Types of Gastric cancer

GASTRIC TUMOURS

Anatomy of the stomach Aetiology of Gastric cancer Types of Gastric cancer Pathology of Gastric Cancer Evaluation of Gastric Cancer Treatment of Gastric Cancer

ANATOMY:

The stomach J-shaped. The stomach has two surfaces (the anterior & posterior), two curvatures (the greater & lesser), two orifices (the cardia & pylorus). It has fundus, body and pyloric antrum.

BLOOD SUPPLY:a. The left gastric arteryb. Right gastric arteryc. Right gastro-epiploic arteryd. Left gastro-epiploic arterye. Short gastric arteries

The corresponding veins drain into portal system. The lymphatic drainage of the stomach corresponding its blood supply.

Anatomy

• Stomach has five layers:– Mucosa

• Epithelium, lamina propria, and muscularis mucosae*

– Submucosa– Smooth muscle layer– Subserosa– Serosa

AETIOLOGY:

Gastric cancer is the second most common fatal cancer in the world with high frequency in Japan.

The disease presents most commonly in the 5th and 6th decades of life and affect males twice as often as females.Contn…

The cause of the disease multistep process but several predisposing factors attributed to cause the disease :

a. Environment e. Atrophic gastritis b. Diet f. Chronic gastric ulcer c. Heredity g. Adenomatous polyps d. Achlorhydria h. Blood group A

i. H. Pyloric colonisation

TYPES OF GASTRIC CANCER:

A. Benign TumoursB. Malignant Tumours

TYPES OF GASTRIC CANCER:

A. Benign TumoursB. Malignant Tumours

THE BENIGN TUMORS:

Although benign tumors can occur in the stomach most gastric tumours are malignant.

The benign groups includes:-1. Non-neoplastic gastric polyps2. Adenomas3. Neoplastic gastric polyps4. Smooth muscles tumours benign

(Leiomyomas)5. Polyposis Syndrome (eg:- Polyposis coli,

Juvenile polyps and P.J. Syndrome) 6. Other benign tumours are fibromas, neurofibromas, aberrat pancreas and

angiomas.

PATHOLOGY OF GASTRIC (MALIGNANT) TUMOURS:

The gastric cancer may arise in the antrum (50%), the gastric body (30%), the fundus or oesophago-gastric juntion (20%).

Types of Malignant Tumours:a. Adenocarcinomab. Leiomyosarcomac. Lymphomasd. Carcinoid Tumours

1. Polypoid or Proliferative

2. Ulcerating

3. Ulcerating/Infiltrating

4. Diffuse Infiltrating (Linnitus- Plastica)

The macroscopic forms of gastric cancers are classified by (Bormann classification) into:-

Microscopically the tumours commonly adenocarcinoma with range of differentiation. The most useful to clinician and epidemiologist is Lauren Histological Classification: a. Intestinal gastric cancer b. Diffuse gastric cancer

Gastric Carcinoma• Diffuse

• M:F 1:1• Onset Middle Age• 5 yr surv overall <10%• Aetiology

– Diet– H. pylori

• Intestinal

• M:F 2:1• Onset Middle Age• 5 yr surv overall 20%• Aetiology

– Unknown– Blood group A association– H. pylori

Early Gastric Cancer: Defined as cancer which is confined to the mucosa and submucosa regard- less of lymph nodes status.

Advanced Gastric Cancer: Defined as tumor that has involved the muscularis propria of the stomach wall.

