Pancreatic carcinoma- types/presentation/management

2. CARCINOMA PANCREAS
PRESENTED by---Dr.JYOTINDRA SINGH
MBBS,MS (Gen Surgery) ,M.Ch( Cardiac Surgery)

3. SEMINAR PLAN
 INTRODUCTION
 ANATOMY
 SURGICAL ANATOMY
 PANCREATIC TUMOURS
 MODE OF PRESENTATION
 PRE OPERATIVE WORK UP
 VARIOUS SURGERIES/ SURGICAL VIDEOS
 RECENT UPDATES
 VARIOUS STUDIES/TRIALS
 TAKE HOME MESSAGE

4. INTRODUCTION
Carcinoma of the exocrine pancreas accounts for
over 90 % of pancreatic tumors and remains an
unreduced oncologic challenge.
By definition,periampullary cancers arise within
2 cm of the major papilla in the duodenum.
Pancreatic adenocarcinoma accounts for 80% tumours
Most common GI malignancy after Ca colon
Least 5 years survival rate of 3 %.
Incidence rate is virtually identical to the
mortality rate

5. INTRODUCTION
Pancreatic cancer is a biologically aggressive tumor
from the onset .
Clinically queisent for a long time and hence present in
advanced state.
Only 20% of pancreatic cancers are operable for cure
Only 10% - 15% of pancreatic cancers are alive 12
months after the diagnosis
Average life of metastatic pancreatic cancer is 6 months

6. ANATOMY AND RELATION OF PANCREAS
Pancreas is a long retroperitoneal organ 15 to 20 cm in
length.
Weighs about 80 gms ,lies against L1 & L2 Vertebra.
It is arbitarily divided into HEAD,NECK BODY & TAIL
Head lies within the concavity of duodenum against second
lumbar vertebra and body overlies the first lumbar vertebra

7. Cuddles L Kidney
Tickles Spleen
Cradles Aorta
Opposes IVC
Dallies with
R Renal
Pedicle
Hugs the duodenum
Wraps the SMV
Hides behind peritoneum
Durman

8. BLOOD SUPPLY
PANCREATIC BRANCHES OF SPLENIC
ARTERY
SUPERIOR PANCREATICODUODENAL
ARTERY
INFERIOR PANCREATICODUODENAL
ARTERY
VENOUS DRAINAGE IS INTO SPLENIC
VEIN ,SUPERIOR MESENTERIC & PORTAL
VEIN

13. VENOUS DRAINAGE

14. PANCREATIC DUCT
Main duct of Pancreas ( DUCT OF WIRSUNG )-
begins in tail of pancreas and runs on the posterior surface
of the body and head of pancreas.
HERRING BONE PATTERN
DIAMETER OF PANCREATIC DUCT
TAIL - 1 to 2 mm BODY - 2 to 3 mm
HEAD - 3 to 4 mm
Upto 5-6 mm of dilatation in a 70 yr old person is considered
normal.
Joins the bile duct in the wall of second part of duodenum to
form hepatopancreatic ampulla ( of Vater )
DUCT OF SANTORINI- begins in lower part of the head and
opens in to duodenum at minor duodenal papilla ( 6-8 cm from

15. Duct of Wirsung
Duct of
Wirsung

16. Duct of Wirsung &Duct of Santorini

18. Incidence

19. INCIDENCE
Annual incidence 10 new cases per 100000 population
Lowest incidence – India and Middle East
Incidence increases steadily with age – with 80 % over 6th
decade of life
Male: Female ratio – 2:1
Pre and post menopausal women ratio is 2: 1

21. ETIOLOGY & RISK FACTORS
HEREDITY - CANCER FAMILY SYNDROMES
CIGARETTE SMOKING
DIET – high intake of animal fat or meat.
OCCUPATIONAL
EXPOSURE TO RADIATIONS
GASTRIC SURGERIES
DIABETES MELLITUS/PERNICIOUS ANAEMIA/ CHRONIC
PANCREATITIS

22. Etiology – hereditary factors
 Most of the pancreatic cancers are sporadic
 7.8% of pancreatic cancer patients give a positive
family history
 Hereditary syndromes
 HNPCC
 PZ syndrome
 Ataxia Telangiectasia
 Hereditary Pancreatitis
 Familial Atypical Mole Melanoma syndrome
 FAP

