Liver Diseases

Benign and Premalignant Liver Masses

Hepatic Adenoma and Focal Nodular Hyperplasia

Hepatic adenoma is a common benign liver mass with malignant potential that frequently occurs in women of childbearing age. It is strongly associated with long-term use of oral contraceptive pills or other forms of estrogen. It is also seen in much less frequency in men who use body building steroids.

The majority of patients with hepatic adenoma are asymptomatic. 20-25% of patients present with right upper quadrant pain or discomfort and as many as 30% experience bleeding into the adenoma. The size of the mass can vary from 1-20 cm in diameter and the risks of malignant transformation into hepatocellular carcinoma liver cancer increases significantly at 4 cm.

Surgical extirpation via liver resection is required for a hepatic adenoma greater than 4 cm. Hepatic adenoma of any size in men requires liver resection due to high probability of malignant transformation.

Focal nodular hyperplasia (FNH) is 10 times more common than hepatic adenoma. It is predominantly diagnosed in women 30 to 50 years old. Most FNHs are found incidentally, but can also be revealed by clinical symptoms such as pain, discomfort, nausea, palpable mass, or increased liver function tests on blood results.

For FNH, complications such as rupture or bleeding are rare and malignant transformation has not been reported. Percutaneous liver biopsy for histologic confirmation is only required in minority of patients. MRI Liver with primovist (intravenous contrast agent) can differentiate a hepatic adenoma from FNH in the majority of the cases. A consultation with a liver specialist is important to avoid a misdiagnosis.

Simple Liver Cysts

Liver cysts occur in about 5% of the general population and up to 10% of those will develop symptoms such as pain, nausea, discomfort, bloatedness, early satiety, and weight loss. When a liver cyst becomes large, it stretches the liver capsule which can cause the above symptoms. Liver cysts can be solitary or multiple and they can occur anywhere in the liver.

Asymptomatic liver cysts do not require surgical intervention.Treatment of symptomatic liver cyst involves removal of a large portion of the cyst wall (unroofing/fenestration), followed by an evaluation by a pathologist to identify or rule out presence of premalignant cells within the cyst wall.

Image 2. Large dominant liver cyst occupying the whole right lobe.

Dr. Papoulas performs this operation laparoscopically via 3 tiny incisions. Most patients are discharged on the same day, only a small number of patients require an overnight stay in the hospital, generally related to other pre-existing medical conditions.

Liver Haemangioma

Haemangioma is the most common primary benign (noncancerous) mass of the liver with a prevalence up to 20%. It is made of proliferation of blood vessels (frequently dilated) and supported by connective tissue septa. Essentially, it is a sponge of blood vessels located within the liver. This lesion is discovered in all ages and genders, although it is more frequent in women between the age of 30 to 50 years old.

Characteristic features of liver haemangioma are typically seen on a triphasic CT scan or MRI liver. A liver biopsy is contraindicated to avoid severe intraabdominal bleeding.Hemangiomas have no risk of malignant transformation. Haemangiomas that are causing symptoms such as pain, nausea, discomfort, right shoulder pain or haemangiomas that are expanding rapidly or causing consumption coagulopathy require surgical removal via a liver resection.

Biliary Cystadenoma

Biliary cytadenoma or mucinous cystic neoplasm of the liver is an uncommon premalignant cystic lesion, which accounts for less than 5% of all intrahepatic biliary cysts and occurs primarily in middle aged women with a peak incidence in the 50s.

It is usually located in the middle of the liver, originating from segment 4. Diagnosis of this lesion can be sometimes difficult and often mistaken with a simple hepatic cyst. The internal surface of those cystic lesions is typically smooth. If solid areas are present, there is high concern for an invasive component.

Due to the potential for malignant transformation to cystadenocarcinoma (cancer), this mass requires a complete surgical removal via liver resection or pericystectomy.

Dr. Michail Papoulas and his team perform this kind of liver resection using the minimally invasive technique via 4-5 small incisions. Most patients only require 2-4 days of hospital recovery.

