| How is anatomy of pancreas? | Review netter for related structures, regions, arterial supply and venous drainage |
| How is exocrine action of pancreas? | 1-2 L/day
Clear, watery, alkaline (pH 8.0-8.3)
> 20 different digestive enz.
Isoosmotic to plasma
Principal cations : Na & K (~165 mmol/L) Principal anions : bicarb & Cl
- secrete min : Cl high, bicarb low
- secrete max : Cl low, bicarb high (active transport)
Passive exchange of intraductal bicarb for interstitial Cl at larger pancreatic duct
digestive enzymes in acinar cells released in response to CCK and cholinergic stimulation (proteolytic, lipolytic and amylase) |
| What are tests related to pancreas function? | Tests
- Fecal fat (fat stain)
- stool trypsin tests
- Trypsinogen (Immunoreactive trypsin)
- Elastase (in stool)
Non-laboratory tests:- ERCP, MRCP, Secretin test (tube in duodenum : amount of certain enzymes and bicarbonate in the pancreatic secretion ) |
| How is endocrine function of pancreas? | Islet of Langerhans:1-2% of pancreatic mass, 20% of total pancreatic blood flow
Insulin : Beta-cell : muscle, liver, fat cells
Glucagon : alpha-cell
Somatostatin : delta cell
Pancreatic polypeptide : PP cells
acini are exposed to higher conc. of the islet hormones than peripheral tissue |
| Table of pancreatic islets peptide products? | . |
| What is acute pancreatitis? | Definition
An inflammatory disease of the pancreas than is associated with little or no fibrosis of the gland
Incidence
About 300,000 case/yr in US
10-20% = severe
about 4,000 Deaths/yr + more than $2billion cost |
| How is etiology of acute pancreatitis? | Alcohol
biliary tract diseases (80-90%)
hyperlipidemia, heriditary, hypercalcemia, trauma, surgical, neoplasm, infection, venum, drugs... (10%)
Idiopathic |
| How is etiology by bile tract diseases acute pancreatitis? | Most common, not clear etiology, common channel hypotheis, incompentent oddi sphincter, PD blockage by heminth/tumor, colocalization (trypsin activate other enzymes |
| How is etiology by alcohol acute pancreatitis? | (2 yr drink, common, absence of other cause, secretion w/blockage mechanism, increased duct permeability, decreased blood flow) |
| How is other etiologies of acute pancreatitis? (tumor and iatrogenic) | Tumor (1-2% of Pancreatitis found Pancreatic carcinoma
Periampullary Tumor
Mechanism :Blockage of secreted juice)
Iatrogenic (Pancreatic Biopsy , Biliary exploration , Distal gastrectomy , Splenectomy B2 Gastrectomy & Jejunostomy
Inc. intraduodenal P. cause backflow of enz.
Any Sugery than cause Low Sys. Perfusion
ERCP (most common) 2-10%
Direct Inj. or Intraductal Hypertension) |
| Picture of etiologies of acute pancreatitis? | . |
| What are drugs associated w/pancreatitis? | mercaptopruine, azatiopirine, diuretics, estrogens, pentamidine, tetracyclins, thiazide... |
| How are other etiologies causing acute pancreatitis? (infection and hyperlipidemia) | Infection (Mumps , Coxsackievirus , Mycoplasma pneumoniae, Found from rising of Antibody titer in about 30% of Pt with pancreatitis with No other cause, No direct evi. that isolated from diseasesd pancreas)
Hyperlipidemia (not hypercholesterol, >1000mg/dl, primary (types I, IV and V) or secondary (alcohol, diabetes, pregnancy, drugs) |
| What are miscellaneous etiologies causing acute pancreatitis? | Hypercalcemia (both acute & chronic Pancreatitis)
Hypersecretion & Calcified causing obstruction
Ascaris Lumbricoides / Clonorchis sinensis
Oriental Cholangitis , CHCA , PD obstruction
Hereditary Pancreatitis :
Mutation of Trypsinogen gene Cationic Trypsinogen (PRSS1)
Pancreatic Divisum
Azotemia
Vasculitis
Scorpion venom : surge of cholinergic n. effect
(as same as Antiacetylcholinesterase inhibitor agent)
Idiopathic pancreatitis |
| How is dx of acute pancreatitis? | Pain (epigastric, knifing, relieved leaning forward)
PE (tachycardia, tachypnea, hypotension, fever, guarding, decreased bowel sounds, maybe distended abdomen and PE
Cullen's sign/ Grey Turners sign)
Investigation (hemoconcentration, BUN, hyperglycemia, hypoalbuminemia, hypocalcemia)
Serum markers (amylase and lipase [2-3 days after amylase, false positive [do p amylase, if >3x normal ->dx], false negative [alcoholic hepatitis may see normal amylase])
ALT>3 times normal found 50% of cases of acute GS pancreatitis |
| How is imaging for acute pancreatitis? | Plain film abdomen (colon cutoff sign, sentinel loop, generalized bowel ileus, others [soft tissue epigastrum density, pancreatic calcifications, opaque GS, pleural effusion])
US (fails to image pancreas complete, superior to CT visualizing gall bladder and gall stones, - US doesn't R/O gall stone [only 50% are positive], detects extrapancreatic dilation, pancreatic edema and fluid, can give false info due to bowel gas)
Contrast CT (Gold STD, indicated in sus of dx, ac pancreatitis clinically not improved for 2-3 days, sus of complications [peripancreatic fluid, necrosis, cysts]) |
| How do we see necrotizing pancreatitis in CT? | Mild disease: no abnormalities, diffuse enlargement of pancreas, loss of normally sharp border, homogenous attenuation, inflammatory stranding in peripancreatic fat and adjacent soft tissue, fluid collections, pseudocysts, pancreatic necrosis
Necrotizing pancreatitis:
Non-enhancement of ≥ 1/3 of pancreas or >3cm of non-enhancement of the pancreas on dynamic, IV contrast-enhanced CT.