23. Etiology – Diabetes – Is it a cause or effect
 Several studies have shown an increased
incidence of pancreatic cancer in diabetics
 Diabetes is considered as an early symptom of
pancreatic cancer rather than being a cause
 The diabetes of Pancreatic cancer is due to islet
cell dysfunction (Islet Amyloid polypeptide)
and not due to the destruction of the gland

24. Etiology – Chronic
Pancreatitis- Is it premalignant
 The incidence of pancreatic cancer in
various entities of chronic Pancreatitis are
as follows
 Hereditary Pancreatitis 25%
 Tropical Pancreatitis 10%
 Alcoholic Pancreatitis 5%

26. Oncogenes in pancreatic cancer
 K ras
 P 53
 P 16
 DPC 4

27. The tumours of the pancreas can be -
A. Non-Endocrineneoplasms
B. Endocrineneoplasms
TUMOURS OF THE PANCREAS

28. ENDOCRINE NEOPLASMS:
These are less common than non-endocrine
tumours and generally benign and sometimes
multiple. They includes:
 Insulinoma
 Glucogonomas
 Others:
- Gastrinomas
- Somatostatatinomas
- Vipomas (Vasoactive Intestinal
Polypeptide)
common

29. PATHOLOGICAL ( WHO ) CLASSIFICATION
PRIMARY ( 93% )
METASTATIC ( 7 % )
A ) DUCT CELL ORIGIN – 90%
1. DUCT CELL ADENOCARCINOMA – 75 %
2. MUCINOUS CARCINOMA
3. CYSTADENOCARCINOMA
B ) ACINAR CELL ORIGIN – 1%
1. ACINAR CELL CARCINOMA
2. CYSTADENOCARCINOMA ( Acinar cell )

30. PATHOLOGICAL ( WHO ) CLASSIFICATION
Uncertain Histogenesis ( 9% )
1. PANCREATOBLASTOMA
2. PAPILLARY AND CYSTIC NEOPLASM
3. MIXED TUMOURS
CONNECTIVE TISSUE ORIGIN ( 1 % )
1. MALIGNANT FIBROUS HISTOCYTOMA
2. OSTEOGENIC SARCOMA
3. LEIOMYOSARCOMA
4. HEMANGIO PERICYTOMA

31. Carcinoma - Pancreas
 A, A cross-section through the head of the pancreas and
adjacent common bile duct showing both an ill-defined
mass in the pancreatic substance (arrowheads) and the
green discoloration of the duct resulting from total
obstruction of bile flow.
 B, Poorly formed glands are present in densely fibrotic
stroma within the pancreatic substance; there are some
inflammatory cells

32. HISTOPATH

33. Case

34. Case -1

35. CLINICAL MANIFESTATIONS
It is unfortunate that malignant pancreatic cancers are
asymptomatic until local or systemic complication develop.
1. Obstruction to bile duct – Jaundice and pruritus
2. Obstruction to duodenum /stomach- Gastric outlet obstruction
3. Ulceration- Gastro intestinal haemorrhage
4. Infiltration of peripancreatic nerve roots produce pain
The onset of symptoms are insidious and progressive
Abdominal pain is usually post prandial and in epigastrium
Pain in upper back denotes retroperitoneal extension

36. Pancreatic Tumors in the Head
Tumors in the head may compress biliary ducts or pancreatic
ducts

37. SYMPTOMS AND SIGNS
CARCINOMA HEAD OF PANCREAS
1. WEIGHT LOSS – AVERAGING ABOUT 40%
2. OBSTRUCTIVE JAUNDICE-
3. DEEP SEATED ABDOMINAL PAIN
4. NON TENDER PALPABLE GALL BLADDER
5. CHOLANGITIS OCCURS IN 10 % OF PATIENTS

38. PANCREATIC TUMOURS IN TAIL

39. CARCI NOMA OF BODY AND TAIL
WEIGHT LOSS
DEEP SEATED PAIN
JAUNDICE- < 10 % OF PATIENT
SUDDEN ONSET OF DIABETES MELLITUS-25% OF
PATIENT
MIGRATORY THROMBOPHLEBITIS- OCCURS IN ABOUT
10% PATIENT

