Pancreas: eat when you can, sleep when you can, don’t touch the pancreas

  • Pancreas  Basics
    • Anatomy
      • Head: arterial supply:  ant/post sup/inf pancreaticoduodenal
      • Uncinate process part of gland below left renal vein
        • Taken during a whipple
      • Junction of smv and splenic behind neck
    • Exocrine: digestive enzymes and bicarb
      • Trypsin
      • Pepsin-pepsinogen (from stomach)
      • Enzymes don’t act in acidic environment: neutralized by bicarb
      • Secretin: specific for pancreas, most potent stimulator of bicarb secretion
      • Cck: work on gb as well
    • Endocrine: need 20% for full function
      • Beta cells: Insulin
        • Throughout pancreas: 10-25% of blood flow
      • Delta Cells: Somatostatin:
        • great inhibitor: block all endocrine and exocrine production
        • Dec splanchnic pressure
      • Alpha Cells: glucagon
  • Embryopathologies
    • Annular Pancreas: incomplete fusion
      • Assoc with downs: 20%
      • Sx Obstruction
      • Dx UGI contrast or endoscopy
        • Smooth obstruction with dilation proximal
      • Tx Duodenoduodenostomy or duodenojejunostomy
        • No bx, no transection
    • Pancreatic divisum: failure of fusion of dorsal to main pancreatic ducts
      • Major (Wirsung) drains head of panc
      • Lesser (Santorini) drains entire panc
      • 10% of normal population
        • 10% will develop pancreatitis
      • Sx caused by stenosis/obstruction of the lesser papilla
        • Assoc with pancreatitis, not ca
      • Tx minor duct papillotomy
    • Accessory Duct: vestigial dorsal panc with incomplete fusion
      • Opens through minor/lesser papilla: duct of Santorini
      • Most commonly remains in continuity with with panc duct  thus occlusion at duodenum doesn’t create sx
      • 3-14% pt with panc divisum may have obstructed accessory which causes pancreatitis
  • Acute Pancreatitis
    • Incidence 17/100,000, mortality 2-3%/yr
    • Etiology: gallstone>etoh>idiopathic (blockage), vascular, infectious, neoplastic, divisum, cf
    • Sx: Pain (95%), N/V (80%), Distention (75%), Guarding (50%)
    • Biochemical: amylase, lipase, alanine aminotransferase (gallstone panc)
      • Lipase = specific
      • Amylase linked to pancreas, parotid, bowel (trauma) and increased in renal failure
        • rises 2-12 hours: elevation degree doesn’t correlate with severity
    • Imaging:
      • u/s biliary duct
        • 30-60% of pt with biliary etiology will suffer subsequent complications of biliary dz within 3 months if they don’t undergo chole
      • Contrast ct (dynamic for non-perfused panc) best for m&m in first 24 hr
        • A nml
        • B mild edema
        • C peripanc infiltrate
        • D peripanc fluid collection
        • E non enhanced or intrapanc fluid collection- m 57% & m 20%
    • Prognostic Criteria
      • Contrast enhanced
      • Ransons 48 hr
        • 24 hours: GALAW
          • gluc 200, ast 250, ldh 350 (now lactate), age (55), wbc 16
        • 48hrs
          • fluid sequestration 6L, base deficit from acidification, diaphragm inc dec frc dec paO2 <60, bun >5, ca <8
        • 4 = 30-40% mortality, 6 = 80-90% mortality
      • Modified Glasgow
      • Apache 2
    • Basic Tx
      • Hydration
      • Analgesia: opioid
      • NG suction: only beneficial in severe
      • No benefit from somatostatin or h2 blocker
      • Nutritional support: Tpn v Enteral feeds
        • TPN not beneficial
        • Enteral feeds via NJ not NG tube
        • Reduce translocation of bact
        • Promote gut immunity
        • Enhance gut blood flow
        • Dec incidence of infected necrosis
      • Abx: imipenem
        • Fever likely due to inflammatory response, not infection early on
        • Pancreatic necrosis 30-50% get infected
        • Ppx questionable: No benefit in mild pancreatitis
        • Cochrane review 2005 10-14d use dec risk of superinfection
        • GI suggests against it
      • Surg exploration
        • Identification of necrosis
        • When in doubt  of diagnosis or hemorrhagic with continuous bleed or abscess