If > 30% gland involved, sensitivity approaches 100% |
| What are indications for CT in acute pancreatitis? | Severe acute pancreatitis (Ranson score ≥3 or APACHE II score ≥8)
Mild pancreatitis with no response to conservative management after 48-72 hours (confirm dx, re-assess severity, identify complications)
May repeat q7-10 day if no improvement or if deterioration. |
| What is DD of acute pancreatitis? | Bowel obstruction
Cholecystitis or cholangitis
Mesenteric ischemia or infarction
Perforated hollow viscus |
| How is severity of acute pancreatitis assessed? | Not predicted by degree of pain, etiology or serum amylase level.
CRP: > 120mg/L in pts with acute pancreatitis typically have necrotizing pancreatitis.
Phospholipase A2: elevated in severe disease, esp those who develop necrosis, ARDS, and shock
Urinary trypsinogen activation peptide: ≥ 10ng/mL has 100% PPV of severe pancreatitis
Peritoneal Lavage: any volume of peritoneal fluid with a dark color or recovery of at least 20mL of free intraperitoneal fluid = 33% mortality |
| How is hematocrit used in severity assessment of acute pancreatitis? | Hematocrit ≥ 47% at admission or failure of admission hematocrit to decrease at 24hrs is strong predictor of development of pancreatic necrosis.
Compromised microcirculation of pancreatic parenchyma precipitated by fluid sequestration with intravascular volume depletion and hemoconcentration leads to development of necrotizing pancreatitis.
Therefore, intense hydration is important. |
| What are scores used in assessment of severity of acute pancreatitis? | Ranson Criteria ≥ 3
APACHE II score ≥ 8
Hematocrit ≥ 44
CT severity index ≥ 6
1992 Atlanta Symposium: evidence of organ failure or local complications |
| What is the Atlanta criteria? | 40 Internationally renowned experts on pancreatic disease met to define severity of pancreatitis
Defined based on outcome: organ failure and/or anatomic complications
Mild acute pancreatitis: minimal or no organ system dysfunction with complete and uneventful recovery; interstitial edema of parenchyma
Severe acute pancreatitis: evidence of life-threatening systemic complications or pancreatic collection |
| What are tools used in assessing severity of acute pancreatitis? | Clinical Risk factor (Ages and Comorbidity,Clinical sign)
Scoring Systems (Ranson score, APACHE-II, Other: Imrie/Gasglow score , SOFA)
Biological marker (not routinely used, C-reactive Protein (CRP) : >150 at 48hr confirm Ac Severe Pan. IL-6 , PMN elastase , Trypsinogen Activation Peptide (TAP))
CT severity Index (CTSI) (Balthazar, Necrosis)
Clinical Risk factor
Ages and Comorbidity (Age > 70 yr, BMI >30 kg/m2, Cardiovascular disease, DM)
Clinical sign (Fever, Shock, respiratory failure, Anuria, neurologic disturbance, Ileus, palpable abdominal mass, abdominal compartment syndrome > 25 mmHg
(>15 mmHg = Abdominal Hypertension) |
| How is Ranson's score for acute pancreatitis? | . |
| What are APACHE criteria? | Multivariate scoring system
12 measurable variables: temperature, heart rate, respiratory rate, mean arterial BP, oxygenation, arterial pH, serum potassium, sodium and creatinine, hematocrit, WBC, and Glasgow Coma Scale
Account for premorbid state and age
Can be used throughout course of illness, but is complex and cumbersome |
| What is CT severity index? (AKA Balthazar) | A: Normal pancreas
B: Enlargement of pancreas, heterogeneous enhancement without peripancreatic disease
C: Pancreatic abnormalities with peripancreatic disease
D: Small or single fluid collection
E: 2 or > fluid collection or pancreatic abscess |
| How are severe and mild pancreatitis seen by Balthazar? | . |
| What are principles of tx of acute pancreatitis? | Adequate Monitoring : Admit to ICU or not
Adequate Resuscitation : Fluid & Electrolyte
Not too much/too low
Hypocalcemia , Met. Acidosis , Hypoalbuminemia , HypoMg.
Pancreatic Rest : NPO
Adequate Pain Control : dec. cholinergic n. stimuli
Avoid MO |
| What are adjunct tx for acute pancreatitis? | Decompressive Nasogastric Tube
H2-Blocker
Secretion-inhibiting Drugs
Atropine , Calcitonin , Somatostatin , Glucagon , Fluorouracil
Protease-inhibiting Drugs
Aprotinin , Gabexate masylate , Camostate , Phospholipase A2 inh.
Anti-inflammatory response Therapy
Indomethacin & Prostaglandin inhibitors
PAF (Platelet-activating factor ) antagonist : PAF acetylhydrolase , Lexipafant
Peritoneal Lavage |
| How is dx of severe pancreatitis? | Ranson score ≥ 3
APACHE-2 ≥ 8
Dev. Local/Systemic complication
MOF
Pseudocyst , necrosis , abscess
ceCT : necrosis >33% (???) |
| How is tx of biliary pancreatitis? | Controversial point : Timing (48-72hr , >72hr)
ERCP , Cholecystectomy with CBD clearance
Indication : for Early ERCP
Obstructive Jx with Cholangitis
Severe pancreatitis
Pancreatitis with obstructive Jx >24hr
Routine Early ERCP : not recommended |
| What is pancreatic necrosis? | Occur about 20% of Pancreatitis pt.
Severe Necrotizing Pancreatitis
Sterile vs Infected : ceCT with FNA
“Air Bubble” found 20% of Infected PN (IPN)
Mortality
<1% in sterile PN
About 40% in IPN
Clinical :
Fevere , Leukocytosis , clinical not imp. In 72hr
Treatment
Antibiotic
Drainage
Catheter-bases Therapy
Surgical Debridement
For Life-Threatening only |
| What is open necrosectomy? | Indication
Infected Pancreatic and/or peripancreatic necrosis
Sterile necrosis with progressive clinical deterioration under Maximum Medical Tx : Controversial
Massive hemorrhage or bowel perforation (colon, duodenum).
