Neoplastic diseases of the Stomach/Pancreas/Liver

John D. B. Dockins, MD Friday Academic Session 12/17/10

 Gastric Cancer - Anatomy - Overview - Epidemiology - Staging - Surgery - Combined Modality Treatment - Treatment Guidelines - Summary


Anatomy .


GE junction  Major Health Problem Worldwide  2009 US Stats .600 new cases .Overview  Cancers of UGI Tract .37.25.150 deaths .Esophagus .Stomach .

 Rampant in Many Countries worldwide - 4th most common Worldwide - Japan’s most common cancer in men  Incidence declining since WWII

- One of least common in US
- 21,130 new cases 2009 - 10,620 eventual deaths 2009  Gastric Adenocarcinoma - Cardiac origination dominates in West - Non-cardiac/Distal dominates East (Japan, Korea, former USSR)

 Often Dx at advanced stage - Japan/Korea earlier detection (↑↑ screening)  Environmental risk factors - H. Pylori - Smoking - High salt intake - Dietary factors  Genetic factors - Higher risk with family history - 1-3% associated with inherited syndromes - E-Cadherin mutations in 25% of a hereditary diffuse gastric cancer (genetic counseling recommended)

 2 Major classifications - Japanese (elaborate, anatomy, nodes) - AJCC and UICC (Western Hemisphere) - 15 LN recommended for adequate staging

Baseline Stage useful in tx strategy
- 50% present w/advanced disease (poor outcome) - Poor performance status, mets., Alk Phos. > 100 U/L

Localized, resectable disease - Outcome based on surgical stage - 70-80% pts. have regional +LN mets. (# has profound influence on survival)


78%) . CT(53%) or PET(47%)  PET – not adequate as primary detection or staging modality .Improved specificity (92% vs.higher accuracy in pre-op staging (68%) vs.Lower detection rate than CT alone .Pre-op Staging  Clinical staging has greatly improved with diagnostic modalities  CT.Lower sensitivity than CT for LN involvement (56% vs. 62%) .routinely used (43-82%) sensitivity for T stage  PET-CT .

Metastatic dz.N stage accuracy 50-95% (operator dependent) .Good for occult metastasis .May be used in unfit if there is consideration for adding radiation to chemo .MSKCC study – 657 staged laparascopically .Usually reserved for medically fit with resectable dz.Distant nodal evaluation suboptimal  Laparoscopy . .assesses tumor depth . in 31% of patients . and perigastric LN .Limitations were 2D evaluation and detecting hepatic mets.T stage accuracy 65-92% .Pre-op Staging  EUS .

Pre-op Staging  Cytogenetic analysis .Reports suggest (+) peritoneal cytology is an independent predictor for ↑ risk of recurrence following curative resection .

total) and extent of lymphadenectomy is controversial .Surgery  Primary treatment for early stage gastric cancer is surgery  Standard goal is complete resection with adequate margins (4cm or greater)  Type of resection (subtotal vs.

associated with post-op nutritional impairment .Significantly fewer complications  Proximal or total gastrectomy both indicated for proximal gastric cancer .R2 . .macroscopic residual dz.50% reach R0 resection of primary lesion  Subtotal gastrectomy is preferred approach for distal gastric cancers .Surgery  Primary goal is to accomplish complete resection with (-) margins (R0) . .Similar outcome as total gastrectomy .R1 – microscopic residual dz.

Surgery     Clinical Staging with CT +/.Marginal survival benefit .T3 tumors – distal. or subtotal gastrectomy T4 tumors. total gastrectomy .en-block resection of involved structures Routine splenectomy should be avoided .Studies do not support prophylactic splenectomy to remove macroscopically negative LN  Placement of feeding jejunostomy considered for those receiving post-op chemoradiation .EUS is done pre-op T1b.Slightly ↑ morbidity and mortality in pts. total. undergoing total gastrectomy + splenectomy vs.

is symptomatic and LN dissection not required   Gastric bypass with gastrojejunostomy to proximal stomach used for palliation of symptomatic obstruction Feeding jejunostomy or venting gastrotomy may also be considered .Distant metastasis .Peritoneal involvement .Surgery  Unresectable disease .Locally advanced disease (involvement or encasement of major blood vessels)   Limited gastric resection is acceptable for symptomatic palliation of bleeding (+ margins acceptable) Palliative gastric resection should not be performed unless pt.

