Exocrine and Endocrine Tumors Classification , Assesment of Resectability and Preop Evaluation

1. Pancreatic Tumor Classification
Preoperative evaluation in
Whipple’s Procedure
Dr.Bhavin Vadodariya
DNB Resident Doctor
Department of Surgical Oncology
Apollo CBCC Cancer Care
Apollo Hospital,Ahmedabad
Date- 06/01/2018

2.  The most unforgiving organ in the human body.

3. Outline
•Classification
PDAC
Cystic neoplams
SPN
Endocrine Tumor
•Preoperative Management
•Assement of resectability
•Management of Obstructive jaundice

4. Neoplasms of the pancreas
 Solid tumors (AdenoCarcinomas)
 Cystic Neoplasms
 Endocrine tumors

5. Pancreatic adeno carcinoma
 5-year survival rate of only 6%.
 9th most common cancer in the US , but 4th in terms
of cancer deaths.
 74% of patients die within the first yearafter
diagnosis.
 Common age >60 years, median age is 72years.

6.  Incidence is about 8 to 9 cases per 1,00,000
 Incidence is lowest in India and parts of middle
east 8.1 and 7.0 per 1,00,000 in men and
women respectively

7. Pathology
 Pancreatic cancer probably arises through a stepwise
progression of cellular changes.
 From Pancreatic intra epithelial neoplasia to invasive adeno
carcinoma.
 75% are ductal adenocarcinoma
 Uncommon varieties include Adeno squamous and Acinar cell
carcinoma.

8. Adenosquamous carcinoma -
It has both glandular and squamous differentiation.
The biologic behaviour similar to typical ductal
adenocarcinoma.
Acinar cell carcinoma - presents as a large tumour,
often 10 cm in diameter or more, the prognosis of patients
with these tumours may be better than with ductal cancer.

9. Pancreatic Intraepithelial
Neoplasia(PanIN)

•Pre cursor lesions for invasive carcinoma
•Three stages of pancreatic intraepithelial neoplasia have
been defined. From PanIN 1 – PanIN 3
•With progressive cellular atypia and architectural
disarray.

11. Location of the tumour
 About two-thirds of pancreatic adenocarcinomas
arise within the head or uncinate process of the
pancreas
 15% are in thebody
 10% in thetail,
 remaining tumours demonstrating diffuse
involvement of the gland.

12.  Tumours in the pancreatic body and tail are generally
larger at the time of diagnosis, and therefore, less
commonly resectable.
 Tumours in the head of the pancreas are typically
diagnosed earlier because they cause obstructive
jaundice.

13. Cystic Neoplasms of Pancreas

14. Pathological classification of cystic
neoplasms of the pancreas: The who
international classification.
 Serous cystic neoplasm (SCN)
 Mucinous cystic neoplasm (MCN)
 Intra-ductal papillary mucinous neoplasm
(IPMN)

15. Serous cystic neoplasm (SCN)
 Microcystic adenoma
 Oligocystic adenoma

16. Mucinous cystic neoplasm (MCN)
Mucinous cystadenoma
Mucinous cystic tumour–borderline
Mucinous cystadenocarcinoma
Non-invasive (carcinoma in situ)
Invasive

17. Intra-ductal papillary mucinous
neoplasm (IPMN)
 Adenoma/low-grade dysplasia
 Borderline/moderate-grade dysplasia
 Carcinoma in situ
 Invasive carcinoma

18. SEROUS CYSTIC NEOPLASM
 First described by Comagno and Oertel in 1978 as
microcystic and glycogen rich and they distinguished
these lesions from mucinous cysts.

19. PATHOLOGY
 Cell of origin is centroacinar cell.
 Soft mass which includes numerous small cysts filled
with clear serous fluid arranged in a characteristic
honeycomb-like pattern.
 unique central calcification give rise to charecterstic
central sunburst,radial or stellate scar pattern on CT.

20.  <10 % are serous oligocystic ( macrocystic )SCNhave
fewer cysts, usually >2cm but histopathologic
appearance is similar to that of microcystic.
 Histologically they are have bland cuboidal epithelial
lining without nuclear pleomorphism or mitoses.
 Syndromic association betweenVHL

21.  EUS-FNA and analysis of fluid – SCN low amylaseand
viscosity.
 CEA < 5ng/ml, CA 19-9 < 37U/L, excludes MCN and
IPMN.

