribution lends itself to preservation of an acceptable remnant liver
Type III patients are very challenging and often tranplantation remains the only option.
Morino et al. Ann Surg 1994; 219:
Gigot et al. Surg Endoscopy 2001; 15:

11. Surgical Treatment Options Classification of Symptomatic PCLD
Type B
Type C
Type D
Limited cyst #
Multiple cysts
≥ 2 sectors preserved
1-2 sectors preserved
Little liver preserved
Schnelldorfer and Nagorney’s classification system considers not only the number and distribution of cysts but also considers the liver parenchyma which would be left behind after operative intervention.
Type B pts with a small number of large superficial cysts can be approached with lap cyst fenestration.
Type C pts can be approached with partial hepatectomy and cyst fenestration of the remnant if at least 1 relatively spareed sector can be preserved with normal inflow and outflow.
For Type D patients, there is typically no relatively preserved sector and inflow or outflow vessels to that sector are often attenuated. Transplantation should be reserved for these type of patient who has severe symptoms with a declining performance status escpecially when renal transplantation is imminent.
Cyst fenestration
Partial Hepatectomy +
Cyst fenestration
Transplantation
Schnelldorfer, Nagorney, et al. Ann Surg Surg 2009; 250:

12. Caroli’s Disease (Type V Bile Duct Cyst)
Segmental, cystic dilatations of the major IH ducts
Ductal plate malformations
Autosomal recessive disorder
Linkage studies localize to chrom 3p, 8q
Associations with ARPKD and medullary sponge kidney
Two subtypes: simple v. complex (fibrocystic)
Caroli’s syndrome: CD + hepatic fibrosis > cirrhosis
Let’s now turn to Caroli’s disease which is a rare cystic disease of the liver with an incidence < 1:1M
Sato et al. Int J Hep 2012.

13. Caroli’s Disease: Clinical Management
Diagnosis
CT: central dots
MRCP: hemi- v. total liver involvement
Complications
Cholestasis
Hepatolithiasis
Cholangitis
Hepatic abscess
Pancreatitis
Biliary cirrhosis
Hepatic fibrosis
Cholangiocarcinoma, 4-13%
Portal HTN

14. Percutaneous lithectomy ESWL Antibiotics Ursodeoxycholate
CD complications
Medical therapy
Hepatolithiasis management
Cyst distribution
Hemi-liver (L>>R)
Partial hepatectomy
Total liver
Hepatic fibrosis
Portal HTN
Transplantation
No fibrosis
HJ + stone clearance
Hemihepatectomy + stone clearance
Medical therapy, plus
ERCP lithectomy
Percutaneous lithectomy
ESWL
Antibiotics
Ursodeoxycholate CT
MRCP
The majority of patients with CD who present for treatment, do so because of acute or recurrent cholangitis. Pts should be started on BS abx to cover GN bacteria and ursodiol can help improve chronic cholestasis. ERCP is useful in clearing lithiasis predominantly involving the major IH ducts but is limited for extensive hepatolithiasis. Percutaneous lithectomy with or without EC shock wave lithotripsy can be used for patients with extensive hepatolithisias involving second order ducts.
CT and MRCP can be used to determine the distribution of cysts and the presence of cirrhosis or portal HTN. For patients with hemiliver cysts, which more often involve the left side, partial hepatectomy can result in excellent long-term results. For pts with cysts throughout the liver, management decisions are more difficult. When HF or BC is present, esp with portal HTN, liver transplantation is really the only option. In the absence of fibrosis, HJ with choledochoscopy can provide good long-term control of cholangitis and possibly decreased incidence of cholangiocarcinoma.

15. Hepatobiliary Cystic Neoplasia
Biliary cystadenoma
Biliary IPMN
Biliary cystadenocarcinoma
Cystic intrahepatic cholangiocarcinoma
Cystic variants of secondary liver tumors
NETs, mucinous adenoca
Lastly, I would like to review intrahepatic biliary cystic neoplasms. This entity represents only 5% of liver cysts but often generates the most respect and interest. One of the major challenges in fully understanding and studying these lesions is that we do not have a concensus vocabulary for properly describing these neoplasms. Many of these tumors are unveiled incidentally during cross sectional imaging of the abdomen for unrelated indications. When they present with symptoms, e.g. abdominal protuberance, RUQ fullness, dyspnea, or rarely, with cholangitis due to biliary mucinosis, these tumors are typically quite large with a median diameter > 8 cm.