D2 – LN along main tunks of celiac axis .D1 – perigastric LN .Surgery  LN dissection – Controversial  Nodal stations defined in proximity to stomach .D0 – no effort to resect LN (palliative) .

Surgery  Japanese surgeons advocate D2 LN dissection .D2 vs D1 LN dissection .D1 vs D2 LN dissection (Japanese instructor) .↑ postop morbidity .Probably influenced long-term mortality .report ↑ overall survival   Several Western trial have investigated D2 LN dissection on outcome British Medical Group .no benefit in overall survival or recurrence free survival  Dutch Group .no benefit in overall survival  Both trials incorporated distal pancreatectomy and splenectomy .

N2 – 7-15 LN .Surgery  Retrospective analysis comparing D2 vs D1 without pancreaticosplenectomy demostrate favorable survival in D2 group  Benefit of aggressive lymphadenectomy is more accurate staging  MSKCC .number of LN.15+ LN improve prognostication and outcome  Likely due to improved staging (don’t erroneously pts.N3 . With occult metastasis . not location is important in prognosis .N1 – 1-6 LN .> 15 LN .

no ulceration .well or moderately differentiated tumors .tumors <30mm  Promising.Limited in US  Indications .used for Tis or T1a tumors .no invasive findings .Major advance in endoscopic surgery .require limited resection (5yr survival>90%) .Surgery  Endoscopic Mucosal Resection (EMR) . Routine use limited to clinical trials (no Class 1 data comparisons  Proper patient selection is key .

.3 vs 54.7 .↓ blood loss .Mortality 3.↓ pain and hospitalization .3 vs 6.8 vs 55.↑ recovery . laparascopic subtotal gastrectomy .7 .5yr OS rates 59.Surgery  Laparascopic resection offers advantages .↑ return of bowel funtion  Hulscher and colleagues .DFS vs.59 pts.8  Not statistically significant  More trials needed .

Undergoing RO curative resection . .median time of death 6 months  High likelyhood of recurrence has stimulated interest in combined modality therapies for resected gastric cancer .Combined Modality Treatment  Adjuvant Therapy  MSKCC analysis of 1172 pts.79% picked up w/in 2yrs.54% locoregional .42% incidence of recurrent disease after long term follow-up .51% distant loci .

Combined Modality Treatment    Adjuvant chemotherapy +/.54% had less than D1 dissection . adjuvant chemoradiation is suggested as standard of care in US Intergroup 0016 trial .radiation has failed to demostrated benefit survival However.Probably equal to outcomes of extensive LN dissection (>15LN) . leucovorin and external beam radiation to observation .Flawed quality control .↑↑ overall and disease free survival .Recommended D2 dissection (10% got it) .compared post-op 5-FU.

radiation not used  Parameters guiding appropriate selection of patient currently unavailable .suggest ↑ resectability and more durable overall survival .Review of Intergroup 0116 .only 64% were able to complete therapy  Potential benefits of pre-op chemotherapy  Oncologic benefit of chemo or chemorads controversial  MAGIC trial compared pre-op chemo to surgery alone .Combined Modality Treatment  Neoadjuvant Therapy .

EUS if potentially resectable H. Radiation Oncology.CBC . weight loss. N/V. Endocopist)  Workup .CT +/.Pylori testing .Upper endoscopy . Nutritionist.CXR .CMP .Usually present with anemia. Surgical.PET . and/or bleeding -H&P .Treatment guidelines  Management requires multidisciplinary approach (Medical.

Into 3 groups  Localized – (Tis or T1a)  Locoregional – (Stage 1-3) .Medically fit w/potential for resection .Medically unfit  Metastatic (Stage 4 or M1) .Medically fit but unresectable .Treatment guidelines  Initial Workup classifies pts.

Surgery for medically fit and T1b tumors .Treatment guidelines  Primary treatment .EMR or surgery for medically fit (Tis or T1) . may be observed or offered surgery if appropriate .4Gy) with senstization or palliative chemotherapy for medically fit patient with unresectable disease .Medically unfit or fit with unresectable disease need restaging after completion of therapy  If complee response.Advancd tumors receive perioperative chemotherapy (Calss 1) or pre-op chemoradiation (Class 2B) for T2 and higher tumors in medically fit .RT (45-50.

