Pancreatic Neoplasm

Pancreatic Pancreatic NeoplasmNeoplasm

5/24/065/24/06

Brent WhiteBrent White

Richard BarthRichard Barth

Facts About Brent & Facts About Brent & GeorgiaGeorgia

Born in Durham, NC Born in Durham, NC 4/8/744/8/74

My family moved to My family moved to Columbus, Georgia when Columbus, Georgia when I was 6 weeks oldI was 6 weeks old

Georgia is known as “The Georgia is known as “The Goober State”Goober State”

Goober=PeanutGoober=Peanut Georgia produces quite a Georgia produces quite a

few peanuts, growing few peanuts, growing 42% of peanuts grown in 42% of peanuts grown in the USthe US

OverviewOverview

During 2006, estimated 32,300 people During 2006, estimated 32,300 people will die in the US of pancreatic cancerwill die in the US of pancreatic cancer

Fourth and fifth most common cause of Fourth and fifth most common cause of cancer deaths in men and women in the cancer deaths in men and women in the US respectivelyUS respectively

Peak incidence in age 60-80Peak incidence in age 60-80 African Americans with slightly higher African Americans with slightly higher

incidence compared with Caucasiansincidence compared with Caucasians

Types of Pancreatic Types of Pancreatic NeoplasmsNeoplasms

Broadly speaking, there are three Broadly speaking, there are three basic types:basic types:

Ductal adenocarcinoma >90% of Ductal adenocarcinoma >90% of pancreatic cancers with a 4% 5-year pancreatic cancers with a 4% 5-year survival (worst of any cancer)survival (worst of any cancer)

Neuroendocrine tumors aka islet-cell Neuroendocrine tumors aka islet-cell tumors, raretumors, rare

Cystic neoplasms account for <1% of Cystic neoplasms account for <1% of pancreatic cancerspancreatic cancers

Clinical Scenario #1 – Clinical Scenario #1 – Adenocarcinoma of the Adenocarcinoma of the

PancreasPancreas 70yo female with PMH of HTN who 70yo female with PMH of HTN who

developed jaundice without developed jaundice without significant abdominal pain, no feversignificant abdominal pain, no fever

Bilirubin 12Bilirubin 12 No significant complaints of No significant complaints of

abdominal painabdominal pain

Clinical Scenario #1 –Clinical Scenario #1 – Adenocarcinoma of the Adenocarcinoma of the

PancreasPancreas What are typical symptoms of pancreatic What are typical symptoms of pancreatic

CA?CA? Abdominal pain->pain can suggest neural Abdominal pain->pain can suggest neural

plexus, tail lesion, unresectability, poor plexus, tail lesion, unresectability, poor prognosisprognosis

AnorexiaAnorexia Weight lossWeight loss JaundiceJaundice Pruritis ->biliary obstructionPruritis ->biliary obstruction Steatorrhea->pancreatic duct obstructionSteatorrhea->pancreatic duct obstruction

Risk Factors for Pancreatic Risk Factors for Pancreatic Cancer?Cancer?

Firmly linked to cigarette smokingFirmly linked to cigarette smoking No clear dietary factorsNo clear dietary factors Increased BMI associated with Increased BMI associated with

increased riskincreased risk Occupational exposures to amines Occupational exposures to amines

(chemistry, hairdressing, rubber (chemistry, hairdressing, rubber work) associated with increased riskwork) associated with increased risk

Risk Factors for Pancreatic Risk Factors for Pancreatic CancerCancer

Previous epidemiology identified Previous epidemiology identified chronic pancreatitis as a risk factorchronic pancreatitis as a risk factor May actually be EtOH, smoking, and a May actually be EtOH, smoking, and a

degree of selection bias instead of degree of selection bias instead of pancreatitis pancreatitis

Familial excess of pancreatic cancer, Familial excess of pancreatic cancer, hereditary cancer syndromes, hereditary cancer syndromes, hereditary pancreatitis, BRCA-2 hereditary pancreatitis, BRCA-2 mutations all associated with mutations all associated with increased risk of pancreatic cancerincreased risk of pancreatic cancer

Adenocarcinoma of the Adenocarcinoma of the Pancreas: WorkupPancreas: Workup

70yo female with painless jaundice...70yo female with painless jaundice... What would widely be regarded as What would widely be regarded as

the single most useful imaging study the single most useful imaging study in this patient’s workup?in this patient’s workup?