        • Serial ct is negative initially necrosis can take 3-10 d to manifest
        • Serial debridement required: necrosectomy
        • Open v closed drainage: experience open packing with drainage
        • Mortality 25-30% for infected necrosectomy
        • Peritoneal lavage no role
    • Gallstone pancreatitis
      • Ercp and Lap chole: procedure of choice
        • Ercp reduces septic complication
      • Tx pancreatitis then chole during same admission
        • Labs don’t have to be normal just down trending
      • Open chole and cbd exploration: more morbidity
      • Pancreatitis with porcelain gb
        • Tx pancreatitis then elective cholecystectomy
    • Complications
      • Acute: Hemorrhage, abscess, fistula (biliary, pancreatic enteric, pseduocyst formation, mortality
      • Chronic: Exocrine/endocrine insufficiency, strictures, hernia, pain
      • Pseudocyst 8% (acute alcoholic panc)
        • 30-50% of pt will develop acute fluid collections: most resolve
          • 10% develop pseudocysts at 4 weeks
          • Most common cause of cystic pancreatic lesion
          • Most resolve spontaneously: <6cm <6wks
          • Less likely to resolve if complicated: infection, rupture and hemorrhage
        • Collection MC in lesser sac
        • Sx obstruction, nausea, hyperamylasemia
        • Dx: u/s best
        • Tx:
          • asym no treat
          • sx and/or >6cmat >6wks
            • Drain ext or int (ct and ercp)
            • Percutaneous aspiration: high recurrence rate
            • External drainage for poor operative risk: 20-30% will develop fistula
            • Int: endoscopic cystogastrostomy, laparoscopy
              • Avoid in cirrhotics: presence of perigastric varices
          • Don’t have to biopsy wall unless open procedure; then, biopsy all
          • No need for somatostatin analogue or tpn
      • Abscess 5%: necrotizing pancreatitis
        • Necrotic material that gets infected
        • Mortality 20%
        • Fever white count stranding of surrounding fat
        • Dx fna with g-stain and cx, radiologic gas
        • Tx
          • Abx: imipenem
          • IR if stable
          • Open debridement with planned return
            • higher complication rate: fistulas
          • Closed drainage: close fascia
          • Complication diabetes
      • Hemorrhage 5%
      • Panc Ascites
        • p/w ascites and wt loss
        • Dx: paracentesis: elevated amylase/lipase
          • ercp shows ductal disruption
        • Tx: npo, hyperal, paracentesis if resp issues, somatostatin pos helpful, stenting duct open proximal duct
        • surgery for major duct disruption
      • Fistula: most will close within 4-6wks
        • Somatostatin doesn’t hasten rate of closure
        • ERCP and stent: close fistula in 85% of pt
      • MCx death pulm insufficiency in first week
      • MCx death >2wks sepsis
  • Chronic Pancreatitis
    • Basics
      • MC alcoholic pancreatitis, 40-50y/o, steatorrhea, wt loss
      • Not assoc with pancreatic adeno
      • Autoimmune type dx with bx findings of lymphocytic invasion
        • Assoc with other autoimmune conditions: sjogren’s and ibd
        • Tx non surgical: corticosteroids very effective
    • Sx: Pain continuous, type 2 dm
    • Dx: axr calcified panc
      • Ercp for pre-op
      • Steatorrhea
        • Dx with 24 hour fecal fat collection
        • <20g: intestinal etiology
        • >20g: pancreatic insufficiency
    • Tx
      • Stop PO etoh
      • Etoh injection to celiac for pain
      • Endoscopic sphincterotomy and duct evaluation
    • Surgery Indications
      • Intractable pain: unrelieved by avoidance behavior, medical tx, endoscopic tx
      • Suspicion of underlying carcinoma
      • Ppx against deteriorating panc endocrine and exocrine function
    • Surgery Goals
      • Relieve pain
      • Preserve quality of life
      • Nutritional status: exocrine/endocrine
      • Avoid life long narcs: earlier than later <2 years
      • Avoid chronic pain pathways from developing in the spinal cord and brain
    • Surgical principles
      • Decompression of the pancreatic duct
      • Denervation
