advances in management of liver cancer

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Management of Liver Cancer Dr. Rajasekhar Perumalla MS, DNB, PDCC, FRCSED Senior Consultant Hepato Biliary Pancreas & Transplant Surgery Global Hospitals & Health City Chennai

What is Liver Cancer? : 

What is Liver Cancer? Primary liver cancer is cancer that begins in the liver An estimated 24,120 people diagnosed in the United States in 2010 More common in other parts of the world Fifth most frequent cause of cancer-related death among men and the ninth most common among women Three types of primary liver cancer: hepatocellular carcinoma (HCC), cholangiocarcinoma (bile duct cancer), and angiosarcoma HCC accounts for over 80% of primary liver cancer cases

What Are Factors that Increase the Risk for Hepatocellular Carcinoma? : 

What Are Factors that Increase the Risk for Hepatocellular Carcinoma? Chronic viral hepatitis (two common types are hepatitis B and hepatitis C) Cirrhosis of the liver, often but not always caused by excessive alcohol consumption Age Gender Chemical exposure (less common in the United States) Eating foods contaminated with the mold aflatoxin (less common in the United States)

Hepatocellular Carcinoma Prevention and Early Detection : 

Hepatocellular Carcinoma Prevention and Early Detection Vaccination for hepatitis B Avoid intravenous (IV) drug use (commonly associated with the transmission of hepatitis C) Avoid alcohol abuse (increases the risk of cirrhosis) Certain medications may control hepatitis B or C infection, decreasing the risk of HCC People with cirrhosis of the liver or chronic viral hepatitis may need to be screened for liver cancer

Symptoms of HCC : 

Symptoms of HCC Pain Right side of the abdomen, Near the right shoulder blade or Upper back Unexplained weight loss Hepatomegaly Weakness or fatigue

Symptoms of Liver Failure : 

Symptoms of Liver Failure Abdominal swelling due to ascites Upper GI Bleed Jaundice Mental confusion

How is Hepatocellular Carcinoma Diagnosed? : 

How is Hepatocellular Carcinoma Diagnosed? Diagnosis is often confirmed with a biopsy Diagnosis can sometimes be confirmed with blood or imaging tests Physical examination Blood test for alpha-fetoprotein (AFP); 50%-70% of people with primary liver cancer have elevated levels Ultrasound of the abdomen Computed tomography (CT or CAT) scan Magnetic resonance imaging (MRI) Angiogram Laparoscopy

Hepatocellular Carcinoma Staging : 

Hepatocellular Carcinoma Staging Staging is a way of describing a cancer, such as the size of a tumor and if or where it has spread Staging is an important tool doctors have to determine a patient’s prognosis Staging is described by the TNM system: the size and location of the Tumor, whether cancer has spread to nearby lymph Nodes, and whether the cancer has Metastasized (spread to other areas of the body) For HCC, this staging system is most useful when the tumor can be surgically removed; otherwise, other factors are used to predict prognosis Treatment and prognosis (chance of recovery) depend on the stage of the cancer and the degree of liver dysfunction

Stage I Hepatocellular Carcinoma : 

Stage I Hepatocellular Carcinoma Earliest stage of HCC Tumor is 2 centimeters (cm) or smaller No spread to the blood vessels, lymph nodes, or other parts of the body

Stage II Hepatocellular Carcinoma : 

Stage II Hepatocellular Carcinoma The tumor involves nearby blood vessels No spread to the regional lymph nodes or other parts of the body

Stage III Hepatocellular Carcinoma : 

Stage III Hepatocellular Carcinoma Stage III is divided into 3 groups (A, B, or C) IIIA: cancer has not spread beyond the liver but the area of the cancer is larger than stage I or II IIIB: cancer involves a major vein around the liver, but it has not spread to nearby lymph nodes or other parts of the body IIIC: any tumor that has spread to organs near the liver (except the gallbladder), or if the tumor is present with perforation of the visceral peritoneum. However, there is no spread to nearby lymph nodes or other parts of the body

Stage IV Hepatocellular Carcinoma : 

Stage IV Hepatocellular Carcinoma Stage IV is divided into two groups (A or B) IVA: any tumor that has spread to the regional lymph nodes but not to other parts of the body IVB: cancer has spread to other parts of the body

Hepatocellular Carcinoma Staging, continued : 

