Carcinoma stomach

Carcinoma stomach is more common in certain parts of the world and is the leading cause of cancer related deaths. It is rampant in Japan and the incidence is almost 70 per 1 lakh. The epidemiological trends of carcinoma stomach are fast evolving and mass upper GI survey has made early detection possible. It can be cured by surgery when detected early.

Etiological factors

Environmental

• Diet: high salt, nitrite or nitrate containing foods
• Low fat/protein diet
• Cigarette smoking
• Previous episodes of chemotherapy
• Exposure to radiation
• Ebstein Barr virus infection (Lymphoepitheloid variety)

Host factors

• Chronic Gastritis
• H. pylori infection
• Previous partial gastrectomy surgery
• Family history of carcinoma stomach is present in 10% of the patients. It is associated with a mutation in the e-cadherin gene.
• Males are at higher risk of developing the disease.
• Blood group A
• Adenomatous polyps of stomach
• Menetrier’s disease (protein losing enteropathy, associated with giant hypertrophy of gastric mucosal cells and anemia; precancerous)

Pathogenesis

Diffuse subtype

Very little known is known about its pathogenesisi. The two known precursor lesions are

• Non metaplastic dysplasia
• Globoid dysplasia

Intestinal subtype

Its pathogenesis is explained by a multifactorial model proposed by Correa et al. Stages of increasingly severe lesions progressing over a period of 2-3 decades to frank carcinoma.

• A/c sup. gastritis (H. Pylori)
• C/c Gastritis (NaCl)
• C/c atrophic gastritis (bacterial overgrowth, low acid + nitrosamines)
• Small intestinal metaplasia
• Colonic metaplasia
• Dysplasia
• Gastric adenocarcinoma

Pathology

Gross morphology:

1. In-situ and intramucosal (superficial) (6%)
2. Polypoid (7%)
3. Fungating
4. Ulcerating (60%)
5. Diffusely infiltrating (25%)

Pathological types

1. Adenocarcinoma (95%) [image:1018 align=right width=250 height=200]
2. Squamous cell carcinoma and Adenocanthoma (3%)
3. Carcinoid, Lymphoma, Sarcoma (2%)

Classification of carcinoma stomach

Lauren's classification (1965)

It has epidemiologic, etiologic, pathologic and prognostic significance.

• Intestinal type (53%): Epidemic, expansive, well differentiated glandular structure, inflammatory cell infiltrate, intestinal metaplasia
• Diffuse type(33%): Endemic, infiltrative, poorly differentiated tiny clusters of small cells, widely infiltrating: Linitus plastica
• Heterogenous type (14%)

Other classifications

Stout classification (1953)

• Fungating
• Penetrating
• Spreading
• Superficial spreading
• Linitis plastica
• No special type

Ming classification (1977)

• Expanding
• Infiltrating

Japanese society for gastric carcinoma classification (1981)

• Papillary
• Tubular
• Poorly Differentiated
• Mucinous
• Signet ring

WHO classification(1990)

• Papillary
• Mucinous
• Tubular
• Signet ring

Early gastric carcinoma

Tumour involves upto the submucosa + lymph node Diagnosed by double contrast barium/endoscopy

Japanese classification

• Type I: protruded
• Type II: superficial, IIa:elevated, IIb: flat
• Type III: excavated

Pathobiological types

• Non aggressive/superficial
• Aggressive/penetrating

Advanced gastric carcinoma

Invasion of muscularis propria. Distribution: Antrum and prepylorus (intestinal), body, fundus (diffuse)

Lesser curvature is the most involved part.

Borrman’s classification

• Type I: polypoid carcinoma (intestinal)
• Type II: ulcerating with clear margin
• Type III: ulcerating and infiltrating
• Type IV: diffusely infiltrating (diffuse)
• Type V: unclassifiable
• Linitis plastica: type IV infiltrating the whole of the stomach

Clinical features

In the initial stages there will be a decrease in appetite and weight loss. As the carcinoma advances the mass may become palpable in the abdomen in the region of the stomach. Most patients present with non-specific gastrointestinal symptoms.

Symptoms

Almost 50% of early gastric cancers cause dyspeptic symptoms. Most common symptoms are:

• Weight loss (62%)
• Loss of appetite
• Abdominal pain (52%)
• Nausea(34%)
• Dysphagia
• Melaena
• Early satiety and ulcer type of pain

A small group may present with acute surgical emergency like perforation, bleed and obstruction.

