HEPATOBILIARY TUMORS

1. HepatoBiliary Tumours
DR KIRAN KUMAR BR

2. Incidence World Wide

4. Pathogenesis

5. Clinical Features
 Tumor-related symptoms include
palpable mass in the upper abdomen
(hepatomegaly),
 acute onset of pain (hemorrhage
from tumor rupture), and
 dull pain in the right upper quadrant
of the abdomen,
 abdominal fullness,
 low-grade fever,
 obstructive jaundice, and
splenomegaly

7. Investigations
• History and physical examination
• HBV and HCV, and AFP
• If HBV or HCV serology is positive, quantitative HBV DNA
• or HCV RNA should be obtained.
• Evaluation of hepatic functional reserve includes prothrombin time,
activated partial thromboplastin time, and serum albumin.
• IHC : HepPar1 , Glypican-3, CD-10 , AFP
• CK-7 and epithelial membrane antigen Fibrolamellar variant
• Fifteen-minute retention rate of indocyanine green (ICG)
• USG Abd
• CT/ MRI

8. Triphasic CT principles

11. AASLD non invasive criteria
• AFP > 200ng/dl
• a typical enhancement pattern (arterial
enhancement and portal or delayed washed
out) on dynamic imaging of hepatic mass >2
cm in a cirrhotic liver.

12. Stagging
• AJCC ,TNM
• OKUDA, the Chinese University Prognostic Index (CUPI) scoring
system,
• the Groupe d’Etude et de Traitement du Carcinoma
Hepatocellulaire (GETCH) staging system
• Cancer of Liver Italian program Scoring

14. Management
• Surgical resection is a reliable method to obtain long-term
disease control. The main limiting factor for resection is liver
function.
• ICG retention test.
• The single most reliable method of assessing hepatic function
is the Child-Pugh classification which remains the most useful
and most widely used in Western series.
• Hepatic Wedge Pressure
• The goal of surgery is to remove gross tumor with a margin of
1 to 2 cm of normal liver.
• Today, however, the 5-year survival after resection can exceed
30%

15. SurgicalResection
• One strategy that may improve outcome after resection is
preoperative portal vein embolization.
• Presence of tumor thrombus within the main portal vein or
vena cava, is a contraindication to resection because of the
very high risk of occult disseminated disease.

16. ICG 15
• In HCC patients with normal bilirubin and without
ascites, if the
• ICG retention 15 minutes (ICG 15) is normal, the
resection volume can be trisegmentectomy or
bisegmentectomy;
• if ICG 15 is 10% to 19%, the resection volume can
be left lobectomy or right monosegmentectomy;
• if ICG 15 is 20% to 29%, the resection can be
subsegmentectomy;
• if ICG 15 is 30% to 39%, the resection can be
done to only a limited area of the liver.

17. Liver Transplant
• Milan study
• solitary tumor 5 cm or
• up to three nodules with tumor size <3 cm.
• overall 3- to 4-year actuarial (75% to 85%)
• recurrence-free survival rates (83% to 92%) can be achieved.
• Risk factors of recurrence after transplantation include tumor
size, number of tumors, vascular invasion, and persistence of
HBV infection.

19. Percutaneus Ablation
• For those with small unresectable lesions, percutaneous
ablation is the most common option survival.
• Ablation can be accomplished by the use of chemicals such as
alcohol or acetic acid or by techniques using extreme
temperatures, such as radiofrequency ablation, microwave, or
laser coagulation or cryoablation.

20. Radio-Frequency Ablation

21. TACE
• TACE combines selectively injecting chemotherapeutic agents
through the tumor artery followed by intra-arterial
embolization of tumor artery with lipiodol, an iodized oily
contrast agent.
• Systematic review of randomized prospective studies in more
recent literature has shown TACE to have a positive impact on
survival.
• For palliative purpose, TACE has been accepted as the
standard treatment for patients with unresectable HCC, and it
can be used selectively for tumors of different locations and
can be repeated if necessary.

23. Radiotherapy
• HCC is a radiosensitive tumor. The major drawback of
radiotherapy in treating HCC is the poor radiation tolerance of
adjacent normal liver.
• Liver is a parallel organ and hence the toxicity is volume
dependent.
• The radiation dose was individualized based on the volume
of normal liver that could be spared without exceeding a
10% to 15% risk of radiation-induced liver disease.
• The prescribed dose ranged from 40 Gy to 90 Gy (median,
60.75 Gy).

24. Radiation Doses
• Dawson et al escalated radiation doses for unresectable
hepatobiliary cancer and observed that patients who received
radiation doses >70 Gy had better median survival (>16.4
months).
• It appears that the higher the radiation doses given, the
higher the tumor response seen.

25. TACE + RT
• The use of lower doses of radiation with TACE in unresectable
HCC has been reported.
• A recent systematic review of 17 trials involving almost 1500
patients157 found that patients treated with TACE and RT had
improved survival rates compared with patients treated with
TACE alone, with an odds ratio of 2.23.

26. Simulation
• At simulation, immobilization in the supine position with arms
overhead can be facilitated with a body cradle.
• Some centers prefer a full-body mold if SBRT is delivered
versus a half-body mold for 3D-CRT.
• If abdominal compression will be used, the patient should be
simulated using the same technique.
• A CT scan (3- to 5-mm cut) with intravenous and oral contrast
should be performed from top of the lungs to the iliac crest.
• If gating is the preferred strategy, the CT data may be acquired
in the exhale phase only.