Hepatocellular Carcinoma Staging, continued Localized resectable: cancer is in one place in the liver, can be removed through surgery and the other part of the liver is healthy Localized unresectable: cancer is found in one part of the liver, but it cannot be removed by surgery Advanced: cancer has spread throughout the liver and/or to other parts of the body, such as the lungs and bones Recurrent: cancer has come back after treatment. It may recur in the liver or another part of the body

How is Hepatocellular Carcinoma Treated? : 

How is Hepatocellular Carcinoma Treated? More than one treatment may be used Surgery, including liver transplantation Radiation therapy Chemotherapy: systemic and regional Targeted therapy Ablative therapies, including percutaneous ethanol injection and radiofrequency ablation Arterial chemoembolization Clinical trials

Cancer Treatment: Surgery : 

Cancer Treatment: Surgery Most successful in patients with small tumors (smaller than 5 cm) and with good liver function Hepatectomy: portion of the liver is removed when the cancer is limited to one part of the liver Liver transplantation: used to treat cancer confined to the liver if a suitable donor is found. Must fulfill strict criteria

Cancer Treatment: Radiation Therapy : 

Cancer Treatment: Radiation Therapy The use of high energy x-rays or other particles to destroy cancer cells Internal radiation therapy: use of implants inside the body. Radioactive beads may be inserted into the artery that supplies the tumor with blood External beam: outside the body – rarely used for HCC Side effects can include fatigue, mild skin reactions, upset stomach and loose bowel movements

Cancer Treatment: Chemotherapy : 

Cancer Treatment: Chemotherapy Use of drugs to kill cancer cells One or a combination of drugs may be used Side effects may include nausea and vomiting, loss of appetite, diarrhea, fatigue, and risk of infection Side effects often go away after treatment is finished

Types of Chemotherapy : 

Types of Chemotherapy Systemic chemotherapy is injected into a vein and travels through the bloodstream to the whole body Regional chemotherapy uses a small pump surgically placed in the body to deliver anticancer drugs directly to the blood vessels that feed the tumor Hepatic arterial infusion is chemotherapy injected into a catheter in the major artery supplying blood to the liver Chemoembolization is similar to hepatic arterial infusion except the flow of blood through the artery is blocked for a short time, so the anticancer drug stays in the tumor longer; the blocking of the blood supply to the tumor also kills the cancer cells

Cancer Treatment: Targeted Therapy : 

Cancer Treatment: Targeted Therapy Targets faulty genes or proteins that contribute to cancer growth and development Sorafenib (Nexavar), an anti-angiogenic and anti-proliferative drug (starves the tumor by disrupting its blood supply), may be used to treat tumors that cannot be removed with surgery Approved in 2007 for treating patients with advanced HCC

Other Treatment Options : 

Other Treatment Options Radiofrequency ablation (RFA) uses heat to kill the cancer cells Percutaneous ethanol injection uses alcohol injected directly into the liver tumor to kill cancer cells Cryosurgery uses extreme cold to freeze and kill cancer cells Biologic therapy (also called immunotherapy) uses the body's own immune system to fight cancer

Current Research : 

Current Research Cancer vaccines: use of the body’s immune system to recognize and attack HCC New combinations of chemotherapy Anti-angiogenic drugs Combinations of different types of treatment Expanding the criteria for liver transplantation Gene therapy: changes to a gene that can then be used to treat cancer

The Role of Clinical Trials for the Treatment of Liver Cancer : 

The Role of Clinical Trials for the Treatment of Liver Cancer Clinical trials are research studies involving people They test new treatment and prevention methods to determine whether they are safe, effective, and better than the standard treatment The purpose of a clinical trial is to answer a specific medical question in a highly structured, controlled process Clinical trials can evaluate methods of cancer prevention, screening, diagnosis, treatment, and/or quality of life

Clinical Trials: Patient Safety : 

Clinical Trials: Patient Safety Informed consent: participants should understand why they are being offered entry into a clinical trial and the potential benefits and risks; informed consent is an ongoing process Participation is always voluntary, and patients can leave the trial at any time Other safeguards exist to ensure ongoing patient safety

Clinical Trials: Phases : 

Clinical Trials: Phases Phase I trials determine the appropriate dose of a new treatment in a small group of people and provide preliminary information about the drug’s safety Phase II trials provide information about the safety of the new treatment and provide the first evidence as to whether or not the new treatment is effective in treating the cancer that is being studied Phase III trials compare two or more different treatments. Most commonly, they test whether a new treatment is better than the standard treatment. Patients are typically divided randomly into two or more different groups. Each group gets a different treatment, and the researchers evaluate which group has had the best results. This is the best way to measure whether a new treatment results in longer life or better quality of life for patients