22. MUCINOUS CYSTIC NEOPLASMS
 They are mucin secreating cystic tumours that lack
communication with the pancreatic duct and contain
mucin secreting columnar epithelium.
 Grossly, individual cysts are typically greater than
2cm and the tumour mass can be as large as
25cm.these tumours are round with smooth surface
and fibrous pseudocapsule.

23.  MCNs are generally contain less than 6 cysts and are
spherical in shape.
 MCNs are typically located in body and tail ( 95 %
).peripheral eggshell like eccentric calcification occur in 15%
of cases and are considered pathognomonic.
 Ovarian like stroma surrounding the columnar epitheliumis
also pathognomonic and it is the presumed reason that are
almost exclusively seen in females( >95% ).

24.  MCNs exhibit characteristics of an adenoma-
carcinoma - sequence

25. INTRADUCTAL PAPILLARY MUCINOUS
NEOPLASM
 IPMNs constitute 15-30% of allcysticlesions.
 They are intraductal proliferation of neoplastic
mucinous cells leading to dilatation of main panreatic
duct or branch ducts.

26.  WHO classification
1. Adenoma
2. Borderline
3. Ca in situ

27. Morphology - IPMN
 main duct type
 branch duct type
 combined type

28. Histology
 Gastric foveolar type – Tall columnar cells, mucin,
scattered Goblet cells – Common in branch type.
 Villous intestinal type- Resemble colonic villous
adenoma- Common in Main duct type.
 Pancreato biliary – lined by cuboidalcells

29. Extra pancreatic malignancies in
patients with IPMN
 Colorectal adenomas andcarcinopmas
 Barrets mucosa and gastriccarcinoma

30. Analysis of the Cystic Fluid
 Differential Diagnosis of Pancreatic Cystic Neoplasms Based on
Analysis of Intracystic Fluid
Cystic Lesion Amylase CEA Viscosity Mucin Stain Cytology
 SCN ↓ ↓ ↓ Negative Glycogen rich
 MCN ↓ ↑↑↑ ↑ Positive Mucinous
 IPMN
 Pseudocyst
↑
↑↑↑
↑↑↑
↑ ↓
↑ Positive
Negative
Mucinous
Inflammatory

33. Solid Pseudopapillary Tumor
(Papillary Cystic Cancer Or Frantz Tumor)

34. • Approximately 90% of solid pseudopapillary tumor
harbor APC/beta-catenin mutation
• Typically occur in women in the second or third
decade of life

35. Regarded as low grade malignant potential tumor.
Pathology
• Lesions may be large, encapsulated, evenly
distributedthroughout the pancreas.
• Strongly positive for beta-catenin, progesterone
receptors, vimentin, CD-10 and CD-56Q.

36. It can mimic the histologic appearance of NET but lacks
the nuclear features of NET and lacks the
neuroendocerine markers such
as chromagranin and synaptophysin.

37. Pancreatic neuro endocrine tumours

38. PNET
 Rare ,annual incidence of approximately 5 cases per
1,000,000 population.
 Functioning and Non functioning
 Sporadically or as a part ofsyndromes.

39. Syndromic pNETS
 10% are associated with an underlying genetic syndrome
(MEN1) and type IV (MEN4) –pNETS in 80-100% of patients
 Small, multifocal and microscopic
 Gastrinomas (>80% duodenal) develop in 54% of MEN-1 patients,
insulinomas in 18% and glucagonomas, VIPomas, somatostatinomas in <5%
 Von Hippel-Lindau disease (VHL),-10% patients develop pNETS
 Neurofibromatosis type I (NF1), tuberous sclerosis complex (TSC)

40.  2% of total pancreatic mass areislets
 APUD cells – 4 cell types, α, β, γ,δ

42. Insulinoma
 Most common 60%
 Origin- β cells almost universally
within the pancreas (1/3head –
1/3 body – 1/3 tail)
 F>M
 90% benign, 10% malignant
 Most solitary, 10% multiple(MEN 1)
 21% MEN 1 – insulinomas
 The median age at diagnosis- 47yrs

43. Gastrinoma /Zollinger-Ellison
Syndrome
 Second most frequent
 1 / 2.5 million
 60% malignant (mets to liver)
 75 % sporadic
 M>F
 Average age -50 years,5 to 10 years earlier in MEN-1
 25 % MEN-1