Gastric Neoplasm:

Pathology:Gastric dysplasia --->

precursor of gastric CAEarly gastric cancer:

– Limited to the mucosa and submucosa, regardless of LN status

– 70% are well differentiated

– Cure rate is 90%

STAGING OF GASTRIC CANCER: a. TNM System

b. CT Staging

c. PHNS Staging System (Japanese)

P-factor (Peritoneal dissemination)

H-factor (The presence of hepatic metastases)

N-factor (Lymphnodes involvement)

S-factor (Serosal invasion)

TNM Classification System

• Distant metastasis (M)

MX Presence of distant metastasis cannot be assessedM0 No distant metastasisM1 Distant metastasis (may be further specified according to size of occurrence)

SPREAD OF GASTRIC CANCER: The diffuse type spreads rapidly

through the submucosal and serosal lymphatic and penetrates the gastric wall at early stage, the intestinal variety remains localized for a while and has less tendency to disseminate. The spread by:

1. Direct (loco regional) 2. Lymphatic 3. Blood (Haematogenous) 4. Transcoelomic

Clinical Manifestation:1. Weight loss due to anorexia and early satiety is

the most common symptoms2. Abdominal pain (not severe) common3. Nausea / vomiting4. Chronic occult blood loss is common;

GIT bleeding (5%)5. Dysphagia (cardia involvement)

Clinical Manifestation:6. Paraneoplastic syndromes ( Trousseau’s

syndrome – thrombophlebitis; acanthosis nigricans – hyperpigmentation of axilla and groin; peripheral neuropathy)

7. Signs of distant metastasis:a. Hepatomegally / ascitesb. Krukenbergs tumorc. Blummers shelf (drop metastasis)d. Virchow’s node e. Sister Joseph node (pathognomonic of advances

dse)

SUMMARY: Often asymptomatic until late stage. Marked weight loss Anorexia Feeling of abdominal fullness or discomfort Epigastric mass Iron Deficiency Anaemia Left supraclavicular mass (Troisier’s Sign) Obstructive Jaundice (Secondary in porta hepatitis) Pelvic mass (Krukenberg)

EVALUATION OF GASTRIC CANCER: History Clinical Examination Investigations

The clinical features of gastric cancer may arise from local disease, its complications or its metastases.

INVESTIGATIONS:A. Upper gastero intestinal

endoscopy with multiple biopsy and brush cytology

B. Radiology: CT Scan of the chest and abdomen USS upper abdomen Barium meal

C. Diagnostic laparoscopy

Diagnosis:1. UGIS (double contrast)2. Endoscopy (Biopsy / Ultrasound)

• GOLD STANDARD• Best pre-operative staging• Needle aspiration of LN w/ ultrasound guidance• Can even give preop neoadjuvant tx

3. CT scan (intravenous and oral contrast):• For pre-operative staging

4. Whole body Positron Emission Tomography scanning (PET):

• Tumor cell preferentially accumulate positron-emitting 18F fluorodeoxyglucose.

Laboratory

• Assists in determining optimal therapy.• CBC identifies anemia, with may be caused

by bleeding, liver dysfunction, or poor nutrition.

• 30% have anemia.• Electrolyte panels and LFTs are also essential

to better characterize patients clinical state.

Investigations for patients with gastric cancer

• Endoscopy & biopsy

• Performance status• Physiological assessment

– Cardio-pulmonary function

• CT chest & abdomen • EUS (endoscopic ultrasound)• Laparoscopy

CT scanning• Technique

– Spiral CT of chest and abdomen

Laparoscopy

• Inspect peritoneal surfaces, liver surface.• Identification of advanced disease avoids

non-therapeutic laparotomy in 25%.• Patients with small volume metastases in

peritoneum or liver have a life expectancy of 3-9 months, thus rarely benefit from palliative resection.

Screening of Gastric Cancer

• Patients at risk for gastric CA should undergo yearly endoscopy and biopsy:

1. Familial adenomatous polyposis2. Hereditary nonpolyposis colorectal cancer3. Gastric adenomas4. Menetrier’s disease5. Intestinal metaplasia or dysplasia6. Remote gastrectomy or gastrojejunostomy

TREATMENTS OF GASTRIC CANCER:

Surgery (Early or Advanced Cancer)

Distal tumours which involve the lower ½ (sub-total or partial gasterectomy).

Proximal tumours which involve the fundus, cardia or body (total gasterectomy).

