Pancreatic

By
tumor
Revathy S
MSc Nursing 2nd year 1
 Introduction
₡ The disease has a poor prognosis and is considered by many to be one of the
deadliest malignancies.
₡ The majority of pancreatic cancers are metastatic at the time of diagnosis.
₡ Pancreatic cancer is one of the most difficult tumors to detect or diagnose
because of the anatomical location of the pancreas. It is also difficult to treat
due to the biological nature of the tumor.
₡ Its onset is insidious, with signs and symptoms that occur late, are vague and
misleading, and mimic other diseases.
₡ The individual with pancreatic cancer typically will ignore the initial signs and
symptoms or rely on self-treatment for months until jaundice or other
prominent and intolerable signs appear. 2
 Epidemiology
• Age is the strongest risk factor for pancreatic cancer,
with the peak incidence occurring between the ages 60
and 80.
• Pancreatic carcinoma incidence is slightly higher in men
than in women.
• The incidence rates of pancreatic cancer are highest in
Western and industrialized countries, and lowest in
underdeveloped nations
3
Incidence

4
 Pancreas
• Large gland found in the abdomen
• 6 inch long
• 3 parts: head, body , tail
• Function
– Exocrine function
– Endocrine function

5
Anatomy & physiology

6
 Risk factors
1 Demographic factors

2 Environmental factors

3 Dietary factors

4 Occupational factor
5 Host factor
 Demographic factors

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 Environmental factors
• Tobacco
– 20% to 30% of pancreatic cancers – tobacco
smoking
• Radiation
– Persons irradiated in infancy for skin hemangioma
have been reported to have an increased risk of
pancreatic cancer
9
 Dietary factors

Carbohydrate Cholesterol Meat Salt

Dehydrated Refined
Fried food Soy beans Nitrosamines
food sugar

10
 Dietary factors
• A decreased risk or perhaps a protective effect has
been reported for fiber, vitamin C, fruits, vegetables,
preservative-free foods, raw foods, and the use of
pressure cooking and microwave cooking
• High body mass index, increased weight, and a low
level of physical activity, all increase the risk of
pancreatic cancer
11
 Occupational factors
• Chemists
• Coal gas workers
• Metal industries
• Aluminum milling
• Leather tanning
• Textile industry
• Building trades
• Transportation
• Butchers
• Flour industry
• Ethylene chlorhydrin
• Halogenated hydrocarbons
• Chlorinated water 12
 Occupational factors
• Increased risk associated with exposure to welding
materials, paint thinners, refuse and detergents, and
floor cleaning agents, as well as petroleum products.

13
 Host factors
• Diabetes
• Chronic pancreatitis
• Genetic syndromes

14
 Risk factors
• The relative risk in persons who have had diabetes for 5 years is
double the risk of persons without diabetes.
• Peptic ulcer surgery and cholecystectomy have also been linked
to pancreatic cancer. The initial symptoms of pancreatic cancer
can mimic biliary tract disease, which in turn may lead to
cholecystectomy and subsequent discovery of pancreatic cancer.
• Post-gastrectomy, there is a 2–5-fold risk presumed to be due to
reduced acidity, leading to change in bacterial flora and
processing of carcinogens.
15
 GENETICS
• Acquired and inherited mutations in cancer-causing genes.
• Activation of the oncogene, K-ras
• The inactivation of multiple tumor suppressor genes, and DNA mismatch
repair
• Mutant K-ras is found in approximately 95% of pancreatic
adenocarcinomas
• p16 tumor suppressor gene is inactivated in approximately 95% of
pancreatic cancers.
• The second most important tumor suppressor gene is p53, which is
inactivated in 70% of pancreatic cancers
16
 Cont..
• The DPC4 (deleted in pancreatic cancer on locus 4) gene is
specific for pancreatic cancer and is inactivated in
approximately 50% of pancreatic cancers.
• The BRCA2 gene is inactivated in only 7% of pancreatic
cancers
• Approximately 4% of pancreatic cancers have been found
to contain genetic alterations in DNA mismatch repair
genes
17
Genetic syndromes that predisposing to pancreatic cancer