Malignant Liver Masses

Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the most common primary liver cancer.Hepatocellular carcinoma is a major cause of morbidity and mortality in patients with background liver disease. About 1-3% of patients with liver cirrhosis from any cause will develop HCC. The most common causes of liver cirrhosis in Europe are alcoholism, hepatitis C virus, and morbid obesity (non-alcoholic steatohepatitis).

Imaging modalities for HCC are contrast-enhanced CT scan and MRI scan. Hepatocellular carcinoma shows a very characteristic appearance on the contrast-enhanced CT scan. Biochemical marker with blood work is also important to support a diagnosis of hepatocellular carcinoma.An elevated alpha fetoprotein (>400ng/ml) is consistent with hepatocellular carcinoma diagnosis.However, not all patients with hepatocellular carcinoma have an elevated alpha-fetoprotein level. A routine liver biopsy is not necessary to diagnose a hepatocellular carcinoma.

Treatment options for hepatocellular carcinoma depend on condition of background liver (degree of cirrhosis), tumor number, tumor location, tumor size, proximity to major vascular and biliary structures, and the volume of future liver remnant. For patient with early cirrhosis and good liver function (Child A), curative treatment is via liver resection to obtain clear margins.Alternatively, for hepatocellular carcinomas less than 3 cm in size, laparoscopic microwave or radiofrequency ablation can be utilized. Strict criteria exist for patients with HCC eligible for liver transplantation. In general, patients with multifocal or large hepatocellular carcinoma are not candidates for liver transplantation. Systemic oral chemotherapy has a relatively limited role in the treatment of hepatocellular carcinoma.

Other non-operative treatment such as transarterial radioembolization using Y-90 and chemoembolization using chemotherapy particles are considered palliative treatment for many liver tumors, including hepatocellular carcinoma. Curative treatment can only be achieved through liver resection, liver transplantation, and liver ablation for small hepatocellular carcinomas.

Dr. Papoulas has wide experience in treating hepatocellular carcinoma using minimally invasive liver surgery with great success. He is the only surgeon in Cyprus trained in both liver surgery and liver transplantation acquiring great experience in the management of those patients.

Intrahepatic Cholangiocarcinoma

Intrahepatic cholangiocarcinoma is an aggressive cancer that originates from the bile duct branches within the liver. It is the 2nd most common primary liver cancer, comprising 5-15% of primary liver malignancies. Risk factors include chronic biliary tract disease such as primary sclerosing cholangitis, presence of stones inside the liver (hepatolithiasis), choledochal cyst, and liver fluke infections commonly seen in Southeast Asia. Most patients, however present without evidence of predisposing factors.

Intrahepatic cholangiocarcinomas are typically asymptomatic until advanced stage where they can present with abdominal pain or jaundice. The only potentially curative treatment option is liver resection with the goal to obtain clear resection margins. Minimally invasive, laparoscopic or robotic, liver resection offers similar oncological results, decreased postoperative complications and fastest recovery compared to the traditional open approach.

Image 3. Subtypes of cholangiocarcinoma according to their location.

Secondary Liver Tumors

Metastatic Colon & Rectal Cancer

The liver is the most common location for tumor metastasis from other organs. The most common cancers that metastasize to the liver are colon and rectal cancer, followed by pancreatic, neuroendocrine, soft tissue sarcoma, breast, stomach, esophageal, melanoma, renal cell carcinoma, ovarian, and uterine cancers. For colon and rectal cancer, the venous drainage follows superior and inferior mesenteric veins which drain into the portal vein and subsequently into the liver.

Approximately 50% of patients with colon and rectal cancer develop liver metastasis. Eventhough cancer has spread to the liver (stage IV disease), the condition is often still curable with liver resection and or microwave/radiofrequency ablation, in addition to systemic chemotherapy treatment.

Minimally invasive liver surgery such as laparoscopic liver resection is the preferred techniqueassociated with decreased postoperative complication, lower postoperative pain, shorter recovery, and earlier administration of systemic chemotherapy.

