neoplastic diseases of the stomach

7/31/2019 Neoplastic Diseases of the Stomach

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Neoplastic diseases of theStomach/Pancreas/Liver

John D. B. Dockins, MD

Friday Academic Session

12/17/10


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Outline

Gastric Cancer

- Anatomy

- Overview

- Epidemiology

- Staging

- Surgery

- Combined ModalityTreatment

- Treatment Guidelines

- Summary


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Anatomy


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Anatomy


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Overview

Cancers of UGITract- Stomach

- Esophagus- GE junction

Major HealthProblem Worldwide

2009 US Stats- 37,600 new cases- 25,150 deaths


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Epidemiology

Rampant in Many Countries worldwide

- 4th most common Worldwide

- Japans 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)


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Epidemiology 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)


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Staging 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 onsurvival)


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Pre-op Staging

Clinical staging has greatly improved with diagnosticmodalities

CT- routinely used (43-82%) sensitivity for T stage

PET-CT

- Lower detection rate than CT alone

- Lower sensitivity than CT for LN involvement (56%vs. 78%)

- Improved specificity (92% vs. 62%)

- higher accuracy in pre-op staging (68%) vs.CT(53%) or PET(47%)

PET not adequate as primary detection or stagingmodality


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Pre-op Staging EUS

- assesses tumor depth

- T stage accuracy 65-92%

- N stage accuracy 50-95% (operator dependent)

- Distant nodal evaluation suboptimal

Laparoscopy

- Good for occult metastasis

- MSKCC study 657 staged laparascopically

- Metastatic dz. in 31% of patients

- Limitations were 2D evaluation and detecting hepatic mets. andperigastric LN

- Usually reserved for medically fit with resectable dz.

- May be used in unfit if there is consideration for adding radiation to chemo


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Pre-op Staging

Cytogeneticanalysis

- Reports suggest(+) peritonealcytology is anindependent

predictor for riskof recurrencefollowing curativeresection


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Surgery

Primary treatment forearly stage gastriccancer is surgery

Standard goal iscomplete resectionwith adequate margins(4cm or greater)

Type of resection

(subtotal vs. total) andextent oflymphadenectomy iscontroversial


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Surgery

Primary goal is to accomplish complete resection with (-) margins(R0)

- R1 microscopic residual dz.

- R2 - macroscopic residual dz.

- 50% reach R0 resection of primary lesion

Subtotal gastrectomy is preferred approach for distal gastriccancers

- Similar outcome as total gastrectomy

- Significantly fewer complications

Proximal or total gastrectomy both indicated for proximalgastric cancer

- associated with post-op nutritional impairment


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Surgery

Clinical Staging with CT +/- EUS is done pre-op

T1b- T3 tumors distal, total, or subtotal gastrectomy

T4 tumors- en-block resection of involved structures

Routine splenectomy should be avoided

- Slightly morbidity and mortality in pts. undergoing totalgastrectomy + splenectomy vs. total gastrectomy

- Marginal survival benefit

- Studies do not support prophylactic splenectomy to removemacroscopically negative LN

Placement of feeding jejunostomy considered for those receivingpost-op chemoradiation


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Surgery

Unresectable disease

- Peritoneal involvement

- Distant metastasis

- Locally advanced disease (involvement or encasement of majorblood vessels)

Limitedgastric resection is acceptable for symptomaticpalliation of bleeding (+ margins acceptable)

Palliative gastric resection should not be performed unless pt. issymptomatic and LN dissection not required

Gastric bypass with gastrojejunostomy to proximal stomachused for palliation of symptomatic obstruction

Feeding jejunostomy or venting gastrotomy may also beconsidered


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Surgery

LN dissection Controversial

Nodal stations defined

in proximity tostomach

- D0 no effort toresect LN (palliative)

- D1 perigastric LN

- D2 LN along maintunks of celiac axis


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Surgery

Japanese surgeons advocate D2 LN dissection

- report overall survival

Several Western trial have investigated D2 LN dissection onoutcome

British Medical Group

- D2 vs D1 LN dissection- postop morbidity- no benefit in overall survival or recurrence free survival