• Hereditary pancreatitis
• Hereditary nonpolyposis colorectal cancer (HNPCC) - less
• Familial breast cancer (linked to BRCA2 tumor suppressor
gene) – most common
• Familial atypical multiple mole melanoma syndrome
(FAMMM) – 12 to 20 fold increased risk- p16 (TSG)
• Ataxia–telangiectasia syndrome – high – ATM gene
• Peutz–Jeghers syndrome – 100 fold greater incidence – p19
18
 Growth factors
• Over expression of EGFR
• Bind to EGF, TGF-α, FGF, amphiregulin, betacellulin, epiregulin
• TGF-β
– promoting tumor angiogenesis, altering the extracellular
array/matrix, and enhancing adhesiveness that facilitates
tumor metastasis
– shorter postoperative survival or worse prognosis in
individuals with pancreatic adenocarcinoma.
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In shorts

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 TYPES

Pancreatic
tumor

Exocrine(95%) Endocrine(5%)
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 Exocrine pancreatic cancer
• Solid tumors
– Ductal adenocarcinoma
– Adenosquamous carcinoma
– Acinar cell carcinoma
– Giant cell carcinoma
• Cystic tumors
– Serous cystic neoplasms
– Mucinous cystic neoplasms
– Intraductal papillary mucinous neoplasms (IPMN)
– Solid and cystic papillary neoplasms (Hamoudi tumor)
22
 Pathophysiology - exocrine
• 2 major types of epithelium: acinar and ductal. The
acinar cells of the pancreas produce digestive
enzymes, whereas the cells lining the pancreatic duct
are responsible for the secretion of fluid and
electrolytes and the conveyance of pancreatic juice to
the duodenum

23
 Adenocarcinoma
• Adenocarcinomas of the pancreas usually are whitish
yellow, hard, nodular, poorly defined, firm masses
surrounded by dense reactive fibrous tissue that
often obstruct and dilate the distal common bile duct
and pancreatic ducts.
• Precursors of ductal adenocarcinoma
– Lesions in small pancreatic duct (PanINs)
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25
 PanINs
• Precursor lesions may progress
from flat duct lesions (PanIN-
1A), to papillary duct lesions
without atypia (PanIN-1B), to
papillary duct lesions with
atypia (PanIN-2), and finally to
carcinoma in situ of the
pancreas (PanIN-3)
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27
 Adenosquamous carcinoma
• Adenosquamous carcinoma of the pancreas is a rare variant
of ductal adenocarcinoma that shows both glandular
(adeno) and squamous differentiation.
• This variation is more common in individuals who have
received previous chemotherapy or radiation therapy.
• The biological behavior of adenosquamous carcinoma is the
same as that of the typical ductal adenocarcinomas.
• Adenosquamous carcinoma has an especially poor prognosis
28
 Acinar cell carcinoma
• Distinct histological appearance and an unusual
clinical presentation.
• Most individuals with acinar cell carcinoma have
biliary or gastrointestinal obstruction because of the
tumor.
• Individuals with acinar cell carcinoma are slightly
better than those with ductal adenocarcinoma
29
 Giant cell carcinoma
• Giant cell carcinoma accounts for approximately 5%
of primary nonendocrine pancreatic malignancies.
• Giant cell carcinomas arise with equal frequency in
the head, body, and tail regions of the pancreas.
• These pancreatic carcinomas are associated with a
poorer prognosis than ductal adenocarcinomas.

30
 Cystic neoplasm
• TYPES
– Serous cystadenomas
– Potentially malignant mucinous cystadenomas
– Malignant cystadenocarcinomas.
– Most serous cystic neoplasms are benign, and the
prognosis for individuals with resected mucinous
cystadenomas is excellent.
31
 Mucinous cystic neoplasm
• Mucinous cystic neoplasms (MCNs) can be precursors
of infiltrating ductal adenocarcimonas of the pancreas.
• These tumors differ from PanINs in that they are grossly
visible and do not involve the ducts of the pancreas.
• It is important to differentiate MCNs from ductal
adenocarcinomas, as MCNs have a better prognosis

32
 Intraductal papillary mucinous neoplasms
• Intraductal papillary mucinous neoplasms (IPMNs)
are grossly visible tumors that grow in the large ducts
of the pancreas and have varying degrees of atypia.
• Found mostly in head of pancreas but can infiltrate
throughout the entire pancreas.