      • Resection of abnormal a parenchyma
    • Surgical decompression operations
      • Puestow: lateral pancreaticojejunostomy: need dilated duct
        • Early pain relief 80%
        • 30% recurrent pain within 5 years: 2’ to persistent/recurrent dz in panc head with inadequate drainage
        • Anastomosis should be >6cm and < 10cm (would involve the head)
      • Whipple: pancreaticoduodenectomy
      • Beger: duodenum preserving pancreatic head resection
      • Frey: local resection of the pancreatic head, coring out, with longitudinal pancreaticojejunostomy
      • Whipple/Beger/Frey
        • Similar pain relief b/w 1-4 years in 80% of pt out to 8.5 years
      • Total pancreatectomy
        • Severe pain exocrine and endocrine failure
        • Periop death 5%
        • Complete pain relief 80%
        • 20% disease related death
        • Autoislet txp
          • Can isolate from diseased pancreas
          • Possible for off site pancreatectomy
          • Portal vein/transhepatic pv delivery
          • All pt undergoing pancreatectomy should be considered
      • Cyst-enteric anastomosis: cyst gastrostomy, Roux en Y cyst jejunostomy
      • Duct stenting w or w/o lithotripsy v surgical drainage
        • Endoscopic tx less effective
        • Pain relief in 32% at 2 years
    • Outcome predictors
      • Good outcome predictors
        • >50 yo
        • dz duration < 2 year: limited narc use
        • isolated episodes of pain > constant
        • hx of dm
        • no previous peustow
        • duct >6mm
        • social support
        • inflammatory dz in pancreatic head
      • Poor predictors
        • Dz duration >10 years
        • No dz in panc head
        • Poor results from previous peustow
    • Sympathectomy
      • Transthoracic v transhiatal
      • Indicated prior to total pancreatectomy
      • Selecting pt
      • Small duct
      • Drug seeking behavior, psychogenic dz
      • Differential epidural anesthesia: placebo, splanchnic v somatic blocks: exclude pt who only benefit with placebo
  • Pancreatic Exocrine Neoplasm
    • Cystic Neoplasm
      • Incidental Cyst
        • <2cm without suspicious findings: mri in 1 yr
        • >4cm consider resection
      • Pancreatic cyst: biopsy
        • Mucinous=tumor=resect
        • Serous=observe= 6 mo f/u
      • Amylase, CEA, Viscosity
        • Serous Cystic neoplasm: low, low, low
        • Mucinous Cystic neoplasm: low, high, high
        • Psuedocyst: High, High, Low
    • Serous Cystadenoma
      • Benign, glycogen-rich epithelial lining
      • Don’t communicate with pancreatic ducts
      • Cluster of grapes central scar appearance
      • Cea <5
      • VonHippel Landau: Found in tail, mostly benign
      • Histo: bland cuboidal epithelium
      • Tx
        • Should be left alone
        • Resection for symptoms or cannot r/o malignant
    • Mucinous cystadenoma: malignant potential
      • 30-50% harbor Ca
      • Distal, female, middle aged, peripheral calcifications, pseudocyst
      • No communication with ductal system
      • Single or multiple septations
      • Calcifications or papillary growths indicate ca
      • Histo: ovarian like stroma pathognomonic
      • Cea >250, tumor markers ca 19-9, 72-4, 125, 15.3, mostly malignant
      • Tx Always resection
        • complete resection with regional node dissection
        • Rad role uncertain
      • 5 yr survival 45%
    • Solid Pseudopapillary
      • Young women (80%)/children
        • MC pancreatic tumor in pt under 21
      • In body and tail
      • Locally invasive, rarely metastatic
      • Surgical resection usually curative: 90% cure if localized
    • IPMN
      • Basics
      • Main duct IPMN: MDIPMN: Diffuse or segmental
        • 70% harbor malignancy
        • 45% have invasive caricinoma in resection specimen
      • Mixed type: behave like MDIPMN: tx the same
      • Branch Duct: BDIPMN Usually in head or uncinate but can occur anywhere
        • Variable risk for cancer
          • Size dependent
            • 1-3cm: reimage at 6 mo then CT cross sectional imaging q 1 year
            • >3cm, mural nodules, positive cytology or symptomatic