CTCT

Adenocarcinoma of the Adenocarcinoma of the Pancreas: CT scanPancreas: CT scan

CT can confirm pancreatic cancer with CT can confirm pancreatic cancer with a sensitivity of 85-95% (sensitivity is a sensitivity of 85-95% (sensitivity is limited by smaller tumor size)limited by smaller tumor size)

Other than the presence of a pancreatic Other than the presence of a pancreatic mass, what else can you determine mass, what else can you determine from CT scan? from CT scan? PRESENCE of METASTASES (along with PRESENCE of METASTASES (along with

CXR)CXR)

RESECTABILITYRESECTABILITY


What makes a pancreatic mass likely What makes a pancreatic mass likely resectable?resectable? No evidence of extrapancreatic diseaseNo evidence of extrapancreatic disease Evidence of nonobstructive superior Evidence of nonobstructive superior

mesenteric-portal vein confluencemesenteric-portal vein confluence No evidence of direct tumor extension to No evidence of direct tumor extension to

the celiac axis and SMAthe celiac axis and SMA EUS, laparoscopy are universally EUS, laparoscopy are universally

regarded as useful adjuncts to CT, not as regarded as useful adjuncts to CT, not as essential howeveressential however


““Borderline” Resectable lesions Borderline” Resectable lesions include: include:

SMV occlusion of a short segment SMV occlusion of a short segment (open vein proximally and distally)(open vein proximally and distally)

Body and tail lesions with + celiac, Body and tail lesions with + celiac, para-aortic nodes in the vicitypara-aortic nodes in the vicity

Tumors briefly involving the IVC Tumors briefly involving the IVC may be borderlinemay be borderline

Adenocarcinoma of the Adenocarcinoma of the Pancreas: WorkupPancreas: Workup

The mass appears “borderline” The mass appears “borderline” resectable per these criteriaresectable per these criteria

Now what?Now what?

GI consultation for ERCP GI consultation for ERCP and EUS!and EUS!

Pancreatic Cancer: Pancreatic Cancer: Endoscopic AdjunctsEndoscopic Adjuncts

ERCP can be utilized to:ERCP can be utilized to: detecting small tumors not visualized on CT detecting small tumors not visualized on CT

(irregular solitary duct stenoses >1cm long, abrupt (irregular solitary duct stenoses >1cm long, abrupt cutoff of main pancreatic duct, or panc and bile duct cutoff of main pancreatic duct, or panc and bile duct obstruction)obstruction)

palliating biliary obstructionpalliating biliary obstruction brush cytology of the pancreatic duct has fair brush cytology of the pancreatic duct has fair

sensitivity (70%) but excellent specificitysensitivity (70%) but excellent specificity EUS can be utilized to:EUS can be utilized to:

aid in diagnosis and characterization of lesionaid in diagnosis and characterization of lesion obtain tissue biopsy; may be associated with lower obtain tissue biopsy; may be associated with lower

risk of peritoneal seeding c/w percutaneous approachrisk of peritoneal seeding c/w percutaneous approach

Pancreatic Cancer: Pancreatic Cancer: Endoscopic AdjunctsEndoscopic Adjuncts

ERCP pictureERCP picture

Pancreatic Cancer: Pancreatic Cancer: Serum MarkersSerum Markers

Is there a role for serum markers? If so, Is there a role for serum markers? If so, what?what? CA 19-9 is a sialylated Lewis A blood group antigen CA 19-9 is a sialylated Lewis A blood group antigen

commonly expressed and shed in pancreatic and commonly expressed and shed in pancreatic and hepatobiliary disease, not tumor specifichepatobiliary disease, not tumor specific