Surgical Treatment

TREATMENT:SURGERY:– The only curative tx for gastric cancer– Except:

1. Can’t tolerate abdominal surgery2. Overwhelming metastasis

– Palliation is poor w/ non-resective operations– GOAL: resect all tumors, w/ negative margins

(5cm) and adequate lymphadenectomy (need for RFS)

– Enbloc resection of adjacent organ is done if needed.

TREATMENT:SURGERY:Radical subtotal gastrectomy

• Standard operation for gastric cancer

Organs resected:1. Distal 75% of stomach2. 2 cm of duodenum3. Greater & lesser omentum4. Ligation of R & L gastric

artery and gastroepiploic vesels

5. Billroth II gastojejunostomy

TREATMENT:SURGERY:Radical subtotal gastrectomy

• Standard operation for gastric cancer

If gastric remnant left is small (<20%) do Roux-en-Y reconstruction

Endoscopic Resection of Gastric Carcinoma

Criteria:1. Tumor < 2cm in size2. Node negative3. Tumor confined on the mucosa

Nodes metastasis is < 1%:1. No mucosal ulceration2. No lymphatic invasions3. <3cm tumor

Treatment of gastric cancer

• Endoscopic treatment– EMR (endoscopic mucosal resection)– ablation

• Surgery• Multimodal treatment

– Neo-adjuvant– Adjuvant

• Palliative treatment

Endsocopic mucosal resection

• T1 mucosal disease– Minimal risk of LN

metastases• Various techniques• Specimen obtained

Distal Pancreatectomy

• Associated with marked increase in morbidity & mortality with or without splenectomy

• Indications for pancreatectomy:– Direct invasion of the tail of the pancreas– Likelihood of splenic artery nodal involvement

Surgical Treatment

Inoperable tumours: Whenever possible it is advisable to do even a limited gastric resection. If resection is impossible an anterior gastrojejunostomy.

Indications for Splenectomy

• If macroscopic disease can be resected & the operation is potentially curative then en bloc splenectomy or pancreaticosplenectomy is worthwhile.

• If it is more palliative then this benefit must be weighed against the potential complications of splenectomy and more extensive operation

Chemotherapy for gastric cancer

(Pre-operatve & post-operative)

Radiotherapy (Pre-intra & post-operatively)

Adjuvant Therapy

• Rationale is to provide additional loco-regional control.

• Radiotherapy- studies show improved survival, lower rates of local recurrence when compared to surgery alone.

• In unresectable patients, higher 4 year survival with mutimodal tx, in comparison to chemo alone.

Chemotherapy

• Numerous randomized clinical trials comparing combination chemotherapy in the adjuvant setting to surgery alone did not demonstrate a consistent survival benefit.

• The most widely used regimen is 5-FU, doxorubicin, and mitomycin-c. The addition of leukovorin did not increase response rates.

Advanced Unresectable Disease

• Surgery is for palliation, pain, allowing oral intake

• Radiation provides relief from bleeding, obstruction and pain in 50-75%. Median duration of palliation is 4-18 months

Outcome

• 5-year survival for a curative resection is 30-50% for stage II disease, 10-25% for stage III disease.

• Adjuvant therapy because of high incidence of local and systemic failure.

• A recent Intergroup 0116 randomized study offers evidence of a survival benefit associated with postoperative chemoradiotherapy

Complications

• Mortality 1-2%• Anastamotic leak, bleeding, ileus, transit

failure, cholecystitis, pancreatitis, pulmonary infections, and thromboembolism.

• Late complications include dumping syndrome, vitamin B-12 deficiency, reflux esophagitis, osteoporosis.

OTHER GASTRIC TUMOURS: Gastric Lymphomas: Primary lymphomas of the stomach of

the non Hodgkin’s type (NHL). The symptoms are similar to those of

gastric cancer (adenocarcinoma). The diagnosis is made principally from endoscopic examination with biopsy and cytology.

