Stomach Neoplasms Professor Ravi Kant FRCS (England), FRCS (Ireland), FRCS(Edinburgh),...

Stomach Neoplasms

Professor Ravi KantFRCS (England), FRCS (Ireland),

FRCS(Edinburgh), FRCS(Glasgow), MS, DNB, FAMS, FACS, FICS,

Professor of Surgery

Stomach Neoplasm

Maltoma Lymphoma GIST CA stomach

Gastric Lymphoma

Most common primary GI Lymphoma .It’s increasing in frequency.

Presentation: Similar to gastric carcinoma. May reveal peripheral adenopathy,

abdominal mass or splenomegaly.

Diagnosis:

1.EGD 2.contrast GI x-ray.

3.CT guided fine needle biopsy.

Treatment :

Gastric Lymphoma Rx is Surgery(Other organs- preferred Rx of

Lymphoma is Chemotherapy or Radiotherapy)

Maltoma

Mucosa associated lymphoid tumour

MALTOMA

Aetiology= H Pylori Rx = Rx of H Pylori = Triple drugs

What are GIST…?? Gastrointestinal Stromal Tumors

are uncommon mesenchymal tumors that arise in the wall of the gastrointestinal tract

It is believed to originate from an intestinal pacemaker cell called the interstitial cell of Cajal.

Cajal cell

An intestinal pacemaker cell, has been proposed the cellular origin of GISTs. It has characteristics of both smooth muscle and neural differentiation on ultrastructural examination

KIT

role of the KIT and platelet-derived growth factor receptor (PDGFR) tyrosine kinase receptors

KIT receptor tyrosine kinase (KIT RTK)

KIT approximately 5% of GIST cells show

not activation and aberrant signaling of the KIT receptor, but rather mutational activation of a structurally related kinase, PDGFR- (PDGFRA).

90% rate of mutations seen in a more recent series searching for potential mutations in each of exons 11, 9, 13, and 17

CD117 CD34 Actin & Desmin

S-100

GIST ++ - -

Desmoid tumor

- + - -

True leiomyosarcoma

- - + -

Schwanoma

- - - +

Diagnosis

CT is the common mode of diagnosis

FDG PET is mandatory ►PET CT scan is ideal MR

GIST & chemoresistance

▲ P-glycoprotein [the product of the multidrug resistance-1 (MDR-1) gene]

▲ MDR protein

Distribution… Stomach 50-60% Small bowel 20-30% Large bowel 10% Esophagus 5% Else where in abdomen 5%

Symptoms… Abdominal pain Dysphagia Gastrointestinal bleeding Symptoms of bowel obstruction Small tumors may be

asymptomatic

Cytologically…

1. Spindle cell GISTs2. Epithelioid cell GISTs Although GISTs can

differentiate along either or both cell types, some show NO significant differentiation at all

Diagnosis…MUST BE DONE

IMMUNOCHEMICALLY

The CD34 antigen (70-78%) The CD117 antigen (72-94%)

Malignant Versus Benign

Size Mitotic count

Very Low risk

<2 cm <5/50 HPF

Low risk 2-5 cm <5/50 HPFIntermediat

e risk<5 cm

5-10 cm6-10/50 HPF<5/50 HPF

High risk >5 cm>10 cmAny size

>5/50 HPF Any count>10/50 HPF

predictors of survival

Male sex, Tumor size > 5cm Incomplete resection

significant on

multivariate analysis

Treatment… Surgical excision is primary treatment

option but recurrence rates are high Resistant to standard chemotherapy

regimens due to over-expression of efflux pumps

Radiation therapy limited by large tumor sizes and sensitivity of adjacent bowel

IMATINIB Since activation of Kit played a

crucial role in the pathogenesis of GIST, inhibition of Kit would be therapeutic

IMATINIB Orally bioactive tyrosine kinase

inhibitor Shown to be effective against

GIST tumors in two trials in the US and Europe reported in 2001 & 2002

Gastrointestinal Stromal Tumor ‘GIST’

Previously leiomyoma & leiomyosarcoma.

<1 % Rarely cause bleeding or obstruction. The origin: Intestinal Cells of Cajal ‘ICC;s’

autonomic nervous system. The distinction b\w benign & malignant is

unclear. In general terms, the larger the tumor & greater mitotic activity, the more likely to metastases.

The stomach is the most common site of GIST.