Dutch Group- D1 vs D2 LN dissection (Japanese instructor)- no benefit in overall survival

Both trials incorporated distal pancreatectomy and splenectomy- Probably influenced long-term mortality


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Surgery

Retrospective analysis comparing D2 vs D1 withoutpancreaticosplenectomy demostrate favorable survivalin D2 group

Benefit of aggressive lymphadenectomy is more

accurate staging

MSKCC- number of LN, not location is important in prognosis- N1 1-6 LN- N2 7-15 LN

- N3 - > 15 LN- 15+ LN improve prognostication and outcome

Likely due to improved staging (dont erroneously pts.With occult metastasis


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Surgery

Endoscopic Mucosal Resection (EMR)- Major advance in endoscopic surgery- used for Tis or T1a tumors- require limited resection (5yr survival>90%)- Limited in US

Indications- well or moderately differentiated tumors- no ulceration- no invasive findings- tumors


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Surgery

Laparascopic resection offers advantages- blood loss- pain and hospitalization- recovery- return of bowel funtion

Hulscher and colleagues- open vs. laparascopic subtotal gastrectomy- 59 pts.- Mortality 3.3 vs 6.7- 5yr OS rates 59.8 vs 55.7

- DFS 57.3 vs 54.8

Not statistically significant

More trials needed


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Combined Modality Treatment

Adjuvant Therapy

MSKCC analysis of 1172 pts. Undergoing RO curativeresection

- 42% incidence of recurrent disease after long termfollow-up- 54% locoregional- 51% distant loci- 79% picked up w/in 2yrs.- median time of death 6 months

High likelyhood of recurrence has stimulated interestin combined modality therapies for resected gastriccancer


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Adjuvant chemotherapy +/- radiation has failed todemostrated benefit survival

However, adjuvant chemoradiation is suggested asstandard of care in US

Intergroup 0016 trial

- compared post-op 5-FU, leucovorin and external beamradiation to observation

- overall and disease free survival

- Flawed quality control

- Recommended D2 dissection (10% got it)

- 54% had less than D1 dissection

- Probably equal to outcomes of extensive LN dissection(>15LN)


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Neoadjuvant Therapy- 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- suggest resectability and more durable overallsurvival

- radiation not used

Parameters guiding appropriate selection of patientcurrently unavailable


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Treatment guidelines

Management requires multidisciplinary approach(Medical, Surgical, Radiation Oncology, Nutritionist,Endocopist)

Workup

- Usually present with anemia, weight loss, N/V,and/or bleeding- H & P- CXR

- Upper endoscopy- CBC- CMP- CT +/- PET- EUS if potentially resectable H.Pylori testing


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Initial Workup classifies pts. Into 3 groups

Localized (Tis or T1a)

Locoregional (Stage 1-3)

- Medically fit w/potential for resection- Medically fit but unresectable- Medically unfit

Metastatic (Stage 4 or M1)


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Primary treatment

- EMR or surgery for medically fit (Tis or T1)

- Surgery for medically fit and T1b tumors

- Advancd tumors receive perioperative chemotherapy(Calss 1) or pre-op chemoradiation (Class 2B) for T2 andhigher tumors in medically fit

- RT (45-50.4Gy) with senstization or palliativechemotherapy for medically fit patient with unresectabledisease

- Medically unfit or fit with unresectable disease needrestaging after completion of therapy

If complee response, may be observed or offered surgery ifappropriate


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Post-op Treatment

- Based on surgical margins and nodalstatus

- Tis, T1NO, T2NO may be observed

- T2N0 with high risk features require

postop chemorads

- T3< require chemorads


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Palliation

Bleeding endoscopy orangioembolization

Ostruction gastrojujunostomy,stenting, PEG

Pain- RT and pain meds

N/V - antiemetics


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Hepatobiliary Cancer

- Anatomy- Epidemiology- Staging

- Surgery- CombinedModality Treatment- Treatment

Guidelines- Summary


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Epidemiology

Hepatocellular Carcinoma

- most common hepatobiliary cancer

Risk factors

- Chronic Hepatitis B/Hepatitis C- hereditary hemochromatosis, porphyria cutanea tarda, alpha 1antitrypsin disorder