33
 Hamoudi tumors
• These tumors have solid, cystic, and papillary
components when viewed microscopically.
• Most individuals are cured after surgical resection

34
 Most common site of metastasis
• Breast, lung, colorectal, melanoma, and renal cell
carcinoma
• Systemic neoplasms such as leukemia and lymphoma
• Most pancreatic lymphomas are non-Hodgkin’s
lymphomas.
• Pancreatic lymphomas are rare, but early recognition is
important because of their dramatic response to
chemotherapy
35
 Endocrine tumors
• Endocrine or islet cell tumors constitute the
remainder of pancreatic malignant tumors
• Many islet cell tumors secrete excessive hormones,
resulting in significant clinical manifestations

36
 Islet cell tumor
• Islet cell tumors arise from the endocrine
parenchyma.
• They usually occur as small, well-circumscribed,
reddish-orange tissue that rarely extends beyond the
pancreas.

37
 Progression of disease
• Tumors of the head of the pancreas are those
arising to the right of the left border of the
superior mesentric vein. The uncinate process
is part of the head of the pancreas.
• Tumors of the body of the pancreas are those
arising between the left border of the superior
mesenteric vein and the left border of the
aorta.
• Tumors of the tail of the pancreas are those
arising between the left border of the aorta
and the hilum of the spleen. 38
• Pancreatic cancer arises in the head, neck, or uncinate
process of the pancreas in 60% to 70% of cases.
• About 15% of tumors develop in the body and tail of the
gland, and the remaining 20% diffusely involve the entire
gland

39
 Tumor of head
• Often detected at a small size (2–3 cm).
• The bile duct is invaded early in the course of the disease - obstruction of the distal
common bile duct - jaundice, which enable detection of smaller tumors.
• Ductal adenocarcinomas usually infiltrate into vascular, perineural, and lymphatic spaces.
These tumors tend to invade local structures, such as the duodenum and retroperitoneum,
either directly or along the course of autonomic nerves of the celiac plexus.
• Some degree of perineural invasion is present in 90% of cases. The portal or superior vein
may also be invaded.
• Venous invasion or encasement by tumor growth may result in obstruction, thrombosis,
ascites, and portal hypertension.
• Vascular encasement and neural infiltration can contribute to severe back pain.
Involvement of the mesenteric vessels may preclude resection of these tumors.
40
 C/M – head of pancreas
• A classic triad of symptoms : jaundice, pain, and weight loss.
• Obstructive jaundice leads to severe pruritus, dark, tea-colored urine and clay-colored
(acholic) stools.
• Two unusual symptoms are depression and superficial thrombophlebitis.
• A triad of depression, anxiety, and feelings of impending doom was first described in 1931.
• The increased incidence of depression in pancreatic cancer is 2 to 3 times greater than
that seen in individuals with other intra-abdominal malignancies.
– Presence of hormonal neuroendocrine agents in pancreatic cancer that circulate and
target the central nervous system.
– Another theorem is that pancreas cancer cells stimulate or produce substances which
inhibit the activity of serotonin or that T lymphocytes cause nonmetastatic tissue
damage in the brain
• Trousseau syndrome 41
 Tumor of body and tail
• In the body and tail of the pancreas, tumors often reach sizes larger than 5 cm before
they produce symptoms.
• Tumors of the body and tail of the pancreas can invade the splenic vein, resulting in
thrombosis and gastric varices
• At the time of detection, the tumor may be fixed to tissues behind the pancreas or to
the vertebral column.
• The tumor may directly invade surrounding organs - kidney, spleen, or diaphragm.
• Invasion of the celiac nerve plexus may account for unrelenting pain.
• Other sites of local invasion, which tends to occur later, include the superior mesenteric
and splenic arteries, transverse colon, stomach, kidneys, and left adrenal gland.
• Obstruction of the portal vein and tributaries can lead to portal hypertension and
esophageal varices. 42
 Cont..
• Characteristically, tumors of the pancreas grow slowly, with late signs and symptoms
of pathology. At the time of diagnosis, 90% of cases have perineural invasion, 70%-
80% have lymphatic spread, 50% have venous involvement, and 20%-25% have
duodenal invasion.
• The liver, peritoneum, and regional lymph nodes are the most commonly involved
structures.
• Supraclavicular nodes (Virchow nodes) may be involved more frequently with
carcinoma of the body and tail of the pancreas.
• Metastatic deposits reach the liver through the portal bloodstream or lymphatics.
• Peritoneal seeding by metastatic deposits also occurs.
• The frequency of lymph node metastasis correlates with the size of the primary tumor.
43
 C/M - Body of pancreas
• Produce late symptoms
• Severe epigastric pain usually is the predominant symptom
• Intense epigastric pain 3 to 4 hours after a meal, caused by the
space- occupying tumor displacing the stomach or by
encroachment at the ligament of Treitz.
• Cancer located in the body and tail of the pancreas produces
more pain and weight loss than lesions in the head of the
pancreas.
• Palpable spleen
44
 C/M – Tail of pancrease
• Most silent and insidious progression of disease
• Left upper quadrant abdominal pain, generalized weakness, vague
indigestion, anorexia, and unexplained weight loss
• Upper gastrointestinal bleeding, splenomegaly, and signs of portal
hypertension and ascites may result from thrombosis of the portal system
or extensive liver damage.
• Courvoisier sign
• In disseminated tumor
– Virchow node
– Sister mary joseph node
– Blumer’s shelf 45
Vichow node, sister mary joseph node, blumer’s shelf

