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Gastric Cancer Epidemiology,[object Object],Amr Mohamed Helmy 	 734,[object Object]
Features of Gastric Cancer,[object Object],1) Second most common cancer ,[object Object],2) Dramatic decline worldwide ,[object Object],3) Wide variation in incidence,[object Object],4) Altered risk among migrants,[object Object]
Age and Sex Distribution,[object Object],Men > women,[object Object],Most are elderly at diagnosis. Median age 65 years,[object Object],Younger patients may represent a more aggressive variant.,[object Object],Cigarettes,[object Object]
Geographic Distribution,[object Object]
Geographic Distribution,[object Object],Highest rates (over 40 per 100,000 in males) are reported from Japan, China, the former USSR, and certain countries in Latin America.,[object Object],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.,[object Object]
Change In Histology Pattern,[object Object],Intestinal gastric cancer ,[object Object],common in males ,[object Object],older age ,[object Object],more prevalent in high-risk areas ,[object Object],linked to environmental factors ,[object Object],The diffuse or infiltrative type,[object Object],frequent in both sexes,[object Object],common in younger age groups,[object Object],worse prognosis,[object Object]
Change In Histology Pattern,[object Object],Worldwide decline in the incidence of the intestinal type.,[object Object],By contrast, the decline in the diffuse type has been more gradual (now accounts for approximately 30 percent of gastric carcinoma),[object Object],Despite the decline in gastric cancer overall, there has been an explosive increase in incidence of cancer of the gastric cardia.,[object Object]
Lymphoma,[object Object],GIT is the predominant site of extranodal non-Hodgkin lymphomas.,[object Object],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. ,[object Object],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.,[object Object],In the United States (US), gastric lymphoma is the most common extranodal site of lymphoma. ,[object Object]
CarcinoidTumour,[object Object],The overall age-adjusted incidence rates were 2.0 for men and 2.4/100,000 for women in 1983-1998. ,[object Object]
GIST,[object Object],The most common nonepithelial benign neoplasm involving the GI tract.,[object Object],Constitute only 1 percent of primary GI cancers. ,[object Object],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). ,[object Object]
Etiology,[object Object],Amr Mohamed Samir 	735,[object Object],Amr Mohamed Dawood	737,[object Object]
Gastric cancer is more common in patients with pernicious anemia, blood group A, or a family history of gastric cancer.,[object Object],Environmental factors appear to be more related etiologically to the intestinal form than the diffuse form.,[object Object]
Factors increasing the risk of gastric cancer:,[object Object],  Family history,[object Object],  Diet (high in nitrates, salt, fat),[object Object],  Familial polyposis,[object Object],  Gastric adenomas,[object Object],  Hereditary nonpolyposis colorectal cancer,[object Object],  Helicobacter pylori infection,[object Object],  Atrophic gastritis, intestinal metaplasia, dysplasia,[object Object],  Previous gastrectomy or gastrojejunostomy (>10 y ago),[object Object],  Tobacco smoking,[object Object],Ménétrier's disease,[object Object]
Factors decreasing the risk of gastric cancer:,[object Object],  Aspirin,[object Object],  Diet (high fresh fruit and vegetable intake),[object Object],  Vitamin C,[object Object]
[object Object],[object Object],[object Object]
2. Atrophic gastritis,[object Object],Chronic atrophic gastritis is the most common precursor for gastric cancer particularly the intestinal subtype and is usually associated with H. Pylori infection.,[object Object]
3. Intestinal metaplasia,[object Object],Gastric carcinoma often occurs in an area of intestinal metaplasia.,[object Object],Type III intestinal metaplasia is most commonly associated with gastric cancer, usually of the intestinal subtype.,[object Object],Eradication of helicobacter pylori infection leads to significant regression of intestinal metaplasia and improvement in atrophic gastritis.,[object Object]