Timing : “as late as possible”
Preparation
Empirical Antibiotic
CT : for road map
Prepare For massive Blood loss
G/M PRC 4-6 u
Invasive monitoring : Central line / Swan-Ganz catheter |
| What is chronic pancreatitis? | Incurable , Chronic inflammatory condition
Multifactorial in etiology
Permanent loss of pancreatic exocrine &endocrine function
Leading to pancreatic insufficiency |
| What are etiologies of chronic pancreatiits? | . |
| How does alcohol cause chronic pancreatitis? | 70% of Pt
Dose and Duration related
Varied in each individual
Onset :
At age 35-40 yr
Or at 16-20 yr of alc. consumption
Mechanism not clear
SAPE theory
Pancreatic Stellate cell (PSC) activation
Multiple-Hit Theory
Necrosis-Fibrosis sequence
Alcohol
Interfere transport of Digestive enz. Colocalization Acinar cell inj.
Depletion of Lithostathine inc. Pancreatic stone formation |
| How does smoking, hyperPTH and hyperlipidemia cause chronic pancreatitis? | Smoking (Strong associated ,Inc. High risk for Chronic Pancreatitis and CA pancreas)
HyperPTH (Caused Hypercalcemia, Induced Pancreatic Hypersecretion + calcium secretion, Caused Chronic calcified pancreatitis, Calculus formation and Obstructive Pancreatopathy)
Hyperlipidemia (Worsen in women with Estrogen replacement Tx, Tx : Control Keep Fasting TG < 300 mg/dL ) |
| How is topical and hereditary causes of chronic pancreatitis? | Tropical (Nutritional)
Found in Indonesia , Southern india , Africa
Adolescent and young adult
Mechanism : not clearly known
Malnutrition
Trace Element def.
Toxin from Food : Cassava root
Hereditary
PRSS1 : Cationic Trypsinogen gene
Autosomal dominant
SPINK1 : PSTI
Pancreatic Secretory Trypsin inibitor= Serine Protease Inhibitor Kazal-1 (SPINK 1)
CFTR gene : Cystic Fibrosis Transmembrane receptor |
| How is pathology histology of chronic pancreatitis? | Early : induration , Nodular scarring , Lobular fibrosis
Then : Loss of normal lobulation , Thicker fibrosis
Then : reduce in acinar cell mass , Ductal dilatation , Ductular epithelium dysplasia , monoNu. Cell infiltrat.
Cystic change
Severe Chronic Pancreatitis : Replacement of acinar tissue by Fibrosis , islet size &number reduced |
| How is stone formation in chronic pancraetitis? | Pancreatic stones
Calcium carbonate crystal
Inh. of stone formation by
Pancreatic Stone Protein : PSP
Lithostathine
Pancreatic thread protein
Sig. dec. in Alcoholic Pancreatitis
Indicator for Advance stage disease |
| How is radiology of chronic pancreatiits? | Using of Imaging for Chronic Pancreatitis
diagnosis
the evaluation of severity of disease
Cambridge Classification
detection of complications
assistance in determining treatment options
Choice of Imaging
US , CT , EUS , MRCP , ERCP
ERCP : Gold standard in Dx and staging of CP
EUS : more sens. than ERCP |
| How is presentation of acute pancreatitis? | Pain (most common, epigastric/LUQ/RUQ, penetrates to back, steady boring pain, aggravated by food relieved by abdomen flex)
Malabsorbation and weight loss (Occur when exocrine capacity <10% Diarrhea & Steatorrhea Bulky , foul-smell ,float , with Oily water Lipase def. Trypsin Def. dec. Bicarb. Secretion)
Apancreatic Diabetes (Type III DM |
| How is mechanism of chronic pancreatitis pain? | Mechanism
Ductal (and also Parenchymal) Hypertension
Inflammation of Parenchyma
Neural involvement
Strategies to relieve pain
Reducing secretion and/or decompress the secretory compartment
Resecting the focus of chronic inflammatory change
Neural ablative procedures |
| How is investigation of chronic pancreaitits? | Measurement of pancreatic products in blood
A. Enzymes
B. Pancreatic polypeptide
Measurement of pancreatic exocrine secretion
A. Direct measurements : CCK/secretin stimulation
1. Enzymes
2. Bicarbonate
B. Indirect measurement
Bentiromide test : PABA excretion (urine) Paraaminobenzoic acid.
Schilling test : Vit B12 absorption
Fecal fat, chymotrypsin, or elastase concentration
[14C]-olein absorption : Triolein Breath test |
| What are imaging techniques in chronic pancreatitis? | Plain film radiography of abdomen
Ultrasonography
Computed tomography
Endoscopic retrograde cholangiopancreatography
Magnetic resonance cholangiopancreatography
Endoscopic ultrasonography |
| What are CT features of chronic pancreatitis? | Pancreatic atrophy, calcifications, and main pancreatic duct dilation |
| How is approach to dx of chronic pancreatitis? | . |
| How is prognosis of chronic pancreatitis? | Depend on
Etiology of disease
Complication
Age
Socioeconomic status
Progressive , cumulative inc. risk of CA |
| How is management of chronic pancreatitis? | . |
| What is pseudocyst complication of chronic pancreatitis? | A collection of pancreatic fluid surrounded by a wall of normal granulations and fibrous tissue, usually persist > 6 weeks.