46
 Clinical manifestation of the cancer of pancreas

• The early signs and symptoms of

pancreatic cancer are vague,
nonspecific, and gradual, which
often contributes to a delay in
diagnosis by both the individual and
the physician
• Specific symptoms usually develop
late and only after invasion or
obstruction of a nearby structure
• Manifestations of disease differ
according to the location of the
tumor
47
 Cont..
• Duodenal obstruction, with nausea and vomiting, is a late
manifestation of pancreatic cancer. Tumor involvement of
the pancreas prevent secretions of the digestive
pancreatic enzymes and may diminish insulin production.
• New onset diabetes may be the first clinical feature in
10%-20% of individuals
• Metabolic disturbances such as hyperglycemia, glycosuria,
and hypoalbuminemia may occur.
48
 Pain in pancreatic tumor
• Pain is often vague and nonspecific.
• A dull, intermittent, diffuse, upper abdominal or back discomfort is initially
experienced by most individuals. The discomfort may be attributed to other
causes such as indigestion or gaseous distention. The discomfort or pain may
become more distinctive. It may progress to continuous midepigastric pain and
frequently radiates to the back flanks or right upper quadrant of the abdomen,
often becoming most pronounced during the evening or night.
• It may be colicky, dull, or vague. The intensity of the pain is affected by activity,
eating, and posture. The pain is often ameliorated when the individual sits or
leans forward, called proning, or lies in the fetal position on their right side
with both knees drawn up to the chest. 49
 Cont..
• The pain can be caused by invasion of the tumor into the splanchnic plexus
and retroperitoneum, as well as by obstruction of the pancreatic duct.
• Pain is a more prevalent symptom in individuals who have tumors in the body
and tail of the pancreas. These tumors are larger at presentation and are
located in the retroperitoneum, which contributes to nerve involvement,
resulting in pain.
• Intractable pain is an early manifestation.
• Epigastric pain radiating to the back or flank pain usually indicates invasion of
splanchnic nerves or compression of organs and is suggestive of advanced
disease.
50
 Pancreatitis
• Acute pancreatitis may be the presenting sign of a
pancreatic neoplasm.
• Consideration must be given to the diagnosis of a
pancreatic tumor in patients who are initially seen
with pancreatitis, especially when there is no obvious
cause for acute pancreatitis, such as gallstones or
alcohol abuse.
51
 Assessment
• History
– Family history
• Physical examination
– Virtually impossible because it is an inaccessible organ, lying behind
the stomach and in front of the vertebral column (Hermit organ)
– Obstructive jaundice
– Palpable liver (30 -50%)
– Hard, well-defined mass that is palpable in the left upper quadrant
of the abdomen – body and tail
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On assessment

