2. Features of Gastric Cancer 1) Second most common cancer 2) Dramatic decline worldwide 3) Wide variation in incidence 4) Altered risk among migrants
3. Age and Sex Distribution Men > women Most are elderly at diagnosis. Median age 65 years Younger patients may represent a more aggressive variant. Cigarettes
5. Geographic Distribution Highest 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.
6. Change In Histology Pattern Intestinal gastric cancer common in males older age more prevalent in high-risk areas linked to environmental factors The diffuse or infiltrative type frequent in both sexes common in younger age groups worse prognosis
7. Change In Histology Pattern Worldwide 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.
8. Lymphoma GIT 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.
9. CarcinoidTumour The overall age-adjusted incidence rates were 2.0 for men and 2.4/100,000 for women in 1983-1998.
10. GIST The 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).
12. 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.
13. 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
14. Factors decreasing the risk of gastric cancer: Aspirin Diet (high fresh fruit and vegetable intake) Vitamin C
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16. 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.
17. 3. Intestinal metaplasia Gastric 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.
18. 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.
64. There are a number of classifications proposed for gastric adenocarcinoma.
65. 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
66. WHO classification Tubular Tubules and acini Becomes solid if poorly differentiated Papillary Fibrovascular stalks Mucinous >50% of tumor is mucin Signet ring >50% of carcinoma is composed of signet ring cells
67. Special types Clear cell variant described as having clear to pale eosinophilic cytoplasm Tubulo-papillary architecture Dysplasia ranges from minimal to severe Round basal or mid-level nuclei in lower grades Location in cardia and pylorus
68. 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
70. Grading WHO (applies only to tubular pattern in WHO classification) Well differentiated – well formed glands Moderately differentiated - may be combined as well (low grade) Poorly differentiated (high grade) Highly irregular glandsor Single cells and clusters
72. Dyspepsia 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 .
73. 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 .
74. 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
75. 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
76. Flatulence: Distention of stomach with gas which usually tend to be belshed but it is more in functional stomach disease more than organic ones .
77. Disturbance of appetite: Anorexia specially to protein meals also anorexia due to other diseases like gastritis ,TB , Anaemia , psychogenic .
78. Others: Heart burn , waterbrash ( water and mucus in mouth) and erucation (acidic gastric contents in mouth)
79. 2- Anemia and Cachexia: Progressive anaemia , loss of weight , dehydration and general weakness and this can be the only presenting picture .
80. 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.
81. 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 …..
82. 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
83. Spread Blood : 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) .
84. 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
86. I. Laboratory Studies CBC : reveals anemia, due to bleeding, liver dysfunction, or poor nutrition. Serum electrolytes. Coagulation studies. Liver and Kidney function tests. Tumor markers: Carcinoembryonic antigen (CEA) Cancer antigen (CA) 19-9
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88. Repeated sampling at the same tissue site, reaching deeper into the gastric wall.
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90. Adenocarcinoma of the cardia. Large, lobulated, ulcerated mass at the gastroesophageal junction
91. Adenocarcinoma in the antrum manifested by ulcerated, circumferential mass and gastric outlet obstruction
105. 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”
108. Helps to assess the presence of nodal or visceral spread and involvement of other peritoneal structures (e.g., ovaries, liver).
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110. N Staging Carcinoma of the body of the stomach associated with regional lymphadenopathy and ascites
111. 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
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117. Along the greater curvature (greater curvature, gastroduodenal, gastroepiploic)
118. Along the lesser curvature (lesser curvature, left gastric, common hepatic, celiac)
130. 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.
131. Pollack, BJ, Chak, A, Sivak MV, Jr. Endoscopic ultrasonography. SeminOncol 1996; 23:336.
133. Karita, M, Tada, M. Endoscopic and histologic diagnosis of submucosal tumors of the gastrointestinal tract using combined strip biopsy and bite biopsy.
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137. 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.
138. 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. 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.
139. 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.
140. 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.
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142. 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).
143. Extent of lymphadenectomy 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.
144. 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.
145. 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.
146. 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.
147. Subtotal gastrectomy 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.
148. 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.
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151. 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%.
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154. 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.
155. Outlook after surgical treatment The difference in staging and a higher standard of surgery in Japan probably accounts for these results.
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159. Gastrointestinal stromaltumor Wedge 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.
160. 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%.
161. Gastric carcinoid tumor Gastric carcinoids should be resected when diagnosed. In patients with small lesions confined to the mucosa resection may be done endoscopicallyusing 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.
162. 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.
175. Complications of gastrectomy Dumping syndrome Afferent loop syndrome Bilious vomiting Blind loop syndrome Weight loss Reactive hypoglycemia Anemia Softening and bending of the bones
176. Dumping syndrome Food is rapidly dumped into the small intestine from the stomach. Some patients experience : Lightheadedness Heart palpitations Sweating Nausea and vomiting after a meal Treated by adjusting the diet (eating smaller, more frequent meals and limiting liquids).
177. Bile reflux gastritis Patients may complain of: Early satiety (feeling of fullness after eating), Abdominal discomfort Vomiting of pure bile It may follow any operation in which the pylorus has been removed or bypassed but is most common following gastroenterostomy.
178. Blind loop syndrome Patients may suffer from: Sudden onset of diahrrea Malabsorption features low vitamin B12 and normal or raised folate due to decreased acidity and increased bacterial overgrowth in the blind ended loop
179. 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.
180. Pernicious anemia loss 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
181. Softening and bending of the bones Deficiency 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.
183. 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
184. 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.
188. 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.
189. 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.
190. 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 ultrasound 3)Culture. 4)Genetic studies: As in The endemic-type tumor which invades large areas of the stomach.
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192. Recent advances in Treatment : Treatment modality of gastric cancer has been improved in the last 40 years The 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.
194. 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 ago 2-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
195. 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 sensitizer Recent trials suggest that neoadjuvent chemotherapy can result in down staging of the tumour Choice of preoperative and postoperative chemotherapy versus postoperative chemotherapy and radiation remains controversial
196. 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.
197. 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.
198. Recent advances in Treatment : Advanced Inoperable (unresectable) Tumour: Many patients present with distant metastases,that cannot be resected completely Early 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. .
199. 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