Natural Hx :
For acute pseudocyst (or <6wk) : 40% solve spontaneous , 20% dev. Complication
For Chronic pseudocyst (7wk up) : about 5 % solve spon. , 50-60% dev. Complication
No malignant potential : af <6cm/asymp. No complication : ไม่ต้อง surviellance |
| What is the indication for surgery in pseudocyst complication? | Symptomatic : often occur in Pseudocyst size > 6cm.
early satiety, gastric outlet obstruction, jaundice, pain , thrombosis
Complication:
GI bleeding (Hemosuccus pancreaticus) , infection, rupture , erod vessel (pseudoaneurysm) |
| How is investigation of pseudocysts? | ceCT : Imaging of choice
EUS : if available
To detect : septation , mural nodule , debris , calcified
To aspirated collection for CEA , CA19-9 ,Amylase
R/O Pancreatic Cystic Neoplasm (PCNs)
Pancreatic Pseudocyst : Hi Amylase (>5000) , -ve Tu.Marker |
| How is tx of pseudocysts? | Rule
cystic neoplasm must not be treated as a pseudocyst
elective external drainage must not be done
If not correct of downstream obstruction
Point of consideration
The thickness of the pseudocyst wall : after 4-6wk
The location of the pseudocyst : near Stomach ,Duodenum
The contents of the pseudocyst : Blood , pus
The pancreas and the pancreatic duct need separate consideration in planning the treatment of a pseudocyst |
| Algorithm of managing pseudocysts? | . |
| What are open surgery options for tx of pseudocysts? | Cystogastrostomy
If Lying posterior to stomach
Cystojejunostomy
Ideal for internal drainage
If located at body and tail
Not adhere to stomach , Bulging through T.colon
Cystoduodenostomy
If located at head of pancreas
Distal pancreatectomy
Extent of resection , depend on ERCP finding
External Drainage
Only if no occlusion of PD |
| What are pancreatic ascites? | internal pancreatic fistulae
Pancreatic Ascites
Pancreatic pleural effusion
Thoracocentsis
Prot level >25 g/L
Marked elevated amylase level
ERCP
Eva. Point of leakage of PD
+/- PD stenting
Tx :
Antisecretory therapy : Somatostatin , Octreotide
Bowel reset + TPN
ICD for Pancreatic Pleural effusion
R-E-Y Pancreaticojejunostomy or Distal pancreatectomy
if fail conservative Tx |
| What is pancreatico-enteric fistula complication? | Most common site
Transverse Colon , Splenic Flexure
Tx
Fistula to stomach / Duodenum
No Mx : solve spont. , leave Fistula
Fistula to Colon
Needed Surgical Correction |
| What is pancreaticocutaneous fistula? | Criteria Diagnosis
Fluid > 50 cc/day, Fluid Amylase> 3 times of Serum Amylase, Persistence leakage >7 days, Low Output Fistula : <200 ml/day, High Output Fistula : >200 ml/day, Spon. Solved about 90%
Tx :
Drainage
Confirm Pancreatic Juice , Record Vol. , Resuscitation , Culture , Skin Protection
Diagnosis
ERCP
Fistulogram / Fistuloscope (after 3 wk.)
Decompression
Drug : Somatostatin , Octreotide
Definitive Surgery Distal Pancreatectomy vs R-E-Y/ Pancreaticojejunostomy |
| What is pancreatic head mass complication? | Inflammatory mass
Found up to 30%
Symptom : pain , stenosis (Duo. , stoma, CBD) Thrombosis (compress PV)
Tx :
DPPHR : Duodenal-preserving Pancreatic Head resection |
| What is splenic/portal vein thrombosis complication? | Occur 4 to 8% of case
Splenic v. Thrombosis
Lt side Portal Hypertension
Sinistral Portal Hypertension
Caused isolated Gastric Varices
Bleeding complication no frequence
Mortality rate of bleeding about 20%
Tx : Splenectomy |
| How is tx of chronic pancretitis? | Principle of Treatment
Pain control , correct Malabsorption&DM
Medical Treatment is 1st choice
Medical Therapy
Analgesia
Stop Drinking : Reduce pain in 60-75% of Pt
Analgesic drug : can up to Narcotics (Oral / Transdermal patch)
Analgesic Enhancing Agent : Gabapentin
Enzyme therapy : Correct Malabsorption + Help in pain control
Conventional (non-enteric coated) form : bind to CCK , reduce in Pancreatic secretn.
Duration of therapy about 1 mo.
Enteric coated form : Help in malabsorption , little to no Help in pain control
Antisecretory therapy : no sig. pain relief |
| What are other tx options for chronic pancreatitis? | Neurolytic Therapy : Celiac Plexus Neurolytic
Using Alcohol
Effective in CA pancreas , but Disapointment in pain control for chronic Pancreatitis
From Schwartz : under EUS-guided Initial control pain=55% , but Beyond 6mo=10%
Endoscopic Management
Surgical Therapy |
| How is endoscopic tx using pancreatic duct stent? | Role
Prox. Pancreatic duct stenosis
Decompression of Pancreatic Leakage
Decompression of Pseudocyst
Prophylaxis PD stenting : Post ERCP
esp in Sphincter of Oddi Dyskinesia
Pancreatic Divisum
Minor papilla Sphincterotomy with Dorsal duct stenting
Idiopathic Pancreatitis : Dec. symp recurrence
After Pancreatic stone Removal Procedure
Transpapillary Drainage |
| What are types of surgery for pancreatic cancer? | Sphincteroplasty
Drainage Procedure
Duval's caudal pancreaticojejunostomy.
Puestow and Gillesby's longitudinal pancreaticojejunostomy.