40. SYMPTOMS AND SIGNS
CARCINOMA OF AMPULLA OF VATER
1. Pain occurs less frequently – usually its colicky
2. Jaundice is often intermittent
3. Chills and fever – due to associated cholangitis

42. Periampullary carcinoma
 Any tumor within 2
cm from the duodenal
papilla is defined as
periampullary cancer.
Ca terminal PD
Distal CBD
Ampullary tumor
Duodenal tumor

43. Periampullary carcinoma
 The individual components of peri
ampullary tumors differ in their
prognosis
 Duodenal carcinoma
 Ampullary carcinoma
 CBD growth
 Pancreatic ca

44. Site
 Pancreatic head-2/3rd
 Remaining part 1/3rd

45. Clinical presentation
 Mid epigastric pain radiating to back
 Weight loss
 Fatigue
 Anorexia
 Symptoms are vague and hence the delayed
presentation

46. Clinical presentation
 Painless progressive jaundice 50-60%
 Pruritus
 Staetorrhea
 Malabsorption
 New onset of Diabetes in older patients

47. Clinical presentation
 Jaundice is a late presentation in uncinate
process growth
 Severe back pain indicate irresectablity and an
omnious sign

48. Physical findings
 Physical findings are rare in pancreatic cancers
and their presence usually indicate advanced
stage
 Resectablity is better when patient presents
with the classical painless progressive jaundice

49. Physical findings
 Palpable GB (Courvoisier’s law)
 Hepatomegaly
 Icterus
 Scratch marks
 Ascites
 Mass
 Virchow’s node
 Pelvic deposit
 Trousseau’s sign

50. Courvoisier Law

51. Assessment
 Confirm the diagnosis
 Stage the disease
 Assess the operability
 General assessment for surgery

52. Have A Great Day…

53. Investigation
 CBC
 LFT
 RFT
 Coagulation profile
 CXR
 ECG
 Echo

54. USG
 Cheap
 Level of obstruction
 Cause of obstruction
 Liver metastasis
 Ascites

55. USG
 Operator dependent
 Miss small metastasis
 Cannot assess operability

56. CT
 “Pancreatic protocol CT” is the gold
standard of investigation to stage the
disease and assess the operability
 Triple phase CT
 Closer cuts
 Water used as an intraluminal contrast
 Helical or multislice

57. CT
 Focal or diffuse mass lesion which is hypo
dense (low attenuation) and hypo vascular
(poor contrast enhancement)
 Dilated MPD and CBD

58. Pancreas

62. “Operability is assessed in the office of the
surgeon and not in the Operating room”

63. CT
 Advantages
 Available easily
 Surgeons are familiar with CT
 Excellent in giving details of operability
 Disadvantages
 May miss liver mets less than 1 cm
 Miss peritoneal mets
 Radiation

64. MRI
 Advantages
 No radiation
 Avoids contrast
 Single investigation that gives all the
information needed
 Disadvantages
 Cost & availability
 Surgeons are unfamiliar

65. MRI
 As it stand today CT is as good as MRI
 Probably in the future, MRI is likely to be used
more frequently and may replace CT

66. Role of Biopsy
Not mandatory

67. Role of Biopsy
 Tissue diagnosis is indicated in cases which
are found inoperable by imaging
 Biopsy is indicated when Neoadjuvant
chemotherapy is planned

68. Why not a biopsy
 May upstage the disease
 Complications of biopsy
 Has a very low negative predictive value

69. What biopsy
 Ideally it should be
done under EUS
guidance
 Targeted
 No tumor seeding
 No complications
like fistula

70. ERCP
Double duct sign
Not routinely done in
pancreatic
Cancer
Preop biliary drainage
Atypical lower CBD
obstruction

71. PET
 It is useful in differentiating pancreatic cancer
from chronic Pancreatitis
 Extra pancreatic disease

72. EUS
 Ideal method to evaluate
lower CBD obstruction
 Guided FNAC
 Vascular invasion
 EUS+FNAC= sensitivity of
90% and specificity of 95%