4. Gastric remnant cancer ,[object Object],stomach cancer can develop, usually years following distal gastrectomy or gastroenterostomy.,[object Object],5. Other premalignant states:,[object Object],Patients with hereditary, non polyposis colorectal cancer have a 10% risk of developing gastric cancer.,[object Object],Ménétrier's disease: gastric mucosal hypertrophy.,[object Object]
Gross Pathology,[object Object],Amr Maher Basiony	733,[object Object],Amr Mohamed Helmy	734,[object Object]
Premalignant Conditions of the StomachPolyps,[object Object],Hyperplastic Polyps,[object Object],[object Object]
	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,[object Object]
	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.,[object Object]
6 to 10 percent of gastric polyps
Found in the antrum
May be flat or polypoid
Range in size from a few millimeters to several centimeters,[object Object]
Most commonly they are present in the corpus
Sessile, broad-based nodules, with a smooth surface contour,[object Object]
Prevalence is higher in older age groups
H. 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),[object Object]
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,[object Object]
Now all gastric ulcers are cancer until proven otherwise with adequate biopsy and follow-up.,[object Object]
Most tumors develop > 10 years following the initial operation
Arise often near the stoma
Quite large at presentation
Equally divided between intestinal and diffuse subtypes
Most cases have been reported following Billroth II gastroenterostomy
Prognosis is similar to proximal gastric cancer,[object Object]
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,[object Object]
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,[object Object]
Gross Pathology,[object Object],Bormann’s Classification: 1926,[object Object]
Gross Pathology,[object Object],Japanese Classification,[object Object],Type 0,[object Object]
Gross Pathology,[object Object],Japanese Classification,[object Object]
Microscopic picture of adenocarcinoma,[object Object],Amr Mohamed Mosa	735,[object Object],Amr Mohamed Halawa	738,[object Object]
There are a number of classifications proposed for,[object Object],gastric  adenocarcinoma.,[object Object]
Lauren classification ,[object Object],Intestinal type,[object Object],Glandular cells .,[object Object],(large , abundant cytoplasm , hyperchromic nuclei),[object Object],Intracellular mucin polarized to surface .,[object Object],Pushed margins , presence of lymphocytes .,[object Object],Metastasizes to nodes, liver,[object Object],Diffuse type,[object Object],Small clamps or single .,[object Object],(small . less cytoplasm , hypochromic nuclei),[object Object],No polarized mucin .,[object Object],Diffuse and infiltrative .,[object Object],Mixtures of above two types,[object Object]
WHO classification ,[object Object],Tubular,[object Object],Tubules and acini,[object Object],Becomes solid if poorly differentiated,[object Object],Papillary,[object Object],Fibrovascular stalks,[object Object],Mucinous,[object Object],>50% of tumor is mucin,[object Object],Signet ring,[object Object],>50% of carcinoma is composed of signet ring cells,[object Object]
  Special types ,[object Object],Clear cell variant ,[object Object],described as having,[object Object],clear to pale eosinophilic cytoplasm ,[object Object],Tubulo-papillary architecture,[object Object],Dysplasia ranges from minimal to severe ,[object Object],Round basal or mid-level nuclei in lower grades,[object Object],Location in cardia and pylorus,[object Object]
Hepatoid,[object Object],Closely resembles hepatocellular carcinoma ,[object Object],Frequently associated with intestinal type / tubulo-papillary gastric adenocarcinoma,[object Object],Eosinophilic to clear cytoplasm,[object Object],Round to oval nuclei with prominent nucleoli,[object Object],Frequent vascular invasion and liver metastasis,[object Object]
Adenosquamous,[object Object],Mixture of two patterns, more than just focal,[object Object]
Grading,[object Object],WHO (applies only to tubular pattern in WHO classification),[object Object],Well differentiated – well formed glands,[object Object],Moderately differentiated - may be combined as well ,[object Object],(low grade),[object Object],Poorly differentiated (high grade),[object Object],Highly irregular glandsor,[object Object],Single cells and clusters,[object Object]
Signs and symptoms,[object Object],Amr Mohamed Halawa738,[object Object]
Dyspepsia,[object Object],Highly 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 .,[object Object]
