This document discusses pancreatic cancer. It begins with an overview of the epidemiology, risk factors, classification, clinical presentation, and diagnosis of pancreatic cancer. Pancreatic cancer has a poor prognosis, with a median survival of 4-6 months. Risk factors include age, smoking, obesity, family history, and chronic pancreatitis. The vast majority (85%) are ductal adenocarcinomas. Symptoms often include abdominal or back pain, jaundice, and weight loss. Diagnosis involves imaging like CT or MRI along with blood tests and biopsy. Genetic testing helps determine underlying causes and guides treatment options.

1. Ahmed
GSR-II
moderator: Dr Hunde(MD,Surgeon)
may 11, 2022

2.  Introduction
 Anatomy of pancreas
 Epidemiology, Risk Factors
 Classification
 Clinical presentation
 Work up
 Reference
2

3.  Fourth leading cause of cancer death
 Median survival time of all pts is 4-6 months
 Genetic and environmental factors
 Surgical resection is still the only potentially curative
treatment

5. 5
Venous Drainage

6. 6
Innervation

7. Epidemiology
 Worldwide, over 265,000 people contract this disease annually,
of w/c 74% die within the first year after diagnosis
 Comprising 6% of all cancer-related deaths
 The incidence is continues to increase, b/c of increased
incidence of risk factors(obesity & DM)
 The etiology is likely involves a complex interaction of genetic
and environmental factors
 It is more common in African Americans and slightly more
common in men than women

8.  Is notoriously difficult to diagnose in its early stages.
 At the time of diagnosis, 52% of all patients have distant
disease,29% have regional spread,&10% localised.
 The relative 5-year survival for localised is 31.5%,for regional
11.5%, for distant 2.7% and the overall 5-year survival rate
for this disease is 7.2%.

9. Lung & bronchus31%
Prostate 9%
Colon & rectum 9%
Pancreas 6%
Leukemia 4%
Liver & intrahepatic4%
bile duct
Esophagus 4%
Urinary bladder 3%
Non-Hodgkin 3%
lymphoma
Kidney 3%
All other sites 24%
26% Lung & bronchus
15% Breast
10% Colon & rectum
6% Pancreas
6% Ovary
4% Leukemia
3% Non-Hodgkin
lymphoma
3% Uterine corpus
2% Brain/ONS
2% Liver & intrahepatic
bile duct
23% All other sites
Men
289,550
Women
270,100
4th leading cause of cancer death

10.  Overall, estimates indicate that 40% of pancreatic cancer cases
are sporadic in nature.
 30% are related to smoking
 20% may be associated with dietary factors.
 Only 5-10% are hereditary in nature.
 Fewer than 5% of all pancreatic cancers are related to
underlying chronic pancreatitis.

11.  Age.
 The risk of developing pancreatic cancer increases with age. Most
pancreatic cancers occur in people older than 60.
 Gender.
 More men are diagnosed with pancreatic cancer than women.
 Race.
 Black people are more likely than Asians, Hispanics, or white people to
develop pancreatic cancer.

12.  Smoking.
 Smokers are two to three times more likely to develop pancreatic
cancer than nonsmokers.
 Obesity and diet.
 Eating a high-fat diet is a risk factor for pancreatic cancer. Research
has shown that obese and even overweight men and women have a
higher risk of dying from pancreatic cancer.

13.  Family history.
 A person’s chance of developing this cancer increases three-fold
if a first-degree relative (mother, father, sister, or brother) had pancreatic
cancer.
 Chronic pancreatitis
 Hereditary pancreatitis
◦ Hereditary pancreatitis
◦ HNPCC
◦ Hereditary breast & ovarian Ca
◦ Peutz-Jeghers syndrome

14.  Chemicals. Exposure to certain chemicals (such as pesticides,
benzene, certain dyes, and petrochemicals) may increase the
risk of developing pancreatic cancer.
 Hepatitis B infection. Hepatitis viruses are viruses that infect the
liver. One recent study has shown that evidence of a previous
hepatitis B infection was twice as common in people with
pancreatic cancer than in people without the cancer