This antigen, when significantly increased, can assist in This antigen, when significantly increased, can assist in differentiating between pancreatic adenocarcinoma and differentiating between pancreatic adenocarcinoma and inflammatory pancreatic diseaseinflammatory pancreatic disease

decrease in serial CA 19-9 correlates with survival of decrease in serial CA 19-9 correlates with survival of pancreatic patients after surgery or chemotherapypancreatic patients after surgery or chemotherapy

Debatable as to whether this is useful as early treatment Debatable as to whether this is useful as early treatment of recurrences have not been shown to improve of recurrences have not been shown to improve outcomesoutcomes

Pancreatic Cancer Pancreatic Cancer StagingStaging

Though TNM staging exists, we can Though TNM staging exists, we can roughly simplify to:roughly simplify to: local/resectable, median survival 17 local/resectable, median survival 17

monthsmonths locally advanced and unresectable, locally advanced and unresectable,

median survival 8-9 monthsmedian survival 8-9 months metastatic disease, median survival of metastatic disease, median survival of

4-6 months4-6 months

Pancreatic AdenoCA AlgorithmPancreatic AdenoCA Algorithm

Pancreatic Cancer: Pancreatic Cancer: Neoadjuvant TherapyNeoadjuvant Therapy

This 70yo female has “borderline” This 70yo female has “borderline” resectable features, has been stented resectable features, has been stented to answer obstructive jaundice via to answer obstructive jaundice via ERCP with EUS demonstrating a ERCP with EUS demonstrating a positive adenocarcinomapositive adenocarcinoma

Is there any role for neoadjuvant Is there any role for neoadjuvant therapy for this patient? If so, what therapy for this patient? If so, what sort of regimen and with what sort of regimen and with what objectives?objectives?

Pipas, Barth et al.Pipas, Barth et al.

24 patients with pancreatic adenocarcinoma24 patients with pancreatic adenocarcinoma Inclusion criteria: biopsy-proven adenocarcinoma Inclusion criteria: biopsy-proven adenocarcinoma

of pancreas (Stage I-III), age>18yo, Karnofsky of of pancreas (Stage I-III), age>18yo, Karnofsky of >70%, Creatinine<2, WBC >3000, Hgb >10g/dL, >70%, Creatinine<2, WBC >3000, Hgb >10g/dL, Plts >100,000Plts >100,000

No history of chemo/XRT or malignancyNo history of chemo/XRT or malignancy Treatment consisted of docetaxel 65mg/m2 IV Treatment consisted of docetaxel 65mg/m2 IV

over 1 hour and gemcitabine 4000mg/m2 IV over over 1 hour and gemcitabine 4000mg/m2 IV over 30 minutes on days 1, 15, 29. On Day 43, XRT at 30 minutes on days 1, 15, 29. On Day 43, XRT at 50.4 Gray with gemcitabine 50mg/m2 IV over 30 50.4 Gray with gemcitabine 50mg/m2 IV over 30 minutes biweekly for 12 dosesminutes biweekly for 12 doses


All but one of 24 patients completed 12 week All but one of 24 patients completed 12 week course of therapycourse of therapy

Grade 3 and 4 toxicities common, but Grade 3 and 4 toxicities common, but manageablemanageable

No tumor progression, 12 responded to No tumor progression, 12 responded to therapy with one radiographic CRtherapy with one radiographic CR

50% of patients had radiographic response, 50% of patients had radiographic response, 17/24 patients underwent resection after 17/24 patients underwent resection after therapy therapy

Of 17 resection patients, 13 (76%) with Of 17 resection patients, 13 (76%) with negative marginsnegative margins