      • Sx
        • N/V/Abd pain/ back pain/wt loss/ anorexia
        • Pancreatitis
        • Sx of exocrine and endocrine panc insufficiency
        • DM, high hba1c
      • Grading
        • Low grade dysplasia-adenoma
        • Moderate: Borderline
        • High: invasive
      • Surgical Indication
        • Symptoms
        • Recurrent pancreatitis
        • Communication with main duct
        • Cancer/risk for developing
          • IPMN  are thought to follow an orderly progression from a benign neoplasm to ca
      • Size dictates plan
        • 1cm 17% (probably lower) Ca risk
          • <1cm: mri/ct at 1 year
        • <2 cm with mural nodule 25% Ca risk
        • >2 cm regardless of nodule 27% Ca risk
          • 1-3cm: eus plus mrcp/ercp
            • high risk: resect
            • Low risk: early repeat of mr/ct
        • <3cm: inc factors
          • older age
          • presence of sx
          • dm
          • Specific radiographic features:
            • solid component
            • main panc ductal dilation >5mm
            • lymphadenopathy
            • presence of mural nodules
            • presence of synchronous lesions
            • an inc in cyst size during follow up
          • Without mural nodules risk of malignancy <40%
          • Cytology
            • HGA: high grade atypia: most sensitive predictor of Ca in all cysts and in small <30mm bd ipmn
            • Cytology detected 30% more cancers in small cysts than dilated MDIPMN or mural nodules
          • Progression to malignancy 5-6 years, varies with subtype
            • Colloid carcinoma 30-50% pt with intestinal type ipmn
            • Ductal adenoca develops in >50% pancreaticobiliary type ipmn, 10-30% gastric branch ipmn
        • >3 cm = resection
      • Recurrence after resection 17%
        • 28% at 2 years
    • Adeno (95%)
      • Basics
        • 33,000 new cases 32,000 deaths/yr
        • Risk: tobacco x2, meat x2.5, endogenous cck, genetic 3-5% (85% k-ras mutation)
        • Age, M>F, Blacks
        • Assoc: dm, chronic panc, smoking, etoh
        • 92% adeno, 5% cystadeno, 3% acinar cell
        • Sx jaundice back pain, migratory thrombophlebitis
      • Dx double duct sign in contrast ercp/mrcp of terminal bile and panc duct
        • Poor yield: CT, fna, duct cytology
        • 85% Ca 19-9, ca 50%, ca 125 (peritoneal carcinomatosis)
      • Adeno Location 75% in head 20 % body 5% tail
        • 65% distant mets
        • 15% locally advanced:
          • chemorad: med survival 17 mo
          • no chemorad 7 mo
        • 20% resectable
      • CT staging: Contrast enhanced CT with 1mm cuts: pancreas protocol
        • High predictive value for unresectability: 90-100%
          • Obvious vascular invasion
          • Distant metastases
        • Low predictive value for resectability: May miss subtle vasc invasion
      • EUS: when to perform
        • Suspected panc mass and negative ct
        • Staging: particularly with ct showing resectable lesion
        • Tissue Dx
        • Unresectable dz: tissue is the issue: neoadjuvant/palliative chemo
      • Poor surgical candidates
        • Median survival
          • Resectable: 24-30mo
          • Local advanced 10-18mo
          • Metastatic 6-10mo
        • Systemic therapy not very effective
      • Pre-Op
        • coagulopathy (vit k)
        • No role for pre-op hyperal: no imp survival
        • Pre-op biliary drainage: no role, elevated infectious complication
        • Major controversy: if surgery planned soon, don’t 2’ infectious issues
        • Stent or not
        • Plastic metal
        • Covered uncovered
        • Factors affecting survival: tumor left at resection, tumor diameter, dna content, LN status
      • Not Operable:
        • LN: celiac, base of mesentery, sma, LN portal mesentery
        • Options
          • Locally invasive without liver mets:
            • Biliary bypass and chemorad (gemcitabine and external beam rad): inc median survival 6 to 22 mo
              • Bypass to cbd or gb
          • Gastric bypass for actual (pre-mortal) or pending obstruction