T3< require chemorads . T2NO may be observed . T1NO.Based on surgical margins and nodal status .Tis.T2N0 with high risk features require postop chemorads .Treatment guidelines  Post-op Treatment .

Palliation  Bleeding – endoscopy or angioembolization  Ostruction – gastrojujunostomy.RT and pain meds  N/V .antiemetics . PEG  Pain. stenting.

Epidemiology .Treatment Guidelines .Summary .Surgery .Staging .Combined Modality Treatment .Anatomy .Hepatobiliary Cancer  .

porphyria cutanea tarda.aflatoxin  Most cases risk factor for HCC mimic risk factors for liver cirrhosis . alpha 1 antitrypsin disorder .most common hepatobiliary cancer  Risk factors .Non-alcoholic fatty liver disease .Chronic Hepatitis B/Hepatitis C .Epidemiology  Hepatocellular Carcinoma .autoimmune hepatitis .hereditary hemochromatosis.excessive alcohol intake .

Combined modalities better  At.periodic screening with U/S and AFP testing every 612mo .risk populations .Epidemiology  Screening for HCC .AFP and liver U/S most widely used .Additional imaging (CT with contrast) recommended with ↑ AFP level or findings of liver mass nodule .U/S alone is better than AFP alone .

Ascites .Paraneoplastic syndromes (hyperlipidemia.Hepatomegaly . Hypercalcemia. Hypoglycemia .Diagnosis and Work-up  HCC is asymptomatic for most of its course  Symptoms Usually nonspecific jaundice anorexia malaise upper abdominal pain  Signs .

1-2cm nodule needs two imaging modalities .Diagnosis and Workup  Imaging   HCC lesions are hypervascular Derive most of blood supply from hepatic artery Triphasic helical CT Trphasic cortrast MRI Classic imaging profile is intense arterial uptake followed by contrast washout or hypodensity in delayed phase Pts w/liver mass on U/S should receive one or more imaging modalities .Tissue sampling recommended when classic pattern not observed or seen with only one modality .classic arterial enhancement in 2 modalities is considered diagnostic of HCC .

Diagnosis and Workup  Biopsy .Highly dependent on operator skill .additional histological tests may be performed Use of biopsy is limited .change in size of a nodule warrants additional imaging or biopsy    .provides cytology and architecture .Needle core biopsy (preferred) or FNA is recommended in some cases FNA .rapid staining and examining samples .nondiagnostic biopsies should be followed closely .possible high false negative and false positive rates NCB .more invasive .May not be required .may have lower complication rate .

Comorbidity assessment .Abdominal LN .Imaging studies to look for mets.Bone .Hepatitis panel . .evaluation of Hepatic function and presence of portal HTN  Common sites of metastasis .Multidisciplinary team .Diagnosis and Workup  Initial Workup .Lung .

Diagnosis and Workup  Chest Imaging and bone scan recommended as part of initial workup  Triphasic CT or MRI .metastatic disease .portal HTN .size. location and estimate of liver remnant in relation to total volume .tumor burden .vascular invasion .

Diagnosis and Workup  Liver function Testing serum bilirubin AST/ALT Alk Phos. PT/PTT/INR albumin protein  Child-Pugh classification .3 classes according to likelihood of survival .


ranges from 6 (less ill) to 40 (gravely ill) .used by UNOS for transplant waiting list stratification .Diagnosis and Workup  Model for End-Stage Liver Disease (MELD) .sometimes used in place of Child-Pugh classification to asses prognosis in liver cirrhosis .numerical scale .


diffuse involvement of many small indistinct nodules .associated with cirrhosis .with or w/out satellite nodules  Diffuse .Less common .usally non-cirrhotic liver .occupies large area .well circumscribed nodules  Massive .Pathology   3 types of HCC identified Nodular .


) .Underlying liver dz complicates management .Management  Vascular invasion major predictor of outcome after resection  Pt.different types of HCC may impact tx. with HCC must be carefully evaluated . response . Transplant surgeons. etc. IR.Treatmentnecessitates involvement of large teams (Hepatologist. pathologists.

