The document discusses malignant biliary diseases, emphasizing gallbladder cancer and cholangiocarcinoma, highlighting their pathophysiology, risk factors, diagnostic challenges, clinical features, and management strategies. Key aspects include aggressive disease progression, late-stage presentations, and the importance of surgical resection for treatment while discussing poor prognosis and survival rates. The document also covers the need for palliative care in advanced cases and the lack of effective chemotherapeutic or radiotherapeutic interventions.

1. Malignant biliary disease
Nabin Paudyal

2. MRCP findings during stricture

3. Gallbladder cancer
• Aggressive disease
• Poor prognosis
• Late stage presentation
• Earlier stage patients More surgical approach is warranted

4. Incidence
• 6th
and 7th
decade
• 2-3 times Women>> Men
• Highest in SEAR
• USA GB cancer is most common cancer of the biliary tract and the
fifth most common gastrointestinal cancer.

5. Cause
• Prevailing theory of gall bladder cancer focuses on chronic inflammation as a prime
cause for development of neoplasia.
• Presence of gallstones is therefore a primary risk factor and stones > 3 cm carry
increased risk of cancer development.
• > 80% of patients with gallbladder cancer have CHOLELITHIASIS.
• Gallstone patients are at 7 times more risk of having gallbladder cancer
• Other risk factors APBJ, choledochal cyst, Primary sclerosing cholangitis, Porcelain
gallbladder.

6. Adenoma-carcinoma sequence in gallbladder
carcinoma
• Severe dysplasia and Carcinoma in situ form gallbladder carcinoma
• Polyposis do not carry increased risk of malignancy
• Single gallbladder polyp > 10 mm carries an increased risk for
malignancy and hence is indicated for cholecystectomy.

7. Pathology and staging
• GB cancer spreads via lymphatics, hematogenously and peritoneal cavity OR
along biopsy or surgical wound tracts
• Morphologically
• Infiltrative (most common) spread in subserosal plane and invade entire GB and even
porta hepatis
• Nodular more circumscribed growth and invade liver
• Papillary limited to GB wall
• Combined
• Lymph nodes
• Drain into cystic and peri choledochal LN Pass into retro portal and pancreaticoduodenal
LN
• From here, the lymph drains into Celiac, superior mesenteric and aortocaval LN.
• Kocherization at the time of surgery is essential to properly stage GB cancer.

8. Gall bladder has rapid infiltration because it doesn’t have submucosa and serosal covering (at liver)

9. Clinical features
• Most patients are asymptomatic as more than 90% of gallbladder cancers are
originating in the fundus or body of gallbladder.
• Most gallbladder have symptoms at the time of presentation with 35% nodal
disease and distant metastasis in 40%.
• By chance if any patient has symptoms of acute cholecystitis with obstruction
of neck of the gallbladder the prognosis may be better as the disease is
caught in earlier stage [भागयमनी को भूतै कमारो]
• Symptoms are similar to hilar cholangiocarcinoma
• At late stages Weight loss, jaundice, abdominal mass are present
• Other symptoms Chronic epigastric pain, early satiety, sense of fullness.

10. Diagnosis
• Not helpful in early stages
• Helps identify advanced disease Anemia, hypoalbuminemia, leukocytosis
and elevated ALP or bilirubin levels are present
• Other increased markers CEA, Carbohydrate 19-9
• Radiological investigations
• USG irregularly shaped lesion in the subhepatic space/ heterogeneous mass in the
gallbladder lumen, asymmetrically thickened gallbladder wall.
• Polyp of more than 10 mm should raise the suspicion of gallbladder cancer
• CT/MRI  Provides information on local extent of cancer and distant metastasis
[peritoneal, hepatic parenchymal, lymphadenopathy, adjacent vascular involvement]

11. Diagnosis
• PET search for metastatic disease when CT or MRI provides limited
information about the primary tumor.
• NEVER BIOPSY
• If diagnosis is suspected Surgeon and patient must be prepared for
definitive operation.
• If unresectable (vascular encasement, extensive hepatic involvement) /
incurable (hepatic OR peritoneal metastasis) biopsy can be taken

12. Mass may be found as
a. Incidental finding on pathological review
b. Mass on imaging

15. Presentation of patients may be as follows
• Patients with gallbladder polyp
• Patients with an incidental finding of gallbladder cancer at the time of
or after cholecystectomy
• Patients suspected of having gallbladder cancer preoperatively
• Patients with advanced disease at presentation.

