Gastric Cancer Epidemiology

Amr Mohamed Helmy 734

Features of Gastric Cancer1) Second most common cancer 2) Dramatic decline worldwide 3) Wide variation in incidence4) Altered risk among migrants

Age and Sex DistributionMen > womenMost are elderly at diagnosis. Median age 65 yearsYounger patients may represent a more aggressive variant.Cigarettes

Geographic Distribution

Geographic DistributionHighest rates (over 40 per 100,000 in males) are reported

from Japan, China, the former USSR, and certain countries in Latin America.

The lowest rates (< 15 per 100,000) are seen in North America (specifically, its white population), India, the Philippines, most African countries, some countries in Western Europe, and Australia.

Change In Histology PatternIntestinal gastric cancer

common in males older age more prevalent in high-risk areas linked to environmental factors

The diffuse or infiltrative typefrequent in both sexescommon in younger age groupsworse prognosis

Change In Histology PatternWorldwide decline in the incidence of the

intestinal type.By contrast, the decline in the diffuse type

has been more gradual (now accounts for approximately 30 percent of gastric carcinoma)

Despite the decline in gastric cancer overall, there has been an explosive increase in incidence of cancer of the gastric cardia.

LymphomaGIT is the predominant site of extranodal non-

Hodgkin lymphomas.Primary NHLs of the GI tract are rare, accounting

for only 1 to 4 percent of malignancies arising in the stomach, small intestine, or colon.

Secondary GI involvement is relatively common, occurring in approximately 10 percent of patients with limited stage NHL at the time of diagnosis, and up to 60 percent of those dying from advanced NHL.

In the United States (US), gastric lymphoma is the most common extranodal site of lymphoma.

Carcinoid TumourThe overall age-adjusted incidence rates

were 2.0 for men and 2.4/100,000 for women in 1983-1998.

GISTThe most common nonepithelial benign

neoplasm involving the GI tract.Constitute only 1 percent of primary GI

cancers. The annual incidence of GIST in the United

States is at least 4000 to 6000 new cases (roughly 7 to 20 cases per million population per year).

EtiologyAmr Mohamed Samir 735Amr Mohamed Dawood 737

Gastric cancer is more common in patients with pernicious anemia, blood group A, or a family history of gastric cancer.

Environmental factors appear to be more related etiologically to the intestinal form than the diffuse form.

Factors increasing the risk of gastric cancer: Family history Diet (high in nitrates, salt, fat) Familial polyposis Gastric adenomas Hereditary nonpolyposis colorectal cancer Helicobacter pylori infection Atrophic gastritis, intestinal metaplasia, dysplasia Previous gastrectomy or gastrojejunostomy (>10 y ago) Tobacco smoking Ménétrier's disease

Factors decreasing the risk of gastric cancer:

  Aspirin

  Diet (high fresh fruit and vegetable intake)

  Vitamin C

Normal

Diet low in vitamin C, E High salt diet Helicobacter pylori

Chronic superficial gastritis

Atrophic gastritis

Intestinal metaplasia

Dysplasia

Cancer

Helicobacter Pylori:Chronic helicobacter pylori infection increases the risk of gastric cancer about threefold when compared to uninfected patients.

Host: high acid secretor

Host: low acid secretor

Predominant antral

gastritis

Minimal corpus

gastritis

Antral gastritis

Corpus gastritis

High antral gastrin

Normal corpus

High antral gastrin

Impaired corpus

function

High acid

Low acid

Duodenal ulcer Cancer

Patients with history of gastric ulcer are more likely to develop gastric cancer, and patients with a history of duodenal ulcer are at decreased risk for gastric cancer.

Premalignant conditions of the stomach

1. Polyps

Hyperplastic polyps can be associated with carcinoma.

Patients with familial adenomatous polyposis have a high prevalence of gastric adenocarcinoma.

2. Atrophic gastritis

Chronic atrophic gastritis is the most common precursor for gastric cancer particularly the intestinal subtype and is usually associated with H. Pylori infection.

3. Intestinal metaplasiaGastric carcinoma often occurs in an area of intestinal

metaplasia.Type III intestinal metaplasia is most commonly

associated with gastric cancer, usually of the intestinal subtype.

Eradication of helicobacter pylori infection leads to significant regression of intestinal metaplasia and improvement in atrophic gastritis.

4. Gastric remnant cancer stomach cancer can develop, usually years following

distal gastrectomy or gastroenterostomy.

5. Other premalignant states:Patients with hereditary, non polyposis colorectal cancer

have a 10% risk of developing gastric cancer.Ménétrier's disease: gastric mucosal hypertrophy.