Usually are discovered incidentally on endoscopy or barium meal

The endoscopic biopsies may be uninformative as the overlying mucosa is usually normal

Small tumorswedge resection Larger onesgastrectomy

35

36

GIST Case history-

submucosal Cajal Cell Gene KIT PGDRF Diagnosis CT PET

Rx Surgery Chemoresistanc

e Imatininb Sumanitib Prognosis Predictor factors

37

GASTRIC CARCINOMA

GASTRIC NEOPLASM

Epithelial

Mesenchymal

1.PrimaryAdenocarcinomaGastrointestinal stromal tumors ‘GIST’Lymphoma

2. Secondary: invasion from adjacent tumors.

BenignBenign MalignantMalignant

Gastric Carcinoma

55 year old Japanese male who is living in Japan & working in industry.

DEFINITION Malignant lesion of the stomach.Epidemiology & Risk Factors

Can occur at any ageBut Peak incidenceIs 50-70 years old.

It is more aggressiveIn younger ages.

Japan has the world highest Rate of gastric cancer.

Studies have confirmed that incidence decline inJapanese immigrant to

America.

dust ingestion from a variety of industrial processes may be a risk.

Twice more commonIn male than in female

Incidence of Gastric Carcinoma:Japan 70 in100,000/yearEurope 40 in 100,000/yearUK 15 in 100,000/yearUSA 10 in 100,000/yearIt is decreasing worldwide.

Gastric Carcinoma:

Risk Factors

Predisposing :

1. Pernicious anaemia & atrophic gastritis (achlorhydra)2. Previous gastric resection3. Chronic peptic ulcer (give rise to 1%)4. Smoking.5. Alcohol.

Environmental:

1.H.pylori infection Sero(+)patients have 6-9 folds risk2.low socioeconomic Status3. nationality (JAPAN)4. Diet (prevention)

Genetic:

1.Blood group A2.HNPCC: Hereditary non-polyposis colon cancer.

Clinical PresentationMost patients present with advanced stage.. why?They are often asymptomatic in early stages.

Common clinical Presentation:The patient complained of The patient complained of loss of appetiteloss of appetite that was that was

followed by followed by weight lossweight loss of 10Kg in 4 weeks. of 10Kg in 4 weeks.

He had notice He had notice

epigastric discomfort & postprandial fullness.epigastric discomfort & postprandial fullness.

He presented to the ER complaining of He presented to the ER complaining of vomiting vomiting of of large quantities of undigested food & epigastric large quantities of undigested food & epigastric distension.distension.

Dyspepsia

epigastric painBloating early satiety nausea & vomiting* dysphagia* anorexia weight loss upper GI bleeding (hematemesis, melena, iron deficiency anemia)

signs

-Anemia.-Wt. loss ( cachexia)-Epigastric mass, Hepatomegaly, Ascitis -Jaundice.-Blumer’s shelf -Virchow's node-Sister Mary Joseph node -Krukenberg tumor-Irish node

Pathology DIO Classification

Lauren Classification:

1. Intestinal Gastric ca. It arises in areas of intestinal metaplasia to form polypoid tumors or ulcers.

2. Diffuse Gastric ca. It infiltrates deeply in the stomach without forming obvious mass lesions but spreads widely in the gastric wall “Linitis Plastica” & it has much more worse prognosis

3. Mixed Morphology.

Morphology

• Polypoid

• Ulcerative

• Superficial spreading

• Linitis plastica

Gastric cancer can be divided into:

Early: Limited to mucosa & submucosa with or

without LN (T1, any N) >> curable with 5 years survival rate in

90%.

Advanced: It involves the Muscularis. It has 4 types( Bormann’s

classification). Type III & IV are incurable.

T1 lamina propria & submucosa

T2 muscularis & subserosa

T3 serosa

T4 Adjacent organs

N0 no lymph node

N1 Epigastric node

N2 main arterial trunk

M0 No distal metastasis

M1 distal metastasis

Staging of gastric cancerSpread of Gastric Cancer

Direct Spread

Blood-borne metastasis

Lymphatic spread

Transperitonealspread

Tumor penetrates themuscularis, serosa & Adjacent organs(Pancreas,colon &liver)

What is important here isVirchow’s node (Trosier’s sign)

Usually with extensive Disease where liver 1st

Involved then lung &Bone

This is commonAnywhere in peritoneal cavity(Ascitis)Krukenberg tumor (ovaries)Sister Joseph nodule(umbilicus)

Complications Peritoneal and pleural effusion

Obstruction of gastric outlet or small bowel

Bleeding

Intrahepatic jaundice by hepatomegaly

Differential DiagnosisDifferential Diagnosis

1.Gastric ulcer

2.Other gastric neoplasms

3.Gastritis

4.Gastric Polyp

5.Crohns disease.

From history,Cancer is not relieved by antacids

Not periodicNot relieved by eating or vomiting.

INVESTIGATIONS

Full blood count –IDA- LFT,RFTAmylase & lipase.Serum tumor markers (CA 72-4,CEA,CA19-9) not specificStool examination for occult bloodCXR ,Bone scan.