          • Duodenal stent v gastrojej: duodenal stent faster for enteral feeds to start but less long term durability
          • Biliary stent placement: Covered metal better: endoscopic better
          • Celiac plexus neurolysis: moderately effective
          • Palliative resection more morbid than bypass without significant change in survival
            • 8.2mo palliative 6.4 mo. Bypass
      • Operable
        • Stage 1&2 with 2b: locally advanced borderline resectable
        • Stage 3 unresectable for cure
          • 2cm, LN to spleen, peripancreatic, LN prepyloric, LN colon mesentery, part of smvsma
          • Peripanc nodes still ok
          • Celiac lymph nodes not ok
          • Portal vein resection has equivalent survival as those without pv involvement so long as rest of stage is no different
          • No benefit in resecting artery
          • No benefit to extended lymphadenectomy
        • Op mortality whipple should be <3%
        • Age isnt a c/i though morbidity higher and survival less
          • Complications inc with age and bmi
        • Neoadjuvant tx appears to offer benefit to 20% of pt
          • Gemcitabine based: Improves progression free survival but greater toxicity
          • Rarely converts unresectable to resectable
        • Adjuvant tx is standard for >stage 2 but additional survival still limited
          • Up to 30% never get it d/t complications
        • Dx Laparoscopy
          • Detects carcinomatosis in most pt (ct as sensitive)
          • Reduces morbitdity and avoids needless laparotomy in most pt with carcinomatosis
          • Reduces costs if yield is 10%
          • Improves staging for subsequent tx
          • Eliminates expensive, useless tx
          • Predictor for pt, clinical trials
        • Laparoscopic whipple:
          • Benefit from distal, subtotal, medial,
          • Reduced los complications
          • Improved QOL
          • Median survival <2years
        • Pancreaticoduodenectomy 10% 5 yr survival
          • Pylorus sparing no better than distal gastrectomy
          • Pyloric preserving done 2’ to dumping symptom risk
          • Mucosal anastomosis of panc duct commonly thought to make less fistula, not true
          • No advantage for total pancreatectomy
          • Expect an intense desmoplastic reaction by tumor
        • Complications
          • Leak 15-25% of cases: most heal with conservative mgmt
            • Octreotide
          • Fistula: 10-40%
            • RF: small duct, soft pancreas, bmi, poor nutrition
            • Octreotide
            • Decreases fistula output
            • Doesn’t affect periop pancreatitis, postop mortality, reoperation rates, icu stay
      • Mets: gemcitabine
  • PNET: Pancreatic neuroendocrine tumors, pancreatic islet cell tumors, pancreatic endocrine tumors
    • Basics
      • Ddx
        • Adeno: much more common
        • Carcinoid
      • Most spontaneous, 10% assoc with MEN1, vonHippel landau, tuberous sclerosis, neurofibromatosis
      • Most nonfunctional and not assoc with hormone hypersecretion
      • Prolonged silent progression
      • Incidental find
      • CT will find 70% of 3cm and 50% of 1cm
      • 50% will have liver mets
      • Serum marker CGA chromogranin A
      • Tx
        • Without mets: parenchymal sparing resection
        • With mets: possible surgical debulking
          • Localized liver: resect
          • Diffuse: chemo
        • Chemo: survival benefit
          • Streptozocin and doxorubicin and 5fu: 37mo survival rate
          • Temozolomide single agent or with capecitabine
          • Bevacizumab, sunitinib, sorafenib
    • Insulinoma
      • MC functional neuroendocrine tumor
      • Basics
        • From beta cells though out panc
        • Females, b/w 40-50
        • most <1.5 cm
        • multiple in familial type
        • children dysidoblastosis
        • majority benign: 20% malig
      • P/w hypoglycemia on fasting or after exercise: resuscitate
        • npo with iv saline
        • check blood gluc q 6, if doesn’t drop <50 in 72 hr done
        • if drops: insulin, c-peptide draw then give gluc
        • visual disturbance mc sx