Modified Puestow procedure
= Partington and Rochelle Procedure
= Longitudinal Pancreaticojejunostomy : side-to-side Roux-en-Y pancreaticojejunostomy
Resection Procedure
Distal Pancreatectomy
Partial 40-80%
Ninety-Five Percent Distal Pancreatectomy
Proximal Pancreatectomy
Whipple procedure
Pylorus Preserving Pancreaticoduodenectomy (PPPD)
Total pancreatectomy |
| What are hybrid procedures in chronic pancreatitis surgery? | Beger Procedure
= DPPHR (Duodenal-preserving Pancreatic Head resection)
Berne modification of the DPPHR
Frey’s Procedure
=LR-LPJ (Local resection of Pancreatic Head with Lateral Pancreaticojejunostomy)
Hamburg modification of the LR-LPJ |
| How to choose which operation to go for? | Size of MPD
Large PD (≥5mm) : Drainage Procedure , better outcome
Small PD (<5mm) : Resection Procedure , Poorer outcome
Presence of Pancreatic Head mass
Distal CBD obstruction
Suspicious of Malignancy |
| What are indications for surgery in chronic pancreatitis? | Chronic intractable abdominal pain unresponsive to nonsurgical treatment
Suspicious Pancreatic Cancer
Persistent CBD obstruction , unresponsive to endoscopic Treatment
Duodenal Obstruction
Splenic v. Thrombosis with Bleeding Gastric Varices
Symptomatic or enlargement pancreatic Pseudocyst
Persistent Pancreatic ascites or fistula |
| What are contraindications for surgery in chronic pancreatitis? | Occlusion of SMV and PV
Chronic Pain from other cause
Inadequate Medical Treatment
For Resection Procedure & Hybrid Procedure (Frey&Beger Procedure)
Unable to cope Apancreatic DM (Brittle DM) : Relative
For Drainage & Hybrid Procedure (Frey & Beger Procedure)
Cannot exclude Pancreatic malignancy
For PPPD
s/p Vagotomy
Hx of Severe PU(peptic ulcer) |
| Describe each procedure in pacreatic surgery | refer to youtube and slides |
| What are denervation procedures? | operative celiac ganglionectomy
Transhiatal splanchnicectomy
Transthoracic splanchnicectomy
with or without vagotomy
Videoscopic transthoracic splanchnicectomy |
| What are types of pancreatic neoplasms? | Neoplasms of the Endocrine Pancreas (Insulinoma, Gastrinoma : ZES, Vasoactive Intestinal Peptide-Secreting Tumor, Glucagonoma, Somatostatinoma, Nonfunctioning Islet Cell Tumors)
Neoplasms of the Exocrine Pancreas
Ampullary and Periampullary Cancer
Cystic Neoplasms of the Pancreas
Pseudocysts
Cystadenoma
Mucinous Cystadenoma and Cystadenocarcinoma
Intraductal Papillary Mucinous Neoplasm
Solid-Pseudopapillary Tumor
Other Cystic Neoplasms
Pancreatic Lymphoma |
| What are endocrine neoplasms of pancreas? | 1% of Pancreatic Tumor
Most common PETs = Insulinoma
Related to MEN1
pituitary tumors
parathyroid hyperplasia
pancreatic neoplasms (Gastrinoma)
amine precursor uptake and decarboxylation cells
Benign vs Malignancy
Present of Local invasion , lymph. or Hepatic metastases
Most are Malignant
But prognosis is far better than CA exocrine pancreas |
| What is key to management of endocrine neoplasms of pancreas? | Clinical Syndrome
Laboratory confirmation
Localization
Surgery
For complete surgical resection
Debulking Tumor for symphtomatic control
Unresectable disease : Chemoembolization |
| What is insulinoma? | the most common PNETs
Whipple Triad
symptomatic fasting hypoglycemia
serum glucose level <50 mg/dL
relief of symptoms with the administration of glucose
10% disease
10% malignancy (the least)
10% metastasis to node
10% multiple lesion
10% found in MEN1
Best Prognosis |
| How is investigation of insulinoma? | Low Blood sugar
Elevated serum insulin level
Elevated C-peptide level
Diagnosis :
NPO with serial Blood exam q4-6hr
Insulin-Glucose Ratio >0.3 |
| How is preop localization of insulinoma? | ceCT : arterial Phase
EUS = Diagnostic modality of choice (sens 70-90%)
Laparoscopy with LUS
Transhepatic Portal venous sampling
Selective arterial stimulation with Hepatic venous sampling (ASVS)
Stimulant : Calcium (for insulinoma) , Secretin (for gastrinoma)
Intraoperative palpate with IOUS |
| How is management of insulinoma? | Mostly Benign + single lesion
Laparoscopic surgery + LUS
Tumor < 2cm , not attach MPD : Enucleation
Tumor >2cm , Resection
Distal Pancreatectomy : for lesion at Body & tail
Whipple / PPPD : for Head &uncinate process
Attach MPD , any size : Resection
If Metastases : Debulking Tumor |
| What is management of insulinoma can't be localized/unresectable/ w/MEN1? | If can’t localized Tumor :
Subtotal Pancreatectomy
Biopsy and Closed then ASVS
Unresectable Insulinoma
Tx of Hypoglycemia : CHO rich diet , inc. meal.
Medication : Diazoxide , Propanolol , Verapamil , Chropomazine
Octreotide : dec. insulin secretion 30%
Chemotherapy :
Streptozotocin, Decarbazine , Doxorubicin , 5-FU
Insulinoma in MEN-I : usual multiple
Subtotal pancreatectomy + enucleation at Head using IOUS |
| What is gastrinoma? | Zollinger-Ellison syndrome (ZES)
abdominal pain, peptic ulcer disease, and severe esophagitis
Suspected if :
multiple ulcers
Fail response to PPI
Ulcer in abnormal location
Severe Esophagitis
PU without H.pylori or Hx NSAID
If no Hx PU , Suspected if
+ve Hx MEN-1 in family
+ Hx PU almost whole family
Unexplained Diarrhea (due to Hyper acidity)
Unexplain Steatorrhea
Hypercalcemia
EGD : found Prominent Gastric /Duodenal fold |
| How is presentation of gastrinoma? | Clinical Presentation
PU 90% , Diarrhea 50% , GERD 50%
Sporadic case 75%
MEN-1 related 25% (most common PNETs in MEN-1)
Disease of 50%
50% Malignancy (may up to 90%)
50% Metastasis
50% Multiple
Location
70-90% in Passaro triangle) , mostly at duodenum wall |
| How is dx of gastrinoma? | Fasting Serum Gastrin (stop PPI before test)
>1000 pg/ml
Secretin Sti. Test : secretin 2u/kg iv
>200 pg/ml
Ddx :
pernicious anemia
treatment with proton pump inhibitors
renal failure
G-cell hyperplasia
atrophic gastritis
retained or excluded antrum
gastric outlet obstruction |
| How is localization of gastrinoma? | Preoperative
ceCT
SSTR (octreotide) scintigraphy : single test of choice
Tu. <1 cm found 85%
Octreotide scan + EUS : Best
Tu. <1cm found 90%
EGD
Intraoperative Localization
Palpation + IOUS
Intraoperative EGD
Duodenotomy |
| How is tx of gastrinoma? | R/O MEN-1 Serum Calcium + Tx HPT
If Metastases
Found intraop : Debulking tumor + Highly Selective Vagotomy
Found Before surgery : Chemotherapy + life-long PPI
Before surgery : PPI
if Tumor ….