16. a. Gallbladder polyp
• Adenomatous polyp are the only polyp with malignant potential
• Predictors of malignancy
• Single polyp
• Size greater than 1 cm
• Age older than 50 years
• Polyp > 1cm Perform laparoscopically
• Polyp < 1cm  undergo surveillance to demonstrate stability, except PSC
where the threshold for cholecystectomy should be lower.

17. b. Gallbladder cancer after cholecystectomy
• Treatment depends upon the depth of penetration of the gallbladder
wall and surgical margins
• T1a Cholecystectomy will suffice.
• T1b and above As perineural, lymphatic or vascular invasion will
increase likelihood of nodal disease extended cholecystectomy is
done in such patients cholecystectomy and en-bloc resection
adjacent liver parenchyma in segments Ivb and V and portal
lymphadenopathy

18. • Extended cholecystectomy directed at obtaining R0 resection disease
including LN basins. Henceforth, removal of hepatoduodenal,
gastrohepatic and retro duodenal LN should be done.
• Cystic duct margin
• 2 cm of apparently normal hepatic parenchyma from gb fossa
• Port site excision [recommended by some surgeons]
• For T2 and more Radical cholecystectomy is done.
• Radical cholecystectomy is cholecystectomy with removal of LN.
• Includes segments IV b and V, lymphadenectomy and extended hepatic or biliary
resection to obtain negative margin

20. c. Patients suspected of having gallbladder
cancer preoperatively
• Offer an attempt at resection
• Patients tend to present at an advanced stage of locoregional disease
• Often require extended liver resection
• Radical resection should be considered for adequate operative candidates
• Begin with diagnostic laparoscopy to identify hepatic OR small-volume
peritoneal metastasis conclude inoperable (if present)
• Metastatic disease Non-operative strategies and palliative care is
considered

21. • For stage T3 and T4 lesions resect at least IV B and V but more often
requires central hepatectomy [segment IV B, V and VIII].
Trisegmentectomy may be required to achieve R0 status.
• Debulking with complete resection of disease is MAINSTAY of
management of gallbladder cancer.

22. d. Patients with advanced disease at
presentation
• Palliation is the goal
• Jaundice, pain and intestinal obstruction are the main presenting
complaints
• Jaundice ERCP, Self expanding Endobiliary metal stents
• Pain Oral narcotics, percutaneous neurolysis of celiac ganglion
• Intestinal obstruction occurs due to gastric outlet obstruction from
local extension of tumor and managed by endoscopic duodenal wall
stent.

23. Adjuvant Therapy
• Majority of gallbladder carcinoma recurrences include distant sites as
a part of recurrence pattern.
• Gemcitabine-based therapy often combined with platinum agent are
typically used for treatment of gallbladder cancer
• T4 lesions, positive LN status, R1 resection  indications for adjuvant
therapy

25. Survival
• Survival depends on stage of presentation, degree of surgical resection
performed
• T status, N status, histologic differentiation, CBD involvement, R0 resection 
independent factors affecting survival
• Overall survival of gallbladder cancer < 15%
Stage of the cancer Prognosis and survival
T1a -1b Excellent prognosis
T2 Depends on extent of nodal status and
radical resection. Survival (5 yr) 20-60%
T3 5 yr survival < 20%
T4 Months

26. Cholangiocarcinoma

27. Introduction
• Rare disease entity with dismal
prognosis
• Second most common liver
malignancy after HCC
• Usually middle third of bile duct
is rarely involved in malignant
transformation.
• Investigations are now focused
on perihilar and intrahepatic
lesions proximal disease
• Lesions involving periampullary
region are known as distal
disease
• More than 2/3rd
of all
cholangiocarcinoma involve
proximal biliary tree near the
bifurcation Klatskin tumor

28. Risk factors
• Congenital lesions
• Choledochal cysts
• Exposure of biliary epithelium to
toxic pancreatic secretions
• 10-20% of cysts turn into malignant if
cyst is not resected by age 20
• Infections/inflammation
• Clonorchis sinensis
• Opisthorchis viverrine
• Cause chronic biliary inflammation,
obstruction and stricture
• Primary sclerosing cholangitis
• Annual risk of 1.5% per year
• Medications and chemical
carcinogens
• Thorotrast
• Oral contraceptive pills
• Asbestos
• Cigarette smoke
• Cirrhosis of liver

