Pancreatic nodules: Topic for residents both exocrine and endocrine nodules facebook: happy friday knight

1. Pancreatic Nodules
Facebook: Happy Friday Knight
Topics for Residents
Thailand

2. ANATOMY

3. • Retroperitoneal organ
• From C-loop to splenic hilum
• 75 – 100 mg
• 15 – 20 cm long
• Anterior to L1 to L2
• Regions: head, neck, body, and tail

4. http://www.anatomy-diagram.info/picture-of-anatomy-of-pancreas-diagram/pancreatic-cancer-anatomy/

5. http://www.buzzle.com/articles/anatomy-of-the-human-pancreas-with-labeled-diagrams.html
In C-loop
Anterior to
portal v. Anterior to splenic vs.
Anterior to
left kidney

6. http://www.abdopain.com/sphincter-of-oddi-dysfunction.html#gallery[pageGallery]/0/

7. https://www.studyblue.com/#recents

8. Brunicardi FC et al. Schwartz’s Principles of Surgery. 10th ed. McGraw-Hill Education, 2015.

9. Brunicardi FC et al. Schwartz’s Principles of Surgery. 10th ed. McGraw-Hill Education, 2015.

10. Brunicardi FC et al. Schwartz’s Principles of Surgery. 10th ed. McGraw-Hill Education, 2015.

11. Brunicardi FC et al. Schwartz’s Principles of Surgery. 10th ed. McGraw-Hill Education, 2015.

12. PHYSIOLOGY

13. • Exocrine pancreas 85%
• Extracellular matrix 10%
• Blood vessels 4%
• Endocrine part 2%

14. Brunicardi FC et al. Schwartz’s Principles of Surgery. 10th ed. McGraw-Hill Education, 2015.

15. Exocrine Pancreas
• Pancreas secretes 500 – 800 ml/day of pancreatic
juice
• Pancreatic juice:
– combination of acinar cells and duct cell secretion
– Colorless, odorless, alkaline, isoosmotic
• Acinar cells: secrete amylase, proteases, lipases
• Centroacinar and intercalated duct cells secrete
water and electrolyte in pancreatic juice

16. Endocrine Pancreas
• Islet of Langerhans
• 5 major cell types:
– Alpha cells: glucagon
– Beta cells: insulin
– Delta cells: somatostatin
– Epsilon: ghrelin
– PP (pancreatic polypeptide): PP

17. Pancreatic Nodules

18. Pancreatic nodule
endocrine exocrine
benign borderline malignant Non-
epithelial
secondary

19. PANCREATIC NEUROENDOCRINE TUMOR

20. • PNETs
• Rare
• Arise from islets of Langerhans
• 2 groups: presence or absence of hormone
function
• Associated with genetic syndromes such as
VHL, MEN – 1, NF – 1, and TSC

21. Jarnagin et al. Blumgart’s Surgery of the Liver, Biliary Tract, and Pancreas. 5th ed. Philadelphia: Elsevier, 2012

22. Jarnagin et al. Blumgart’s Surgery of the Liver, Biliary Tract, and Pancreas. 5th ed. Philadelphia: Elsevier, 2012

23. • Insulinoma
• Gastrinoma
• Glucagonoma
• VIPoma
• somatostatinoma

24. Insulinoma
• Most common functioning PNET
• Most favorable prognosis due to benign in
nature
• Can be sporadic or associated with MEN -1

25. Insulinoma
• Clinical picture:
– Fasting hypoglycemia and neuroglycogenic
symptoms: weakness, sweating, tachycardia,
altered mental status, diplopia, seizures, coma
– Hypoglycemia causes a release of
cathecholamines
– Whipple triad

26. Insulinoma
• Diagnostic criteria
– Fast for <48hr with documented blood glucose <
50 mg/dl
– Relief symptoms after oral glucose intake
– Elevated insulin level ( > 5 to 10 mcU/ml)
– Increase serum proinsulin level (>22 pmol)
– Absence of urinary or plasma sulfonylurea
– Elevated C-peptide level

27. Insulinoma
• Localization:
– Most are solitary benign adenoma
– Less than 1.5 cm
– Most insulinomas are vascular and can be
visualized on arterial phase imaging
– Somatostatin receptor scintigraphy (SRS) is limited