Specific:UGI endoscopy with biopsy Double contrast studyCT, MRI & USLaparoscopry

EGD esophagogastroduodenoscopy

Diagnostic accuracy is 98%

if up to 7 biopsies is taken.

Double Contrast barium upper GI x-ray

Diagnostic accuracy 90%

WHY?

Diagnostic study of Choice

1.Early superficial gastric mucosal lesion can be missed.2. can’t differentiate b/w benign ulcer & Ulcerating adenocarcinoma.

X-ray showing Gastric ulcer With symmetrical radiating

Mucosal folds.By histology, no evidence of Malignancies was observed.

X-ray showing Extensive carcinoma involving the cardia & Fundus

Pyloric stenosis

CT,MRI & US:

Laparoscopy:

Help in assessment of wall thickness, metastases (peritoneum ,liver & LN)Help in assessment of wall thickness, metastases (peritoneum ,liver & LN)

Detection of peritoneal metastases Detection of peritoneal metastases

THE GOLD STANDARD It allows taking biopsies Safe (in experienced hands)

UGI ENDOSCOPY

UGI ENDOSCOPY,contd. You may see an ulcer (25%),

polypoid mass (25%), superficial spreading (10%),or infiltrative (Linitis plastica)-difficult to be detected-

Accuracy 50-95% it depends on gross appearance, size, location & no. of biopsies

IF YOU SEE ULCER ASK UR SELF…BENIGN OR MALIGNANT?

BENIGN MALIGNANTRound to oval punched out lesion with straight walls &

flat smooth base

Irregular outline with necrotic or hemorrhagic

base

Smooth margins with normal surrounding

mucosa

Irregular & raised margins

Mostly on lesser curvature Anywhere

Majority<2cm Any size

Normal adjoining rugal folds that extend to the

margins of the base

Prominent & edematous rugal folds that usually do not extend to the margins

Management

• Surgery

• Chemotherapy NO PROVEN BENEFIT

• Radiotherapy

TreatmentTreatment

Initial treatment:

1.Improve nutrition if needed by parenteral or enteral feeding.

2.Correct fluid &electrolyte

& anemia if they are present.

Preoperative Care

Preoperative Staging is important because we don’t want to subject the patient to radical surgery that can’t help him.

PRE-OPERATIVE CARECareful preoperative stagingScreen for any nutritional deficiencies &

consider nutritional supportSymptomatic control Blood transfusion in symptomatic anemiaHydrationProphylactic antibioticsABO & cross matchAsk about current medications &

allergiesCessation of smoking

BASIC SURGICAL PRINCIPLES

3 TYPES: TOTAL,SUBTOTAL,PALLIATIVE

ANTRAL DISEASESUBTOTAL GASTRECTOMY

MIDBODY & PROXIMAL TOTAL GASTRECTOMY

TOTAL (RADICAL) GASTRECTOMY

o Remove the stomach +distal part of esophagus+ proximal part of duodenum + greater & lesser omentum + LN

o Oesophagojejunostomy with roux-en-y .

SUBTOTAL GASTRECTOMY

Similar to total one except that the PROXIMAL PART of the stomach is preserved

Followed by reconstruction & creating anastomosis

( by gastrojejunostomy, Billroth II )

PALLIATIVE SURGERY

• For pts with advanced (inoperable) disease & suffering significant symptoms e.g. obstruction, bleeding.

• Palliative gastrectomy not necessarily to be radical, remove resectable masses & reconstruct (anastomosis/intubation/stenting/

recanalisation)

POSTOPERATIVE ORDERS

• Admit to PACU

• Detailed nutritional advise (small frequent meals)

Post-Operative Complications

1.1.Leakage from duodenal stump.

2.2.Secondary hemorrhage.

3.3.Nutritional deficiency in long term.

2.Chemotherapy: Responds well, but there is no effect on

survival.Marsden RegimenEpirubicin, cisplatin &5-flurouracil (3 wks)6 cyclesResponse rate : 40% .

3. Radiotherapy: Postperative-radiotherpy: may decrease the

recurrence.

Preventive measuresPreventive measuresBy dietBy dietConvincing:Convincing:vegetable & fruits.Probable:Probable: Vit. C &EPossiblePossible

Carotenoids, whole grain cereals and green tea.

Smoking cessation

Cessation of alcohol intake

Early diagnosis remains the Key Problem

PROGNOSTIC FEATURES2 important factors influencing survival in

resectable gastric cancer: depth of cancer invasion presence or absence of regional LN

involvement• 5yrs survival rate: 10% in USA 50% in Japan

E-medicine web siteThe Washington Manual of Surgery

Bailey & Love’s short practice of surgeryClinical surgery ( A. Cuschieri).