Dr. Papoulas routinely undertakes laparoscopic liver resection for metastatic colorectal cancer to the liver, frequently during the same operation as the primary colon cancer resection (combined colon and liver resection). Dr. Papoulas and his colorectal surgeonpartner is the only team in Cyprus that offers the ability of a simultaneous resection of both the colon cancer and the

liver metastasis, using minimally invasive laparoscopic techniques.

Image 4. Computed tomography of a patient with a solitary metastasis in the right liver lobe (segment IV).

Metastatic Neuroendocrine Tumor

Dr. Michail Papoulas routinely performslaparoscopic liver resection for metastatic neuroendocrine tumors to the liver, often in combination with microwave liver ablation to achieve tumor free status. Most hepatobiliary surgeons recommend liver resection if more than 90% of the liver metastases can be excised, and less than 75% of the liver parenchyma is involved.

Signs and symptoms of carcinoid tumors vary greatly among patients.Most neuroendocrine tumors are slow growing, but some of them can be highly aggressive similar to other cancers with a very poor prognosis.

When liver resection cannot be offered due to whatever reasons, an alternative treatment approach, such as bland embolization, transarterial chemoembolization, and radioembolization could be considered. These are not curative options however they can help retard the metastatic tumor progression and minimize symptoms.

Metastatic Breast Cancer

Metastatic breast cancer most often spreads to the bones, lungs, liver, or brain. Liver metastases are present in 15% of patients newly diagnosed with metastatic breast cancer, and liver is the only site of distant metastasis in 1/3 of these patients.Increasing data on liver resection for metastatic breast cancer have shown improved long-term survival in many patients especially when it is used in conjunction with systemic chemotherapy and hormonal therapy.

Dr. Michail Papoulas and his team offers minimally invasive laparoscopic liver surgery for selected patients with liver metastasis from breast cancer. The clinical results as well as long-term oncologic outcomes are excellent. Many patients can achieve years of disease-free interval. Liver biopsy is sometimes necessary for histological confirmation, prior to starting the cancer treatment. Dr. Papoulas has published an article regarding the outcomes of Breast Cancer Liver Metastases following referral to tumour board meeting at King’s College Hospital in the International Journal of Surgery.

Benign and Premalignant Biliary Duct Diseases

Benign Biliary Stricture

Benign biliary strictures may occur from chronic inflammation of the pancreas and bile duct, traumatic injury to the liver and bile duct, bile duct injury following cholecystectomy, or bilioenteric anastomosis following Whipple’s operation or liver transplantation. Benign biliary strictures evolve gradually over a period of time after the initial insult. Most patients present with jaundice, dark urine, pale stools,skin itchiness, generalized weakness, loss of appetite, fever, or chills.

Investigations include liver ultrasound, CT and MRI/MRCP in order to assess the location and extend of the biliary stricture. Blood work shows elevated liver function test, most specifically bilirubin level.Further workup with ERCP (Endoscopic retrograde cholangiopancreatography) by an interventional gastroenterologist may be necessary to investigate and potentially treat the biliary stricture. Endoscopic biopsies should be obtained for any suspicious lesions within the bile duct during ERCP to rule out occult bile duct cancer.

Endoscopic and percutaneous techniques, including biliary stricture dilatation followed by placement of an endobiliary stent(s) are the first-line treatment. Most benign biliary strictures can be managed this way. The biliary stents are usually left in place for about 8-12 weeks prior to removal.

In a small number of patients (15%), endoscopic and percutaneous techniques fail to resolve benign biliary stricture. Surgical treatment is needed for patients whose strictures are refractory to endoscopic and percutaneous interventions. Referral to see an experiencedliver surgeon is crucial, due to the complex nature of biliary tract operations.

Minimally invasive laparoscopic or robotic biliary resection and reconstruction using a segment of intestine called Roux-en-Y hepaticojejunostomy is the most common approach of treating a benign biliary stricture.Dr. Papoulas offers biliary tract surgery on a routine basis using minimally invasive techniques. Our team works collaboratively with our interventional radiologists and endoscopists to achieve the best long-term outcomes.

