- Basics
- Site of Origin
- 59% Extremity
- 19% Trunk, ant abd wall (desmoid), flank
- 15% Retroperitoneum
- 9% Head and neck
- Risk Factors
- Trauma: burn, scar, chronic tissue irritation, chronic lymphedema
- Genetics
- Neurofibromatosis: Von Recklinghausen’s Disease
- Gardner’s Syndrome
- Tuberous Sclerosis
- Li-Fraumeni Syndrome
- Fap- desmoid
- Radiation: 10 year latency after radiation therapy or exposure
- Periphery of radiation (bad)
- Chemical: polyvinyl chloride, burns
- Lymphedema: Stewart-Treves Syndrome
- Classification: Based on soft tissue they resemble
- Presentation: MC painless lump, slow growing
- Radiologic Eval
- Plain Xray: location of bone tumor assoc fractures and cortical disruption
- CT scan abd & pelvis: always use IV contrast
- CT scan chest: look for mets
- Pre op cxr v ct: cxr adequate
- metadata > 1 cm mets matter
- MRI: if lesion is >4cm
- Bone Scan: detects mets, eval cortical and intraosseus extent of bone tumors
- Angiogram if necessary to assess vascular relationship to tumor
- Staging TGNM
- Tumor Size
- T1 <5cm: a superficial to fascia, b invades
- T2 >5cm
- Grade: Extent of differentiation mitotic rate, necrosis
- Path most imp for grade
- >25 mitosis for 50 high power fields = high grade = radiation tx
- Subtype not very imp
- Histo: Most important prognostic factors
- Low grade: 5-10% metastic
- Intermed: 25-30% metastatic
- High Grade: 50-60% metastatic
- Mets: MC pulm, retroperitoneal spread to liver first
- Route of tumor dissemination: hematogenous because they are mesenchymal cell origin
- Extremity and bone tumors usually spread to lung and then bone
- Abd, pelvic, and retroperitoneal: go to liver and lung
- Sarcoma rarely met to LN
- Primitive tumors: small cell, synovial, clear cell, angiosarcoma, rhabdo, epithelioid
- Chemo sensitive
- Pos nodes means complete LND
- Stage 4: mets or nodes
- Dx: made by biopsy
- FNA: not very helpful, small cells lots of fibrosis
- Core Needle Biopsy: ok but need to tract out in line of incision
- Excisional: tumor <3cm: ok but don’t enucleate
- Incisional Biopsy: orient biopsy scar with proposed resection lines
- Most deep, fixed, within musc
- Exception: DMFB: firm in SubQ
- Imaging before doesn’t’ change anything unless worry about neurvasc involvement
- Tx
- Complete surgical resection including biopsy sites
- Radical Surgery: improves local control
- <10% recurrence if: <5cm tumor, superficial, 1 fascial compartment, margin of 2cm
- DO NOT SHELL OUT: Wide local excision: 2cm margin preferable
- Muscle group excision
- Compartmental excision
- Drain inline with incision
- Amputation: reserved for recurrences and tumors that render extremity useless
- Radiation: Intermed to high grade tumor (high grade or low grade >5cm; high mitosis >10)
- Improves local control: no survival benefit
- high grade do respond
- Inadequate margins: limb preserving procedures, close margins around nerves or vasc structures
- all op area 5000 cgy and tumor bed 6500: external beam = brachytherapy
- Pre op vs post op:
- pre less fibrosis and edema worse wound healing
- post opposite; high grade in sensitive loc do pre
- Chemo
- No survival benefit after complete resection
- Doxorubicin, dacarbazine, ifosfamide (20-50% respond)
- Postop beneficial with positive margins and high grade histo
- DTIC clinical trial: adriamycin; Iphosphomide
- Adriamycin and ifosfamide demonstrate response rates of 20-30%
- 80% of skeletal sarc will develop recurrence
- 50% of pt with high grade sts will recur
- Neoadjuvant best in osteosarc, ewings, rhabdomyosarc
- Improves limb sparing, improves overall survival
- Metastatic Dz = metastectomy
- 44% occur in lungs: f/u with Chest CT
- Tx: Surgery should be considered even if multiple and bilateral
- Stapled metastasectomy with minimal lung removed
- Not an option if:
- Primary dz not well controlled
- other systemic sites involved as well
- recurrent pulm nodules within 1 year of prior lung resection
- Recurrence
- RF: >50 yo, >grade 2, retroperitoneal, tumor depth, size >5cm, pos margins, path: mfh, angiosarc, rhabdomyosarc
- Up to 50% of retroperitoneal and intra-abdominal sarcomas will recur after initial resection
- Retroperitoneal Sarcomas: local recurrence, liver and lung mets
- Extremity sarcomas: pulmonary metastases