Management  Partial Hepatectomy .No portal HTN .Child-Pugh score A .potentially curative in early stage HCC who are eligible .can be performed with low morbidity and mortality (5% or less) .some studies report 5yr survival over 50% .70% with good functional reserve .High incidence of recurrence .Child-Pugh score B may be considered in selected cases (normal LFT’s) .Careful patient selection is essential  Resection recommended only in setting of preserved liver function .

Management  Liver Transplantation .avoids complications associated with a small FLR . With early HCC . potentially curative option for pts. Of choice in early HCC and moderate to severe cirrhosis (Child class B and C) .treats cirrhosis .removes detectable and undetectable LN .UNOS specify that candidates for transplant should not be candidates for resection  Initial tx.attractive.

temperature (RFA. acetic acid) .low complication rate (4% and 0%) . cryoablation.most common methods are RFA percutaneous ethanol injection (PEI) . microwave) .Chemical exposure (ethanol.Management  Local Regional Therapy – directed at inducing selective tumor necrosis  Has not been established as comparable to transplant or hepatectomy  Alation .can be performed laparascopically. open or percutaneous .

Management  Embolization .absence of extrahepatic disease .not amenable to ablation .all HCC tumors may be amenable to embolization provided that the blood supply may be isolated . subsegment. inoperable – embolization.Limited to segment. or lobe .Unresectable/inoperable disease . 3-5cm inoperable ablation + embolization .based on tumor blood supply .>5cm.catheter based infusion of particles targeted to the branch of hepatic artery feeding tumor .

Generally reserved for very advanced liver disease  Usually only given to unresectable HCC in presence of clinical trial  Sorafenib.not suitable for transplant .local disease only in pts non-operable .unresectable .recommended for Child Class A .Management  Systemic therapy.

then every 6mo  Reevaluation undertaken for progression or recurrence .Surveillance  Cross sectional imaging every 36months for 2yrs. then annually  AFP levels if initially elevated should be measured every 3mo for 2yrs.

Gallstones .Gallbladder cancer  Risk factors .chronic inflammation .calcification (porcelain gallbladder) .

evaluation of hepatic reserve .CT abdomen to assess extent and nodal disease .Chest XR or CT .Often dx.LFTs.aggressive tumor .Diagnosis and Workup  Often diagnosed at advanced stage .Cholangiography (MRCP preferred over ERCP or PTC unless intervention planned) .CEA Ca 19-9 (not specific) . as incidental finding at surgery or on pathology review following cholecystectomy  Workup of suspicious mass on U/S or jaundice .clinical presentation mimics biliary colic or chronic cholecystitis .

often have early spread to lymph nodes and bloodstream  Poor prognosis .5yr survival 39% stage 1 .1% stage 4 .Pathology and Staging  80% adenocarcinomas .


Management  Surgery only curative modality  All pts. gastrohepatic ligament Nodal disease outside of this area is unresectable . needCT/MRI and chest imaging prior to surgery  Staging laparoscopy should beconsidered prior to laparotomy  Recommended surgery for known diagnosis cholecystectomy en-bloc hepatic resection lymphadenectomy with or without bile duct excision Portahepatis.retroduodenal.

possible chemotherapy or chemoradiation (usually in clinical trial) .Recommend extended cholecystectomy .biliary drainage .T1a may be observed (no muscle involvement) .Should not be performed by inexperienced surgeon or unknown resectability  Unresectable disease .Management  Surgery for tumor detected after cholecystectomy . then hepatic resection and lymphadenectomy .biopsy to confirm diagnosis .74% found to have residual dz during reexploration .supportive care .T1b or greater require metastatic workup.

Cholangiocarcinoma  Tumors originating from epithelium of bile duct  Distinguished by anatomic site  Intrahepatic .peripheral cholagiocarcinomas .located within hepatic parenchyma  Extrahepatic hilar cholangiocarcinomas(Klatskins tumors) usually near junction of left and right hepatic ducts more common hilar is most common type .

gallstones not related .May be associated with chronic inflammation .Primary sclerosis cholangitis .Hep C may be associated with intrahepatic forms .chronic calculi .Choledochal cysts .liver fluke infections .Cholangiocarcinoma  Risk factors .No predisposing factors have been identified in most patients .

may be detected as isolated intrahepatic mass on imaging  Extrhepatic likely to present with .weight loss .Diagnosis and workup  Typically asymptomatic  Intrahepatic likely to present with .fever .jaundice followed by obstruction .abdominal pain .biliary obstruction uncommon .