Well capsulated , size <2cm , not attach MPD : Enucleation
Well capsulated , size <2cm , at duodenal wall
Full thickness resection
Attach MPD / size>2cm / Deep in pancreas
Resection (whipple / PPPD or Distal pancreatectomy
Postop Octreotide |
| How is tx and prognosis of ZE syndrome and MEN1? | ZE syndrome
Def. of Postop Cure
Normal Fasting Serum gastrin
-ve on Octreotide scan
-ve on CT
-ve on Secretin stimulation test
In MEN-1 : often Multiple & Metastases
Controversial
Prognosis :
Depended on liver metastases
+ve met : 5yr survival about 20%
-ve met : 5yr survival about 80%
Large tumors + liver metastases+ located outside of Passaro's triangle
the worst prognosis. |
| What is VIPOMA? | vasoactive intestinal peptide-secreting tumor (VIPoma) syndrome
WDHA syndrome
watery diarrhea , > 5L/d , tea-colored
Hypokalemia
Achlorhydria
Verner Morrison syndrome
Diagnostic test
Multiple measure of serum VIP level
Due to episodic secret VIP
>200
Localization : as other PNET
Mostly at Tail of Pancreas & usual Metastases |
| What is DD and tx of vipoma? | Ddx :
Villous Adenoma :mucus diarrhea + HypoK
ZE : Diarrhea + PU
Carcinoid Tumor : diarrhea + Facial Flashing
UC : Blood diarrhea
Tx
Fluid and Elec. Resuscitation
Octreotide
Surgical Resection / Debulking Tumor |
| What is glucagonoma? | Diabetes
Usually mild diabetes
Dermatitis
Necrolytic migratory erythema
Diarrhea , Dementia , DVT
Diagnostic test
Serum Glucagon level >500 pg/ml, Hyperglycemia, Hypoproteinemia, Localization, Body and tail : same as VIPoma
Tx
Control DM
Nutritional support : TPN
Octreotide
DVT prophylaxis
Distal Pancreatectomy with Splenectomy or Debulking Tumor |
| What is somatostatinoma? | Rare Type
Presentation (GS, DM (inh. Insulin secretion), Steatorrhea (inh. Pancreatic & Bile excretion), abdominal pain (25%), jaundice (25%), and cholelithiasis (19%)., Hypochlohydra and achlohydra, Wt loss)
Localization
Mostly Proximal , at pancreaticoduodenal groove
Periampullary area 60%
Often Metastases
Dx : Serum Somatostatin Level >10 ng/ml
Tx :
Resection if possible
Debulking Tumor
Cholecystectomy |
| What is non-functional islet cell tumors? | The most 2nd islet cell tumor
Clinical silent mostly Metastases
stain positive for pancreatic polypeptide (PP), and elevated PP levels
Related to Other Multiple neoplasia synd
VHL : von Hippel-Lindau syndrome
Slowly Growth
5yr survival is common |
| What are pancreatic cystic neoplasms? | Inc incidence as inc. use of CT scan
Most of these lesions are benign or slow growing
Better prognosis than Exocrine pancreas tumors.
Female > male (exc. IPMN : male>female)
Most asymptomatic
Point of Consideration
Cyst of pancreas , or not?
Pseudocyst(80-90%) or PCN(10-20%)
If PCN : Operation vs Observation |
| ًWhat is the algorithm of management of PCN? | . |
| What are classifications of PCNs? | SCN (30%, Females, 60 yrs, head of pancreas, extremely rare malignancy , associated w/VHL, asymptomatic unless large, nonsepcific endoscopy, single, spongy round well circumscribed, thin wall, cuboidal cell w/glycogen rich cytoplasm, abscent PD communication)
MCN (50%, Females, age 40-50, pancreas body, malignant 40%, 60% sx, macrocysts filled w/mucus septum thick wall, tall columnar cells, abscent PD communication)
IPMN (17%, males, elderly>65, head, 75% malignant, ass w/CRC, stomach, other cancers, sx pancreatitis 40% and 60% asx, endoscopy shows bulgin ampulla/mucin extrution similar to MCN histology, PD communication is present) |
| What is SCN management? | Observation : F/U with CT or MRI q6mo in first 2yr , then annually
Surgery when indication
Resection |
| How is MCN management? | Classical finding :
Rim Calcification (peripheral)
No PD communication
Cystic Fluid
Clear , mucus , “string sign”
Mucin stain +ve
Cyto :Mucinous cell
Low Amylase , High CEA , High CA 15-3
High risk for Malignancy
Tx
Surgical resection , if possible |
| What is IPMN? | Proliferation of mucinous cell in pancreatic duct , forming Papillary stroma
Classification
Main Duct Type : found 75% , risk CA 70%
Branch Duct type : found 15-20% , risk CA 25%
Combined type : found 10-15 |
| What are findings in IPMN? | Finding on CT
Microcyst + Macrocyst
No thick capsule
MD : PD dilatation , may seen filling defect/mural nodule
BD : Gr. Of cyst , no Duct dilation
EUS + FNA
Mucin +ve ,Mucinous cell
If +ve Hx Pancreatitis : High Amylase
Tumor marker : rising (except CA 15-3)
ERCP
Bulging Ampulla
Mucin extrution : Fish-eye deformity
Dilated PD |
| How is tx of IPMN? | Nonoperative : for BD type
Asymptomatic
Size < 3cm
No mural nodule , no thick septum
No PD dilatation
-ve on Cytology
Operative Mx : Problem = Margin ?