- autoimmune hepatitis

- Non-alcoholic fatty liver disease

- excessive alcohol intake

- aflatoxin

Most cases risk factor for HCC mimic risk factors for liver cirrhosis


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Epidemiology

Screening for HCC

- AFP and liver U/S most widely used

- U/S alone is better than AFP alone

- Combined modalities better

At- risk populations

- periodic screening with U/S and AFP testing every 6-

12mo- Additional imaging (CT with contrast) recommendedwith AFP level or findings of liver mass nodule


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Diagnosis and Work-up

HCC is asymptomatic for most of its course

Symptoms Usually nonspecific

- jaundice

- anorexia- malaise- upper abdominal pain

Signs

- Hepatomegaly- Ascites- Paraneoplastic syndromes (hyperlipidemia,Hypercalcemia, Hypoglycemia


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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 bycontrast washout or hypodensity in delayed phase

Pts w/liver mass on U/S should receive one or more imagingmodalities

- 1-2cm nodule needs two imaging modalities

- classic arterial enhancement in 2 modalities is considereddiagnostic of HCC

- Tissue sampling recommended when classic pattern not observedor seen with only one modality


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Biopsy- May not be required- Needle core biopsy (preferred) or FNA is recommended in somecases

FNA

- may have lower complication rate- rapid staining and examining samples- Highly dependent on operator skill- possible high false negative and false positive rates

NCB- more invasive- provides cytology and architecture

- additional histological tests may be performed

Use of biopsy is limited- nondiagnostic biopsies should be followed closely- change in size of a nodule warrants additional imaging or biopsy


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Initial Workup

- Multidisciplinary team

- Hepatitis panel

- Comorbidity assessment

- Imaging studies to look for mets.

- evaluation of Hepatic function and presence of portal HTN

Common sites of metastasis- Lung

- Abdominal LN

- Bone


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Chest Imaging and bone scan recommended as partof initial workup

Triphasic CT or MRI

- tumor burden

- metastatic disease

- vascular invasion

- portal HTN- size, location and estimate of liver remnant inrelation to total volume


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Liver function Testing

- serum bilirubin- AST/ALT- Alk Phos.- PT/PTT/INR- albumin- protein

Child-Pugh classification

- 3 classes according to likelihood of survival


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Model for End-Stage Liver Disease (MELD)

- numerical scale

- ranges from 6 (less ill) to 40 (gravely ill)

- sometimes used in place of Child-Pughclassification to asses prognosis in livercirrhosis

- used by UNOS for transplant waiting liststratification


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Pathology

3 types of HCC identified

Nodular- associated with cirrhosis

- well circumscribed nodules

Massive- usally non-cirrhotic liver

- occupies large area- with or w/out satellitenodules

Diffuse- Less common- diffuse involvement of manysmall indistinct nodules


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Management

Vascular invasion major predictor of outcome afterresection

Pt. with HCC must be carefully evaluated

- Underlying liver dz complicates management

- different types of HCC may impact tx. response

- Treatmentnecessitates involvement of large teams

(Hepatologist, IR, Transplant surgeons, pathologists,etc.)