Signs

There are no physical signs for early gastric carcinoma.The signs which occur in the late stages are:

• Palpable abdominal mass
• Supraclavicular node (Virchow's)
• Sister Mary Joseph nodule (near umbilicus)
• Blummer’s shelf (rectum)
• Krukenberg’s tumor (ovaries)
• Hepatomegaly, jaundice, ascites, anemia

Modes of spread of tumor

1. Serosa, peritoneum
2. Transcoelomic (Krukenberg tumour)
3. Direct invasion (pancreas, colon, liver, spleen)
4. Lymphatic (Virchow’s node/Troisier’s sign)
5. Blood (liver)

TNM classification

Pimary tumor (T)

• Tx Primary tumor cannot be assessed
• T0 no evidence of any primary tumor
• Tis Carcinoma in situ
• T1 invades lamina propria or submucosa
• T2 invades muscularis or subserosa
• T3 penetrates serosa
• T4 invades adjacent structures

Regional lymph node (N)

• Nx Regional Node cannot be assessed
• N0 No regional node involvement
• N1 Perigastric Nodes (ST 1—6)
• N2 Along the named vessels (7—11)
• N3 Hepatoduodenal, Mesenteric, Retropancreatic
• N4 Para-aortic

Metastasis (M)

• Mx Cannot be assessed
• M0 No metastasis
• M1 Distant metastasis

Stage grouping

Stage	T	N	M
Stage 0	Tis	N0	M0
Stage IA	T1	N0	M0
Stage IB	T1	N1	M0
Stage II	T1	N2	M0
	T2	N1	M0
	T3	N0	M0
Stage IIIA	T2	N2	M0
Stage IIIA	T3	N1	M0
	T4	N0	M0
Stage IIIB	T3	N2	M0
Stage IV	T4	N1/2	M0
	Any T	N3	M0
	Any T	Any N	M1

Differential diagnosis

• Acid peptic disease
• Gastritis
• Carcinoma of the pancreas
• Carcinoma of the transverse colon

Investigations

Modalities: Laboratory tests, Upper GI radiological studies, Endoscopic studies with tissue diagnosis, Pre-operative staging procedures

Laboratory tests

In early cancer the routine tests are usually normal. They may be useful to detect:

• Anaemia (hypochromic microcytic) due to Fe deficiency reflecting blood loss) in advanced cancer and 20% of early carcinomas
• Achlorhydria (60% of patients)
• Occult blood in stools

Radiological studies with Barium

It is done with barium. Air and barium introduced together coats gastric mucosa with a thin film enhancing mucosa. It has been the mainstay of investigation for many years especially double contrast studies and is used in Japan for mass screening. Radiological studies should ideally precede endoscopy. They have 90% diagnostic accuracy.

Typical findings

• loss of mucosal detail
• ulceration
• mass effect
• distortion of gastric sillhouette

Improvisations

• High density barium
• Carbon dioxide
• Simethicone

Endoscopy

It is a highly observer dependent investigation and flexible fibre-optic endoscopy give most definitive results. It can facilitate tissue diagnosis (biopsy & exfoliative cytology) which is an important advantage. Only gastric biopsy differentiates malignant from benign ulcer.

Factors assessed

• location
• size
• distance from/or involvement of cardia or pylorus
• ulcerating/fungating/infiltrating
• stomach wall distensibility
• peristaltic waves

Disadvantages

• Only 50% Infiltrating CA diagnosed
• Cannot detect tumours <3cm diameter
• Difficult to detect Ca at cardia/lesser curvature
• Cannot detect recurrent tumours (lavage cytology increases accuracy of brush cytology/biopsy)
• Difficult to predict resectability
• Failure to get adequate sample

Tissue diagnosis via Endoscopy

Its accuracy is related to number of biopsies obtained and about 10 biopsies can result in 100% accuracy. The working recommendation is to obtain 4-6 biopsies. Areas immediately adjacent to ulcer arechosen for biposy. Brushings are useful in Infiltrating carcinomas having no apparent defect. Cytology is superior to biopsy; together they can achieve 100% accuracy.

Pre-operative stage determination

Modalities: CT, USG, MRI They can identifu hepatic metastasis, enlarged lymph nodes (perigastric nodes are difficult to pick up) and presence of intra peritoneal deposits. To increase accuracy of pre-operative lymph node involvement, localisation with monoclonal targetted isotopes, endoscopic lymphangiography, dynamic CT, endoluminal USG may be used.

Endoscopic USG

It has the highest sensitivity and specificity for correct T & N staging of which it is more accurate for T staging. This method of ultrasonography can disclose perigastric lymph nodes effectively and easily detect submucosal tumours. The failure to allow pre-operative differentiation of mucosal from submucosal carcinoma is a disadvantage.

Laparoscopy

It is valuable as an initial operative assessment to exclude extensive local disease and can detects small intraperitoneal and liver metastasis not detected by CT scans. When combined with endoscopic USG, laparoscopy can be most accurate to select patients for potentially curative resection.

Treatment

The options are based on the stage and type of carcinoma detected and can be:

• Curative surgery
• Chemotherapy
• Radiotherapy
• Newer methods
• Palliation

Prognosis

Serosal invasion is the most important factor affecting prognosis. The presence of lymph node metastasis, free cells in peritoneum, diffuse type carcinoma, deep tumor and advanced age are other bad prognostic factors. The median survival and 5-year survival rate of resected patients in relation to UICC stage is

UICC stage	Median survival (months)	5-year survival (per cent)
Stage Ia		85.2
Stage Ib		69.2
Stage II	40.8	43.7
Stage IIIa	18.9	28.6
Stage IIIb	13.8	17.7
Stage IV	8.4	8.7

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