This document discusses periampullary tumors, which arise near the ampulla of Vater. It defines periampullary tumors and lists the components that can be involved, including the bile duct, pancreatic duct, and duodenal mucosa. It then discusses cholangiocarcinoma, a type of bile duct cancer that can present as a periampullary tumor. Risk factors, clinical presentation, diagnosis, staging, treatment and prognosis of periampullary tumors are summarized. Surgical resection offers the best chance of survival, while unresectable tumors may be treated with stenting, radiation or chemotherapy to relieve symptoms.

2. Dr. Imran Zahid
PGR surgical unit-1

3. Defination
 Periampullary tumors are neoplasms that arise in the
vicinity of ampulla of Vater
or
 Tumors that are located within one cm of papilla of
vater.

5. Components of Periampullary tumor
 Terminal common bile duct
 Terminal pancreatic duct or head of pancrease
 Adjacent duodenal mucosa

9. Cholangiocarcinoma
 Cholangiocarcinoma is the bile duct cancers arising in
the intra-hepatic, peri-hilar, or distal (extra-hepatic)
biliary tree, exclusive of gallbladder or ampulla of
Vater.

10. Distal cholangiocarcinoma/
periampullary tumor
 Tumor that arise from terminal bile duct is called
periampullary tumor.

11. Introduction
 Arise from the epithelial cells of the bile ducts
 Tumor distribution
 – Peri-hilar tumors 50%
 – Distal extra-hepatic tumors 40%
 – Intra-hepatic tumors 10%

12. Epidemiology
 3% of all GI malignany
 The high prevalence in Asian descent is attributable to
endemic chronic parasitic infestation
 Highest prevalence rate in males and females in their
60s and 70s
 The male-to-female ratio - 1:15 in <40 yrs of age
1:2.5 in 60s & 70s

13. Risk factors
 Primary sclerosing cholangitis
 Fibrocystic liver disease
 Parasitic infection
 Cholelithiasis and hepatolithiasis
 Lynch syndrome & biliary papillomatosis
 Viral Hepatitis
 Toxins
 Diabetes
 Obesity
 HIV

14. Primary sclerosing cholangitis
 Primary sclerosing cholangitis (PSC) is a chronic,
idiopathic, cholestatic liver disease characterized
histologically by peribiliary inflammation and fibrosis.
 It can lead to end stage cirrhosis and is a recognized
risk factor for hepatobiliary cancers
 30% cholangiocarcinoma diagnosed in PSC ± UC
 Develops at younger age (30-50yrs) in PSC
 Lifetime risk of cholangiocarcinoma in PSC – 10-15%

15. Risk factors
 • Parasitic infection
 Liver flukes: Clonorchis and Opisthorchis
 Intra-hepatic cholangiocarcinoma
 Chronic inflammation in proximal biliary tree
 • Cholelithiasis & hepatolithiasis
 Strong risk factor for gall bladder cancer
 Association with cholangiocarcinoma
 Strong association between hepatolithiasis and
cholangiocarcinoma

16. Molecular pathology
Precursors to cholangiocarcinoma
 Biliary intra-epithelial neoplasia (BilN) – more common
 Intra-ductal papillary neoplasm (IPMN)
 Precursors harbor mutations in p53 & loss of SMAD4
 Molecular defects involves oncogenes & tumor suppresor
genes
 Oncogenes
 K-ras, c-erbB-2, BRAF, PIK3CA, CTNNB1, EGFR
 Tumor suppressor genes
 p53, SMAD4, CDKN2A

17.  Molecular pathology
 Neoplastic transformation - association with a constitutive
production of IL-6, which has positive cytoplasmic
immunohisotchemical staining and over-expression of IL-6
messenger RNA and protein in cholangiocarcinoma cells
 Cholangiocarcinoma growth facilitated by increased
angiogenesis mediated by over-expression of VEGF, COX-2,
and TGF-b1

18. Pathology
 Adenocarcinoma - >90%
 Sclerosing
 Most common type
 Characteristic feature - desmoplastic reaction
 Extensive fibrosis – pre-operative diagnosis difficult
 Early invasion of bile duct wall – low resectibility and
cure rate

19. Pathology
 Nodular
 Presented as constricting annular lesion of bile duct
 Highly invasive – most pts have advanced diseases at
time of diagnosis
 Very low resectibility and cure rate
 Papillary
 Rarest
 Usually present as bulky mass in CBD lumen causing
biliary obstruction in early period
 Highest resectibility and cure rates

20. Histological types
 Carcinoma insitu
 Adenocarcinoma intestinal type
 Mucinious adenocarcinoma
 Clear cell adenocarcinoma
 Signet ring cell adenocarcinoma
 Adenosqumaous carcinoma
 Squmaous cell carcinoma
 Papillary carcinoma invasive and non-invasive