28. Insulinoma
• Treatment:
– Relief symptoms of hypoglycemia
– Insulin antisecretagogues: diazoxide, verapamil,
octreotide, dilantin
– Definitive treatment: resection (enucleation)
– Before resection  exclude familial syndrome
– Most common complication: pancreatic leak
(enucleation more than resection)

29. Insulinoma
• Treatment for MEN – 1 patients:
– Remove only tumor
– Resection not recommend
– Use bimanual palpation or intraoperative US

30. Insulinoma
• Treatment in metastasis:
– resection both primary tumor and metastatic
tumor for palliation of hypoglycemic symptoms:
debulking
– chemoembolization
– RFA
– Liver transplantation
– Streptozotocin, 5-FU, doxorubicin

31. Gastrinoma
• Or Zollinger-Ellison syndrome: gastrin-
producing tumor with acid hypersecretion 
intractable PU
• Second most common
• 60% malignant
• 50% liver, LN, distant metastasis
• 10-year survival approaches 90%

32. Gastrinoma
• Higher suspicion of ZES should be in
– Recurrent PUD
– PUD with diarrhea
– Ulcers in unusual locations: distal duodenum and
jejunum
– Refractory to medical treatment
– With complications: bleeding and perforation
– Young age
– Hyperparathyroidism, pituitary disorders, or a familial
history of endocrinopathies

33. Gastrinoma
Jarnagin et al. Blumgart’s Surgery of the Liver, Biliary Tract, and Pancreas. 5th ed. Philadelphia: Elsevier, 2012

34. Gastrinoma
• Localization
– CT
– US
– MRI
– SRS – effective
– EUS

35. Gastrinoma: Passaro’s Triangle
Brunicardi FC et al. Schwartz’s Principles of Surgery. 10th ed. McGraw-Hill Education, 2015.

36. Gastrinoma: Treatment
• Primary goal:
– Remove primary tumor
– Control acid production
– Prevent malignant progression
• Surgical resection is recommended for
sporadic resectable disease
• Lesions at head: enucleation
• Lesions at body and tail: distal
pancreatectomy

37. Gastrinoma: Treatment
• During surgery, duodenotomy in all patients to
– Enucleate in tumor less than 5 mm
– Full-thickness excision of duodenal wall
• In MEN -1 with ZES: controversial
• Unresectable: highly selective vagotomy
• Debulking is not useful
• ZES with hyperparathyroidism:
parathyroidectomy prior to ZES surgery

38. http://medical-dictionary.thefreedictionary.com/selective+vagotomy

39. Glucagonoma
• Rare
• Frequently large
• 60 – 70% malignant
• Most located in body and tail of pancreas

40. Glucagonoma
• Clinical presentation:
– 4D:
• DM
• Dermatitis (necrolytic migratory erythema – 70%)
• DVT
• depression
– Chronic anemia, stomatitis, weight loss,
generalized weakness

41. Jarnagin et al. Blumgart’s Surgery of the Liver, Biliary Tract, and Pancreas. 5th ed. Philadelphia: Elsevier, 2012

42. Glucagonoma: Treatment
• Assess nutritional status
• Somatostatin analogues
• Spleen-preserving distal pancreatectomy: only
30% achieve
• But both primary and metastatic lesion should
be removed if safe

43. VIPoma
• Vasoactive intestinal peptide (VIP) tumor
• VIP: stimulate secretion of water to pancreatic
juice and bile and inhibit gastric juice
• Rare
• Majority is benign and solitary
• 3 – 5 cm
• WDHA or Verner-Morrison syndrome: watery
diarrhea, hypokalemia, achlorhydria

44. VIPoma: Treatment
• resection
• Electrolyte imbalance correction
• Somatostatin therapy
• Debulking of metastatic tumor

45. Somatostatinoma
• Somatostatin: inhibit GI secretion
• Rare
• Hyperglycemia (insulin), cholelithiasis
(cholecystokinin), steatorrhea, and diarrhea
(pancreatic enzyme and bicarbonate)
• 5 – 6 cm
• 60-70% with metastasis

46. Somatostatinoma: Treatment
• resection
• debulking
• Cholecystectomy
• octreotide

47. Nonfunctional PET
• Histologically express endocrine
differentiation but lack clinical syndrome of
hormone production
• >75% of PET
• 60% malignant
• 8% with MEN-1

48. Nonfunctional PET
• Clinical presentation:
– MEN -1
– Pain
– obstruction
• Diagnosis:
– Serum tumor marker: PP, neurotensin, protein S,
neuron-specific enolase, chromogranin
– CT