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Diagnosis

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 Ultrasound
• US can detect intrahepatic and extrahepatic bile duct
obstruction, a pancreatic mass, liver metastases
larger than 1 cm in diameter, and ascites. It is not
sensitive in defining local nodal spread or
involvement of the major blood vessels in the area.
• This imaging modality has largely been replaced by
computerized tomography (CT)
55
 CT
• CT is superior in defining the level of obstruction.
• It can also demonstrate the presence of a pancreatic
mass and enlarged lymph nodes adjacent to the
pancreas, as well as detect liver metastases, local
vascular invasion, or thrombosis.
• CT is more accurate in the diagnosis of unresectability.

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CT

57
 MRI & PET
• Major indications for MRI and PET include the detection
of small neoplasms, characterization of metastatic
disease, and particularly differentiation between
pancreatic carcinoma and chronic pancreatitis
• Use of enhanced PET combined with CT increases
sensitivity of detecting tumors of less than 1 cm and also
improves diagnosis of metastatic disease.
• limited availability and higher cost
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PET-CT

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 Cholangiography
• Cholangiography is indicated in the evaluation of the jaundiced individual to
define the site of biliary obstruction
• Using ERCP, both biliary and pancreatic ductal systems can be visualized. In
addition to delineating the site of obstruction, biopsy specimens for cytological
analysis can be obtained.
• A diagnostic ERCP may be important if the differential diagnosis includes chronic
pancreatitis and clinical deterioration.
• ERCP may be most useful to evaluate the nonjaundiced individual with vague
gastrointestinal symptoms in whom an early nonobstructing cancer is suspected
or in the person with obstructive jaundice presumed to have pancreatic cancer
but in whom no mass is evident on CT
60
• Dual duct sign
ERCP & Double duct sign

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Classification and staging

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Staging

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 Management
• Surgery
– best therapeutic option and the only opportunity for
cure
– Most surgical procedures for this disease are
palliative.
– Only about 10% to 20% of carcinomas of the head of
the pancreas are resectable and potentially curable at
surgery
67
 Surgery
• Neoplasms of the head of
the pancreas is a
pancreaticoduodenectomy
(Whipple procedure).

68
 Pancreaticoduodenectomy (whipples procedure)

• For carcinoma – head of pancreas

• Includes resection of the distal stomach, gallbladder, distal
common bile duct, head of the pancreas, and duodenum
• Gastrointestinal continuity is restored by anastomosing the
common bile duct and the remaining pancreas to the
jejunum proximal to the gastrojejunostomy. Some surgeons
anastomose the remaining pancreas to the back of the
stomach because they believe it is safer and decreases the
potential for pancreatic fistula formation. 69
 Whipple procedure
• The gastrojejunostomy is performed to allow alkaline bile and
pancreatic juices to enter the jejunum before acidic gastric
secretions.This step decreases the potential for ulceration at
the gastrojejunostomy.
• The distal gastrojejunostomy also reduces reflux of intestinal
contents into the bile duct and pancreas. The risk of
ulceration has been greatly reduced by the use of
postoperative prophylactic acid antisecretory agents such as
H2 -receptor antagonists and proton pump inhibitors
70
Classic pancreaticoduodenectomy (whipples)

71
Pylorus preserving pancreaticododenectomy (whipples)

• This procedure preserves the entire stomach, including the pylorus, and a small cuff of
proximal duodenum. It has the advantage of maintaining a normal gastric reservoir and
environment, thereby avoiding potential nutritional problems associated with the
classic Whipple procedure such as weight loss, dumping syndrome, diarrhea, and
anastomotic ulcer at the gastrojejunostomy site.
• This procedure requires less time and is technically easier to perform. Delayed gastric
emptying that may occur following this operation generally resolves over time with
conservative treatment (gastric decompression, parenteral or enteral nutrition, and
prokinetic agents).
• Erythromycin, a motilin agonist, also has been prescribed to improve gastric emptying
after surgery.
• Concern is limited surgical margins and inadequate removal of lymph nodes in the area
draining the cancer, which may compromise cure. 72
Pylorus preserving pancreaticododenectomy (whipples)

