Hepatoma.pptx

A Case presentation as well as Topic Presentation on Hepatoma

1. Case Presentation By: Dr. Noshirwan P. Gazder FCPS TRAINEE YEAR 1

2. History 60 year old male known case of Hypertension for the last 8 years, Pan Consumer , H/o Hepatitis C came via ER with complaints of: Fever for 1 month Right Upper Quadrant Pain for around 2 weeks History of 4 kg weight loss in the last 3 months

3. History of Presenting Complains As per my patient he was in his usual state of health when he developed Fever for 1 month . The fever was documented at 100 F which was intermittent, gradual in onset, occasionally associated with chills. He also gave complaints that he would break out into sweats at night. Fever was relieved by taking paracetamol. He gave complaints of on and off nausea with decreased appetite for the last one month and gave history of 4 kgs weight loss within a period of 3 months . He had no ear discharge, cough , diarrhea or urinary complaints. For about 2 weeks however, he had developed Right upper quadrant pain, pain was sudden in onset, gnawing in character, non-radiating, associated with no aggravating factors. It was usually limited for about 6 to 8 hours and would then improve eventually on its own. He had shown himself in a local clinic 1 week back, where the doctor assumed he was having typhoid and was started on oral ciprofloxacin. That showed no improvement.

4. Past Medical History: Hypertensive for the last 8 years, Compliant to meds. Chronic Hepatitis C Treated with DAA ( Direct Acting AntiVirals: Sofosbuvir / Velpatasvir) in 2018 for 3 months- ETR was achieved then lost to follow up. No H/o previous hospital admissions. Past Surgical History: H/o blood transfusion around 30 years ago, as he underwent an RTA and had fractured his Left Femur and was operated on the same leg as well. Name of Procedure was unknown; No record was available. Family history: No history of Ischemic heart disease, tuberculosis, asthma, thyroid disorders, autoimmune diseases or cancers in the family Travel history: No recent travel from Karachi

5. Drug H istory : Tab. Amlodipine 5 mg 1+0+0 Tab. Rosuvastatin 10 mg 0+0+1 Cap. Omeprazole 40 mg 1+0+0 (30 mins before breakfast) S tarted on Ciprofloxacin 500 mg 1+0+1 by local clinic doctor 1 week back.

6. Personal History: Regular Tobacco Pan Consumer; No h/o drug use, smoking or alcohol consumption. Appetite: Decreased 4 kgs weight loss within a period of 3months Sleep: Normal Micturition: Normal Social History: He is a resident of North Nazimabad. Office worker by profession. He Lives in a 2 room house with his wife and sons. Drinks boiled water and eats mostly meals cooked at home. No contact history of tuberculosis. No pets or birds in his house.

7. System Review Respiratory System SOB/ Dyspnoea Sputum Haemoptysis Chest pain Hoarseness Wheezing Cardiovascular Chest pain Paroxysmal Nocturnal Dyspnoea Orthopnoea Short Of Breath(SOB) Palpitations Cyanosis Gastrointestinal/Alimentary Nausea/vomiting Abdominal pain Oral ulcers Regurgitation/heart burn Haematemesis , melaena , haematochagia Jaundice Nervous System Speech problem Head ache Seizures Visual/Smell/Taste/Hearing problem Abnormal sensation Change of behaviour - ve - ve - ve - ve

8. System Review Urinary System Back Loin Pain Urgency Hesitancy Terminal dribbling Nocturia Incontinence Character of urine Musculoskeletal System Back plus neck pain Radiating from occiput Swelling Red eyes Deformities Skin rash Painful/ cold fingers Endocrine System Swelling in neck Fatigue Thirst Sweating - ve - ve - ve HEMATALOGICAL System Bruises Epistaxis Lumps Gum bleeding - ve