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Management

Partial Hepatectomy

- potentially curative in early stage HCC who are eligible- can be performed with low morbidity and mortality (5% orless)- some studies report 5yr survival over 50%

- 70% with good functional reserve- High incidence of recurrence- Careful patient selection is essential

Resection recommended only in setting of preserved liverfunction

- Child-Pugh score A- No portal HTN- Child-Pugh score B may be considered in selected cases(normal LFTs)


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Management

Liver Transplantation

- attractive, potentially curative option for pts. Withearly HCC- removes detectable and undetectable LN

- treats cirrhosis- avoids complications associated with a small FLR- UNOS specify that candidates for transplant shouldnot be candidates for resection

Initial tx. Of choice in early HCC and moderate tosevere cirrhosis (Child class B and C)


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Management

Local Regional Therapy directed at inducingselective tumor necrosis

Has not been established as comparable to transplantor hepatectomy

Alation- Chemical exposure (ethanol, acetic acid)- temperature (RFA, cryoablation, microwave)- can be performed laparascopically, open or

percutaneous- most common methods are RFA percutaneousethanol injection (PEI)- low complication rate (4% and 0%)


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Management

Embolization

- based on tumor blood supply

- catheter based infusion of particles targeted to the branch ofhepatic artery feeding tumor

- Limited to segment, subsegment, or lobe

- all HCC tumors may be amenable to embolization provided thatthe blood supply may be isolated

- Unresectable/inoperable disease

- not amenable to ablation

- absence of extrahepatic disease

- >5cm, inoperable embolization, 3-5cm inoperable ablation +embolization


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Management

Systemic therapy- Generally reserved forvery advanced liver disease

Usually only given to unresectable HCC inpresence of clinical trial

Sorafenib- recommended for Child Class A

- unresectable- not suitable for transplant- local disease only in pts non-operable


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Surveillance

Cross sectional imaging every 3-6months for 2yrs, then annually

AFP levels if initially elevated shouldbe measured every 3mo for 2yrs,then every 6mo

Reevaluation undertaken forprogression or recurrence


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Gallbladder cancer

Risk factors

- Gallstones

- chronicinflammation

- calcification(porcelaingallbladder)


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Often diagnosed at advanced stage

- aggressive tumor

- clinical presentation mimics biliary colic or chronic cholecystitis

- Often dx. as incidental finding at surgery or on pathology review

following cholecystectomy

Workup of suspicious mass on U/S or jaundice

- LFTs, evaluation of hepatic reserve- CEA Ca 19-9 (not specific)- CT abdomen to assess extent and nodal disease

- Chest XR or CT- Cholangiography (MRCP preferred over ERCP or PTC unlessintervention planned)


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Pathology and Staging

80% adenocarcinomas

- often have earlyspread to lymph nodes

and bloodstream

Poor prognosis

- 5yr survival 39%stage 1

- 1% stage 4


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Management

Surgery only curative modality

All pts. needCT/MRI and chest imaging prior tosurgery

Staging laparoscopy should beconsidered prior tolaparotomy

Recommended surgery for known diagnosis

- cholecystectomy

- en-bloc hepatic resection- lymphadenectomy with or without bile duct excision- Portahepatis,retroduodenal, gastrohepatic ligament- Nodal disease outside of this area is unresectable


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Management

Surgery for tumor detected after cholecystectomy

- 74% found to have residual dz during reexploration

- Recommend extended cholecystectomy

- T1a may be observed (no muscle involvement)

- T1b or greater require metastatic workup, then hepatic resectionand lymphadenectomy

- Should not be performed by inexperienced surgeon or unknownresectability

Unresectable disease- biopsy to confirm diagnosis- biliary drainage- possible chemotherapy or chemoradiation (usually in clinical trial)- supportive care


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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


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Cholangiocarcinoma

Risk factors

- No predisposing factors have been identified in mostpatients

- May be associated with chronic inflammation

- chronic calculi

- Primary sclerosis cholangitis

- Choledochal cysts

- liver fluke infections

- gallstones not related

- Hep C may be associated with intrahepatic forms


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Diagnosis and workup

Typically asymptomatic

Intrahepatic likely to present with

- fever- weight loss- abdominal pain- biliary obstruction uncommon- may be detected as isolated intrahepatic mass onimaging

Extrhepatic likely to present with- jaundice followed by obstruction


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Workup

- LFTs

- CEA and Ca 19-9 (not specific)- Delayed contrast CT/MR (helpful indetermining resectability)