CT Scanning is important in staging the disease.

Treatment:- Well-localized disease should be treated with resection (surgery) followed by radiotherapy or chemotherapy. - Extensive disease by adjuvant chemo-

therapy & radiotherapy than surgery.

Leiomyosarcoma: Arise in the stomach representing

1% of gastric tumors. They may be sessile or pedanculated

projecting into the gastric lumen or extragastrical or both (dumb-bell tumour).

Presentation due to blood loss anaemia or epigastric mass or vague dyspepsia.

Malignancy is suggested by the size more than 5 cm and confirmed by noting increased mitosis on histology.

Stromal tumours

• GIST (Gastro-Intestinal Stromal Tumour)– Presentation

• Incidental• Bleeding

– Pathology• Blend sheets of spindle cells• Previously mistaken for leiomyomata• Origin cell – interstitial cell of Cahal• C-kit +ve • Actin -ve

Stromal tumours

• Prognostic factors– Size (>4cm)– Resection margins

– Mitoses– Vacuoles on EUS

Stromal tumours

• Surgical Treatment– Excision with clear margins– No lymphadenectomy required

• Non –surgical treatment– Glivec (imatinib)– Recurrence / inoperable– ? Neoadjuvant / adjuvant

Gastric Carcinoid Tumour: Are very rare. There is established association between atrophic gastritis & carcinoid & pernicious anemia.

Gastric carcinoids are best treated by local resection. If very small by endoscopic resection.

Gastric Carcinoid Tumours

• <1% of gastric tumours• 4-41% of GIT carcinoid tumours • Most ECL/argyrophil cell origin (80%)• 3 clinico-pathological subtypes:

– Type 1, 2 & 3

Gastric Carcinoid Tumours

• Type 1 : Hypergastrinaemia with Autoimmune chronic atrophic gastritis (Type A) – Pernicious anaemia

• Type 2 : Hypergastrinaemia with hypertrophic gastropathy – Zollinger-Ellison syndrome

• Type 3 : Sporadic, no relation to hypergastrinaemia

Gastric Carcinoid Tumours : Rindi et al

n = 45 Type 1 Type 2 Type 3Mc+/-SMc 26 (92%) 6 (86%) 3 (30%)Musc Prop 1 (4%) 1 (14%) 3 (30%)Serosa 1 (4%) 0 4 (40%)Multiple 18 (64%) 6 (86%) 0Solitary 10 (36%) 1 (14%) 10 (100%)Metastases 0 2 (29%) 6 (60%)

Type 1 Gastric Carcinoid

• Type 1 Gastric carcinoid tumours : associated with Type A Autoimmune Chronic Active Gastritis

• Autoimmune process leads to destruction and gradual atrophy of chief and parietal cells of body/fundus - sparing of body/fundic neuroendocrine cells

• Hypochlorhydria or achlorhydria

Gastric Carcinoid Tumours

• Hyperplastic precursor sequence • Hypergastrinaemia -- Neuroendocrine

hyperplasia -- Dysplasia -- Neoplasia• Pernicious anaemia only present in 20-46% of

patients (latent effect)• Natural history : most probably remain

stationary; some regress and some metastasize

Results of therapy – stomach cancer

• Surgery with curative intent– 42% of patients

• 5 year survival – 60%– Node positive - 35%– Node negative - 88%

Sue Ling et al (1993) BMJ

Multimodal therapy

• Adjuvant chemotherapy– Possible small advantage– OR 0.84 (0.74 – 0.96)– Western 0.96– Asian 0.58

• Janunger 2001

• Neo-adjuvant chemotherapy (ECF)– MAGIC trial

• Surgery +/- chemo– 503 patients– Higher curative resection

rate • 79% vs 69%

– Better survival at 2 years• 48% vs 40%

Palliative chemotherapy

• Median survival benefit 3 – 6 months• Combination therapy superior• 50% gain improvement in QOL