Gross PathologyAmr Maher Basiony 733

Amr Mohamed Helmy 734

Premalignant Conditions of the StomachPolyps

Hyperplastic Polyps 75 percent of gastric polyps Associated with H. pylori is common Small, dome-shaped, or stalked polyps Average size 1.0 cm, range 0.1 to 12 cm Single or multiple They primarily occur in the antrum They often regress following H. pylori

eradication

Premalignant Conditions of the StomachPolyps

Fundic Gland Polyps Small (0.1 to 0.8 cm), hyperemic, sessile,

flat, nodular lesions Occur exclusively in the gastric corpus Sometimes be large Removal of polyps greater than 1 cm in

size is recommended Associated with Long-term therapy with

proton pump inhibitors (PPIs) Regression has been reported following

an H. pylori infection.

Premalignant Conditions of the StomachPolypsGastric Adenomas

Adenomatous polyps6 to 10 percent of gastric polypsFound in the antrumMay be flat or polypoidRange in size from a few millimeters to several

centimeters

Premalignant Conditions of the StomachGastric Carcinoid Tumours

May grow as a polypoid lesionMost commonly they are present in the corpus Sessile, broad-based nodules, with a smooth

surface contour

Premalignant Conditions of the StomachAtrophic GastritisThe most common precursor for gastric cancerPrevalence is higher in older age groupsH. pylori is involved in the pathogenesis of

atrophic gastritis. Three distinct patterns have been descriped

• Autoimmune (involves the acid-secreting proximal stomach),

• Hypersecretory (involving the distal stomach)• Environmental (involving multiple random areas

at the junction of the oxyntic and antral mucosa)

Premalignant Conditions of the StomachIntestinal Metaplasia

A precursor lesion to gastric cancer. Eradication of H. pylori infection leads to

significant regression of intestinal metaplasia and improvement in atrophic gastritis.

Treatment of H. pylori infection is a reasonable recommendation

Premalignant Conditions of the StomachBenign Gastric Ulcer

Inadequately biopsied ulcers was mistakenly labeled as "benign"

Now all gastric ulcers are cancer until proven otherwise with adequate biopsy and follow-up.

Premalignant Conditions of the StomachGastric Remnant CancerStomach cancer can develop in the gastric

remnantMost tumors develop > 10 years following the

initial operationArise often near the stomaQuite large at presentationEqually divided between intestinal and diffuse

subtypesMost cases have been reported following Billroth

II gastroenterostomyPrognosis is similar to proximal gastric cancer

Premalignant Conditions of the Stomach Dysplasia

gastric dysplasia is the universal precursor to gastric adenocarcinoma

Patients with severe dysplasia should be considered for gastric resection

EMR is recommended if the severe dysplasia is localized

Patients should be followed with endoscopic biopsy surveillance, and Helicobacter eradication

Premalignant Conditions of the Stomach Early Gastric Cancer

It is adenocarcinoma limited to the mucosa and submucosa of the stomach, regardless of lymph node status

Approximately 10% of patients with early gastric cancer will have lymph node metastases

There are several types and subtypes:Approximately 70% of early gastric cancers are

well differentiated, 30% are poorly differentiated

Small intramucosal lesions can be treated with EMR

Gross PathologyBormann’s Classification: 1926

Type I (polypoid carcinoma) clearly demarcated, ulcerated, late metastasis, good prognosis.

Type II (ulcerating carcinoma) sharply defined margins; difficult to differentiate from benign ulcer, requires biopsy, good prognosis.

Type III (ulcerating and infiltrating)

no clear-cut margins, submucosal infiltration, extends to serosa; most common gross type, relatively poor prognosis.

Type IV (diffuse infiltration): early metastasis; includes linitis plastica (leather-bottle stomach); Poorest prognosis.

Gross PathologyBormann’s Classification: 1926

Gross PathologyJapanese Classification

Type 0

Gross PathologyJapanese Classification

Type 1

Polypoid tumors, sharply demarcated from the surrounding mucosa, usually attached on a wide base.

Type 2

Ulcerated carcinomas with sharply demarcated and raised margins.

Type 3

Ulcerated carcinomas without definite limits, infiltrating into the surrounding wall.

Type 4

Diffusely infiltrating carcinomas in which ulceration is usually not a marked feature.

Type 5

Non-classifiable carcinomas that cannot be classified into any of the above types.

Microscopic picture of adenocarcinomaAmr Mohamed Mosa 735Amr Mohamed Halawa 738

There are a number of classifications proposed for

gastric adenocarcinoma.

Lauren classification Intestinal type

Glandular cells . (large , abundant cytoplasm , hyperchromic nuclei) Intracellular mucin polarized to surface . Pushed margins , presence of lymphocytes . Metastasizes to nodes, liver

Diffuse type Small clamps or single . (small . less cytoplasm , hypochromic nuclei) No polarized mucin . Diffuse and infiltrative .