- Chest imaging- Cholangiography in patients with jaundice(MRCP vs. ERCP vs. PTC)


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Pathology and staging

>90%adenocarcinomas

Divided into 3types

- Mass forming

- periductal

- intraductal


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Management

Intrahepatic cholangiocarcinoma- Complete resection on curative modality- most pts. Not candidates for surgery due to advanced dz. Atpresentation

Surgery involves removing entire lobe or segment along theinvolved 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, chemorads, clinical trial, supportivecare


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Management

Extrahepatic cholangiocarcinomas

- complete resction main curative strategy

Surgical procedure based on location- Proximal 1/3 hilar resection with lymphadenectomy and en-blocliver resection- Mid 1/3 major bile duct excision with lymphadenectomy,assessment of margins- Distal 1/3 Pancreaticoduodenectomy

R0 resection may be observed, chemo, or chemorads (nostandard)

Liver transplant only other possible curative modality forextrahepatic cholangiocarcinoma

- unresectable dz.- normal biliary function


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Management

Distal strictures- ERCP with brushing and stenting

Unresectable disease- biliary drainage (PTC or ERCP +stent)- biopsy- clinical trial, chemo, or chemorads (no

standard)

Metastatic disease as above


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Surveillance

No data to support aggressive surveillance

Imaging every 6mo to 2yrs

Although most pts. With hepatobiliarycancers found at advanced stage, all shouldbe evaluated for treatment

Careful selection and multidisciplinaryapproach are essential


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Pancreatic Adenocarcinoma

36,800 die eachyear

4th MCC death inUS men andwomen

Peak incidence 7thand 8th decades

African Americanhave higherincidence thanwhites


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Anatomy


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Pancreatic adenocarcinoma

Risk factors

- Cigarette smoking

- Increased BMI

- incresed meat and dairy products

- occupational exposure to chemicals(benzidine andbetanaphthylamine)

- chronic pancreatitis

- alcohol intake


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Pancreatic adenocarcinoma

Familial pancreatic cancer is rare

- 5-10% may have genetic

predisposition

- May be associated with BRCA2

mutations

- Assess family history


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Diagnosing and staging

Ductal adenocarcinoma >90% of pancreatic malignancies

Presenting symptoms- weight loss- jaundice- floating stools- pain

- dyspepsia- nausea- depression

No early warning signs

May be considered in diabetics presentin>50 or with unusual

manifestations

Pts. Should undergo helical or spiral CT with pancreatic protocol ifpancreatic cancer is suspected


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Imaging

CT best and most widely used

- Triphasic (arterial, late arterial, venous)

- Thin slices

Helps to distinguish resectable vs. unresectable

CT is primary means through which stage is determined

70-85% determined to have resectable tumors by CT were able toundergo resection (specificity > sensitivity)

MRI may be sued if CT isnt possible

EUS is complementary to CT

Chest imaging


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Laparoscopy is a a valuable staging tool may pick up implants missed by CT

Tumor antigens

- Ca 19-9 should be performed afterbiliary decompression

- low postop Ca 19-9 levels and declininglevels ater surgery are associated withimproved survival


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Staging and resectability

Patients with stage 0, 1, or 2 are generallyconsidered resectable

Some surgeons will resect patients withstage 3 tumors

Pts. With tumor confined to the pancreas

and resected LN w/o vascular invasion arecandidates for surgery


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Chemoradiation

Neoadjuvant therapy is not routinelyperformed- may be used in locally invasive

disease- 10% downstaging

Adjuvant therapy is the standard ofcare with chemotherapy +/- radiation


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Surgery

Pancreaticoduodenectomy is treatment

- delayed gastric emptying in 15%

Postop chemotherapy is given

Palliation may involve biliary drainage forrecurrent or metastatic disease

Sympathetic denervation may beperformed for intractable pain


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References

NCCN guidelines

Cameron

neoplastic diseases of the stomach

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