Hepatocellular carcinoma (HCC) is the most common type of liver cancer and the third leading cause of cancer deaths worldwide. Risk factors include hepatitis B and C infections, aflatoxin exposure, and alcohol use. Screening with ultrasound and alpha-fetoprotein (AFP) levels can detect HCC early in high-risk patients with cirrhosis. Treatment depends on tumor stage but may include surgical resection, liver transplantation, radiofrequency ablation, chemoembolization, or the drug sorafenib for advanced disease. Prognosis is generally poor due to late stage at presentation, with a 5-year survival rate of less than 10% for untreated HCC.

1. HEPATOCELLULAR
CARCINOMA
PRESENTER: ALPHONCE NGERECHA
FACILITATOR: DR. IGEMBE NKANDALA

2. Outline
• Introduction
• Epidemiology
• Screening
• Clinical presentation
• Management
• Prognosis

4. Introduction
• Hepatocellular carcinoma (HCC): most common cancers worldwide
with approximately 550,000 to 600,000 new HCC cases globally each
year
• HCC is the third leading cause of cancer deaths worldwide, with a
prevalence 16 to 32 times higher in developing countries than in
developed countries
• This cancer has a heterogeneous geographical distribution based on
the prevalence of risk factors in different parts of the world.
• It is frequent in Sub-Saharan Africa and southeast Asia where it is
responsible for a large proportion of cancer deaths

5. Epidemiology in Tanzania
• In BMC
• 3104 patients who were registered with malignancies
during the study period, 155 (5%) were
histopathologically confirmed cases of hepatocellular
carcinoma

6. Risk factors (Jaka et al, 2014
• The high incidence rate may be related to the high
prevalence of
• Hepatitis B viral (HBV) infection
• Aflatoxin B1 contamination
• Some hepatotoxic drugs
• Hepatitis C virus (HCV), cigarette smoking, and alcohol
are also etiologic agents in this environment
• The transformation of hepatocytes to the malignant
phenotype may occur irrespective of the etiological
agents

7. Etiological risk factors (BMC)
• 52.1% patients stated a history of ingestion of foods stored in
humid conditions (a likely suspected source of aflatoxin B1
exposure).
• 59.9% patients had a past history of jaundice and 22.5% had
scarification marks.
• The use of traditional herbal concoctions was documented in
57.7% patients.
• A history of heavy alcohol consumption was reported in 60.6%
patients.
• A past blood transfusion was documented in 19.7% patients.

8. Screening
• Hep B carriers in China randomized to screening or not
(19,000 subjects)
• Screen with AFP and US every 6 months
• 37% reduction in mortality related to HCC
• Recommends screening in patients with cirrhosis or
advanced hepatic fibrosis regardless of cause since
they are the highest risk group for HCC

9. Types
• HCC: invasive, males 4-8 to 1 over females, <20% resectable;
90% have cirrhosis; 80% AFP +; mean age 55; molecular
subsets being identified
• Those with HBV less likely to have cirrhosis than those with
HCV (although 70-80% do have cirrhosis)
• Concurrent risks for HBV: high viral load, HCV or delta virus co-infection, ETOH,
tobacco, early childhood infection)
• Concurrent risk factors among HCV patients include increased age, male sex, HIV or
HBV co-infection, probably diabetes and obesity
• Fibrolamellar variant: circumscribed; Male:female 1:1; cirrhosis,
HBV+, AFP+ only about 5%; 50-70% resectable; mean age 25
• Note also that natural history varies between cases with some
surviving 2 year or more with HCC and no rx.; mean surv. 6-9
mos for advanced HCC

10. Clinical features
• Bruit approx. 25%
• Right upper quad pain, mass and wt loss;
Tumor fever can occur
• Liver failure symptoms as presentation also:
mainly due to replacement of already
reduced liver parenchyma
• Propensity for vascular invasion and this can
contribute to liver failure

11. Clinical features
• GI bleeding: if from varices this has poor prognosis: In
one study 25% of HCC deaths were due to variceal
hemorrhage
• Tumor rupture can occur at presentation (2-5%) and
these can be rescued surgically or through embolization
(see series in JCO)
• If jaundice is from biliary obstruction by tumor this has
better prognosis than from liver failure
• Hypoglycemia, erythrocytosis, hypercalcemia, PCT,
hypertrophic osteoarthropathy, virilization

12. Clinical features
• Mets: lung, peritoneum, adrenal gland, bone
• Risk of vascular invasion and multicentricity
• Importance of staging liver function: Child’s
classification A-C

13. Clinicopathological presentation
• The duration of symptoms before presentation ranged from 2 to 48
weeks with a median of 16 weeks of 12 to 20 years).
• The majority of patients had symptoms of more than 16 weeks
duration at the time of presentation.
• A pre-existing medical illness in 6.3%) patients

14. In our settings
• Right upper abdominal pain 97.2
• Weight loss 92.9
• Right hypochondrial swelling 81.7
• Pallor 71.8
• Jaundice 52.1
• Itching 49.3
• Ascites 47.9
• Hematemesis 23.9
• Hepatic bruit