Choledochal Cyst

Choledochal cysts, are rare congenital dilations (enlargements) of the bile ducts, a biliary tube that drains bile, produced by the liver, into small intestine. They are increasingly diagnosed in adults. Choledochal cysts are inflammatory in nature. Left untreated, choledochal cyst frequently leads to recurrent biliary infection, biliary stasis, or pancreatitis (inflammation of the pancreas) and ultimately the risk of biliary cancer due to chronic inflammation.

There are 5 types of choledochal cysts, based on the location of cyst within the biliary tree. The most common type of Choledochal Cyst is Type I (80-90% of cases)presenting as a fusiform dilatation of a portion or entire common bile duct, with normal intrahepatic duct.

Choledochal cyst is a premalignant condition with substantial risk of malignant transformation into cholangiocarcinoma, a bile duct cancer. Diagnosis of choledochal cyst is obtained with CT scan or MRI/MRCP scan.

The standard treatment for choledochal cyst is via complete cyst resection with or without liver resection, depending on type of the choledochal cyst, followed by a reconstruction of the biliary tree. Choledochal cyst that involves liver parenchyma requires a partial liver resection.

Type 5. Todani classification of choledochal cysts. Type I is the most common found in almost 80-90% of patients with choledochal cyst.

Intraductal Papillary Biliary Neoplasm

Intraductal papillary neoplasm of the bile duct (IPNB) is a rare type of bile duct tumors characterized by a papillary growth found inside the bile duct lumen. It is regarded as a biliary counterpart of intraductal papillary mucinous neoplasm (IPMN) of the pancreas. IPNB displays a spectrum of premalignant lesion towards invasive bile duct cancer/cholangiocarcinoma.

The most common clinical presentations are intermittent jaundice (yellowing of the skin and eyes), cholangitis (biliary infection), and intermittent abdominal pain. Around 30% of patients are also found to have stones in their bile duct/ biliary tree. The most common radiologic findings are bile duct dilatation (diffuse duct ectasia, localized bile duct dilatation or cystic dilatation) and intraductal masses.

Ultrasonography, CT scan, MRI/MRCP, and video-endoscopic examination of the bile duct are usually obtained to assess tumor location and extension. Video-endoscopic/cholangioscopic biopsy can confirm the histology and assess the extent of tumor. Thick mucinous/gelatinous material can sometimes be found in the biliary duct.

The standard treatment for this disease is surgical resection of the involved biliary duct and surrounding liver parenchyma, followed by complete resection of regional lymph nodes (lymphadenectomy). The treatment is essentially similar to that for bile duct cancer/cholangiocarcinoma. The use of liver transplant surgery for this disease is very limited.

Dr. Papoulas offers both the traditional and minimally invasive techniques for biliary and liver resections. Our team works collaboratively with our interventional radiologists and interventional endoscopists to achieve the best long-term outcomes.

Extrahepatic Bile Duct Cancer & Klatskin Tumor

Primary extrahepatic biliary tumors are relatively uncommon and they typically present with jaundice (yellowing of skin and eyes) caused by biliary blockage. Bile duct cancer is one of the most difficult cancers to treat due to its aggressive biology and unfavorable location. Klatskin tumor occurs at the bifurcation of the left and right bile duct. This is a very confined area, surrounded by important blood vessels that bring blood and oxygen to the liver (hepatic artery and portal vein).

Involvement of the surrounding vessels (hepatic artery and portal vein) is important to recognise before the operation. When hepatic artery or portal vein on the opposite side of the Klatskin tumor is involved, the disease is considered unresectable. Neoadjuvant chemotherapy is often given in an attempt to convert the Klatskin tumor from unresectable to resectable.

Surgical resection with negative margins is the only effective therapy for bile duct cancer, including the Klatskin tumor.It is very important to consult an experienced liver surgeon to evaluate surgical resectability. Dr. Michail Papoulas has a significant experience in treating this disease with excellent outcomes. He has published the contemporary surgical approach to hilar cholangiocarcinoma in the Israel Medicine Association Journal describing the state of art surgical technique and approach. The majority of Klatskin tumor resection is performed via traditional open operation.