LFTs . ERCP vs.Diagnosis and Workup  Workup . PTC) .Cholangiography in patients with jaundice (MRCP vs.Delayed contrast CT/MR (helpful in determining resectability) .CEA and Ca 19-9 (not specific) .Chest imaging .

intraductal .periductal .Pathology and staging  >90% adenocarcinomas  Divided into 3 types .Mass forming .



Not candidates for surgery due to advanced dz.Complete resection on curative modality .most pts.Management  Intrahepatic cholangiocarcinoma . At presentation Surgery involves removing entire lobe or segment along the involved duct     R0 resetion associated with longer survival rates 20-43% 5yr survival R0 resections may be observed   R1 or R2 need individualized therapy Unresectable disease – chemo. supportive care . clinical trial. chemorads.

complete resction main curative strategy  Surgical procedure based on location . or chemorads (no standard) Liver transplant only other possible curative modality for extrahepatic cholangiocarcinoma . . chemo. assessment of margins .Management  Extrahepatic cholangiocarcinomas .normal biliary function   .Mid 1/3 – major bile duct excision with lymphadenectomy.unresectable dz.Distal 1/3 – Pancreaticoduodenectomy R0 resection may be observed.Proximal 1/3 – hilar resection with lymphadenectomy and en-bloc liver resection .

or chemorads (no standard)  Metastatic disease – as above .biliary drainage (PTC or ERCP +stent) . chemo.Management  Distal strictures .biopsy .ERCP with brushing and stenting  Unresectable disease .clinical trial.

all should be evaluated for treatment  Careful selection and multidisciplinary approach are essential . With hepatobiliary cancers found at advanced stage.Surveillance  No data to support aggressive surveillance  Imaging every 6mo to 2yrs  Although most pts.

Pancreatic Adenocarcinoma  36.800 die each year  4th MCC death in US men and women  Peak incidence 7th and 8th decades  African American have higher incidence than whites .

Anatomy .

occupational exposure to chemicals(benzidine and betanaphthylamine) .incresed meat and dairy products .alcohol intake .Increased BMI .chronic pancreatitis .Cigarette smoking .Pancreatic adenocarcinoma  Risk factors .

May be associated with BRCA2 mutations .Pancreatic adenocarcinoma  Familial pancreatic cancer is rare .5-10% may have genetic predisposition .Assess family history .

Should undergo helical or spiral CT with pancreatic protocol if pancreatic cancer is suspected    .pain .Diagnosing and staging   Ductal adenocarcinoma >90% of pancreatic malignancies Presenting symptoms .dyspepsia .weight loss .depression No early warning signs May be considered in diabetics presentin>50 or with unusual manifestations Pts.nausea .jaundice .floating stools .

Imaging  CT best and most widely used .Thin slices  Helps to distinguish resectable vs. venous) . unresectable      CT is primary means through which stage is determined 70-85% determined to have resectable tumors by CT were able to undergo resection (specificity > sensitivity) MRI may be sued if CT isn’t possible EUS is complementary to CT Chest imaging . late arterial.Triphasic (arterial.

 Laparoscopy is a a valuable staging tool – may pick up implants missed by CT  Tumor antigens .Ca 19-9 – should be performed after biliary decompression .low postop Ca 19-9 levels and declining levels ater surgery are associated with improved survival .

Staging and resectability  Patients with stage 0. or 2 are generally considered resectable  Some surgeons will resect patients with stage 3 tumors  Pts. With tumor confined to the pancreas and resected LN w/o vascular invasion are candidates for surgery . 1.


may be used in locally invasive disease .radiation .Chemoradiation  Neoadjuvant therapy is not routinely performed .10% downstaging  Adjuvant therapy is the standard of care with chemotherapy +/.

delayed gastric emptying in 15%  Postop chemotherapy is given  Palliation may involve biliary drainage for recurrent or metastatic disease  Sympathetic denervation may be performed for intractable pain .Surgery  Pancreaticoduodenectomy is treatment .

References  NCCN guidelines  Cameron .

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