30. Staging and classification
• Pathologic subtypes
• Sclerosing
• Nodular
• Papillary (@PNS)
• Sclerosing variety are mostly located in proximal
region
• Papillary and nodular are located in distal region
and are manifested as intraluminal growth
• Nodular A firm mass based in the duct wall
can be seen growing into the duct lumen
• Papillary Polypoidal lesion that is soft with less
periductal fibrosis
• TNM classification
• 3 staging subdivisions
• Intrahepatic
• Perihilar
• Distal bile duct
• Tumors within bile duct and those
extending outside the duct but not
invading any nearby structure usually have
good prognosis.
• Factors influencing prognosis
• R0 resection
• LN invasion

34. Clinical features
•Depends on site of obstruction
• Painless jaundice
• If unilobar obstruction
• Ipsilateral lobar atrophy, with contralateral hypertrophy
• Liver compensates until late stages
• If obstruction at or below hepatic bifurcation
• Earlier manifestations
• Features of obstructive jaundice
• Submucosal spread of tumor may lead to perineural invasion

35. Diagnosis and assessment of resectability
• Presentation
• Features of obstructive jaundice
• Hyperbilirubinemia, Increased ALP
• Late stages PT increase, Albumin decrease
• Tumor markers
• CA-19-9, CEA (for postoperative surveillance)
• Radiologic evaluation
• USG Hilar cholangiocarcinoma Gallbladder and Extrahepatic biliary tree
decompressed
• USG Distal cholangiocarcinoma EHBD dilation, gallbladder distention

36. • CT scan in cholangiocarcinoma
• Triphasic CT
• Assessment of metastasis, Evaluation of resectability
• Location of tumor
• Relation with vascular structures
• Identification of aberrant anatomy and determination of segmental or lobar
involvement
• Cholangiography
• ERCP/ PTC / MRCP
• Helps determine the proximal extent of resection

37. Imaging
Ultrasound :
• Used as a screening examination in patients with RUQ pain, a palpable
mass, or unexplained jaundice.
• Nonspecific appearance as a hypoechoic hepatic mass.
• Satellite lesions and capsular retraction may be seen.
• Hypovascular with minimal Doppler evidence of internal blood flow.
• Biliary dilatation, portal venous invasion, hepatic venous invasion and
portal lymphadenopathy.

38. Imaging
• Multiphasic CT with IV contrast of the abdomen and pelvis.
• Hypodense with irregular, infiltrative margins.
• Variable delayed enhancement in the portal venous phase.
• Biliary dilatation, portal or hepatic venous involvement , lobar atrophy.
• Identification of aberrant anatomy and segmental or lobar involvement
• Helpful for preoperative planning.
• Chest CT (with or without contrast) should be performed.

41. Imaging: MRI
• Hypointense on T1-weighted, hyperintense on T2-weighted images
• Pooling of contrast within the lesions on delayed images (6 to 8
minutes)
• Venous and arterial involvement by tumor
• Cholangiopancreatography is a noninvasive method of obtaining
cholangiograms.

44. • Tissue diagnosis before resection of the tumor in operative patients is
unnecessary.
• Brush cytology Reports unreliable Negative cytology thus does not
alter subsequent management

45. Preoperative biliary Drainage
• Distal bile duct cancer- single catheter, whereas in perihilar- multiple
• When intrahepatic bile ducts are isolated , PTC and multiple direct
segmental transhepatic drainages may be necessary.
• Future liver remnant should be assessed prior to drainage.

46. Preoperative biliary Drainage
• Indications:
• Total bilirubin >10 mg/dl
• Cholangitis
• Neoadjuvant treatment
• Hyperbilirubinemia induced malnutrition
• Hepatic or renal insufficiency
• PVE
• Target bilirubin <2-4 mg/dl
• When drainage is done, total bilirubin decreases @ 20% per day from the baseline

47. Management

48. Pre-operative Portal venous embolization
• Important in the presurgical management.
• Patients who undergo extensive liver resection.
• Increase the functional liver by inducing compensatory hypertrophy.
• Sizable compensatory hypertrophy of the non embolized segments
• In right PVE, the volume of the left lobe increases by 130 cm3
on
average within 2 weeks after embolization.
• Estimated resection volume decreases by approximately 10%.