9. Examination: General Impression: A 60 year old male, lying on bed comfortably, oriented to time, place and person. Vitals: Blood Pressure:110/80 mm/Hg Pulse: 98/min, regular Temperature: 100 F Respiratory Rate: 19 breaths/min Oxygen saturation: 98 % on room air -Weight 54kg , Height: 170cm BMI: 18.6 kg/m2

10. Examination : HEENT: Normocephalic, atraumatic, no bruises Nose, mouth,pharynx,ears WNL EYE: No Anemia/ Jaundice , VA:6/6, reactive to light, EOMI NECK: Supple, no lymphadenopathy, No JVD, swelling in neck or carotid bruit HEART: Normal S1 and S2, no murmurs, rubs or gallops. CHEST: No tenderness, clear breath sounds bilaterally, no rales, wheezes or ronchi , trachea central, tactile fremitus normal. ABDOMEN: No scar marks, Tender in Right hypogastrium upto epigastrium, Tip of spleen palpable, No other organomegaly, - ve Murphys sign, - ve for Renal punch, - ve fluid thrill , bowel sounds were audible. NEURO: Mental status: alert, Cranial nerves:Intact , Motor: 5/5 upper and lower extremities. Sensory: intact to touch and pinprick. DTRs: 2+ symmetric in upper and lower extremities, - babinski . Cerebellar: Intact EXTREMITIES: No clubbing, cyanosis or edema. Pulses 2+ and symmetric. No tremors. MUSCLOSKELETAL: No warmth or erythema, no tenderness, normal range of motion, motor/sensory/reflexes, pulsations LYMPHNODES: Axillary, Groin were not palpable .

11. Differential Diagnosis Liver Abscess Cholecystitis / Cholangitis Viral Fever Pancreatitis Typhoid Malignancy Viral Hepatitis

12. INVESTIGATIONS:

13. CXR

14. U/S Abdomen

15. Patient was admitted under Gastroenterology services who started the patient on: Inj. Drotaverine 40 mg IV 12 hrly Inj. Paracetemol 1 gm IV SOS Tab. Mebeverine 135 mg 1+1+1 Tab. Amlodipine 5 mg 1+0+0 Tab. Rosuvastatin 10 mg 0+0+1 Cap. Omeprazole 40 mg 1+0+0 (30 mins before breakfast) CT Triphasic was advised, along with Alpha Feto Protein and PT/INR

16. CT TRIPHASIC

17. PT / INR: 13.6/1.33 Alpha Feto Protein: 7199.14 ng /ml ( <15 ng /ml) HCV RNA PCR QUALITATIVE : Negative For SVR-1 CHILD CLASS: Class A

18. Review was given to Interventional Radiologist, who after reviewing CT report advised patient to undergo TACE. TACE was performed using Epirubicin ( Anthracyclines ) and Lipiodol ( selective uptake and retention in hyperarterialyzed liver tumors ) No Post-Procedure complications were noted.

19. The Patient was subsequently discharged on Tab. Amoxicillin / Clavulanic acid 625 mg 1+1+1 for 7 days Tab. Amlodipine 5 mg 1+0+0 Tab. Rosuvastatin 10 mg 0+0+1 Tab. Mebeverine 135 mg 1+1+1 Tab. Domperidone 10 mg 1+1+1 Syp . Lactulose 30 ml 0+0+1 Tab. Paracetomol 2 Tabs SOS Cap. Omeprazole 40 mg 1+0+0 (30 mins before breakfast ) Was advised OPD F/U in one week

20. Hepatocellular Carcinoma

21. Hepatocellular carcinoma (HCC) is a primary tumor of the liver that usually develops in the setting of chronic liver disease, particularly in patients with cirrhosis due to alcohol use, chronic hepatitis B or C virus infections, or nonalcohol-associated steatohepatitis (NASH). HCC is the fourth leading cause of cancer-related deaths in the world according to the World Health Organization, and the most rapidly growing cause of cancer deaths in the United States. The prognosis of patients with this tumor remains poor, with a five-year survival rate of 18 percent.