Frozen section of Transected margin
Intraoperative Pancreatoscopy
Intraductal US
Total Pancreatectomy |
| What are SPN (solid pseudopapillary neoplasms? | Solid Cystic Tumor , Franz Tumor , Hamoudi Tu
Very rare
Female , 20-25 yr
Head , Body , tail
Gross & CT finding :
Multiloculated mass : Cystic – Solid mass
FNA
Necrotic tissue
Low CEA , Low Amylase
Histo. = Papillary element
Tx
Complete Resection
If Metastases : Metastasectomy |
| How is epidemiology of exocrine pancreatic tumors? | the worst prognosis (5% 5-year survival rate)
Etiology : unknown
More common in elderly (esp. >60 years old)
More common in African Americans
Slightly more common in men |
| What are risk factors of exocrine tumors? | Risk Factor
Family History : 2-3 times risk
Cigarette smoking : at least 2 times
Coffee &alcohol : ??
Other GI malignancy
Hi-fat , Low-fiber / Fruits / vegetables
Pre-existing type II DM
Chronic Familial Pancreatitis : 20 times
Oncogenesis :
Likely initiated with Mutation of K-ras oncogene |
| How are the genetics of exocrine ca? | K-ras mutation
Found mutation in 90% of Pt with CA pancreas
w/o in DNA from serum ,stool , Pancreatic Juice , Pancreatic tissue
HER-2/neu oncogene
EGFr , overexpression in CA Pancreas
Tumor-suppressor genes
P53 , p16 & DPC4 (Smad4) , BRCA2
Multiple mutations in above genes
Gene related to expression of GF and GFr |
| What is syndrome related pancreatic cancer? | Familial cancer syndrome
BRCA2
Familial atypical multiple mole-melanoma syndrome
Hereditary pancreatitis
FAP (Fam. Adenomatous polyposis)
HNPCC (Hereditary nonpolyposis CC)
Peutz-Jeghers synd.
Ataxia-telangiectasia |
| How is pathology of pancreatic cancer? | Precursor lesion (Pancreatic intraepithelial neoplasia ,PanIN-1A PanIN-1B PanIN-2 PanIN-3, more genes mutation , more progressive atypia &Arch. disarray, Goal : to improved ability to detect of these lesion)
Location:
66% in Head and Uncinate Process, Dx earlier ,
Symptomatic,15% in Body, 10% in Tail , Usually larger & more progress at time of Dx, Asymptomaic, Other diffuse involvement
Cell types (ductal adenocarcinoma 75%, adenosquamous carcinoma poor prognosis, acinar cell carcinoma uncommon larger tumor >10cm better prognosis) |
| What are microscopic findings in ductal adenocarcinoma? | . |
| How is TNM of pancreatic cacner? | Staging
T1-4
Size cutoff at 2 cm (T1) / or more(T2)
beyond Pancrease resectable (T3) / Unresectable (T4)
N0 vs N1
M0 vs M1
Unresectable Dz Poorer prog. than N+,resectable Dz |
| How is staging of pancreatic cancer | Stage at Diagnosis
7% : Localized stage
5yr-SR = 20.3%
26% : +ve Regional LN involvment / T3 up
5yr-SR = 8.0%
52% : metastasis (Distant stage)
5yr-SR = 1.7%
15% : unknown stage information
5yr-SR = 4.1% |
| How is presentation of pancreatic cancer? | Asymptomatic
Symptomatic
Pain : often 1st symptom
Low Threshold for CT scan
Esp : Elderly Pt , inc. Insulin in DM , new-onset DM in elderly
Jx : may found in Lesion at Head
Wt loss : sign of advance Dz
Distend / Palpable GB found 25% |
| How is dx of pancreatic cancer? | CA 19-9 (Elevated in 75% , False +ve in Obstructive Jaundice , Benign HBP disease 10%, Fail for using as early detective screenning test, Using for F/U : progression & Recurrence Dz)
Pt with Jaundice
US
If +ve Dilatation with Stone ERCP
if +ve Dilatation without stone CT
Pt with Jaundice with suspected of CA Pancreas
or CT scan for 1st step |
| How is imaging study of pancreatic cancer? | CT scan : single most versatile &cost-eff. Accuracy : to predict unresectable = 90-95%, Unresectable Dz, Invasion to Hep. a. or SMA Enlarge LN outside the boundaries of resection (+ascites +distance Metastasis), Invasion of SMV or PV with not patent or Unable to recon., Not accuracy in predicting resectable Dz, Miss small Hep. Nodule , Miss invasion to artery)
PET
May help in diff. Chronic Pancreatitis vs CA pan.
EUS
For detect small Pancreatic mass
For Transluminal Bx : esp for Neoadj. Tx or DDx
More sens. For PV/SMV invasion
Less eff. in detect SMA invasion |
| How is use of diagnostic lap in pancreatic cancer? | About 20% of Pt with Resectable Dz on Preop. investigation , is unresectable Dz at Op.room
Diag.Lap. : imp. Acc. For predict resectability to 98%
Gen. Explor peritoneal surface
Lig. of Treitz , Base of the T.colon
Incised Gastocoloic Lig. , explor Lesser sac.
US probe using for exam. : Liver , Porta., PV , SMA
% of +ve pt. by Lap. Dx
10-30% in lesion at head
50% in lesion at body and tail |
| What are advantages and indications for diagnostic lap? | Advantage of Diag.Lap.
Less morbidity than open
Recovery more rapid
Time to palliative CMTx / radiation , more rapid
Less psychologic effect
Indication suggestive for Diag. Lap.