Pain:,[object Object],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 .,[object Object],it is not responsive to medical treatment , vomiting or alkali .,[object Object],it is usually due to high tone of the stomach wall or involving of nerve or peritoneum.,[object Object],It is visceral type of pain , vague , located in upper abdomen specially in epigastric region . ,[object Object],N.B ,[object Object],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 .,[object Object]
Vomiting:,[object Object],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 .,[object Object],it is a good sign if there is relief after vomiting which exclude out the malignancy potential ,[object Object]
Nausea:,[object Object],Sickness sensation without actual vomit + sweating + feeling to faint .,[object Object],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 .,[object Object],Nausea usually precede vomiting ,[object Object]
Flatulence:,[object Object],Distention of stomach with gas which usually tend to be belshed but it is more in functional stomach disease more than organic ones .,[object Object]
Disturbance of appetite:,[object Object],Anorexia specially to protein meals also anorexia due to other diseases like gastritis ,TB , Anaemia , psychogenic .,[object Object]
Others:,[object Object],Heart burn , waterbrash ( water and mucus in mouth) and erucation (acidic gastric contents in mouth),[object Object]
2- Anemia and Cachexia:,[object Object],Progressive anaemia , loss of weight , dehydration and general weakness and this can be the only presenting picture .,[object Object]
3- Mass:,[object Object],Mass in epigastrium or left hypochondrium , it may be the only presentation and it indicate a late inoperable tumor .,[object Object],It is irregular , tender , mobile or fixed.,[object Object]
Complication:,[object Object],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.,[object Object],Secondaries to the liver , pyloric obstruction …..,[object Object]
Spread:-,[object Object],Direct :,[object Object],It extends to seroperitonium then to the near by organs (pancreas , spleen , liver , transverse colon ) .,[object Object],Tumor in cardia : spread to esophagus ,[object Object],Tumor in pylorus : to duodenum .,[object Object],Lymphatic : (very aggressive ),[object Object],to lymphnodes in greater and lesser curvature .,[object Object],celiac and para aortic ,[object Object],mediastinal (for tumors of the cardia),[object Object],virschaw lymph nodes ,[object Object]
Spread,[object Object],Blood :,[object Object],from portal vein to liver and maybe lung or bone .,[object Object],transperitoneal :,[object Object],1-krunkenburg syndrome (or maybe by blood) .,[object Object],2-sister mary Josef nodules .,[object Object],3-malignant ascites .,[object Object],4-Blumer’s shelf (mass during rectal examination) .,[object Object]
Paraneoplastic manifestations:-,[object Object],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.,[object Object],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,[object Object]
Investigations,[object Object],Amr Mohamed Dawood	737,[object Object]
I. Laboratory Studies,[object Object],CBC : reveals anemia, due to bleeding, liver   dysfunction, or poor nutrition.,[object Object],Serum electrolytes.,[object Object],Coagulation studies.,[object Object],Liver and Kidney function tests.,[object Object],Tumor markers:,[object Object],Carcinoembryonic antigen (CEA) ,[object Object],        Cancer antigen (CA) 19-9,[object Object]
II. Endoscopy,[object Object],Room set-up and patient positioning for endoscopy,[object Object],[object Object],[object Object]
Repeated sampling at the same tissue site, reaching deeper into the gastric wall.
Multiple samples should be obtained around the ulcer crater. ,[object Object]
Adenocarcinoma of the cardia.  Large, lobulated, ulcerated mass at the gastroesophageal junction,[object Object]
Adenocarcinoma in the antrum manifested by ulcerated, circumferential mass and gastric outlet obstruction,[object Object]
Endoscopic view of an ulcerating adenocarcinoma,[object Object]
III. Endoscopic ultrasonography (EUS),[object Object],[object Object]
Can be used to guide for biopsy.
Has the ability to detect sarcomas and other tumors arising from the submucosa and the musculosa (GIST).,[object Object]
Mucosa
Muscularis mucosa
Submucosa
Muscularispropria
Serosa,[object Object]
Can not be used to assess distant nodal or liver metastases.