27. Breath Control Techniques

28. Volumes
• The gross tumor volume is typically defined as
radiographically abnormal areas seen on CT or MRI.
• The clinical target volume is defined as the gross
tumor volume plus 1 cm based on surgical reports that
at least a 1-cm resection margin is necessary for a
successful partial hepatectomy.
• The planning target volume includes the clinical target
volume plus 0.5 cm for daily patient setup variation
and between 0.5 and 2.5 cm (determined under
fluoroscopy or four-dimensional CT scanning) in the
cranialcaudal dimension to account for liver motion
from respiration

29. • The normal liver is defined as the gross tumor
volume subtracted from the total liver volume.
• Using three-dimensional treatment planning, it
has been possible to safely irradiate two thirds of
the normal liver to 48 to 52.8 Gy and one-third of
the liver to 66 to 72.6 Gy (fraction size of 1.5 to
1.65 Gy twice daily with at least 4 hours of
separation).

31. Radiation Induced Liver Disease
• Radiation-induced liver disease typically occurs 4 to 8 weeks
after the completion of RT and clinically resembles veno-
occlusive disease.
• Clinical feat: fatigue, vague upper abd pain
• They may have signs and symptoms of ascites with rapid
weight gain and increased girth.
• Lab: alkaline phosphatase levels to 3 to 10 times normal and
moderate elevations of transaminase levels but little to no
increase in bilirubin or lactate dehydrogenase (LDH) levels at
first presentation.

32. RILD
• Irradiation of the whole liver to a total dose of 30 Gy in 2-Gy
fractions or less has little risk of a complication. The risk rises
greatly above a dose of 33 Gy, and it has been estimated that at 42
Gy there is an approximately 50% risk for symptoms
• Evaluvated using CT : Although the use of axial beam arrangements
shows typical straight-line borders between the liver and areas of
radiation change.
• Treated conservatively using steroids and diuretics.

33. Chemotherapy
• In metastatic setting cisplatin, gemcitabine, capecitabine,
paclitaxel, irinotecan, etoposide, and fludarabine, have been
investigated and found to have minimal activity.
• One of the most studied combinations is a regimen of
cisplatin, interferon-α2b, doxorubicin, and 5-fluorouracil
(PIAF). At expense of more toxicities.
• A randomized phase III study of 188 patients comparing PIAF
with doxorubicin. Showed no statistically significant difference
in median survival (8.6 months vs. 6.8 months, P = 0.83),
despite a doubling in response (21% vs. 10%, P = 0.058).

34. Chemo regimes
• The combination of gemcitabine and the platinum agent
oxaliplatin (GEMOX) showed a partial response of 18% and
56% of patients had stable disease. This translated into a
median survival of 11.5 months.
• CAPEOX : a phase II study that reported partial responses in
6% of patients, stable disease in 58% and a median survival of
9.3 months

35. Anti Angiogenic Agents
• Sorafenib
• is an oral multikinase inhibitor that targets VEGF receptor
(VEGFR) (–2/–3), in addition to RAF kinase and platelet-
derived growth factor receptor (PDGFR)-β tyrosine kinases.
• (SHARP trial), showed a clinically and statistically significant
improvement in median overall survival of 10.7 months versus
7.9 months.
• Bevacizumab is a humanized anti-VEGF A monoclonal
antibody that has also been studied in HCC.
• Erlotinib, Sunitinib , Brivanib

36. Sorafinib dosing
• S. Bilurubin <1.5g/dl dosed 400mg Bd
• while those with a bilirubin 1.6 to 3 × ULN should be
considered for a 200 mg twice daily.
• Sorafenib at 200 mg once daily was recommended for
patients with an albumin less than 2.5 mg/dL and any bilirubin
level.
• There was no safe dose identified for patients with a bilirubin
greater than 3 × ULN.

37. Adenocarcinoma of Gall Bladder
• Gallbladder carcinoma is not common; it is the fifth most
common cancer of the gastrointestinal tract.
• the ratio of females to males is 2.5 to 1.
• Cholelithiasis, an anomalous junction of pancreaticobiliary
ducts, and porcelain gallbladder are factors that predispose to
gallbladder cancer.
• Cigarette smoking, alcohol consumption, and obesity may
also increase the risk.
• Patients with polyps >10 mm in diameter may be at increased
risk for gallbladder

38. • In general, gallbladder carcinoma is diagnosed late, which
accounts for the poor prognosis.
• Lymphatic metastasis is initially to cystic and pericholedochal
nodes and then to the pancreaticoduodenal system, with later
potential spread to the rest of the celiac axis or the superior
mesenteric or aortic nodes.
• 62% in pT2 disease, and 81% in pT3 or pT4 disease.

41. Management
• Surgery is the only potentially curative therapy, but only 10%
to 30% of patients are eligible for resection.
• The prognosis is related to the possibility of curative
resection, primary tumor extension, and regional lymph node
metastasis.
• ADJUVANT THERAPY
• After “curative” resection, locoregional relapse in the tumor
bed or regional nodes is common.
• Factors predicting recurrence are positive surgical margins,
lymph node metastasis, and perineural invasion

44. Adjuvant Rt doses
• Post op EBRT with 3DCRT or IMRT , target volume should
cover draining lymph nodes to 45Gy @1.8Gy/fx and
• 50.4-59.4Gy @1.8Gy/Fx to the tumour bed depending on the
margin postivity.

45. • THANK YOU