21. Clinical presentation
 Cholangiocarcinomas become symptomatic when the tumor
obstructs the biliary drainage system, causing painless jaundice
that is the leading symptom more than 90% in patients.
 Common symptoms
 Pruritus – 66%
 Abdominal pain – 30-50%
 Weight loss – 30-50%
 Fever – up-to 20%
 Cholangitis is unusual
 Signs
 Jaundice – 90%
 Hepatomegaly - 25-40%
 Right upper quadrant mass – 10%

22. Courvoisier’s Law

23. Diagnosis
 Laboratoty investigations
 T.bilirubin > 10mg%
 Elevated both toal and direct bilirubin
 2- 10 fold increase ALP
 SGOT, SGPT – initially normal, elevated in chronic
biliary obstruction

24. Tumor Markers
 CA 19-9
 Widely used for detecting cholangiocarcinoma,
particularly in PSC
 Elevated CA 19-9 – pancreatic exocrine and
neuroendocrine tumors, biliary cancer, HCC, gasrtric
cancer, colo-rectal cancer, acute cholangitis, cirhhosis
 Some tumor produce low level or no CA 19-9
 Sensitivity 89%
 Specificity 86%

25. Tumor markers
 CEA
 Neither sufficiently sensitive nor specific to diagnose
cholangiocarcinoma
 Elevated CEA – gastritis, PUD, diverticulitis, COPD,
DM, liver disease
 Biliary CEA elevated five-fold compared to those with
benign strictures

26. Diagnosis
 Radiographic evaluation/USG
Most of jaundiced pt undergo initial USG abdomen to
confirm biliary ductal dilatation, localize site of
obstruction and exclude gallstones
Obstructing lesion suggested by ductal dilatation
(>6mm) in absence of stones.
Papillary tumor - polypoidal intra-luminal masses•
Nodular lesions – smooth masses with mural
thickening

27.  CT scan
Useful for detection of intra-hepatic tumors, level of
biliary obstruction, liver atrophy
CBD tumor – distended gall bladder, dilated
inntrahepatic and extra-hepatic ducts
• PV branch invasion – biliary duct dilatation within
atrophied lobe with hypertrophic c/l lobe
A helical CT scan can detect cholingiocarcinoma greater
1cm, relatiomship between the tumor and adjacent
organs and vascular involvement.

28.  MRI
MRI is best modality for diagnisis and staging of
cholangiocarcinoma

29.  ERCP
Preoperative cholangiography (diagnostic or
therapeutic) in biliary obstruction
– Distal obstruction
– Pre-operative biliary drainage is needed
– Tissue diagnosis/ cytology
Endoscopic brush cytology – sensitivity 35-70%
Endoscopic cytology + biopsy – sensitivity 43-88%

30.  Endoscopic ultrasound
To visualize local extent of primary tumor and status
of regional nodes in distal bile duct lesion
EUS-guided FNAB of tumors / enlarged nodes

31.  PET scan
Visualization of cholangiocarcinoma is possible due to
high glucose uptake of bile duct epithelium
• Detect nodular tumor up-to 1cm
• Less helpful in infiltrating tumors
• Most important role in identifying occult metastasis

32. TNM classification
 T1 Histologicaly confined to bile duct
 T2 Invasion beyond bile duct
 T3 Invasion of gall bladder, pancreas,
 duodenum, other adjacent organs without
 involvement of celiac axis or SMA
 T4 Involvement of celiac axis or SMA
 N1 Regional nodal metastasis
 M1 Distant metastasis

33. Staging
 Stage 0 Tis, N0, M0
 Stage I A T1, N0, M0
 Stage I B T2, N0, M0
 Stage II A T3, N0, M0
 Stage II B T1-3, N1, M0
 Stage III T4, Any N, M0
 Stage IV Any T, Any N, M1

34. Treatment
Depends on resectability of tumor.
Resectability Criteria
Absence of retro-pancreatic and para-celiac nodal
metastases or distant liver metastases
Absence of invasion of the portal vein or main hepatic
artery
Absence of extra-hepatic adjacent organ invasion
Absence of disseminated disease

35.  Radiological criteria for unresectability
Encasement or occlusion of the main PV proximal to its
Bifurcation
Involvement of b/l hepatic arteries

36. Surgical Management
 Pancreaticodudenectomy (Classical whipple )
 Pylorus preserving Pancreaticodudenectomy
(Modified whipple)
 Local excision(Transdudenal Papillodudenectomy)

37. Adjuvant therapy
For resected, margin-positive disease -
Fluoropyrimidine-based chemo-radiotherapy followed
by additional Fluoropyrimidine-based or
Gemcitabine-based
chemotherapy, or if the nodes are positive,
Fluoropyrimidine-based or Gemcitabine-based
chemotherapy alone.

38. Prognosis
Depends on extent of local invasion of primary lesion
Lymph node involvement
Vascular invasion
Perineural invasion
Uninvolved surgical margins
If tumor is resectable, five year survival is 20-60%
(avarege 35%)

39. Paliative Treatment
If tumor is unrescable and advance paliative treatment
can be used
1. Stent (Plastic/metal)
2. Photodynamic therapy
3. Paliative radiotherapy
4. Chemotherapy