Can not differentiates between malignant and benign ulcers.,[object Object]
It may show thickened or enlarged gastric folds, filling defects, mass or ulcer.,[object Object]
Fungating mass of the body of the stomach,[object Object]
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”,[object Object]
Linitisplastica "leather-flask" appearing stomach,[object Object],[object Object],[object Object]
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.,[object Object]
N Staging,[object Object],Carcinoma of the body of the stomach associated with regional lymphadenopathy and ascites,[object Object]
M StagingThe liver is the most common site for hematogenous metastases. Less common sites are the lungs, adrenal glands, kidneys, bone and brain.,[object Object],Pulmonary metastases and left pleural effusion,[object Object]
IV. Staging laparoscopy,[object Object],[object Object],Laparoscopic evaluation of metastasis.,[object Object]
[object Object]
Peritoneal cytology may be done, which increases the sensitivity of laparoscopy.,[object Object]
[object Object]
Nodal stage is based upon the number of positive lymph nodes and not the proximity of the nodes to the primary tumor.,[object Object]
Along the greater curvature (greater curvature, gastroduodenal, gastroepiploic)
Along the lesser curvature (lesser curvature, left gastric, common hepatic, celiac)
Pancreatic and splenic area
Involvement of intraabdominal nodal groups (e.g. retropancreatic, portal, mesenteric, and paraaortic)    is classified as distant metastases.,[object Object]
The 2002 AJCCTNM staging of gastric carcinoma,[object Object],[object Object],TX - Primary tumor (T) cannot be assessed,[object Object],T0 - No evidence of primary tumor,[object Object],Tis - Carcinoma in situ, intraepithelial tumor without invasion of      	lamina propria,[object Object],T1 - Tumor invades lamina propria or submucosa,[object Object],T2 - Tumor invades muscularispropria or subserosa,[object Object],T3 - Tumor penetrates serosa (ie, visceral peritoneum) without 	invasion of adjacent structures,[object Object],T4 - Tumor invades adjacent structures,[object Object]
[object Object],NX - Regional lymph nodes (N) cannot be assessed,[object Object],N0 - No regional lymph node metastases,[object Object],N1 - Metastasis in 1-6 regional lymph nodes,[object Object],N2 - Metastasis in 7-15 regional lymph nodes,[object Object],N3 - Metastasis in more than 15 regional lymph nodes,[object Object],[object Object],MX - Distant metastasis cannot be assessed,[object Object],M0 - No distant metastasis,[object Object],M1 - Distant metastasis,[object Object]
The AJCC 2010 modifications,[object Object],[object Object],[object Object]
N1 = 1-2 positive nodes (compared to 1-6 in the  	        2002 criteria)
N2 = 3-6 positive nodes (compared to 7 - 15 in            	       2002)
N3 = >7 positive nodes (compared to >15 in 2002)
Positive peritoneal cytology is classified as M1 disease.
Stage grouping have been changed.,[object Object]
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. SeminOncol 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.,[object Object]
Operability ,[object Object],[object Object],Incurable patients are those with:,[object Object],Haematogenous metastases,[object Object],Involvement of the distant peritoneum,[object Object],N4 nodal disease and disease beyond the N4 nodes,[object Object],Fixation to structures that cannot be removed. Involvement of another organ does not indicate incurability, provided that it can be removed.,[object Object]
[object Object],N3 nodal involvement,[object Object],Involvement of the adjacent peritoneum,[object Object],[object Object],[object Object]
The subpyloric nodes are dissected and the first part of the duodenum is divided, usually with a surgical stapler.,[object Object],The hepatic nodes are dissected down to clear the hepatic artery. This dissection also includes the suprapyloric lymph nodes.,[object Object],The lymph node dissection is continued to the origin of the left gastric artery. ,[object Object]
The dissection is then continued along the splenic artery taking all of the nodes at the superior aspect of the pancreas and in the splenichilum.,[object Object],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.,[object Object]
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.,[object Object]
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. ,[object Object],Gastrointestinal continuity is reconstituted by means of a Roux loop. ,[object Object]
[object Object],A purse-string is placed in the cut end of the oesophagus.,[object Object],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.,[object Object]
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.,[object Object],The jejunojejunostomy is undertaken in the usual fashion(end to side).,[object Object]
Extent of lymphadenectomy,[object Object],There 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. ,[object Object]
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. ,[object Object]
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 splenicartery. 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.,[object Object]
The difference between D1 and D2 operations depend upon the tiers of lymph node removed. In general, D1 resection involves the removal of perigastricnodes while D2 resection involves removal of the lymph nodes along the major arterial trunks along with the perigastric nodes. ,[object Object]
Subtotal gastrectomy,[object Object],For 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.,[object Object]
After the resection the gastrointestinal continuity is restored by:,[object Object],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.,[object Object],Reconstruction using a Roux loop to avoid marked enterogastric reflux and bile reflux oesophagitis that occurs with Billroth II/ polya type gastrectomy.,[object Object]
Palliative surgery:,[object Object],[object Object],[object Object]
3.  Gastric exclusion and oesophagojejunostomy is practiced by some surgeons.,[object Object],[object Object],[object Object]
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%.,[object Object]

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