Mixtures of above two types

WHO classification Tubular

Tubules and aciniBecomes solid if poorly differentiated

PapillaryFibrovascular stalks

Mucinous>50% of tumor is mucin

Signet ring>50% of carcinoma is composed of signet

ring cells

Special types Clear cell variant described as having clear to pale eosinophilic cytoplasm

Tubulo-papillary architectureDysplasia ranges from minimal to severe

Round basal or mid-level nuclei in lower gradesLocation in cardia and pylorus

Hepatoid Closely resembles hepatocellular carcinoma

Frequently associated with intestinal type / tubulo-papillary gastric adenocarcinoma

Eosinophilic to clear cytoplasm Round to oval nuclei with prominent nucleoli Frequent vascular invasion and liver metastasis

Adenosquamous Mixture of two patterns, more than just focal

Grading

WHO (applies only to tubular pattern in WHO classification)Well differentiated – well formed glandsModerately differentiated - may be combined

as well (low grade)Poorly differentiated (high grade)

Highly irregular glands orSingle cells and clusters

Signs and symptoms

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DyspepsiaHighly suspicion for any elderly man above

40 complaining of dyspepsia which does not clear completely under simple medical treatment to stop medication and be investigated for gastric carcinoma .

Pain: it differs from that of peptic ulcer that it is not usually

induced after meals but more to be induced after meat and protein meals .

it is not responsive to medical treatment , vomiting or alkali .

it is usually due to high tone of the stomach wall or involving of nerve or peritoneum.

It is visceral type of pain , vague , located in upper abdomen specially in epigastric region .

N.B In gross picture type 2 and 3 (non infiltrating – infiltrating

ulcer) there is peptic ulcer like pain and even relieved by antacid and this is dangerous cause it delay the diagnosis but usually there is achlorhydra .

Vomiting:Feature of organic stomach diseases like

peptic ulcer or gastric carcinoma, it occurs in the moment of highest pain ,induced by tension and hyper tonicity of the stomach .

it is a good sign if there is relief after vomiting which exclude out the malignancy potential

Nausea:Sickness sensation without actual vomit +

sweating + feeling to faint .It happen due to hypotonia of gastric

musculature , It is usually psychic in origin but as well in organic diseases like carcinoma or chronic gastritis .

Nausea usually precede vomiting

Flatulence:Distention of stomach with gas which usually

tend to be belshed but it is more in functional stomach disease more than organic ones .

Disturbance of appetite:Anorexia specially to protein meals also

anorexia due to other diseases like gastritis ,TB , Anaemia , psychogenic .

Others:Heart burn , waterbrash ( water and mucus

in mouth) and erucation (acidic gastric contents in mouth)

2- Anemia and Cachexia :Progressive anaemia , loss of weight ,

dehydration and general weakness and this can be the only presenting picture .

3- Mass: Mass in epigastrium or left hypochondrium ,

it may be the only presentation and it indicate a late inoperable tumor .

It is irregular , tender , mobile or fixed.

Complication:Haematemesis , may be few in amount or

copious associated with food particles , in peptic ulcer the amount is always higher than that of gastric carcinoma.

Secondaries to the liver , pyloric obstruction …..

Spread:-Direct :It extends to seroperitonium then to the near by

organs (pancreas , spleen , liver , transverse colon ) .

Tumor in cardia : spread to esophagus Tumor in pylorus : to duodenum .Lymphatic : (very aggressive )to lymphnodes in greater and lesser curvature .celiac and para aortic mediastinal (for tumors of the cardia)virschaw lymph nodes

SpreadBlood :from portal vein to liver and maybe lung or

bone .transperitoneal :1-krunkenburg syndrome (or maybe by

blood) .2-sister mary Josef nodules .3-malignant ascites .4-Blumer’s shelf (mass during rectal

examination) .

Paraneoplastic manifestations:-rarely seen at initial presentation. Dermatologic

findings may include the sudden appearance of diffuse seborrheic keratoses or acanthosis nigricans which is characterized by velvety and darkly pigmented patches on skin folds. Neither finding is specific for gastric cancer.

Other paraneoplastic abnormalities that can occur in gastric cancer include a microangiopathic hemolytic anemia , membranous nephropathy , and hypercoagulable states (Trousseau's syndrome) . Polyarteritis nodosa has been reported as the single manifestation of an early and surgically curable gastric cancer

Investigations

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I. Laboratory Studies

1) CBC : reveals anemia, due to bleeding, liver dysfunction, or poor nutrition.