Tumor >4cm
Tumor at body or tail
Equivocal finding of Metas or ascites on CT scan
Marked wt loss
Marked Elevated CA19-9 (>1,000 u/ml) |
| How is managemnt in CA pancreas Jx? | Found PreOp. , unresectable Dz
No Bypass , DO ERCP with stenting
Found Intraop. , unresectable Dz
Go-on Bypass , not ERCP
Found Intraop. , unresectable Dz with s/p stent
Do Bypass , if possible
Choledochojejunostomy : procedure of choice
Cholecystojejunostomy : may do if
Poor performance , unable to do prolong Surgery
Patent Cystic duct and common duct above lesion. |
| How is paliative surgery and endoscopy in pancreatic cancer? | Palliative Tx is needed in 85-90% of Pt
Imp. QOL
Prob : Pain , Jx , Duodenal Obstruction
Pain : oral narcotic use Celiac plexus n.block
Jx : as previous slide
Dudenal obstruction :
Found 20%
Prophylaxis Gastrojejunostomy : controversial
Con : Anas. Leakage , delay Gastric emptying time
Procedure :
Antecolic , prefered than retrocolic
50 cm distance from Gastrojej. To Bilio-enteric anastomosis
Dec. risk for Cholangitis , more easier if anastomosis leakage
Gastrojej. Placed at most dependence part , greater Curvature
Not do Vagotomy |
| How is paliative chemo and radiation in pancreatic cancer? | Chemotherapy
5-FU Gemcitabine : FDA proven for standard Tx
imp symp. , imp. pain control , imp. Performance
Imp. SURVIVAL only 1-2 mo.
Combination , Still in clinical research
Gemcitabine +
topoisomerase I inhibitors / platinums / taxanes.
Targeted Tx :
Antiangiogenic
epidermal growth factor receptor agents. |
| How is pancreaticoduodenectomy? | 3 Phase
Assessment of resectability
Resection phase
Reconstruction phase
Incision :
upper Midline incision / Bilat Subcostal incision |
| What are complications of pancreaticoduodenectomy? | Mortality rate <5% in High Vol. center
Surgeon perform >15 case/yr
From Sepsis , Hemorrhage , Cardiovas. Event
Post-op. complication
Delay Gastric Emptying time
Pancreatic Fistula / Leakage
Hemorrhage |
| How is management of complications of pancreaticoduodenectomy? | Delay Gastric Emptying time
Common
Tx conservative : iv Erythromycin
Mostly self-limit
Pancreatic Fistula / Leakage : 10% of Pt
Octreotide :
North American : no benefit
Europe : routine use
Selective used if PD <3mm. (High rate complication)
Duct-to-mucosa VS Invagination
Depend on size PD and Pancreatic Texure
Large PD , Fibrotic Pancreas : Duct to mucosa
Small PD , soft Pancreas : Invagination
PD stent :
Reduce incidence of Pancreatic fistula in some study |
| How is management of hemorrhage in pancreaticoduodenectomy? | Hemorrhage
Intraop. Hemorrhage
Compress PV and SMV
Postop. Hemorrhage
Inadequate Ligation of vessel.
Biliary-Pancreatic leakage
Stress ulcer , Marginal ulcer
Tx : PPI |
| How is the outcome of pancreaticoduodenectomy? | Median survival after Pancreaticoduodenectomy
22 mo.
Maj. Cause of death : Recurrence Tumor
Still Needed
Only 1 modality to inc. survival
Best for palliative symptom
Tell Pt and his/her relative before Sx |
| How is adj tx of pancreatic cancer? | 5-Fu combination + radiation
Gemcitabine combination
Better but more toxic
Needed more study
Neonatal adj:
Adv.
Dec. the tumor burden at operation
Inc. rate of resectability
Killing some Tu. Cell before spread intraop.
Buying time
Make Pt with Occult Metas.Dz , shown.
Less Futile surgery.
By evi. : not inc. Morbidity /mortality
May dec. rate of Pancreatic fistula
BUT no survival advantage |
| How is post op surveillence for pancreatic cancer? | Most common recur.
Hepatic Metastasis
F/U q6mo
PE
Lab test : CA19-9 , LFT
CT scan :
after complete Chemotherapy
rising CA19-9
New symptoms suggest recurrence
Surgery for recurrence Dz :
Only for Gastric Outlet obstruction /Bowel Obstruction |
| How is periampullary cancer? | Around 2 cm from ampulla of Vater
4 type :
CA head of pancreas
Ampullary cancer
Distal CBD cancer
Duodenal Cancer
Most AdenoCA
Tx : Pancreaticoduodectomy |
| How is management of periampullary adenoma? | Result From endoscopic biopsy
Mx of small Tu. (2cm or less)
Local Excision if no malignancy
EUS : Help in eva. of Duodenal invasion
Endoscopic / Transduodenal excision :
2-3 mm margin
If post-op. Patho. Reveal Invasive cancer
Reop. For Whipple
FAP
Even patho =Duodenal Adenoma
High recurrence rate & High CA
Op. of choice = Standard (not PPPD) Whipple |
| What is pancraetic lymphoma? | Clinical Presentation as AdenoCA Pancreas
Rare
Confirm Dx
Percut. Bx or EUR-guided Bx needed
If fail , Explor.Lap. With Bx is indication.
Tx
Endoscopic Stenting
Medication
No role of Surgical resection |
| What is heterotopic pancreas? | Rest of Pancreatic tissue
Common at Stomach & Duodenum
May found at Meckel diver.
Finding :
Nodule , yellow , firm , central umbilication
Histo : exocrine + endocrine gl.
No risk CA
Mostly asymp.
Tx :
Indication : Symp. Or Incidental found
Mx :
Local excision |
| What is annular pancreas? | Congenital anomaly
Band of ventral Pancreas , engulf 2nd part Duo.
Ass. Abnormality
Duodenal atresia / stenosis
Down’s synd.
Presentating age :
at infant 50%
At >40yr : 50%
Presentation :
Upper Gut obstruction
Film : Double Bubble sign
Mx
Excision of Band
Duodenoduodenotomy 1st DuodenoJejunostomy 2nd Gastrojej. 3rd |
| What is pancreatic divisum? | Failure in fusion of Ventral & Dorsal Pancreas
Presentation : Pancreatitis
Young , Recurrence Pancreatitis
Dx
MRCP
ERCP : contrast local in Uncinated
Tx :
Endoscopic sphincterotomy
Inserted Stent into minor papilla
Opened Sphincteroplasty
If Dev. Chronic Pancreatitis : Tx as CP |