44. VIPOMA(Verner-Morrison Syndrome)
 0.05-0.2 new cases per million adults
 Third most common neuroendocrine tumor of the pancreas
 Solitary, found in body or tail, usually detected at >3cm size
 2/3 malignant
 Male-to-female ratio in children - 1:1,
in adults. - 1:3

45. Glucagonoma
 Tumor of islet alpha cells
 Mainly body and tail
 1 per 20 million
 Mean age of 55 years (19-84 years).
 W>M
 50% malignant
 5-10 cm at diagnosis

46.  Migratory necrolytic erythema 2/3 cases – aminoacid
and trace element deficiency
 4D syndrome (dermatitis, diabetes, diarrhea, DVT)
 Fasting plasma glucagon >50pmol/ml:Diagnostic

47. Somatostatinoma
 Rare fewer than 100 cases in literature
 70% to 90% of tumours – malignant
 Location – usually head
 Clinical findings – unpredictable
 Diarrhea
 Gallstones – 59 %
 Steatorrhea
 Mild diabetes – 75%

49. Preoperative Evaluation in
Whipple’s Surgery

50. Assessment of Resectability

51. CT Scan for pancreas
 Multi-detector spiral CT and is the single most useful
diagnostic and staging modality.
 It gives information about adjacent vascular
structures such as the portal, superior mesenteric,
and splenic veins, as well as the superior mesenteric
artery (SMA) and celiac axis.

52. Phases of an pancreatic protocol
 Early arterial phase (15-20 s after injection of
contrast)
 Late arterial phase (35-40 s)
 Hepatic or portal venous phase(50-60s)
 Nephrogenic Phase (100s)
 Delayed phase (6-10minutes)

53.  The non contrast phase - pancreatic calcifications, for
localization of the precise levels the post contrast
study.
 The early arterial phase permits evaluation of
pancreatic vasculature without interference from
venous opacification.

54.  The late arterial phase - distinguish pancreatic
neoplasms from adjacent normal pancreatic tissue, to
evaluate hyper-vascular liver metastases
(neuroendocrine tumors of the pancreas).
 The 4th phase portal venous phase - for hypo-
vascular liver metastases

60. Unresectability in CT
 Unresectability is defined on multiphase CT by
involvement of
1. ≥ 180 degrees of the celiac axis
2. hepatic or superior mesenteric artery, enlarged lymph
nodes outside the boundaries of resection
3. ascites, and distant metastases.
 Invasion of the superior mesenteric vein or portal vein is
not in itself a contraindication to resection as long as the
veins are patent. Resection of vein with reconstruction is
possible.

61. CT images
Dilated intrahepatic ducts. Double-duct sign” with dilated common bile duct and
pancreatic ducts. There is a stent in the common bile duct
(S)

62. Pancreas cancer mass with stent through it (arrow).
Superior mesenteric artery (SMA) (A) is adjacent to
tumor.
Tree-dimensional CT vascular reconstruction
Portal and superior mesenteric veins
do not appear involved.

64. ERCP
 ERCP may be of benefit in patients with biliary
obstruction and cholangitis - endoscopic stent can be
placed for decompression.
 With current capabilities of CT and MRI, ERCP is rarely
necessary.

65. Endoscopic retrograde cholangiopancreatogram
(ERCP) of patient with pancreas cancer with abrupt
cut-off of main
pancreatic duct secondary to tumor.
ERCP of patient with pancreas cancer with obstruction
of both main pancreatic duct and common bile duct

66. Completion cholangiogram after endoscopic placement of
stent

67. Indications for pre operative
decompression of biliary system.
 Cachexic patient for nutritionalimprovement.
 In patients withcholangitis
 If plan is non operativemanagement.
If bilirubin is > 12 mg%,
Sepsis, Hepatorenal syndrome,

68. •Surgery is done after 2-3 weeks once bilirubin level
drops down adequately.
•If ERCP is not possible then percutaneous transbiliary
drainage (PTBD) or cholecystostomy using Foley’s or
Malecot’s catheter is done.
•Surgical resection (Whipple’s) is done after 3 weeks.