2) Serum electrolytes.

3) Coagulation studies.

4) Liver and Kidney function tests.

5) Tumor markers:

Carcinoembryonic antigen (CEA)

Cancer antigen (CA) 19-9

II. Endoscopy

Room set-up and patient positioning for endoscopy

Upper GI endoscopy is the diagnostic procedure of choice in the work-up of gastric carcinoma.

Multiple biopsy specimens (7 or more) should be obtained from any visually suspicious areas.

Repeated sampling at the same tissue site, reaching deeper into the gastric wall.

Multiple samples should be obtained around the ulcer crater.

Lesions may be:

1. Fungating cauliflower lesion.

2. Mucosal ulceration.

3. Diffuse infiltrative (linitis plastica).

Adenocarcinoma of the cardia. Large, lobulated, ulcerated mass at the gastroesophageal junction

Adenocarcinoma in the antrum manifested by ulcerated, circumferential mass and gastric outlet

obstruction

Endoscopic view of an ulcerating adenocarcinoma

III. Endoscopic ultrasonography (EUS)

EUS helps to determine the depth of tumor invasion.

Can be used to guide for biopsy.

Has the ability to detect sarcomas and other tumors arising from the submucosa and the musculosa (GIST).

The gastric wall is visualized as 5 concentric bands:Mucosa Muscularis mucosaSubmucosa Muscularis propria Serosa

EUS cannot permit assessment of tissue beyond a depth of about 5 cm.

Can not be used to assess distant nodal or liver metastases.

Can not differentiates between malignant and benign ulcers.

IV. RadiologyBarium study

Provides preliminary information that may help to determine if a gastric lesion has benign or malignant features.

It may show thickened or enlarged gastric folds, filling defects, mass or ulcer.

Barim study of upper gastrointestinal study shows a superficial ulcer in the gastric antrum (arrow) with

thickened folds radiating towards the ulcer

Fungating mass of the body of the stomach

Barium meal showing infiltrating gastric carcinoma in the region of the incisura. There is irregular narrowing affecting both the

lesser and greater curvatures (arrow) ‘Apple core sign”

Linitis plastica "leather-flask" appearing stomach

The tumor tend to infiltrate the submucosa and muscularis propria, superficial mucosal biopsies may be falsely negative.

Computed Tomograohy (CT)

It is widely used for tumor staging.

Demonstrates accurately the size and location of the tumor.

Helps to assess the presence of nodal or visceral spread and involvement of other peritoneal structures (e.g., ovaries, liver).

Can not detect metastases smaller than 5 mm.

CT scan showing infiltrating carcinoma Carcinoma of the cardia with liver metastasis

T Staging

N Staging

Carcinoma of the body of the stomach associated with regional lymphadenopathy and ascites

M StagingThe liver is the most common site for hematogenous metastases. Less common sites are the lungs, adrenal glands, kidneys, bone and brain.

Pulmonary metastases and left pleural effusion

IV. Staging laparoscopyMore invasive modality.

Laparoscopic evaluation of metastasis.

Has the advantage of directly visualizing the liver surface, the peritoneum, local lymph nodes and other abdominal metastases.

Peritoneal cytology may be done, which increases the sensitivity of laparoscopy.

TNM staging

The staging schema of the AJCC (American Joint Committee on Cancer) is based upon:

Tumor (T)

Nodal involvement (N)

Metastasis (M)

T stage is dependent on depth of tumor invasion and not size.

Nodal stage is based upon the number of positive lymph nodes and not the proximity of the nodes to the primary tumor.

Regional nodes include those located:

o Along the greater curvature (greater curvature, gastroduodenal, gastroepiploic)

o Along the lesser curvature (lesser curvature, left gastric, common hepatic, celiac)

o Pancreatic and splenic area

Involvement of intraabdominal nodal groups (e.g. retropancreatic, portal, mesenteric, and paraaortic)

is classified as distant metastases.

The 2002 AJCC TNM staging of gastric carcinoma

Primary tumor (T)

TX - Primary tumor (T) cannot be assessedT0 - No evidence of primary tumorTis - Carcinoma in situ, intraepithelial tumor without invasion of lamina

propriaT1 - Tumor invades lamina propria or submucosaT2 - Tumor invades muscularis propria or subserosaT3 - Tumor penetrates serosa (ie, visceral peritoneum) without invasion of

adjacent structuresT4 - Tumor invades adjacent structures

Regional lymph nodes (N) NX - Regional lymph nodes (N) cannot be assessed N0 - No regional lymph node metastases N1 - Metastasis in 1-6 regional lymph nodes N2 - Metastasis in 7-15 regional lymph nodes N3 - Metastasis in more than 15 regional lymph nodes

Distant metastasis (M) MX - Distant metastasis cannot be assessed M0 - No distant metastasis M1 - Distant metastasis

The AJCC 2010 modifications

Tumors arising at the gastroesophageal junction (GEJ)

or at the cardia that extend to the GEJ or esophegus are

staged using the TNM system for esophageal cancer

rather than that of the gastric cancer.