49. Nonfunctional PET: Treatment
• Standard oncologic resection
• In hepatic metastasis: liver resection
– Extensive liver disease: hepatectomy with RFA,
TACE
• In MEN-1:
– Controversial
– Goal: resect all gross disease while preserve
pancreatic function

50. Exocrine Tumor

52. Benign and Premalignant Tumors:
Cystic Neoplasm

53. • Majority of pancreatic cysts: pseudocysts from
pancreatitis
• Most common serous neoplasm: SCA, MCN,
IPMN
• Serous cysts can be differentiated from
mucinous cysts by
– Cross sectional Imaging
– EUS
– Fluid analysis

54. Serous Cystadenomas
• Microcystic and glycogen rich
• benign
• When > 10 cm will cause symptoms from local
compression

55. Chapter 10: tumors of exocrine pancreas. WHO
Gross:
• Septations
• Thick fibrous walls
• Innumerable small cysts 
honeycomb apperance
• Clear, thin fluid
• Calcified central scar with
or without hemorrhage

56. Serous Cystadenomas
• Histology:
– Bland cuboidal epithelial lining without nuclear
polymorphism or mitoses
– No mucin is present
– Glycogen may be detected

57. Chapter 10: tumors of exocrine pancreas. WHO

58. Serous Cystadenomas
• Risk of malignancy less than 1%
• Serous cystadenocarcinomas or malignant
cystadenomas are just case reports
– 36% metastasis
– But long term prognosis is excellent
– Early symptoms: early satiety, obstructive
jaundice, and pain

59. • Treatment: resection when symptomatic
Serous Cystadenomas

60. Mucinous Cystic Neoplasms (MCNs)
• Mucin-producing cystic tumor
• Contain mucin-producing columnar
epithelium
• Lack communication with pancreatic duct
• Exclusively found in females
• Mostly found in body and tail
• Often symptomatic
• 2 – 25 cm

61. • Gross and histology:
– Often unilocular at distal pancreas
– May contain septa within primary lesion
Mucinous Cystic Neoplasms (MCNs)

62. Intraductal Papillary Mucinous
Neoplasms (IPMNs)
• Mucinous cystic tumor with ductal
involvement and mucin production
• Papillary projection of columnar lined
epithelium with varying degrees of dysplasia

63. • SCN: microcystic, honeycomb, stellate scar
• MCN: macrocystic, body and tail location, no
communicate with duct, peripheral
calcifications
• IPMN: macrocystic ductal involvement
• Solid pseudopapillary: cyst with solid
component, ductal dilation
• Pseudocyst: unilocular, associated with
pancreatitis
Radiographic features

65. Classification
• MD-IPMN: segmental dilatation of MPD
>5mm without other cause of obstruction
• BD-IPMN: pancreatic cyst > 5mm in diameter
that communicate with MPD
• Mixed type

66. M.Tanaka et al. International consensus guidelines 2012 for the management of IPMN and MCN of the pancreas.
Pancreatology. 2012:12;183-97.

67. Investigation
• Pancreatic protocol CT
• MRI: procedure of choice for evaluating
pancreatic cyst
• MRCP
• EUS-FNA
• Cyst fluid analysis: CEA
• ERCP with brushing pancreatic juice: cytology

68. • Worrisome feature:
– Cyst ≥ 3 cm
– MPD dilatation of 5 – 9 mm
– Thickened enhanced cyst walls
– Non-enhanced mural nodules
– Abrupt change in MPD caliber with distal
pancreatic atrophy
– lymphadenopathy

69. M.Tanaka et al. International consensus guidelines 2012 for the management of IPMN and MCN of the pancreas.
Pancreatology. 2012:12;183-97.