      • dx: whipple’s triad (within 3 d fast)
        • serum insulin high (c-peptide)
        • fasting <45mg/dl
        • hypogly sx
        • 72 hour fast under monitored conditions: glucose <45 with serum insulin higher than 5 and high c-peptide >0.7 and proinsulin
        • r/o factitious hypoglecmia with c-peptide and proinsulin levels
        • ct scan, fractionated portal blood,
        • octreotide not helpful
        • somatostatin receptor scintigraphy don’t work to image
      • Tx: surgical exploration
        • Intraop u/s: resection location based
        • Distal pancreatectomy
        • Enucleation in body and head
        • Resect metastatic lesion
        • Chemo
          • Diazoxide
          • Dilantin
          • Ocreotide
          • Streptazosin
    • Gastrinoma
      • Basics
      • Incidence: .5-3/100,000
        • Second MC functional neuroendocrine tumor
        • 30% familial (men1), 70% sporadic
        • 60% malignant
        • Usually multicentric
        • 2M>F
      • Gastrinoma triangle: duodenum wall mc
        • Cystic to cbd, portion 2-3 duodenum, panc head and neck
      • Sx Acid secretion: pain & diarrhea
      • Dx basal acid o/p >15 meq/hr
        • post antrectomy >5 meq/hr
        • basal/max >0.6  (close to 1)
        • fasting serum gastin level (>500)
      • gastrin assay high gastrin, high acid (ph 2.5)
        • no acid: pernicious anemia
      • stimulation study
        • Ca infusion: gastrin must go up by 400
        • Secretin infusion: must go up 100 over baseline (over 200)
          • must be off PPI for 1 wk, bridge with h2 blockers
          • ppI increase serum gastrin 5x
          • hold h2 blockers 24hrs prior to test
      • Localize lesion
      • Ct scan: 60%, U/s: 60%, Angio: 60%
          • EUS better for pancreatic  than duodenal tumors (can ID only 50%)
          • Intraopduodenotomy for localization
        • Somatostatin receptor scintigraphy with single photon emission computed tomography
          • Most sensitive tests: 80-85% Tx of choice
        • Fractionated portal venous blood: 95% (hemobilia, intraperitoneal hemorrhage)
      • Manage
        • Familial: not for operation
          • Medical management: check hypercalcemia men-1, ctrl this
          • Ctrl acid with ppi
          • Med management fails, Highly selective vagotomy (worsens diarrhea)
          • Simvastatin
          • Med management fails: last resort total gastrectomy
        • Sporadic
          • Enucleation, excision
        • Metastatic:
          • Can enucleate
          • Total gastrectomy
          • Simvastatin
          • Chemo
            • Streptazosin: most effective
              • Diabetic after 1 dose
      • ZES: Zollinger-Ellison Syndrome
        • Sx: Refractory Ulcers, Diarrhea
        • Distal cluster of H pylori neg ulcers
    • VIPoma
      • 50y/o,  Solitary >3cm
      • 50% malignant: can include  somatostatin, glucagon, insulin
      • Sx watery dia, achlorhydria, hypoK
      • Dx: Localize with octreotide scan
      • Tx
        • Correct elyte, fluid and dia
        • Excise lesion
        • If in liver excise liver lesion
    • Glucagonoma
      • Basics: 60-80% malignant found 80% in the tail and body
      • Sx: 4D’s: diabetes, dermatitis, DVT, and depression
        • Dermatitis 90%: migratory dermatitis: pathogmnomonic
        • Necrolytic migratory erythema: predates other systemic symptoms
        • Dm 90%
        • Wt loss 90%
        • Anemia, abd pain, diarrhea, dvt, pe (10%)
          • Anemia: kupfer metabolism imp in hemoglobin metabolism
        • Hypocholesterolemia
      • Dx: ct scan
        • Octreotide scan
      • Tx: resection/ablation
        • Octreotide: worsen dm, improve skin
    • Somatostatinoma
      • Basics
        • 1: 40mill
        • Assoc with NF
        • Present very large, commonly with gallstones from cholestasis
        • 90% Malig
      • 75% panc, 25% sb and periampulary/duodenal wall
      • Sx diabetes, cholelithiasis, steatorrhea, jaundiced and level >10
        • Hyperchlohydria
      • Dx/ Octreotide scan
      • Tx/ Resection

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