22. Sequence of cellular lesions in liver leading to the development of hepatocellular carcinoma 

23. CLINICAL FEATURES Most patients are asymptomatic until late stages of the disease. The majority of HCC cases occur in the setting of chronic liver disease. Among patients with more advanced liver disease, symptoms and physical findings are often due to underlying cirrhosis rather than the tumor itself. Such as features of liver decompensation (eg, variceal bleeding or ascites) due to the extension of HCC into the hepatic or portal veins as the initial manifestation of the tumor.

24. Symptomatic Patients   Patients with advanced lesions may present with mild to moderate upper abdominal pain, weight loss, early satiety, or a palpable mass in the upper abdomen. Hypoglycemia : usually occurs in advanced HCC, is thought to result from the tumor's high metabolic needs. Less than 5 percent of tumors secrete insulin-like growth factor-II, which can cause severe, symptomatic hypoglycemia sometimes early in the course of the disease. Erythrocytosis : tumor secretion of erythropoietin (EPO). Hypercalcemia : Seen in association with osteolytic metastases, but it may also be seen in the absence of bony metastasis due to secretion of parathyroid hormone. Diarrhea: Patients with HCC may infrequently present with intractable diarrhea and associated electrolyte disturbances (eg, hyponatremia, hypokalemia, metabolic alkalosis). Its related to secretion of peptides that cause intestinal secretion. These include vasoactive intestinal polypeptide, gastrin, and peptides with prostaglandin-like immunoreactivity

25. Intraperitoneal bleeding: Can occur due to tumor rupture, Tumor rupture is often associated with sudden onset of severe abdominal pain with distension, an acute drop in the hemoglobin and hypotension, and is most commonly diagnosed by abdominal imaging. Tumor rupture is a life-threatening complication, and control of bleeding may require emergent angiography and embolization of the bleeding vessel, or surgery. Extrahepatic metastases : For patients who do not undergo surveillance, extrahepatic metastases are present at the time of diagnosis in approximately 10 to 15 percent of cases. Extrahepatic metastases are more common in patients with advanced stage primary tumors (>5 cm, large vessel vascular invasion). The most common sites of extrahepatic metastases are lung, intra-abdominal lymph nodes, bone, and adrenal gland, in that order. Brain metastases are rare overall (0.2 to 2 percent).

26. Serum Markers Alpha-fetoprotein : The most commonly used serum marker for HCC is serum alpha-fetoprotein (AFP) concentration. AFP is a glycoprotein that is normally produced during gestation by the fetal liver and yolk sac, and the serum concentration can be elevated in patients with HCC. When elevated, the AFP is 75-91% specific, and values greater than 400 ng/mL are generally considered diagnostic of HCC in the proper clinical context, including appropriate radiologic findings. Serum levels of AFP are typically higher for advanced HCC compared to early HCC, but overall, AFP levels do not correlate well with the clinical features of the tumor. The differential diagnosis of an elevated AFP includes the following: Elevated serum AFP may be seen in patients with chronic liver disease such as acute or chronic viral hepatitis, but without HCC. Elevated serum AFP also occurs in pregnancy, with tumors of gonadal origin (both germ cell and non-germ cell) and in a variety of other malignancies, of which gastric cancer is the most common.

27. For patients at high risk for developing HCC, the diagnosis can be made with dynamic contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) tailored for liver lesion evaluation. If the lesion demonstrates specific imaging characteristics, a diagnosis of HCC can be made radiographically, avoiding the need for a biopsy. High-risk patients are candidates for surveillance. This includes most patients with cirrhosis and subsets of those with chronic hepatitis B virus infection.  Diagnostic approach to a solid liver lesion in a high-risk patient is determined initially by the size of the lesion, as detected on surveillance US. DIAGNOSTIC APPROACH

28. IMAGING HCC can be diagnosed on contrast-enhanced computed tomography (CT), magnetic resonance imaging (MRI), or ultrasound (US). In most high-risk patients, HCC can frequently be diagnosed on imaging alone, avoiding the need for biopsy. These are categorized as LR-5 in the Liver Imaging Reporting and Data System (LI-RADS) for high risk patients. The choice of modality should be individualized based on available scanner technology, imaging expertise, and patient contraindications and preferences. Contrast-enhanced CT, MRI, or US are all sufficiently accurate to diagnose HCC. Very few false positive diagnoses are observed with any of these modalities if the diagnostic criteria are rigorously applied.