- Aggressive f/u is life prolonging
- Follow up imaging q 4 mo
- Sarcomas that recur usually do so within 5 years
- Poor prognostic features: liposarc >1cm/mo, large >5cm, short disease free interval
- Slow growing sarcomas with long dz free interval should consider re-resection
- R0 resection, resect all prior incision, drain and specimen bed sites
- Consider neoadjuvant chemo/xrt if lesion is large, fast growing, near critical structures or difficult to achieve limb-spaing approach
- Resection is preferred treatment for recurrences
- Amputation
- Pulmonary metastasectomy: up to 40% 5 year survival
- Chem and radiation generally palliative at best
- Subtypes
- MC: malignant fibrous histiocytoma, liposarcoma, leiomyosarcoma
- MFH: mc soft tissue sarcoma, lower extremities, 20% of all extremity sarcoma
- Pleomorphic high grade sarc categorized here as well
- Liposarcoma: 2nd mc sts, usually lower extremities, 25% of extremity sarcomas and 45% retroperitoneal sarcomas
- Leiomyosarcoma: 20% of retroperitoneal sarcoma
- Bone sarcomas are classified according to the matrix they produce
- Osteosarcoma
- MC bone tumor
- Usually teenagers (15)/adolescents: male predominate
- In pt over 40 yo it is usually assoc with pagets dz or prior bone irradiation
- 80-90% occur in metaphysis of long bones:
- distal femur > proximal tibia > proximal humerus
- MCsx: painful soft tissue swelling and tenderness
- Tx: neoadjuvant chemo followed by limb sparing surgery
- Chondrosarcoma
- Usually 40-60yo
- Commonly occur along pelvis, femur and shoulder girdle
- Rarely responds to chemo (may be considered in young patient with high grade tumor
- Ewing’s sarcoma
- Almost always occur around 20yo, Caucasian
- 90% assoc with distinct chromosomal translocation 11:22 q24 q12 which results in a chimeric protein EWS/FLI-1
- Destructive intramedullary lesions that affect the diaphysis
- Dermatofibrosarcoma: lateral microscopic extensions
- Check CD34, 30-50
- Tx/ wide local excision with 4cm
- GIST: AKA leiomyosarcoma
- Arise from interstitial cells of cajal: gastric pacemaker cells
- Expresses CD34 (hematopoetic progenitor cell)
- Expresses CD 117/c-kit (growth factor receptor)
- Can affect any portion of GI tract: stomach most common
- Sx appear late and are subtle
- Bleeding and ulceration may occur
- Obstruction from larger tumor
- Malignant GIST similar presentation to benign but:
- Size >5cm
- High mitotic rate (>10 mitoses/high power field)
- Necrosis
- Invasion of other structures
- Metastases
- Endoscopy: EUS: shows submucosal tumor: possibly with ulceration
- Biopsies often nondiagnostic
- CT scanning of Abd/Pelvis
- Complete surgical resection best tx if it is possible: 2-4cm margin optimal
- Survival dependent on size/resectability
- 75% 5-year survival for smaller resected tumors
- 20-40% overall for malignant GIST tumors
- Chemo: C-kit inhibitor: imatinib
- Indication: metastatic, locally advanced and incompletely resected gist tumor
- 54% demonstrate tumor reduction: 20% tumor stability
- ckit oncogene expression: 40% recurrence
- targets tyrosine kinase inhibitor
- Recurrence in 40-90% surgically tx pt
- RF: tumor size, mitotic index, tumor location, tumor rupture during surgery
- Desmoid: nsaid, sulindac, tamoxifen
- Retroperioneal Sarcoma:
- Ddx
- renal cell, adrenal (primary adrenal coricocarc, pheo)
- lymphoma (other nodes, b sx, tumor marker ldh)
- non seminomatous extra gonadal germ cell tumors (Bhcg, afp)
- Represent 15% of sarcoma
- Dx delayed d/t lack of sx
- Usually >10cm at time of presentation
- 50% are larger then 20cm at diagnosis
- Liposarc, MFH, and leiomyosarcomas most common
- Radiologic assessment
- Chest, abd and pelvic ct scan with IV/PO contrast
- Assess for liver and lung mets
- Assess vascular invasion
- Tx: Complete surgical resection
- Difficult to achieve tumor free margins
- on the test you must get 1cm
- in practice very hard: attempt to get grossly clear margin
- Achievable in 40-60% of pt
- Survival 103 mos v 18 mo with incomplete resection
- Often involves radical extirpative procedures: bowel resection, nephrectomy, pancreatectomy
- Gluteal tumor: abut the sciatic nerve
- Fem nerve involvement: lose knee extension
- Sciatic nerve involvement: lose most leg
- Local recurrence: chemo and rad pos