15.  Diabetes has been known to be associated
with pancreatic cancer for many years.
 glucose intolerance is present in
 80% of patients with pancreatic cancer,
 20% have overt diabetes,
 Preexisting type 2 diabetes increases the
risk for development of pancreatic cancer by
about twofold

16.  Broadly speaking, there are three basic types:
 Ductal adenocarcinoma >90% of pancreatic cancers with a 4%
5-year survival (worst of any cancer)
 Neuroendocrine tumors aka islet-cell tumors, rare
 Cystic neoplasms account for <1% of pancreatic cancers

17.  Much less commonly, tumors begin in the islets of
Langerhans, the endocrine component.
 These are known as islet cell tumors or pancreatic
neuroendocrine tumors.
 These can be functionally inactive islet cell carcinomas or
benign or malignant functioning tumors such as insulinomas,
glucagonomas, and gastrinomas.

18.  Tumor grows without producing hormones is called
non-functioning.
 If the tumor produces a hormone(s), the hormone(s)
may cause metabolic imbalances, such as a very low
blood sugar level (such as the case with
insulinomas) or a very high blood sugar level (such
as with glucagonomas), or other problems like
severe diarrhea (a symptom of VIPomas, which
produce a substance called vasoactive intestinal
peptide).
 Most pNETs are sporadic
 but they can be associated with hereditary
endocrinopathies including
MEN1,VHL,NF1,sydromes

19.  most common functional pNETs.
 Whipple’s triad.
 Sx. fasting hypoglycemia,
 serum glucose level <50 mg/dL,
 relief of Sx. with given glucose.

20.  90% are benign and solitary, and only 10%
are malignant.
 evenly distributed throughout
 head, body, and tail of the pancreas.
 Dx. Routine laboratory studies
 low blood sugar,
 elevated Serum insulin levels & C-peptide levels
 usually localized
 CT scanning and EUS.

21.  ZES is caused by Gastrinoma,
◦ an endocrine tumor that secretes gastrin, leading
to acid hypersecretion and peptic ulceration.
 Time of Dx, 21% of pts have diarrhea.
 70-90%,found in Passaro’s triangle
 Approximately 50% of gastrinomas
metastasize to LN or liver and therefore
considered malignant
 Dx. hormonal test, >1000 pg/mL
 SSTR (octreotide) scintigraphy in combination with CT

22.  very rare tumor of the pancreatic alpha cells
that results in the overproduction of the
glucagon.
 typically associated with
◦ rash (NME), wt loss and mild DM
 Dx. confirmed by serum glucagon levels,
>500 pg/mL

23.  rare pNET arise delt cells of endocrine
pancreas.
 originate proximal pancreas or
pancreatoduodenal groove.
 60% ampulla & periampullary
 The most common presentations are
 abdominal pain 25%, jaundice 25%,
 cholelithiasis 19%.
 Dx. confirming elevated serum somatostatin levels,
>10 ng/mL.

24.  Cystic neoplasms of the pancreas account for fewer than 5% of
all pancreatic tumors.
 Consist of benign serous cystadenomas, premalignant
mucinous cystadenomas, and cystadenocarcinomas.
 Intraductal mucinous pancreatic neoplasms can be benign or
malignant and usually manifest as a cystic dilation of the
pancreatic ductal system.

25.  It is important to determine if the cancer started in the
exocrine or endocrine component of the pancreas, as the
diagnosis and treatment of each type is much different.
 The most common type of pancreatic cancer is called ductal
adenocarcinoma, or simply, adenocarcinoma.