N categories were modified as follow:

o N1 = 1-2 positive nodes (compared to 1-6 in the 2002 criteria)

o N2 = 3-6 positive nodes (compared to 7 - 15 in 2002)

o N3 = >7 positive nodes (compared to >15 in 2002)

Positive peritoneal cytology is classified as M1 disease.

Stage grouping have been changed.

REFERENCES Bailey and Love’s, short practice of surgery, 25th edition.Schwartz’s principles of surgery, 9th edition.AJCC (American Joint Committee on Cancer) Cancer Staging

Manual, 7th ed, Edge, SB, Byrd, DR, Compton, CC, et al (Eds), Springer, New York 2010. p. 117.

Pollack, BJ, Chak, A, Sivak MV, Jr. Endoscopic ultrasonography. Semin Oncol 1996; 23:336.

Byrne, MF, Jowell, PS. Gastrointestinal imaging: endoscopic ultrasound. Gastroenterology 2002; 122:1631.

Karita, M, Tada, M. Endoscopic and histologic diagnosis of submucosal tumors of the gastrointestinal tract using combined strip biopsy and bite biopsy.

Kienle, P, Buhl, K, Kuntz, C, et al. Prospective comparison of endoscopy, endosonography and computed tomography for staging of gastric tumors. Digestion 2002; 66:230.

TreatmentAmr Mohamed Samir 735

Operability Patients with incurable disease should not be subjected to

radical surgery that cannot help them.

Incurable patients are those with:Haematogenous metastasesInvolvement of the distant peritoneumN4 nodal disease and disease beyond the N4 nodesFixation to structures that cannot be removed.

Involvement of another organ does not indicate incurability, provided that it can be removed.

Controversies with respect to operability include patients with:

N3 nodal involvementInvolvement of the adjacent peritoneumRemaining patients are considered operable and should

undergo curative resection. Most of the patients should have neoadjuvant chemotherapy as it improves survival.

Total gastrectomyThe operation is best performed through a long upper

midline incision. The stomach is removed en bloc, including the tissues of

the entire greater omentum and lesser omentum. The transverse colon is completely separated from the

greater omentum.

The subpyloric nodes are dissected and the first part of the duodenum is divided, usually with a surgical stapler.

The hepatic nodes are dissected down to clear the hepatic artery. This dissection also includes the suprapyloric lymph nodes.

The lymph node dissection is continued to the origin of the left gastric artery.

The dissection is then continued along the splenic artery taking all of the nodes at the superior aspect of the pancreas and in the splenic hilum.

The access to the nodal tissues around the upper stomach and oesophagogastric junction is achieved by separation of the stomach from the spleen, if the spleen is not going to be removed.

The oesophegus is divided at an appropriate point using a combination of stay sutures and a soft non crushing clamp, usually of the right angled variety.

It is important that the proximal and distal resection margins are well clear of the tumour as their involvement carries an appalling prognosis. If in doubt, a frozen section should be performed.

Gastrointestinal continuity is reconstituted by means of a Roux loop.

Effective oesophagojejunostomy is achieved by:

A purse-string is placed in the cut end of the oesophagus.

The side of the oesophagus is stapled onto the side of the Roux loop by means of a circular stapler. The anastomosis can also be fashioned end to end.

The blind open end of the Roux loop may then be closed either with sutures or with a linear stapler. The Roux loop may be placed in either, an anticolic or retrocolic position.

The jejunojejunostomy is undertaken in the usual fashion(end to side).

Extent of lymphadenectomyThere remains some controversy about the extent of the

lymphadenectomy required for the optimal treatment of curable gastric cancers. In Japan, at least a D2 gastrectomy (removal of second tier of lymph nodes) is performed on all operable gastric cancers. They usually preserve the spleen and pancreas.

The Japanese research society for gastric cancer has numbered the lymph node stations that potentially drain the stomach. Generally, these are grouped into level D1 nodes which are perigastric, D2 nodes which are along the hepatic and splenic arteries, and D3 nodes which are the most distant.

Overall, it seems that the oncological outcome may be better following a D2 gastrectomy. The traditional radical gastrectomy removes the spleen and the distal pancreas en bloc with the stomach which is adequate for the clearance of the lymph nodes around the splenic artery. However, there now seems doubt that this substantially increases the complication rates. Therefore, it’s no longer routinely done as part of the D2 gatrectomy.