AdenocarcinomaAdenocarcinoma

70yo female undergoes 70yo female undergoes docetaxel/gemcitabine followed by docetaxel/gemcitabine followed by gemcitabine with XRT and appreciable gemcitabine with XRT and appreciable response is seen on repeat CTresponse is seen on repeat CT

Whipple OperationWhipple Operation Utility to pylorus preservation?Utility to pylorus preservation? Extended lymphadenectomy?Extended lymphadenectomy? Does type of pancreatic anastamosis matter?Does type of pancreatic anastamosis matter? Do stents decrease pancreatic fistulas?Do stents decrease pancreatic fistulas?

Case #2Case #2

28yo surgical resident was golfing, 28yo surgical resident was golfing, badly. Suddenly, according to his badly. Suddenly, according to his partners, he began acting “crazy” partners, he began acting “crazy” and drove the golf cart wildly around and drove the golf cart wildly around the green, through a sandtrap and the green, through a sandtrap and into a small creek. He was into a small creek. He was incoherent when he was brought to incoherent when he was brought to the ER and found to have a serum the ER and found to have a serum glucose of 32.glucose of 32.

How is insulinoma How is insulinoma diagnosed?diagnosed?

Whipple’s Triad:Whipple’s Triad: symptoms of hypoglycemia during fasting or exercisesymptoms of hypoglycemia during fasting or exercise serum glucose <45mg/dL during symptomsserum glucose <45mg/dL during symptoms relief of symptoms with administration of glucoserelief of symptoms with administration of glucose

Definitive test is 72-hour fast with Definitive test is 72-hour fast with measurement of insulin and glucosemeasurement of insulin and glucose

75% of patients develop symptoms and GB<40 within 24 75% of patients develop symptoms and GB<40 within 24 hourshours

insulin:glucose ratio >0.4 is indicative of insulinomainsulin:glucose ratio >0.4 is indicative of insulinoma

Elevated c-peptide proinsulin levels are Elevated c-peptide proinsulin levels are confirmatory along with screening for confirmatory along with screening for antiinsulin antibodies, sulfonylureasantiinsulin antibodies, sulfonylureas

What percent are What percent are malignant?malignant?

10% are malignant, indicated by 10% are malignant, indicated by metastasesmetastases

Metastases usually to regional Metastases usually to regional peripancreatic lymph nodes, liverperipancreatic lymph nodes, liver

generally sporadic, solitary, benign, generally sporadic, solitary, benign, <2cm occurring in equal distribution <2cm occurring in equal distribution throughout the pancreasthroughout the pancreas

How are insulinomas How are insulinomas localized?localized?

Non-invasive preoperative imaging Non-invasive preoperative imaging studies fail to localize 30-35% of studies fail to localize 30-35% of insulinomasinsulinomas

CT/MRI, etc. generally reserved by CT/MRI, etc. generally reserved by most endocrine surgeons to r/o most endocrine surgeons to r/o hepatic metastaseshepatic metastases

Intraoperative U/S and palpation are Intraoperative U/S and palpation are the GOLD standard for finding an the GOLD standard for finding an insulinoma, 96-100% sensitivityinsulinoma, 96-100% sensitivity

What is proper operation What is proper operation for insulinoma?for insulinoma?

Generally wide Kocher maneuver, superior Generally wide Kocher maneuver, superior and inferior pancreatic border mobilization, and inferior pancreatic border mobilization, medial reflection of the spleenmedial reflection of the spleen

Bimanual palpation with U/SBimanual palpation with U/S Enucleation of the lesion Enucleation of the lesion Secretin can assist in identifying pancreatic Secretin can assist in identifying pancreatic

duct leak after enucleation completedduct leak after enucleation completed What about lesion in pancreatic head?What about lesion in pancreatic head? Need to monitor glucose levels q15 minutes Need to monitor glucose levels q15 minutes

until lesion outuntil lesion out

Case #3Case #3

A patient has a gastric ulcer A patient has a gastric ulcer diagnosed endoscopically and is diagnosed endoscopically and is treated with Cimetidine. One month treated with Cimetidine. One month later, the ulcer is still present later, the ulcer is still present despite treatment.despite treatment.