26. Ductal
-Adenosquamous (4% of
all)
-Signet ring cell
-Undifferentiated
(anaplastic)
-Mucinous colloid (2%)
85 %
IPMN invasive ca 2-3%
MCN with invasive ca 1%
Solid pseudopapillary <1 %
Acinar cell ca <1 %

27. WHO classification
:
 Based upon morphologic and
histologic features.
 Benign — such as serous
cystadenoma are reliably
cured by surgical removal
alone.
 Premalignant lesions — MCN
and IPMN
Malignant:
Ductal adenocarcinoma – ~ 85 %
- Signet ring cell carcinoma
- Adenosquamous carcinoma (~
4% of all pancreatic malignancies )
- Undifferentiated (anaplastic) ca.
- Mucinous non-cystic
(colloid)ca.(~2%)
 IPMN with an associated invasive ca 2-
3%
MCN with an associated invasive ca – 1%
Solid-pseudopapillary neoplasm – <1 %
Acinar cell carcinoma – <1 %
Pancreatoblastoma – <1%
Serous cystadenocarcinoma – <1 %

28.  Ducts represent only 4% of the tissue but are
source of 90% of pancreatic malignancies
◦ 2/3rd in the head or uncinate process
◦ 15% in the body
◦ 10% in the tail
 Most cases are sporadic
 Ampullary and periampullary tumors present in a
similar fashion but have a slightly better
prognosis

29.  Gross pathology
◦ Majority are gritty, hard, scirrhous, gray-white and poorly
circumscribed
 Histology and grading
◦ Most are moderately to poorly differentiated, with varying degrees of
duct-like structures and mucin production

30.  typically involves adjacent structures  duodenum, the PV, or SM vessels.
 striking tendency for perineural invasion both within and beyond the pancreas.
represents the most common site of disease
recurrence after resection.
 Occasionally local extension to the spleen, adrenal glands, vertebral column, transverse
colon, and/or stomach.
 Regional peripancreatic LNs frequently harbor metastatic deposits.

31.  pancreatic tumors, 95% develop from the exocrine portion of
the pancreas, including the ductal epithelium, acinar cells,
connective tissue, and lymphatic tissue.
 Approximately 75% of all pancreatic carcinomas occur within
the head or neck of the pancreas, 15-20% occur in the body of
the pancreas, and 5-10% occur in the tail.

32.  The molecular genetics of pancreatic adenocarcinoma have
been well studied.
 Of these tumors, 80-95% have mutations in the KRAS2 gene,
and 85-98% have mutations, deletions, or hypermethylation in
the CDKN2 gene.
 50% have mutations in p53 and about 55% have homozygous
deletions or mutations of Smad4.

33.  Families with BRCA-2 mutations, which are associated with a
high risk of breast cancer, also have an excess of pancreatic
cancer.
 Assaying pancreatic juice for the genetic mutations associated
with pancreatic adenocarcinoma is invasive but may be useful
for the early diagnosis of the disease

34.  Certain precursor lesions have been associated with
pancreatic tumors arising from the ductal epithelium of the
pancreas.
 The main morphologic form associated with ductal
adenocarcinoma of the pancreas has been pancreatic
intraepithelial neoplasia or PIN.
 These lesions arise from specific genetic mutations and
cellular alterations that all contribute to the development of
invasive ductal adenocarcinoma.

35.  The initial alterations appear to be related to KRAS2 gene
mutations and telomere shortening.
 Thereafter p16/CDKN2A is inactivated.
 Finally, the inactivation of TP53 and MAD4/DPC4 occur.
 These mutations have been correlated with increasing
development of dysplasia, and thus the development of ductal
carcinoma of the exocrine pancreas.

36.  It is postulated that telomere-shortening, and mutations of
the oncogene K-RAS occur at early stages
 inactivation of the p16 tumor suppressor gene occurs at
intermediate stages
 inactivation of the p53, SMAD4 (DPC4), and BRCA2 tumor
suppressor genes occur at late stages.

37.  It is important to note that while there is a general temporal
sequence of changes, the accumulation of multiple mutations
is more important than their occurrence in a specific order.