The difference between D1 and D2 operations depend upon the tiers of lymph node removed. In general, D1 resection involves the removal of perigastric nodes while D2 resection involves removal of the lymph nodes along the major arterial trunks along with the perigastric nodes.

Subtotal gastrectomyFor tumours distally placed in the stomach it seems

unnecessary to remove the whole stomach. The operation is very similar to total gastrectomy except that the most proximal part of the stomach is preserved, the blood supply being derived from the short gastric arteries.

After the resection the gastrointestinal continuity is restored by:

The simplest form of reconstruction is to close the stomach from the lesser curve, near the oesophagogastric junction with staples or sutures and then perform an anastomosis of the greater curve to the jejunum as in Billroth II/ polya type gastrectomy.

Reconstruction using a Roux loop to avoid marked enterogastric reflux and bile reflux oesophagitis that occurs with Billroth II/ polya type gastrectomy.

Palliative surgery:In inoperable patients with resectable tumours having

significant symptoms of, either obstruction or bleeding, palliative resection is appropriate. A palliative gastrectomy need not be radical and it is sufficient to remove the tumour and reconstruct the gastrointestinal tract.

In inoperable patients with non resectable tumours obstructing the distal stomach, other palliative procedures need to be considered. Palliative procedures include:

1. High gastroenterostomy which is a poor operation that very frequently doesn’t allow the stomach to empty adequately and may produce the additional problem of bile reflux.

2. A Roux loop with wide anastomosis between the stomach and the jejunum may be a better option, even though this may not allow the stomach to empty well.

3. Gastric exclusion and oesophagojejunostomy is practiced by some surgeons.

In inoperable patients with non resectable tumours situated in the cardia, either palliative intubation, stenting or another form of recanalisation can be used.

Endoscopic resection:

In has been demonstrated in some centers that some patients with early gastric cancer can be adequately treated by an endoscopic mucosal resection. The addition of laparoscopic lymph node sampling may be considered in selected patients. This procedure should be limited to patients with:

Tumors less than 2 cm in sizeNegative lymph node samplingConfined to the mucosa on endoscopic ultrasonogrophyAbsence of other gastric lesions

If the resected specimen shows no ulceration, no penetration of the muscularis mucosa, no lymphatic invasion, and size less than 3 cm, then the risk of lymph node metastases is less than 1%.

Other treatment modalities

In patients with advanced gastric cancer where radical surgery is not curative, radiotherapy and chemotherapy may be used.

Radiotherapy: Its use is controversial as there are a number of

radiosensitive tissues in the region of the gastric bed, which limits the dose that can be given. However, it may have a role in the palliative treatment of painful bony metastases.

Chemotherapy:

Gastric cancer may respond well to combination cytotoxic chemotherapy and neoadjuvant chemotherapy improves outcome following surgery.

In operable tumours, patients should receive chemotherapy before surgery. The best results are obtained using a regimen of a combination of epirubicin, cis platinum, and infusional 5-fluorouracil or an oral analogue such as capicitabine.

In inoperable tumors or patients with advanced disease chemotherapy is considered palliative. The patients receive a first line chemotherapy including the same regimen as in operable tumors, although oxaliplatin is being substituted for cis-platinum as it has fewer side effects. Second line treatment using combinations that include taxotere are increasingly being used.

Outlook after surgical treatment

The difference in staging and a higher standard of surgery in Japan probably accounts for these results.

Japan West

Curative resection(%)

75% 25% - 50%

Five year survival rate(%)

50% - 70% 25% - 30%

Pattern of relapse following surgical treatment:The most common site of relapse following radical

gastrectomy is the gastric bed, due to inadequate extirpation of the primary tumor.

Widespread nodal metastases, distant nodal metastases and liver metastases are all common.

Dissemination to the lung and bones only occurs after liver metastases are already established.

Gastric lymphomaLow grade MALT lymphoma is not a surgical lesion.

Remarkably, when helicobacter pylori is eradicated and the gastritis improves the low grade MALT lymphoma often disappears.

If low grade MALT lymphoma persists after helicobacter pylori eradication, radiation should be considered for disease clinically confined to the stomach, while chemotherapy with or without radiation is used for more advanced lesions.

In High grade gastric lymphoma most patients are currently treated with chemotherapy and radiation, without surgical resection.

For disease limited to the stomach and regional nodes, radical subtotal D2 gastrectomy may be performed, especially for bulky tumors with bleeding and/ or obstruction.

Palliative gastrectomy may have a role in the treatment of tumor complications.