- 5 yr survival 40-50%
- Pancreas Basics
- Anatomy
- Head: arterial supply: ant/post sup/inf pancreaticoduodenal
- Uncinate process part of gland below left renal vein
- 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
- 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
- <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%
- 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
- 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
- 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
- Metastatic:
- Can enucleate
- Total gastrectomy
- Simvastatin
- Chemo
- Streptazosin: most effective
- 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
- 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
- Dx/ Octreotide scan
- Tx/ Resection
Skin Cancer
- Skin Cancer:
- 40% of all cancer cases
- >1 million cases/yr
- 40-50% US population affected
- 95% curable
- Geographic risk: highest rates of UV radiation: South Africa and Australia; In US Florida and Texas
- Melanoma
- Increasing in incidence
- US: inc from 1:1500 (1935) to 1:74 (today)
- Risk factors:
Familial: skin type and color; h/o malignant melanoma
- Environmental
- >3 blistering sunburns before age 20
- Outdoor jobs >3 years in adolescent years
- Use of sunlamps and tanning beds
- Other
- Actinic keratosis, elastosis
- Marked freckling on upper back
- Large number of normal nevi
- Atypical nevi, congenital giant nevi
- Characteristics
- Asymmetrical: one half the lesion is shaped differently
- Border: irregular, blurred or ragged
- Color: inconsistent pigmentation with varying shades of black or brown
- Diameter: >6mm or a progressive change in size
- Evolution: history of change of lesion
- Types
- Superficial Spreading (60%): prolonged radial growth phase, notching scalloping, areas of regression
- Nodular: (15%): darker and thicker than superficial spreading, rapid onset; commonly blue-black or blue-red (5% amelanotic)
- Lentigo Maligna (%5) enlarge slowly, usually large, flat, tan or brown
- Acral Lentiginous: (rare: Asians 46%, blacks 70%) on soles, palms, subungual, usually large, tan or brown, irregular borders. Anti-reggae.
- Desmoplastic (1.7%) rare locally aggressive, occur primarily on neck and head in elderly
- Dx
- <1.5cm : excisional biopsy
- >1.5cm: Incisional Biopsy
- Punch biopsy OK: look at ‘worst’ part
- Goals
- Narrow excisional bx: 2-3mm
- Rule out lesions with potentially similar features:
- seborrheic keratosis
- pigmented basal cell ca
- solar lentigines
- atypical nevi
- Determine depth of invasion
- Identify prognostic features of the primary: ulceration and regression
- Tests: get LDH (terrible prognosis, upstages), LFT
- Staging: Breslow
- T1 0-.75mm Thin
- T2 .75-1.49mm Intermed
- T3a 1.5-3.0mm Intermed
- T3b 3.01-4mm Intermed
- T4 >4mm Thick
- Prognostic factors:
- MULD: Mitotic rate, Ulceration, LDH, Depth of invasion
- Male sex
- Trunk/head and neck
- Age:
- Mortality increases with increasing age
- Lymph node metastases higher in younger patients
- Nodular sub-type
- High mitotic rate (>6 mm2)
- Recommended margins
- Melanoma in Situ: 5mm
- <1mm = 1cm
- 1-2mm = 1-2cm
- >2mm = 2 cm
- May be modiefied by anatomic considerations
- Negative peripheral margins important in ill defined lentigo maligna lesions
- On the digits: Amputation at least one joint proximal to the tumor and sentinel node bx
- Risk of nodal disease
- <1mm w/o ulceration <5%
- 1-4mm = 20%
- >4mm = 35%
- Sentinel Lymph Node Bx:
- Radiocolloid and vital blue dye (given intradermal) improve accuracy
- Excision of primary should occur at time of SLNB
- Can be performed after: no decrement in identifying SLN after previous wide excision
- Indications: >1mm, any ulcerated, >1 mitosis/mm2
- All pt with invasive melanoma
- Primary melanoma >1 mm
- M75 with ulceration, deep invasion, regression, truncal location, and mitoses
- Pt with nevomelanocytic lesions assessed by bx in which biology is uncertain
- If positive: 2.2x risk of recurrence and deaths
- Lymphadenectomy
- Deep inguinal lymph node dissection for: > 4 positive lymph nodes on superficial dissection, positive Cloques node (subinguinal), enlarged ileo-obturator lymph nodes on CT, clinically palpable or extracapsular invasion of femoral lymph nodes
- A/E: 30% have lymphedema, wound complications, or other a/e