29. Diagnosis on CT or MRI  — For a lesion to be considered suspicious for HCC (in a non-high risk patient) or definitely HCC or LR-5 (in a high-risk patient), it should be ≥1 cm and demonstrate non-rim arterial phase hyperenhancement relative to the liver parenchyma. In addition, the following features are assessed: Non-peripheral washout appearance  – Hypoenhancement when compared to liver in portal venous or delayed phase of contrast administration Enhancing capsule appearance  – Smooth border around most or all of the lesion that enhances visibly in the portal venous or delayed phase of contrast administration Growth  – ≥50 percent increase in size in ≤6 months (a threshold of ≥5 mm increase in size is recommended to ensure that the change represents biological growth and not measurement error). Assessment of growth cannot be made comparing the CT or MRI to a prior US or CEUS.

30. Treatment Using tumor stage to select treatment is complicated by the fact that many of the staging systems (including the Tumor, Node, Metastasis [TNM] staging system of the combined American Joint Committee on Cancer [AJCC]/Union for International Cancer Control [UICC]) are based upon surgical findings and do not incorporate other important factors, such as underlying liver dysfunction and performance status. The Barcelona Clinic Liver Cancer (BCLC) staging system has been a dominant approach to HCC, particularly outside of the United States. The BCLC classifies patients with HCC into four categories: early, intermediate, advanced, and terminal.

31. Radiofrequency ablation (RFA) In this method, heat is generated by passing electrical current through the tumor and surrounding tissues. The technique is limited in large lesions because of difficulty passing electrical current through desiccated tissue that has high impedance. The 5-year survival is 70%. RFA is generally avoided in subcapsular lesions, as there is an increased risk of peritoneal seeding.Outcomes in patients with solitary HCC <2 cm treated with RFA are similar to surgical resection.

32. Transarterial chemoembolization (TACE) Selective arterial embolization combined with selective injection of a chemotherapeutic agent (doxorubicin, cisplatin) mixed with a contrast agent. Improves survival in patients with intermediate stage HCC. 1-year survival: 80%; 2-year survival: 60%. Contraindications: portal vein thrombosis, extrahepatic spread. Complications: Nausea, vomiting, abdominal pain.Post-embolization syndrome (fever, abdominal pain, and ileus) Treatment is supportive.

33. Chemotherapy agents used in TACE: Doxorubicin: Slows or stops the growth of cancer cells by blocking an enzyme called topo isomerase 2 (which is needed for cancer cells to divide and grow) Cisplatin : Binds to the N7 reactive center on purine residues and can cause DNA damage in cancer cells, blocking cell division and resulting in apoptotic cell death. 

34. TACE is a treatment, not a cure . Approximately 70 percent of the patients will see improvement in the liver and, depending on the type of liver cancer, it may improve survival rates and quality of life.

35. Atezolizumab-Bevacizumab: Atezolizumab, a Programmed Death Ligand ( PD-L1) monoclonal antibody, plus bevacizumab, an anti-VEGF monoclonal antibody, (atezo/bev) has become a new standard-of-care as the first-line therapy for patients with advanced hepatocellular carcinoma (HCC). Durvalumab-Tremelimumab: Durvalumab (blocks the interaction of PD-L1 with PD-1), Tremelimumab ( stimulates immune system to attack tumor cells by inhibiting a protein molecule called cytotoxic T lymphocyte associated 4 (CTLA-4) on immune cells). Sorafenib : Exerts its action through inhibition of several kinases involved in both tumour cell proliferation and angiogenesis.

36. Thank You