Gastrointestinal stromal tumorWedge resection with clear margins is adequate surgical

treatment. Sometimes adjacent structures are invaded by the primary tumor. If safe, en bloc resection of the involved surrounding organs is appropriate to remove all tumor when the primary is large and invasive.

Imatinib (gleevec) a chemotherapeutic agent yields excellent results in patients with metastatic or unresectable gastrointestinal stromal tumors. However, 50% of patients develop resistance to imatinib within two years.

Five year survival for patients with low grade lesions is about 80%, while those with high grade lesions have a five year survival of about 30%.

Gastric carcinoid tumorGastric carcinoids should be resected when diagnosed.In patients with small lesions confined to the mucosa

resection may be done endoscopically using endoscopic mucosal resection given that there are only few lesions and the margins are histologically negative.

Larger lesions may be removed by D1 or D2 gastrectomy.

Surgical debulking may be useful in certain patients with metastatic disease.

Somatostatin analogue is useful in controlling the symptoms of carcinoid syndrome but apparently does not prolong the survival in patients with metastatic gastric carcinoid.

Outlook after surgical treatment

Five year survival rate (%)

Node negative patients 90%

Node positive patients 50%

Type I gastric carcinoid 100%

Type III gastric carcinoid

50%

REFERENCESCurrent surgical therapy, ISBN: 978-1-4160-3497-1, 9th

edition.

Bailey and Love’s, short practice of surgery, 25th edition.

Schwartz’s principles of surgery, 9th edition.

Complications of Gastrectomy

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IndexComplications of anesthesiaComplications of any surgeryComplications of gastrectomy

UncommonReaction to the anesthesia drugs. Problems related to intubation or inserting the breathing

tube.Aspiration. Increased heart rate or elevated blood pressure. Waking during surgery or being awake throughout the

surgery (very rare).Malignant hyperthermia, a reaction that causes the

patient’s temperature to rise rapidly, is life threatening.

Complications of anesthesia:

Complications of any surgery:

WoundsBleedingDelayed Healing After SurgeryBlood Clots Caused by SurgeryInfectionsPeritonitisCardiovascular RisksPulmonary RisksDeath

Complications of gastrectomy Dumping syndromeAfferent loop syndromeBilious vomitingBlind loop syndromeWeight loss Reactive hypoglycemia Anemia Softening and bending of the bones

Dumping syndromeFood is rapidly dumped into the small

intestine from the stomach. Some patients experience :1. Lightheadedness2. Heart palpitations3. Sweating4. Nausea and vomiting after a mealTreated by adjusting the diet (eating smaller,

more frequent meals and limiting liquids).

Bile reflux gastritisPatients may complain of: 1. Early satiety (feeling of fullness after

eating),2. Abdominal discomfort3. Vomiting of pure bile It may follow any operation in which the

pylorus has been removed or bypassed but is most common following gastroenterostomy.

Blind loop syndromePatients may suffer from:1. Sudden onset of diahrrea2. Malabsorption features3. low vitamin B12 and normal or raised folatedue to decreased acidity and increased

bacterial overgrowth in the blind ended loop

Reactive hypoglycemia Blood sugar levels become too high after a

meal stimulating the release of insulin, occurring about two hours after eating.

A high protein diet and smaller meals are advised.

Pernicious anemialoss of the intrinsic factor (IF) secreting

parietal cells in the stomach lining.IF is essential for the uptake of vitamin B12. patient will suffer from a vitamin B12

deficiency. This can lead to pernicious anemia which

severely reduces erythropoiesis. Treated by giving the patient direct injections

of vit B12

Softening and bending of the bonesDeficiency of Vitamin D and calcium.Softening and bending of the bones can

produce pain and osteoporosis. According to one study, the risk for spinal

fractures may be as high as 50% after gastrectomy.

Recent Advances

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The American Cancer Society estimates that in 2007 there were an estimated one million new cases, nearly 70% of them in developing countries, and about 800,000

deaths

Recent advances in Pathophysiology: Recent Understanding the vascular supply of the

stomach allows understanding of the routes of hematogenous spread.

Recent Understanding the lymphatic drainage can clarify the areas at risk for nodal involvement by cancer.

Recent studies suggest that the disease is multi factorial → that leads to discovery of many factors that may cause gastric cancer like Helicobacter pylori infection, radiation exposure.

Recent advances in Diagnosis :

Recent advances in Diagnosis :1-History: Understanding that Early disease that has no specific

symptoms; some patients with incidental complaints are diagnosed with early gastric cancer. Patients may complain of indigestion, nausea or vomiting, dysphagia, postprandial fullness, loss of appetite, melena, hematemesis, and weight loss.

Recent advances in Diagnosis :2-Physical examination: Signs may include enlarged lymph nodes such as Irish

node (anterior axillary).