70. • High-risk stigmata
– MPD ≥ 10 mm
– Enhanced solid component
– Obstructive jaundice with cystic lesion of
pancreatic head

71. Management
• Resection
• Mucosal ablation by ethanol injection under
EUS guidance

72. Resection
• Recommended for all surgically fit patients
with MD-IPMN and MCN
• pancreatectomy

74. Solid Pseudopapillary Neoplasms
• Seen in young female
• Large 8-10 cm
• Indolent malignant: complete resection is
curative
• Solid with cystic degeneration
• Degenerative change + preservation of the
cells around microvasculature =
pseudopapillary microscopic pattern

75. Jarnagin et al. Blumgart’s Surgery of the Liver, Biliary Tract, and Pancreas. 5th ed. Philadelphia: Elsevier, 2012

76. • Cells are round to oval shape with nuclear
grooves
• Calcifications
• Intracytoplasmic hyaline globules
• Aggregates of foamy macrophages
• Express vimentin, progesterone receptors,
CD10, CD56, synaptosin
Solid Pseudopapillary Neoplasms

77. M.Tanaka et al. International consensus guidelines 2012 for the management of IPMN and MCN of the pancreas.
Pancreatology. 2012:12;183-97.

78. Jarnagin et al. Blumgart’s Surgery of the Liver, Biliary Tract, and Pancreas. 5th ed. Philadelphia: Elsevier, 2012

79. Malignant Tumors:
Pancreatic Cancer

80. Pancreatic Ductal Adenocarcinoma
• 4th leading cause of death in men, 5th in
women

81. Jarnagin et al. Blumgart’s Surgery of the Liver,
Biliary Tract, and Pancreas. 5th ed. Philadelphia:
Elsevier, 2012

82. • Clinical presentation
– Vary base upon location and stage
– Majority = right side: obstructive jaundice, epigastric
pain radiate to back, nausea and vomiting, gastric
outlet obstruction
– Left side: pain
– Positive Virchow node and Sister Mary-Joseph nodule
– Rectal shelf
– Ascites, hepatomegaly
– palpable abdominal mass
– New-onset DM
Pancreatic Ductal Adenocarcinoma

83. • Laboratory:
– Elevated LFT
– Hyperbilirubinemia
– High CA 19-9 (marker of treatment response)
Pancreatic Ductal Adenocarcinoma

84. • Imaging:
– Pancreatic protocol MDCT
– MRI and MRCP
– EGD in GOO
– ERCP in periampullary tumor
– EUS: pancreatic cancer with no mass in cross-
sectional imaging
– 18FDG-PET
Pancreatic Ductal Adenocarcinoma

85. • Diagnostic biopsy
– Reserved for patients with
• unresectable
• metastatic disease
• True diagnosis and management is dilemma
– No need prior to surgical resection
Pancreatic Ductal Adenocarcinoma

86. https://cancerstaging.org/references-tools/quickreferences/Documents/PancreasSmall.pdf

87. • Resectable: I, II
• Locally advanced unresectable: III
• Distant metastasis: IV
Pancreatic Ductal Adenocarcinoma

88. • Surgery:
– Resectable, borderline resectable, unresectable
– Only potentially curative
– PPPD and distal pancreatectomy
PDAs: Treatment

89. NCCN guidelines: Pancreatic Adenocarcinoma. Version 2.2016

90. • Radiation: recommend in all groups with
different dose
PDAs: Treatment

91. • Adjuvant Therapy:
– 5FU
– Gemcitabine
– Xeloda
PDAs: Treatment

92. • In borderline resectable disease:
– Chemotherapy or chemoradiation are usually
initiated to downstage tumor
PDAs: Treatment

93. NCCN guidelines: Pancreatic Adenocarcinoma. Version 2.2016

94. NCCN guidelines: Pancreatic Adenocarcinoma. Version 2.2016

95. • Palliation:
– Gemcitabine, 5-FU, FOLFIRINOX
– erlotinib
– Treat obstructive jaundice: self-expanding metal
stent
– Treat GOO: gastrojejunostomy
– Treat pain: celiac plexus nerve block
PDAs: Treatment

96. • Lymphagioma
• sarcoma
Non-epithelial Tumor

97. • = metastasis
• From renal cell cancer, lung, colon, and breast
cancers
Secondary Tumor

98. References
Jarnagin et al. Blumgart’s Surgery of the Liver, Biliary Tract, and Pancreas. 5th ed.
Philadelphia: Elsevier, 2012
Brunicardi FC et al. Schwartz’s Principles of Surgery. 10th ed. McGraw-Hill
Education, 2015.
NCCN guidelines: Pancreatic Adenocarcinoma. Version 2.2016
Chapter 10: tumors of exocrine pancreas. WHO
M.Tanaka et al. International consensus guidelines 2012 for the management of
IPMN and MCN of the pancreas. Pancreatology. 2012:12;183-97.
http://pancreaspictures.org/p/3/pancreas/picture-3