- MSLT2 trial: positive node: dissection or u/s obs
- 5 year survival: depth, with and w/o ulceration
- <1mm 95% 91%
- 1-2mm 89% 77%
- 2-4mm 78% 63%
- >4mm 67% 45%
- Adjuvant Therapy: chemo, biochemo, immune, braf inhibitor
- Adjuvant for high risk melanoma: significantly prolongs relapse free survival, 26% risk reduction
- 15% overall survival improvement, 1 year benefit
- stage 4 (6-9mo median survival, 5 year 6%)
- Indication: Pt high risk for systemic dz
- Ulcerated
- Positive LN
- Thick primary >4mm
- Regional Recurrence
- Chemo
- Dacarbazine: response 20%, no change in survival
- Temozalmide: oral agent, crosses bbbb, no change in survival
- Combo: Cisplatin, vinblastine, dacarbazine
- Improved response 25-30%, no change in survival
- Immunotherapy:
- IL2
- T cell growth factor, produced by t cells
- Induces T and NK cell proliferation
- Strong anti tumor properties
- Approved for melanoma and renal cell
- INFalpha
- IFN alpha 2b: for stage 3
- Survival benefit 1 month
- Targeted therapies:
- Zelboraf: vemurafanib: inhibitory molecule selective for V600E mutation
- BRAF: mutated: acquired to activate map kinase pathway
- Selects out the 40-60% of melanoma with NRAF mutation
- Response rate 48%, survival at 6 mo 84 v 64 with dacabazine as control
- Unknown MOA: protein death 1
- A/e cutaneous scc and keratoacanthoma
- MAB:
- Ipilimumab & nivolumab trial for metastatic tx/ 4 mo gain (10mo total)
- Ipilimumab: CTL4 blocker: increases antitumor T cell survival
- A/e: colitis, rash, elevated LFTs
- Increased survival rates 21 v 12% v vaccine
- Metastatic Melanoma
- Considerations: Prior disease free interval, sites of dz, amount of tumor burden, ability to resect entire disease, pt performance, potential to down stage with systemic therapy
- Mucosal melanoma: poor actors: locally excise
- Unlikely to have braf mutation
- Occular melanoma: go to liver even after enucleation
- Ckit mutation: studying gleevec
- Seborrhaic Keratosis
- MC benign skin tumor
- Greasy/waxy stuck on raised appearance, oval
- Clonal origin: neoplastic not hyperplastic
- RF: sun exposure , age
- Familial predisposition with postulated AD inheritance
- MC location: face, neck, back
- Never found on mucosa, palms or soles
- “Never occur before 30”
- Can spontaneous regress, assoc with pregnancy, inflammatory skin conditions and malignancy
- Tx: Ablative: cryotherapy, laser, electrodessication, surgical
- Basal Cell
- Basics
- MC skin cancer 90%
- Arise from lowest layer of the skin
- Rarely metastasize or spread
- RF: UV radiation: Sun exposed areas
- Canthi of eye and nose
- 86% on face
- Failure to heal
- Indolent
- MC: modular type: face; waxy central cupping no ulceration
- Superficial scaly plaque, sm compared to squamous cell 15% and truncal, no raised edges
- Tx MOHs surgery: tangential/ transverse chemo fix and map and plan next cut: failure rate less than half other modalities; involve plastic surgeon; cold knife or radiate, can freeze, electodesicate;
- mets very rare, occur only if neglected
- no chemo no LN resections
- Txlocal excision with clean margin’s
- 2-3mm margin
- Squamous cell
- RF: UV: exposure, chronic inflam sites, long standing wounds: scar, burn, pilonidal, anal fistulae, xeroderma
- Tx goal: complete removal: excision with narrow margin is acceptable
- Curettage: dermatologist
- Cryotherapy: liquid nitrogen
- Mohs Surgery: Best for face, neck, hands
- Radiation Therapy: inaccessible locations, recurrence
- Topical Chemotherapy: fluorouracil
- Surgical: 2-3mm margin
- Merkel Cell Carcinoma
- Cutaneous neuroendocrine tumor with keratin filaments and cytoplasmic dense core neuroendocrine granules
- Oval shaped synaptic receptor cells
- RF: UV, ICed, polyomavirus
- Occurs in sun damaged skin and lymphatic spread is common
- More common in immunosupporessed
- tx wide excision 1-2cm margin with SNLBx and positive in most
- Chemo: platinum
- Rad: >2cm do radiation
- Bad prognosis, high propensity for local recurrence
- Bowen
- Carcinoma in situ of the skin
- RF: sun exposure, chronic immunosuprresion, hpv
- Tx: WLE
- Spitz Nevi
- Solitary benign melanotic proliferations
- Children < 10 y/o
- Pink/red and dome shaped
- Pattern: starburst transitions to reticular
- Adults: brown or black
- Tx: Excision with 2mm margin