16. Making the diagnosis US is most useful Cyst aspiration is not helpful
Assess for multiloculation
Thickened septae
Mural nodularity
Intracystic debris
Papillary projections
Cyst aspiration is not helpful
CEA
CA 19-9
Fluid cytology
The most common of the neoplastic cysts are biliary cystadenoma and IPMN of the IH bile ducts. Discriminating either one of these tumors from a simple cyst of the liver can be challenging. US is probably the most important diagnostic test and having access to a skilled sonographer is crucial for characterizing these cysts. Unlike simple cysts, cystic neoplasms are typically unifocal and have a predilection for the central liver, namely segment IV. They contain internal septae and if thickened, and coinciding with mural nodularity, may indicate transformation into a biliary cystadenocaricnoma.
Percutaneous cyst aspiration for cytology and fluid marker levels is not helpful. As shown in this scatterplot, cyst fluid levels for CEA and CA 19-9 can not discriminate a simple cyst from biliary cystadenoma or from cystadenocarcinoma.
Ca BCA SC
Ca BCA SC
Seo et al. Eur J Gastro/Hep Int J Hep 2010; 22:

17. *Arnaoutakis et al. Ann Surg 2015;261:361–367

18. Biliary cystadenoma Bile duct IPMN
Ovarian stroma supporting columnar epithelium
Female prevalence
Mucin production
No bile duct communication unless fistula
Large cyst, often segment IV
Concomitant cystadenocarcinoma (0-15%)1-3
Bile duct IPMN
Pancreatic IPMN resemblance
No ovarian stroma
Male prevalence
Bile duct communication
Cystadenocarcinoma (30%)1-3
Describe each cyst separately. While fenestration with cyst lining ablation has been applied to biliary cystic neoplasms with acceptable recurrence rates, This should be avoided. Open technique cyst enucleation is usually the treatment of choice for non-invasive cystic neoplasms and provides excellent recurrence-free survival. But, keep in mind that biliary IPMN, like its pancreatic counterpart, may involve bile ducts adjacent to the cyst and place the patient at risk for local recurrence after enucleation.
1DeVaney et al. Am J Surg Path 1994; 18:
2Koffron et al. Surgery 2004; 136:
3Seo et al. Eur J Gastro/Hep Int J Hep 2010; 22:

19. Biliary cystadenocarcinoma
Arises in both cystadenoma and IPMN-B*
Incidence- rare ~10%
US and MRI detect subtle characteristics
Mural nodularity, enhancement, hemorrhage, thick septae
Formal resection/hepatectomy required
EH bile duct resection may be required if central ducts involved
*IPMN of the bile duct may progress to invasive cancer more rapidly than cystadenoma.
US and MR better than CT at detecting subtle signs of invasive cancer

20. Treatment
Resection
Hepatic Lobectomy
Liver transplant

21. *Arnaoutakis et al. Ann Surg 2015;261:361–367

22. Survival Median RFS - 12.1 years (95% CI 6.5– 18.1)
1-year, 3-year, and 5-year RFS was 89.1%, 72.6%, and 61.4%, respectively.
1-year, 3-year, and 5-year OS was 95.0%, 86.8%, and 84.2%, respectively.
*Arnaoutakis et al. Ann Surg 2015;261:361–367

23. Survival
After excision, long-term outcomes were better among patients with BCA versus BCAC.
*Arnaoutakis et al. Ann Surg 2015;261:361–367

24. Recurrence
Incidence of recurrence is higher among patients who underwent an unroofing/fenestration(48.6%) versus for patients who had a partial or major hepatectomy (15.7% and 10%, respectively P < 0.001)
*Arnaoutakis et al. Ann Surg 2015;261:361–367

25. Summary Hepatic cysts are common.
Diagnostic imaging includes USG, CT or MRI
Simple hepatic cysts warrant treatment if
Large
Symptomatic- pain, pressure
Compressive effects leading to biliary dilatation
Simple cysts can be treated by fenestration (lap or open), enucleation.
Hepatobiliary cystic neoplasms should be resected
Benign: enucleation
Malignant: partial hepatectomy

26. THANK YOU Acknowledgements Dr.Michael Jacobs MD, FACS
Dr.Janak Parikh MD, MSHS
Lauri Bolo ACNP-C