How is ZE diagnosis How is ZE diagnosis made?made?

Elevated serum gastrin level, elevated Elevated serum gastrin level, elevated basal acid secretory rate both only basal acid secretory rate both only suggest possible gastrinomasuggest possible gastrinoma

Secretin stimulation testSecretin stimulation test discontinue acid-inhibitory medicationdiscontinue acid-inhibitory medication basal serum gastrin levelsbasal serum gastrin levels 2 U/kg of secretin IV bolus, then serum gastrin 2 U/kg of secretin IV bolus, then serum gastrin

measured at 2, 5, 10, and 20 minutes latermeasured at 2, 5, 10, and 20 minutes later Positive response is gastrin >200pg/mL above Positive response is gastrin >200pg/mL above

basal levelbasal level

How would you control How would you control gastric acid secretion?gastric acid secretion?

Proton pump inhibitor titrated to Proton pump inhibitor titrated to achieve non-acidic gastric pHachieve non-acidic gastric pH

Where are gastrinomas? Where are gastrinomas? How would you localize How would you localize

it?it? Most are found in the duodenum, Most are found in the duodenum,

pancreas, or lymph nodes near the head of pancreas, or lymph nodes near the head of the pancreas, 10% of the time they are the pancreas, 10% of the time they are heart, liver, bile ducts, ovary, etc.heart, liver, bile ducts, ovary, etc.

Localization with somatostatin receptor Localization with somatostatin receptor scintigraphy (SRS) (only 30% of scintigraphy (SRS) (only 30% of gastrinomas <1.1cm)gastrinomas <1.1cm)

SRS and EUS can, in tandem, improve SRS and EUS can, in tandem, improve detection of small gastrinomas within the detection of small gastrinomas within the wall of the duodenumwall of the duodenum

At operation, what is the At operation, what is the likelihood of finding likelihood of finding metastatic tumor? metastatic tumor?

Metastatic tumor to liver is found in Metastatic tumor to liver is found in 5-14% of cases, nodal metastases in 5-14% of cases, nodal metastases in 50% of patients50% of patients

Where are most Where are most gastrinomas found?gastrinomas found?

Gastrinoma triangle is Gastrinoma triangle is where most tumors are where most tumors are found (70-90%)found (70-90%)

Tumor detection can be Tumor detection can be improved via palpation, improved via palpation, IOUS, extended Kocher IOUS, extended Kocher maneuver, maneuver, transillumination of the transillumination of the duodenum, and duodenum, and duodenotomyduodenotomy

Hypercalcemia and Hypercalcemia and GastrinomaGastrinoma

If patient has MEN-1 (hyperparathyroidism, If patient has MEN-1 (hyperparathyroidism, pituitary adenoma, islet-cell tumor), can they pituitary adenoma, islet-cell tumor), can they be cured with surgery for gastrinoma?be cured with surgery for gastrinoma? Seldom can biochemical cure be achieved due to Seldom can biochemical cure be achieved due to

multicentric nature of disease in MEN-1multicentric nature of disease in MEN-1 93% of patient with MEN-1 alive 15 years after 93% of patient with MEN-1 alive 15 years after

diagnosis, if they are on PPI’s and have no liver diagnosis, if they are on PPI’s and have no liver metsmets

some advocate surgical treatment only in sporadic some advocate surgical treatment only in sporadic form of disease; others propose operating on form of disease; others propose operating on MEN-1 gastrinomas only when 2.5-3cm in size in MEN-1 gastrinomas only when 2.5-3cm in size in order to reduce possibility of metastasesorder to reduce possibility of metastases

Pancreatic Neoplasm

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