38. Genes PanIN-1 PanIN-2 PanIN-3 Invasive PDAC
KRAS2 36% 44% 87% >95%
CDKN2A/p16 30% 55% 71% ~90%
P53 Rare Rare Rare ~79%

40. Abdominal pain: common presenting symptom
 it is mid epigastric in location, w/c radiate to the back(sign retroperitoneal
invasion)
 The pain worse when the patient is lying flat
 About 1/3 of pts may not have pain at time of presentation, 1/3 of pts have
moderate pain & the rest have severe pain
Jaundice: due to obstruction of the distal BD
 associated with nausea, pruritus, dark urine and pale stools
Weight loss, anorexia, malaise, fatigue

41. On physical examination
 Evidence of jaundice: icteric sclera & skin
 Skin excoriations from unrelenting pruritus.
 Mild-to-moderate midepigastric tenderness
 Palpable GB (Courvoisier sign) in ¼ of pts
 In advanced case there may be ascites, a palpable abdominal
mass, hepatosplenomegaly, supraclavicular nodes and tumour
deposits in the pelvis

42.  relatively uncommon
 5/100000 population
 <5% of all pancreatic tumors
 4th & 6th decades of life.
 most pNETs are nonfunctional
 Most pNETs are sporadic
 but they can be associated with hereditary endocrinopathies including
MEN1,VHL,NF1,sydromes

43. History and P/E
Laboratory Evaluation
CBC
RBS
LFT
Coagulation profile
Nutritional assessment

44. 44

45. Multidetector CT
 Imaging study of choice
 For an accurate determination of:
◦ Level of biliary obstruction
◦ Tumor and critical vascular anatomy
◦ Presence of regional or metastatic ds
 Defines any arterial or venous aberrations
 Excellent sensitivity (85%)
 Not as accurate in predicting the need for venous resection

46.  Non-Contrast phase
◦ Evaluation of calcifications
 Early Arterial Phase
◦ Evaluates vasculature without interference from venous
opacification
 Late Arterial Phase
◦ Distinguish ca from normal tissue by contrast enhancement
◦ Hypervascular liver mets in neuroendocrine ca
 Routine Portal Venous Phase
◦ Hypovascular liver mets in Adenocarcinoma

47. ◦ Relatively Hypovascular, hypoattenuating tumors
 Neuroendocrine tumors:
◦ Hypervascular, hyperattenuating tumors

49.  Conventional
Ultrasound
◦Initial study in OJ
◦Sensitivity (75-89%),
specificity (90-99%)
◦Affected by:
Experience
Presence or absence
of duct obstruction
Extent of tumor
 EUS/FNA:
◦For PV/SMV invasion
◦Less effective for SMA
invasion
◦Provide tissue dx
◦Sensitivity and
specificity of 92%-95%
◦For small Tumors (<2
cm)

50. ERCP:
 Once used for diagnosis
 Can be Therapeutic
 A slight increase in
complications
 Early surgery is preferable
to stenting
 MRCP:
◦Non-invasive
◦Detailed 3-D anatomy
◦For cystic lesions
◦The “double-duct”
sign
◦No risk of inciting
pancreatitis

51.  All the current staging modalities  ~80%
accuracy in predicting resectability
 Improves accuracy of predicting resectability
to ~98%
 Avoid Nontherapeutic Laparotomy:
◦10% to 30% (head) & 50% (body and tail)
 Possibly best applied on a selective basis:
◦>4 cm
◦Tumors located in the body or tail
◦Equivocal findings of metastasis or ascites
on CT

52.  Limited role
 Insensitive for early
cas
 Less specific
 May be as initial Ix:
◦ CA19-9
◦ CEA
◦ α-fetoprotein
CA19-9:
 79% Sensitive & 82%
specific
 For Surveillance
 Normal level < 37U/ml
 Small ca (<1 cm)
37-100
 Mets> 1,000 U/ml
 Limitation:
◦Elevation in benign ds
◦10% to 15% do not

53.  Tells us whether the lesion is amenable to surgical resection.
 Only 20% of all patients presenting with pancreatic cancer are
ultimately found to have easily resectable tumors with no
evidence of local advancement.
 No survival benefit is achieved for patients undergoing
noncurative resections for pancreatic carcinoma.

57. Stage grouping is according to
Resectability:
Stages I and
II
Localized
Resectable
Stage III Locally Advanced
Unresectable

59. .
T
A
Resectable pancreatic adenocarcinoma in the head and
uncinate process, showing well-preserved fat plane
(arrow) between tumor (T) and SMA(A).