15. Diagnosis
• Physical exam and history
• Alpha-fetoprotein (AFP) tumor marker test: An increased level of AFP
in the blood may be suggestive of HCC
• Cut of value (>400ng/mL Diagnostic) Zhang et al, 2019 (cut off of 10ng/ml
surveillance Jasirwan et al, 2020 (sen 86, sp 71.2%)
• Liver function tests:
• USS
• CT scan
• MRI
• Biopsy

16. Triphasic CT

17. Staging:
• Tumor: Radiological
• Functional status: ECOG
• Child Pugh: Liver function
• Encephalopathy
• Ascites
• PT (INR)
• Bilirubin
• Albumin

18. Barcelona Staging
• Factors in liver function and stratifies according to treatments
appropriate for each stage
• Very early stage
• PS0; Child’s A; one lesion <2cm
• Early stage
• 1 to 3 lesions <3cm; PS0; Child’s A
• Intermediate stage
• Multinodular disease; PS0; Child’s A
• Advanced stage
• Advanced stage
• Vascular invasion, M1, N1, PS1-2
• Terminal Stage
• Child’s C; PS>2
• Other staging systems: Okuda, CLIP not as useful

19. Therapy
• Curative modalities first
• Resection, Transplant, Possibly RFA in early stage lesions
• Modalities that extend overall survival second
• RFA or chemoembolization (intermediate stage)
• Sorafenib (advanced stage but preserved liver function: trials
mostly Child’s A some B)
• Terminal Stage no evidence of survival benefit
• Do no harm

20. Therapy: Surgery
• First question is resectability: functional reserve and tumor
location: 5yr surv about 30-40%
• <20% of pts with cirrhosis and HCC are resectable
• Resectability greater with Hep B since they can present
with HCC without cirrhosis more often
• Is resection better than transplant?
• Transplant cures cirrhosis and can remove other occult synchronous
lesions
• Downside of transplant is waiting time and need for
immunosuppression; live donor transplant can shorten wait
• Bridging therapy with TACE or RFA

21. Indications for Transplant
• Tumor <5cm if single; <3cm if 1-3 tumors
• Expanded UCSF criteria lead to similar survival results but not
adopted thus far due to shortage of organs
• Absence of vascular invasion
• Not more than 3 nodules
• Better histology is associated with improved survival post
transplant
• Other restrictions: age <70, AFP highly elevated

22. Ablative therapies
• RFA if approx 3.5cm diameter (can be up to 3 lesions)
• For RFA location important (heat dissipates if near vessels; hard to
do if near capsule of liver); Microwave ablation may be better;
laparoscopic RFA may be needed in some cases
• RFA proven better than ethanol injection
• Chemoembolization if larger but isolated to liver
• The trials that showed benefit of this selected intermediate stage
patients (no advanced liver disease; no vascular invasion; no
shunting; no extrahepatic disease; largest tumor 4-7cm; can be
multinodular)

23. Transarterial Chemoembolization (TACE)
• Doxo 75 mg not adjusted for BSA
• Other agents sometimes used: carboplatin, MitoC
• Clinical pathway with anesthesia involvement, prophylactic
antibiotics
• Monitor for pain, fever, hepatic dysfunction
• Problem is proper selection reduces number of patients who
are eligible or get survival benefit
• Not clear yet if embolization alone is as good as
chemoembolization

24. Chemo-embolization
• Major risk is hepatic decompensation so avoid chemoembolization in
advanced cirrhosis
• Other issues: post embolization syndrome (fever, nausea, elevated
LFTs); rare pancreatitis or cholecystitis due to embolization of other
vessels
• Portal vein involvement is not an absolute contra-indication although
although major vessel involvement not included in the randomized
trials
• Two small randomized trials and a meta-analysis show survival benefit to
chemoembolization
• LLovet et al, Lancet 2002; 359: 1734-39
• Lo et al, Hepatology, 2002; 1164

25. TACE or RFA as bridge to transplant
• Transplant waiting list can be long especially if lesion less than
2 cm
• MRI not considered diagnostic for lesions <2cm so do not get the
increased MELD points until >2cm
• Could wait for it to grow to >2cm which moves patient higher on
list or could RFA
• Chemoembolization can also be done as bridge to transplant
after patient is listed
• Lahey clinic requires 2 chemoembolization
• No real evidence base for the bridging approach

26. Advanced HCC:
Sharp Trial: Phase III trial: Sorafenib: first
phase III showing a survival benefit
• Low actual response rate a significant survival extension of approx 3
months was found
• Limitations are that the group predominantly had good liver function:
? Application to others
• We are working on summary of our experience in a group of patients
with less favorable starting characteristics

27. Sorafenib: other studies
• Subgroup analyses of SHARP trial
• Survival benefits for HCV positive = 6.1 months; for
extrahepatic spread or macroscopic vascular invasion = 2.2
months; PS 1 to 2 = 3.3 months
• Randomized trial of sorafenib in Asian patients (Lancet
Oncology 2009 Vol10:p.25)
• Median overall survival sorafenib (#150 patients): 6.5
months
• Placebo median survival (#76 patients): 4.2 months
• Majority had Hep B (differs from SHARP) and probably as a
group more advanced disease accounting for lower survival