73. Angiography
No longer used

74. Barium studies – only historical
 Pad sign – widening of C loop
 Reverse 3 sign or Frostberg sign

75. Tumor markers
 CA 19-9
 CEA
 CA 125
 CA 50
 SPAN-1
 DUPAN-2

76. Staging
 TX primary tumor cannot be assessed
 T0 no evidence of primary tumor
 T1 confined to pancreas
T1a less than 2 cm
T1b more than 2 cm
 T 2 tumor extend to involve the bile
duct, duodenum and peripancreatic
tissue
 T3 involvement of stomach, spleen, colon,
vessels

77. Staging
 NX nodes cannot
be assessed
 N0 no evidence
of nodes
 N1 regional
nodes present
 MX cannot be
assessed
 M0 no metastasis
 M1 distant
metastasis

78. Stage grouping
 Stage I
 T1 N0 M0
 T2 N0 M0
 Stage II
 T3 N0 M0
 Stage III
 Any T N1 M0
 Stage IV
 Any T Any N M1

79. Prognosis
 Tumor size
 Node positivity
 Type of resection (R0 or R1)

80. Operability
 Ca head 20%
 Ca body&tail 3%
 Ampullary 80%

93. Preop preparation
 Vitamin K
 Hydration
 Correction of electrolytes
 Preop nutrition

94. PANCREATIC SURGERIES
 WHIPPLES OPERATION – OPEN / LAPROSCOPIC/ ROBOTIC
 PYLORUS PRESERVING PANCREATICODUODENECTOMY
 DUODENUM PRESERVING RESECTION OF HEAD OF
PANCREAS
 SUBTOTAL PANCREATECTOMY/TOTAL
PANCREATECTOMY
 ENUCLEATION
 LAPROSCOPIC STAGING
 LAPROSCOPIC PALLIATIVE BYPASS
 PAIN –PALLIATIVE SURGERIES
 PANCREATIC TRANSPLANTATION
 ROBOTIC SURGERIES

95. Pancreaticoduodenectomy
Pancreaticoduodenectomy offers the
surgeon the only chance to cure a
patient with carcinoma of the head
of the pancreas and periampullary
region

96. “Pancreaticoduodenecomy is the
Cadillac of operations”
but
“It is not a Cadillac that he ( surgeon)
is driving but a formula 1 Ferrari”

97. Attitude of the surgeon towards
pancreatic cancer
 Nihilistic
 Activist
 Realist

98. Sir Allen O Whipple

99. Pancreaticoduodenectomy
 Walter Kausch was the first to successfully
perform pancreaticoduodenectomy in Berlin
1912
 Allen Whipple popularized the operation in US
in 1935
 Now this operation is called Kausch-Whipple
procedure

100. Pancreaticoduodenectomy
 This operation suffered a very bad reputation
due to the operative mortality of over 25% and
morbidity of over 50%
 Some authorities have even suggested that, this
operation be abandoned

101. Pancreaticoduodenectomy –
consecutive series without mortality
J Howard-41
cases
1968
J Cameron
145 cases
1993
Aranha
152 cases
2003
Michael Trede- 118 cases 1990

102. OPERATIVE STEPS
Incision- transverse subcostal / midline
Exploration/mobilization- kocherization
Cholecystectomy/dissection of hepatoduodenal ligament
Mobilization of pancreatic neck
Partial gastrectomy
Division of pancreas
Dissection of retropancreatic vessels
Division of jejunum
Reconstruction

103. Whipple – 6 well defined operative steps
1. Cattle Brasch maneuver
2. Extended Kocherization
3. Portal Dissection, division
of Bile duct
4. Division of Stomach
5. Division of Jejunum
6. Pancreatic Neck
transection

104. Reconstruction after Classical Whipple’s operation
Hepaticojejunostomy
Gastrojejunostomy
Pancreaticojejunostomy

105. PANCREATICODUODENECYTOMY- PYLORUS
PRESERVATIION
Incision- transverse subcostal / midline
Exploration/mobilization- kocherization
Cholecystectomy/division of the bile duct
Exposure of superior mesenteric vein
Division of duodenum
Division of gastroduodenal artery
Division of pancreatic neck
Dissection of uncinate process
Resected specimen-gallbladder,distal bile duct,2nd 3rd &4th part
of duodenum,proximal jejunum and head ,neck & uncinate
portion of pancreas
Reconstruction