73
 Total pancreatectomy
• Total pancreatectomy may be
performed for tumor
involving the entire gland,
tumor that extends across the
neck and body of the gland,
or when the pancreatic
remnant is too soft and friable
to allow a safe pancreatic-
enteric anastomosis.
74
 Total pancreatectomy
• An en bloc resection of the distal stomach, duodenum,
gallbladder, and distal common bile duct, along with the
entire pancreas, spleen, and a wide margin of
peripancreatic tissue including lymph nodes.
• It eliminates the problem of residual tumor at the
margins of the pancreas, tumor spillage when the
pancreas is divided, and pancreatic fistula.
• No change in morbidity and mortality 75
 Total pancreatectomy
• Individuals who have a total pancreatectomy develop pancreatic
endocrine and exocrine insufficiency and become brittle
diabetics with glucose levels that may be difficult to control.
• Pancreatic enzyme supplementation is necessary for a lifetime.
• Done when there is evidence of tumor throughout the entire
pancreas or when the pancreas is considered to be unsafe for
anastomosis. Reasons for an unsafe anastomosis are that the
pancreas is too soft and friable, or acute edematous pancreatitis
develops during surgery after manipulation of the gland.
76
Total pancreaticoduodenectomy

77
 Radical pancreatectomy
• An extended or radical pancreaticoduodenectomy
has also been performed as an alternative or
modification of the original regional pancreatectomy.

78
 Extended pancreaticoduodenectomy
• Pancreaticoduodenectomy or sometimes a total
pancreatectomy, along with an extensive retroperitoneal
lymph node and soft tissue resection.
• Resection of the superior mesenteric vein, portal vein, or
superior mesenteric artery may also be performed.
• Done because lymph node involvement is an important
prognostic factor in individuals with carcinoma of the
head of the pancreas.
79
Extended or radical pancreatoduodenectomy

80
 Regional pancreatectomy

• Regional pancreatectomy
has been found to have
higher morbidity and
mortality rates, with no
improvement in survival
over the standard
pancreaticoduodenectomy

81
 Distal pancreatectomy
• If tumors of the body and tail of the pancreas are detected
early - A distal pancreatectomy with a splenectomy is
performed in these patients. The prognosis is poor, with
few patients surviving for more than 2 years.
• Most individuals with adenocarcinomas of the body or tail
of the pancreas are unresectable and survive for only a
short period. Exploratory laproscopy and FNAB to
diagnose: which is necessary
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Distal pancreatectomy

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84
 Pretreatment considerations
• Emesis risk
• Prophylaxis for infusion reactions (oxaliplatin)
• Vesicant / irritant property(Oxaliplatin and FU are irritants)
• Infection prophylaxis
• Dose adjustment for baseline liver or renal dysfunction
• Maneuver to prevent neuro toxicity
• Cardiac issues
85
 Monitoring parameters
• CBC with differential and platelet count prior to each treatment.
• Electrolytes (especially potassium and magnesium) and liver and renal function prior
to each treatment.
• Irinotecan is associated with early and late diarrhea, both of which may be severe. For
patients who develop abdominal cramping and/or diarrhea within 24 hours of
receiving irinotecan, administer atropine (0.3 to 0.6 mg IV) and premedicate with
atropine during later cycles.
• Patients must be instructed in the early use of loperamide for late diarrhea. Patients
who develop diarrhea should be closely monitored and supportive care measures (eg,
fluid and electrolyte replacement, loperamide, antibiotics, etc) should be provided as
needed.
• Assess changes in neurologic function prior to each treatment.
86
•
Prognosis

87
 Reference
• Connie Henke Yarbro, Debra Wujcik, Barbara Holmes
Global. Cancer nursing. Principles and practice. 7th edition,
Johnes and Bartlett publishers. Massachusetts. 2011
• Jim Cassedy. Donald Bissett. Roy A. J. Spence OBE.
Miranda Payne. Gareth Morris-Stif. Oxford handbook of
oncology. 4th edition. Oxford university press. 2015
• Holland-Fri. cancer medicine. 9th edition. Wiley Blackwell.
2017
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