28. Updated Barcelona Clinic Liver Cancer (BCLC) treatment
strategy for managing hepatocellular carcinoma, 2022

29. Treatment modalities for HCC in our
setting (TZ STG 2021)
Pharmacological Treatment
• Recommended systemic regimen used for palliation
• S: doxorubicin (IV) 60 mg/m2 over 30 minutes day 1
given every 3 weeks for 4–6 cycles.
• S: sorafenib (PO) 400mg daily until disease
progression or unacceptable toxicity

30. Fibrolamellar HCC Dx and Rx
• The diagnosis of fibrolamellar carcinoma (FLC) is typically
made on the basis of clinical presentation and imaging
studies
• Negative serum tumor markers may also support the
diagnosis.
• Pathology is the gold standard in confirming the diagnosis.
• If diagnostic uncertainty persists following cross-sectional
imaging or in the setting of metastatic disease,
percutaneous core biopsy guided by ultrasound or
computed tomography (CT) may confirm the diagnosis.

31. Tumor markers
• Commonly used tumor markers for HCC, such as AFP,
are of little help for diagnosing and monitoring disease
progression with FLC.
• Only 7 to 11 percent of patients have an elevated serum
AFP level, and it is typically in the range of 100 to 200
ng/L

32. Treatment:
• Resection
• Options for unresectable nonmetastatic disease
• Liver transplant (controversial, selected pts with no extra hepatic
d’se
• Embolization (Alternative for non resection non transplant)
• Systemic therapy:
• Cisplatin, epirubicin, and fluorouracil (FU) combinations
• Sorafenib modestly prolongs survival
• Radiation therapy — External beam radiation therapy has
shown little benefit for FLC

33. GALL BLADER CANCERS

34. Introduction
• Gallbladder cancer is an uncommon but highly fatal
malignancy
• Fewer than 5000 new cases are diagnosed each year in
the United States.
• The majority are found incidentally in patients
undergoing exploration for cholelithiasis
• A tumor will be found in 1 to 2 percent of such cases
• The poor prognosis associated with GBC is thought to
be related to advanced stage at diagnosis,

35. Epidemiology
• Historically, there is a female predominance for gall stone
disease and gall bladder cancer.
• There is a variation, worldwide, in the prevalence of gall bladder
cancer with the highest rates in South American countries, India
and parts of Asia.
• Correlates with the prevalence of gall stone disease but also the
prevalence of salmonella typhi infection worldwide
• It is postulated that chronic irritation from gall stone disease and
inflammation from infection can act as a promotor for malignant
transformation.

36. Epidemiology
• Accounts for 2 to 4% of malignant GI tumors
• 2-3 times more common in females than males
• 90% of patients have gallstones
• Larger stones (3cm) are associated with tenfold
increased risk of cancer
• Polypoid lesions of the gallbladder (>10 mm)
• Calcified "porcelain" gallbladder >20% incidence

37. Risk factors
• Demographic: Adv Age, Female, Obesity, Genetic predisposition
• GB pathologies: Cholelithiasis, porcelain GB, Polyps, Congenital
anomaies, microlithisias
• Chronic inflammation: PSC (6-14% GB masses with 50-60%
malignancy, (Fung et al 2019), Ulcerative colitis
• Infections: Liver flukes, Chronic S. typhi, Paratyphi, H. Pylori
• Exposure to carcinogens (azotoluene, nitrosamines, smoking, rubber,
COCs, Methyldopa)

38. Pathology
• 80 and 90% of the tumors are adenocarcinomas
• papillary, nodular, and tubular
Squamous cell
Adenosquamous
Oat cell

39. Gallbladder Cancer spreads:
• Lymphatics
• Venous drainage
• Direct invasion into the liver parenchyma

40. Clinical Manifestation
• Abdominal discomfort
• Right upper quadrant pain
• Nausea & vomiting
• Jaundice
• Weight loss
• Anorexia
• Ascites
• Abdominal mass

41. Diagnosis
• FNAC /Biopsy (guided)
• Ultrasonography
• CT scan
• Percutaneous transhepatic or endoscopic cholangiogram (in jaundiced)
• MRCP

43. CT scan of a patient with gallbladder cancer

44. Staging:(AJCC 7th Edition)

45. Treatment
• Surgery :
• Radical Cholecystectomy, Liver resection with
regional lymphadenectomy
• Radiotherapy
• Adjuvant (pT1b onwards)
• Chemotherapy
• Concurrent
• Adjuvant
• Palliative

46. Prognosis
• 5-year survival rate of all patients <less than 5%
• Median survival: 6 months
• T1 disease treated with cholecystectomy have an
excellent prognosis (85 - 100% 5-year survival rate)
• 5-year survival rate for T2 lesions treated with an
extended cholecystectomy and lymphadenectomy
compared with simple cholecystectomy is over 70%
versus 25 to 40%, respectively
• Patients with advanced but resectable gallbladder cancer
are reported to have 5-year survival rates of 20 to 50%
• Median survival for patients with distant metastasis at the
time of presentation is only 1 to 3 months

47. Thank you