106. Pylorus preserving Pancreaticoduodenectomy

107. Reconstruction after PPPD

108. Duodenum- preserving resection of the head of pancreas
Incision- transverse subcostal / midline
Exploration/mobilization- kocherization
Exposure of the pancreas
Dissection of the neck of pancreas
Resection along the CBD
Pancreatic remnant
Reconstruction
Bile duct anastomosis
Stenosis of the pancreatic duct

109. TOTAL PANCREATECTOMY
This involves the en bloc resection of
The whole of pancreas
The spleen
Distal half of stomach
Duodenum
Proximal 10 cm of jejunum
Gall bladder
Cystic and common bile duct

110. TOTAL PANCREATECTOMY
Incision- Transverse muscle-cuting incision
Exploration/mobilization- kocherization
Mobilization of duodenum/head of pancreas
Exposure of body and tail of pancreas
Dissection of the vessels- hepatic artery is traced
Mobilization of spleen and pancreas
Limited gastrectomy/pylorus preserving resection
Reconstruction – choledochojejunostomy/bowel anastomosis

111. Total Pancreatectomy Reconstruction

112. REGIONAL PANCREATECTOMY
TYPE O – TOTAL PANCREATECTOMY
TYPE I -- RESECTION OF PORTAL VEIN SEGMENT
TYPE II a – Type I plus resection of proximal SMA
TYPE II b– Type I plus resection of celiac axis/hepatic artery
TYPE II c-- Type I plus resection of celiac axis & SMA

113. PANCREATIC ENDOCRINE DISEASE
Principles- whether tumour functioning or non-functioning
tumour benign or malignant
sporadic occurrence or part of MEN-I
Operative steps
IOUS- localization of islet cell tumours
delineation of proximity of tumour to pancreatic duct
demonstration of multiple tumours as part of MEN-I
ENUCLEATION- CUSA
DISTAL PANCRETECTOMY

114. PANCREATIC CANCER- LAPROSCOPIC STAGING
7.5 Mhz linear array transducer
Port-infraumbilical and right flank
Search for serosal deposit
Lesions on liver sampled/GB visualised
Transducer placed on porta hepatis
Look for dilataion of pancreatic duct
Position of tumour relative to pancreatic duct/portal vein
Lymphnodes more than 10 mm -significant

115. PANCREATIC TRANSPLANTATION
Suitable donors between 20 and 50 yrs
Pancreatic blood flow to be maintained- warm ischemia
Gland should be perfused with a cold preservation fluid-
hypertonic citrate solution
Pancreas removed avoiding damage to the gland– injection of
collagenase enzyme into the pancreatic duct under pressure.
Pancreas transported to processing centre-within four hours-
cold ischemia

116. RECENT UPDATES/CHANGING
APPROACH
 Preop biliary drainage
 Preop imaging, CT vs. MR vs. EUS
 Role of biopsy
 Diagnostic laparoscopy
 PJ vs. PG
 Classical Whipple vs. PPPD
 Vascular resections
 Extended lymphadenectomy
 Drainage

117. Controversies
 Role of octreotide
 Order of reconstruction
 Adjuvant therapy
 Palliative resections
 Palliative bypass

118. Preop biliary drainage
 For
 Reduce the mortality and morbidity of surgery
 Improves the liver function
 Reduces the bleeding
 Improves the nutrition
 Buys time

119. Preop biliary drainage
 Against
 Does not reduce the mortality and morbidity
 More infectious complications
 It takes 6 weeks for the improvement of hepatic
microsomal functions
 Makes the duct small and fibrotic – adds to
technical difficulty

120. Preop biliary drainage -
consensus
 Indicated
 Cholangitis
 Impending renal failure
 Surgery is likely to be delayed
 Bilirubin of more than 20 mg%
 Nutritionally very poor
 Neoadjuvant chemotherapy is planned

121. Preop biliary drainage -
consensus
Routine preop biliary
drainage is not
recommended and there is
no evidence to support it

122. Diagnostic laparoscopy
 30% of patients found operable by imaging are
found to have small liver mets or peritoneal
mets, on diagnostic laparoscopy
 Warshaw et al

123. Diagnostic laparoscopy
With the advent of high quality
CT, Helical and Multislice,
occult peritoneal and liver
metastasis are documented in
only 10% in some series

124. PJ vs. PG
 Merits of PG
 Stomach is in proximity to pancreatic stump
 Better vascularity
 Acid in stomach inactivates enzymes
 Absence of enterokinase
 Even if leak occurs the enzymes are not activated
and hence fatal bleeding do not occur