70. In a large multicenter randomized trial comparing early
surgery vs preoperative biliary drainage followed by
surgery in patients with cancer of the pancreas head,
the rates of serious complications were 39% (37 of 96
patients) in the early surgery group and 74% (75 of 106
patients) in the patients submitted to preoperative
biliary drainage (P ≤ 0.001).

71. A follow-up report from the same trial showed that
there was a significant delay in time to surgery (1 wk vs
5 wk), but no influence on survival rate.
While there was an increase in overall infectious
complications following surgery in the stented group,
the detrimental effects of pre-operative biliary stenting
were likely limited to those with subsequent bacterial
colonization of the biliary tree due to stent placement

72. Tissue diagnosis
 A tissue diagnosis of adenocarcinoma is not
required prior to an attempt at a curative
resection.
 Fibrosis in pancreatic cancer- may miss the
malignant glands, so sensitivity is less.
 Does not change treatment decision in a
planned curative surgery.

73. FNA is required if
1.Patients undergoing neoadjuvant therapy.
2. If the diagnosis of carcinoma is uncertain.
3.In suspected neuroendocrine cancers, lymphomas,
cystic lesions, FNA result may alter the treatment.

74. Medical Management of Obstructive
Jaundice

75. Hydration
•Adequate hydration is important in prevention of
dehydration postoperatively.
•Dehydration is common in obstructive
jaundice.
•Repeated monitoring by doing electrolytes
•Correction of hypoglycaemia and dilutional
hyponatraemia due to water retention; avoiding isotonic
saline infusion

76. Coagulopathy
•Correction of coagulopathy, prevention of renal failure,
infection, hepatic encephalopathy and electrolyte
imbalance
•Injection vitamin K IM 10 mg for 5 days.
•Fresh Frozen plasma—often requires 6 bottles or more
Blood transfusion in case of anaemia.
•Repeated monitoring by doing prothrombin time.
•

77. •Antibiotics like third generation cephalosporins.’
•Often TPN may be required preoperatively which is also
continued postoperatively.’
♦ Pulmonary function study and respiratory physiotherapy to
have adequate postoperative pulmonary function.

78. Role of Mannitol
Patient is prone to develop hepatorenal syndrome
postoperatively, leading into renal failure due to
sludging of the bile salts, due to toxins and sepsis; and
so mannitol should be given intravenously for 3 days
prior to surgery to flush the kidney (200 ml IV twice a
day).

80. Preoperative smoking and alcohol consumption
•For alcohol abusers, 1 month of abstinence before
surgery is beneficial and should be attempted.
•For daily smokers, 1 month of abstinence before surgery
is beneficial.
•For appropriate groups, both should be attempted.

81. Preoperative nutrition
Routine use of preoperative artificial nutrition is not
warranted, but significantly malnourished patients
should be optimized with oral supplements or enteral
nutrition preoperatively

83. Perioperative oral immunonutrition (IN)
The balance of evidence suggests that IN for 5-7 days
perioperatively should be considered because it may
reduce the rate of infectious complications
in patients undergoing major open abdominal surgery.

84. Oral bowel preparation
Extrapolation of data from studies on colonic surgery
and retrospective studies in PD show that MBP has no
proven benefit. MBP should not be used.

87. Preoperative fasting and preoperative treatment
with carbohydrates
•Intake of clear fluids up to 2 h before anaesthesia does not
increase gastric residual volume and is recommended
before elective surgery.
•Intake of solids should be withheld 6 h before anaesthesia.
•Data extrapolation from studies in major surgery
suggests that preoperative oral carbohydrate treatment
should be given in patients without diabetes.

89. Anti-thrombotic prophylaxis
•LMWH reduces the risk of thromboembolic
complications, and administration
should be continued for 4 weeks after hospital discharge.
•Concomitant use of epidural analgesia necessitates close
adherence to safety guidelines.
•Mechanical measures should probably be added for
patients at high risk

91. Antimicrobial prophylaxis and skin preparation
•Antimicrobial prophylaxis prevents surgical-site
infections, and should be used in a single-dose manner
initiated 30-60 min before skin incision.
•Repeated intraoperative doses may be necessary
depending on the half-life of the drug and duration of
procedure.

93. Epidural analgesia
Mid-thoracic epidurals are recommended based on
data from studies on major open abdominal surgery
showing superior pain relief and fewer respiratory
complications compared with intravenous opioids.

94. Thank you