49. Operative management
• Even with clinical suspicion of the disease Adequate surgical
candidates' exploration should proceed even in the absence of
confirmed tissue diagnosis
• 7-15% of patients with suspected malignant disease will have benign
disease
• Staging laparoscopy is important initial step at the time of resection
to reduce the incidence of nontherapeutic laparotomy

50. Management of distal CC
• Operative management includes Pancreaticoduodenectomy
• Intra-operative frozen section to determine R0 resection status is
preferred.
• 5 year survival – up to 50% when R0 is achieved.

51. Management of Proximal CC
• Regional nodal tissue and en bloc resection of the CBD with resection
of hepatic parenchyma as necessary to achieve negative margins
• Resection depends upon Bismuth-Corlette classification

53. Type of cholangiocarcinoma Operation procedure
a. Type I and II lesions Common duct resection
Cholecystectomy
5-10 mm of resection margin
[Type II resection also may require partial hepatic resection (commonly including caudate lobe). Resection of bile
duct and nodal tissue requires complete skeletonization of hepatic artery and portal vein]
b. Type III and IV lesions • Complex resection and reconstruction
of portal vein, hepatic artery or both.
• If secondary biliary radicals are also
resected Trans anastomotic stenting
• Hepatic resection in selected cases to
achieve negative margins
Negative margin status is the most important variable associated with outcome of patients with cholangiocarcinoma

55. Prognosis and survival rate
• As high as 59% have been reported
• With vascular resection and reconstruction techniques
• Role of lymph node resection is debated.
• There has been no demonstrable benefit of routine lymph node dissection
however LN are one of the most important prognostic factors in
cholangiocarcinoma.

56. Palliation
• In unresectable cases or incurable diseases all attempts to palliate their
symptoms non-operatively should be used
• Goals
• Relief of jaundice
• Alleviation of pain Oral/ IV narcotics
• Relief of duodenal obstruction Endoscopic duodenal stenting
• Palliation may be
• Endoscopic ERCP for distal CC
• Percutaneous PTC for proximal CC
• In either cases, placement of self expanding metallic stent is used

57. Medical therapy
• No improved survival by chemotherapy
• Radiotherapy has also no benefit in survival
• Studies report < 10% of clinical response rate Radiotherapy
• Neither radiotherapy nor chemotherapy is used routinely in patients
in adjuvant/ neoadjuvant setting

58. Outcomes
• Depend on stage of presentation and completeness of surgical
resection to negative margin
• With use of CBD resection with partial hepatectomy negative
margin rates is as high as 75%
• 5 year survival rate 20-45% in most series with available expertise.
• Defined by LN metastasis.
• Unresected cases Median survival is 5-8 months.

59. Should we go for liver replacement?
• Controversial
• Limited to research protocols

60. Intrahepatic cholangiocarcinoma

61. Introduction
• 40-60% of the bile duct malignancies are IHC where biliary confluence is
the most commonly involved area (Klatskin tumor)
• Second most common primary hepatic neoplasm
• MC risk factors include
• PSC
• Choledochal cyst
• Hepatolithiasis
• Recurrent pyogenic cholangitis
• Hepatitis B/ Hepatitis C
• NASH
• Diabetes

62. Clinical Features
• Similar to HCC
• Asymptomatic Early stages
• Symptoms include
• RUQ pain
• Weight loss
• Jaundice (relatively uncommon)
• Incidental mass
Laboratory investigations
• Normal ALP
• CEA and CA 19-9 may be elevated
• May be normal as well
• IHC is a diagnosis of exclusion
• Search for primary tumor with UGI / LGI
endoscopy, CT abdomen/pelvis, chest
• CT/ MRI Focal hepatic mass that
may be associated with biliary dilation
• Contrast study shows
• peripheral/ central enhancement
• persistent enhancement on delayed
phase due to fibrotic nature of
cholangiocarcinoma

63. Management
• Complete resection
• Focused on R0 resection margin
• Generally up to 60% resectable
• Completely resected cases have 3 year survival rates from 16-65%, 5 year
survival rates from 24-44%
• Factors associated with poor outcome
• Multifocal tumors
• LN metastasis
• Vascular invasion
• Positive margin
• @ V-L-M-P

64. • Because of rarity of the tumor little is known about the effectiveness of
radiotherapy and chemotherapy
• Application of radiotherapy and chemotherapy is not done in routine use
• BILCAP study Role of adjuvant capecitabine for IHC

65. 25% reduced death risk was noted in the study

66. What's new in intrahepatic cholangiocarcinoma?