125. PJ vs. PG
 Two randomized controlled trials fail to
demonstrate superiority of one method over
the other
 Dilated duct, texture of pancreas and surgeon’s
experience are more important than the viscera
used for drainage

126. Classical Vs PPPD
 PPPD is oncologically as radical as classical
whipple except for tumors encroaching on the
D1 and pylorus
 RCTs have failed to show any significant
benefit of PPPD over classical whipple

127. Vascular
involvement
 Resection of SMV is
accepted provide it
enables to perform R0
resections
 Involvement of SMA is
a contraindication for
resection

128. Extended
lymphadenectomy
 Studies have shown
that extended
lymphadenectomies
can be done with
acceptable morbidity
 Extended
lymphadenectomy do
not improve the
survival

129. Octreotide
 There have been totally six RCT across the
Atlantic, three from Europe ( Buchler et al, Beger
et al , Pedrazolli et al) and three from US ( Yeo et
al, Sarr et al and Lowy et al)
 The European trials favor use of octreotide and the
American trials do not favor
 Recently published meta analysis of these trials
have shown a benefit f octreotide in reducing the
complications

130. Adjuvant therapy
 Chemotherapy
 Radiotherapy
 Chemo radiotherapy

131. Adjuvant therapy
 The ESPAC trial has shown that the only
factor that positively affect the long term
survival is administration of adjuvant
chemotherapy
 Ideally all patients undergoing surgery for
cancer pancreas should be given adjuvant
chemotherapy

132. Palliation
 Jaundice (pruritus)
 Duodenal obstruction
 Pain
 Bleeding

133. Palliative resections – Is it
acceptable
 Palliative resections and palliative bypass has
the same survival
 Hence palliative resections are not accepted

134. Palliative resections
 The series from John Hopkins has shown
survival benefits in R1 and few cases of R2
Whipple

135. Palliative resections
 The consensus is that one should not willfully
perform a palliative resection, and the aim of
the surgeon should always be a R0 resection

136. Palliative bypass
 Operative palliation is not the standard of care
for a patient with inoperable Ca pancreas with
obstructive jaundice
 Endoscopic palliation is the treatment of
choice

137. Palliative bypass
 A selected group of patients with good
performance status
 Patients who are found to be inoperable on
the table
 Endoscopy facilities not available or not
possible for technical reasons

138. Palliative bypass
 Options of by-pass
 Choledochojejunostomy ( Loop or Roux en Y)
 Cholecystojejunostomy
 Hepaticojejunostomy

139. Palliative bypass-prophylactic GJ
 The current recommendation is to perform a
prophylactic GJ along with the biliary bypass
even if there is no gastric outlet obstruction

140. Laparoscopy in palliation
 Depending on the expertise of the surgeon,
procedures can be done with laparoscopy

141. Palliation of pain
 Neurolysis ( 20 ml of absolute alcohol injected
on either side of the celiac axis to destroy the
celiac ganglia)
 At laparotomy
 CT guided
 EUS guided
 Thoracoscopic splanchnectomy

142. ROBOTIC SURGERIES

143. TAKE HOME MESSAGE
Survival rate of patients after the establishment of diagnosis is
very dismal.
Surgical resection if possible ,is the only curative treatment but
it can play a role only in very small percentage of cases
Post surgery five year survival rate is least in pancreatic
malignancy.tive
Newer approaches are less radical and more effective
Concept of regional pancreatectomy has increased poet op
survival period
Survival can be further increased by- early detection
- avidance of surgery in presence of metastasis
- operative technique with avoidance of local spillage
- avoiding preoperative blood transfusion.

144. REFERENCES
 BAILEY & LOVE’S- SHORT PRACTISE OF
SURGERY
 SABISTON TEXTBOOK OF SURGERY
 MASTERY OF SURGERY by Fischer
 OXFORD TEXTBOOKOF SURGERY
 MAINGOTS ABDOMINAL OPERATION
 MAYO CLINIC GI SURGERY
 CANCER PRINCIPLES- De Vita
 SURGERY BY CORSON
 RECENT ADVANCES- WOLTERS KLUWER
 RECENT ADVANCES- RSG

145. Questions?