Blumer shelf (ie, shelflike tumor of the anterior rectal wall) may also be present.

Paraneoplastic syndromes such as dermatomyositis, acanthosis nigricans, and circinate erythemas are poor prognostic features.

Recent advances in Diagnosis :3-Investigation:1)Laboratory Studies: Electrolyte panels Carcinoembryonic antigen (CEA) is increased in 45-50% of

cases. Cancer antigen (CA) 19-9 is elevated in about 20% of cases.2)Imaging Studies: Esophagogastroduodenoscopy has a diagnostic accuracy of

95%.. Biopsy of any ulcerated lesion Endoscopic ultrasound3)Culture.4)Genetic studies: As in The endemic-type tumor which invades large areas of the

stomach.

Recent advances in Treatment :Treatment modality of gastric cancer has been improved

in the last 40 yearsThe 5-year survival rate for curative surgical resection

ranges from 30-50% for patients with stage II disease and from 10-25% for patients with stage III disease.

Recent advances in Treatment :

Recent advances in Treatment :Early Operable Tumour:A)In surgical treatment:1-EMR&ESD EMD (endoscopic mucosal resection) ESR (endoscopic submucosal dissection) *These are the method to remove the tumor using endoscopic

technique that has developed over 20 years ago2-Sentinal Lymph Node First LN to which the cancer spread (1st station of metastasis )

that should be taken as Biopsy It can be diagnosed by intraoperative mythelene blue dye trace

or by radio isotope and using gamma camera

Recent advances in Treatment :Early Operable Tumour:B) In adjuvant chemotherapy: The taxanes represent a new class of drugs with considerable activity in a

number of tumor types. Early-phase trials of paclitaxel and docetaxel, alone or in combination, have

shown encouraging results in the treatment of patients with advanced gastric cancer.

In the recently reported interim analysis of the phase III V325 trial, docetaxel, when combined with cisplatin and 5-FU, proved to be superior to the standard cisplatin plus 5-FU regimen in terms of response rate, time to tumor progression, and overall survival..

Recent trials suggest that adjuvent chemotherapy act as radio sensitizerRecent trials suggest that neoadjuvent chemotherapy can result in down

staging of the tumourChoice of preoperative and postoperative chemotherapy versus

postoperative chemotherapy and radiation remains controversial

Recent advances in Treatment :Early Operable Tumour:C)In adjuvant radiotherapy: Intraoperative radiotherapy Some studies suggest that intraoperative radiotherapy

(IORT) shows promising results.This alternative method of delivering radiotherapy

allows for a high dose to be given in a single fraction while in the operating room so that other critical structures can be avoided.

Recent advances in Treatment :Early Operable Tumour:D)Adjuvant chemoradiotherapy:A recent studies performed in the United States demonstrated a

survival benefit associated with postoperative chemoradiotherapy compared with surgery alone.

In this study, patients underwent an en bloc resection.Patients with T3 and/or N+ adenocarcinoma of the stomach or

gastroesophageal junction were randomized to receive a bolus of 5-fluorouracil (5-FU) and leucovorin (LV) and radiotherapy or observation.

Patients who received the adjuvant chemoradiotherapy demonstrated improved disease-free survival (from 32% to 49%) and improved overall survival rates (from 41% to 52%) compared to those who were merely observed.

This regimen is considered the standard of care in the United States.

Recent advances in Treatment :Advanced Inoperable (unresectable)

Tumour:Many patients present with distant metastases,that cannot be

resected completelyEarly results reported in 2007 by Japanese clinicians suggest

some improvement in both response rates and survival with the oral fluoropyrimidine used alone or in combination with cisplatin.

Recent results combines 3 investigational drugs: Tegafur (a prodrug of 5-FU), Gimeracil (an inhibitor of fluorouracil degradation) and Oteracil (Potassium oxanate) a GI tract adverse-effect modulator. These results remain to be confirmed by ongoing studies in Europe and North America.

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Recent advances in Treatment :Advanced Inoperable (unresectable)

Tumour:Bevacizumab, a monoclonal antibody against vascular

endothelial growth factor (VEGF). future treatment strategies may be guided by the use of gene

signatures.Some studies reveals that in patients receiving chemotherapy

after gastrectomy for advanced gastric cancer, intratumoral mRNA expression of thymidylate synthase (TS) is an independent prognostic factor for response to chemotheray have improve recurrence-free survival and overall survival

Overexpression of human epidermal growth factor receptor 2 (HER2) is a significant negative prognostic factor for gastric cancer. trial of usage of trastuzumab with chemotherapy in HER2-positive advanced gastric cancerimprove the prognosis of advanced gastric cancer

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