Clinical Trials Resources : 

Clinical Trials Resources Coalition of Cancer Cooperative Groups (www.CancerTrialsHelp.org) CenterWatch (www.centerwatch.com) National Cancer Institute (www.cancer.gov/clinical_trials) EmergingMed (www.emergingmed.com)

Coping with Side Effects : 

Coping with Side Effects Side effects are treatable; talk with the doctor or nurse Fatigue is a common, treatable side effect Pain is treatable; non-narcotic pain-relievers are available Antiemetic drugs can reduce or prevent nausea and vomiting For more information, visit www.cancer.net/sideeffects

After Treatment : 

After Treatment Talk with the doctor about developing a follow-up care plan Doctor may recommend regular physical examinations, imaging tests, and blood tests Fear of recurrence is common; talk with your doctor about ways to cope

Where to Find More InformationCancer.Net Guide to Liver Cancer(www.cancer.net/liver) : 

Where to Find More InformationCancer.Net Guide to Liver Cancer(www.cancer.net/liver) Overview Medical Illustrations Risk Factors Symptoms Diagnosis Staging Treatment Clinical Trials Side Effects After Treatment Current Research Questions to Ask the Doctor Patient Information Resources

Cancer.Net (www.cancer.net) : 

Cancer.Net (www.cancer.net) Comprehensive, oncologist-approved cancer information Guides to more than 120 types of cancer and cancer-related syndromes Coping resources Survivorship information Cancer information in Spanish Weekly feature articles The latest cancer news For patient information resources, please call 888-651-3038

Hepatocellular Cancer : 

Hepatocellular Cancer One of the Common Cancers Risks Factors Cirrhosis Chronic Hepatitis B& C Anabolic Steroids Oral Contraceptives Metabolic disorders

Diagnosis : 

Diagnosis Radiological Imaging – Ultrasonogram – Hypoechoic or Heterogenous echoic Mass lesion Contrast CT- Contrast enhancing lesion in arterial phase, with washout in delayed phase

Diagnosis : 

Diagnosis MRI – Only when CT findings are equivocal

Role of Biopsy : 

Role of Biopsy No Routine Biopsy

Alfa Feto Protein : 

Alfa Feto Protein Levels > 200ng/ml is highly suspicious of hepatocellular carcinoma Useful in screening for HCC in Cirrhosis

Treament Options : 

Treament Options Curative Options Surgery ResectionLiver Transplantation Radio Frequency Ablation

Treament Options(Contd) : 

Treament Options(Contd) Palliative Options Trans Arterial Chemo Embolisation Yitrrium Radioembolisation Percutaneous Alcohol Embolisation Sorafenib

Liver Resection : 

Liver Resection

Liver Resection : 

Liver Resection Surgical resection and liver transplantation have been advocated as the only therapies with potentially curative intent Indication- Non Cirrhotics & Childs A Cirrhotics 5 year survival-40-50%

Slide 39: 

Upto 70% of Liver can be resected safely in Non cirrhotics Child A cirrhotics can also undergo major resections

Liver Resection in Cirrhosis : 

Liver Resection in Cirrhosis

Formal L Hepatectomy : 

Formal L Hepatectomy

Cirrhosis & R lobe HCC : 

Cirrhosis & R lobe HCC

Formal R Hepatectpmy : 

Formal R Hepatectpmy

Resection for recurrence : 

Resection for recurrence 3year survival without resection-< 10% for recurrent tumor 3 year survival following resection of the recurrent tumor – upto 50% survival

Liver transplantation : 

Liver transplantation Advantage- resection of the malignancy & elimination of the cirrhotic liver Excellent results for patients within – Milan Criteria

Milan Criteria : 

Milan Criteria Single tumor smaller than 5 cm or Up to three tumors with the largest being smaller than 3 cm 5 year Survival-60- 74%

Modified MilanCriteria : 

Modified MilanCriteria Single tumor< 6.5cm Or < 3 tumors ,each 4.5cm, sum of diameter < 8 cm

Radiofrequency Ablation : 

Radiofrequency Ablation Tumor 3-5 cm

Transarterial Chemo Embolisation : 

Transarterial Chemo Embolisation Selective catheterisation & intra arterial chemotherapy Adriamycin 3 year survival -30%

Radio Embolisation : 

Radio Embolisation Radio active Yittrium theraspheres Radio iodine 131 labelled particles

Sorafenib : 

Sorafenib Molecular Therapy Improves overall survival by 3 months

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