gastric cancer is when malignant or cancerous cells arise in the stomach this cancer can appear in any part of the stomach and it's classified into adenocarcinoma lymphoma carcinoid tumor and lyomyosarcoma depending on the types of cells it originates from Adeno means gland so adenocarcinoma arises from columnar glandular epithelium lymphoma arises from lymphocytes carcinoid tumor is originated in the G cells of the stomach and lyomyosarcoma arises from smooth muscle cells from the gastric wall gastric cancer is generally considered a poor prognosis cancer because it doesn't cause specific symptoms until later stages now the stomach has four regions the cardia the fundus the body and the pyloric antrum there's also a pyloric sphincter or valve at the end of the stomach which closes while eating keeping food inside the stomach to digest the gastric wall is made up of four layers from the outside in there's the adventitia or serosa the muscular layer the submucosa and the mucosa the mucosa comes into direct contact with food and it also has three layers of its own the innermost layer is the epithelial layer and it absorbs and secretes mucus and digestive enzymes the middle layer is the lamina propria and it has blood lymph vessels and mucosa-associated lymphoid tissue or malt for short which Are nodules of immune cells called lymphocytes in charge of eliminating pathogens that could pass through the epithelial layer the outermost layer of the mucosa is the muscularis mucosa and it's a smooth muscle layer that contracts and helps with the breakdown of food the epithelial layer dips down below the surface of the stomach lining to form gastric pits and these pits are contiguous with gastric glands below which contain various epithelial cell types each secreting a variety of substances so for example fovealer cells or Surface mucous cells secrete mucus which is a mix of water and glycoproteins that coats the stomach epithelial cells with all of these digestive enzymes and hydrochloric acid floating around the stomach and duodenal mucosa would get digested if not for this mucus which coats and protects the epithelial cells within the glands particularly in the body and fundus of the stomach are parietal cells which secrete hydrochloric acid to help maintain an acidic pH in the stomach there are also Chief cells that secrete pepsinogen to digest proteins and then there are G cells that secrete gastrin which has a number of effects including stimulation of parietal cells to secrete hydrochloric acid now adenocarcinoma is the most common type of gastric cancer and it originates in the columnar glandular epithelium it it's further divided into two subtypes intestinal or well-differentiated adenocarcinoma and diffuse or undifferentiated adenocarcinoma intestinal type is the most common in most cases it's caused by the bacteria helicobacter pylori or H pylori for short H pylori releases some virulence factors like CAG a that go inside the epithelial cells and cause extensive damage the immune system detects this damage and causes an inflammatory response within the gastric lining causing gastritis as long as H pylori remains in the stomach it continues to damage the mucosa and local inflammation persists leading to Chronic gastritis when this happens the normal epithelium of the stomach gets continuously damaged and repaired over time the stomach cells in the epithelium change and start to resemble intestinal epithelium this is called metaplasia which is when one type of cells in the body changes to resemble cells in another part of the body over time these metoplastic cells might accumulate mutations in the genes that are in charge of the cell cycle and cell division tumor suppressor genes which normally code for proteins that stop the cell cycle or promote apoptosis are the cell Cycle's very own brake pedal while proto-oncogenes which normally code for proteins that promote the cell cycle are the cell cycles accelerator pedal mutations can occur in both when this happens metaplastic cells start dividing uncontrollably and more mutations accumulate with each division So eventually these mutations might make the cells malignant meaning they gain the ability to invade neighboring tissues and spread to distant sites this type of adenocarcinoma typically appears on the Lesser curvature of the antrum as a large irregular ulcer with heaped up edges histologically it's a well-differentiated cancer meaning they resemble normal intestinal cells alternatively diffuse type of adenocarcinoma can appear in any part of the stomach and it's mostly related to genetic mutations in the cdh1 gene a tumor suppressor Gene that codes for a membrane adhesion molecule called e cadherin normally ecad herein helps epithelial cells stick to one another and it also transmits signals that control the progression of the cell cycle but when e-cadherent isn't working properly cells detach and start dividing uncontrollably this type of adenocarcinoma has an increased ability to spread and invade adjacent structures so it's way more aggressive than the intestinal type diffuse adenocarcinoma can appear in any part of the stomach and it can cause gastroglinitis or linnitus plastica where the stomach wall grows thick and hard and looks like a leather bottle this is the result of diffuse adenocarcinoma invading the connective tissue of the submucosa causing it to become thicker and more rigid histologically their Signet ring cells scatter throughout the connective tissue that look well like a Signet ring because the cytoplasm has giant vacuoles that push the nucleus to the edge of the cell now there's other less common types of gastric tumors like lymphomas carcinoid tumors and lyomiosarcomas lymphomas arise mostly from lymphocytes found in malt or mucosa-associated lymphoid tissue these cells more specifically B lymphocytes or B cells are in charge of recognizing and responding to any pathogen that crosses the epithelial layer so a chronic H pylori infection for example can cause excessive b-cell proliferation which makes these cells more prone to having mutations and developing lymphoma histologically it usually appears as diffuse lymphocytes surrounding the normal lymphoid nodules and epithelial cells carcinoid tumor arises in neuroendocrine cells like the G cells of the stomach it's a well-differentiated tumor that usually appears as a protruding Mass from the mucosa called Apollo although it mainly appears in the stomach it can also arise in other parts of the digestive tract like the intestine or the pancreas which also have G cells finally lyomyosarcoma arises from smooth muscle cells from the gastric wall and it's extremely rare under the microscope cancerous cells can look like spindle epithelial or undifferentiated cells complications for gastric adenocarcinoma include metastasis to the peritoneum to lymph nodes like the ones around the umbilicus and the left supraclavicular node or vercal's node or to distant organs most frequently the liver the bilateral metastases of diffuse adenocarcinoma to the ovaries causes a particular tumor called the kruckenberg tumor which has abundant Signet ring cells other complications are perineoplastic syndromes which are problems caused by the primary tumor on other organs without necessarily being metastasis perineoplastic syndromes include the laser trela sign which is seborrheic keratosis or brownish spots all over the skin it results from the stimulation of keratinocytes by growth factors produced by the gastric cancer cells polyarteritis nodosa refers to inflammation and necrosis of multiple medium-sized arteries including those that Supply the kidneys and the heart so they can eventually lead to kidney failure or myocardial infarction now cancer cells stimulate vascular and inflammatory cells to release tissue factor which then activates the coagulation Cascade therefore there's an increase in blood coagulability that leads to thrombosis or generation of blood clots trousseau syndrome consists of the appearance of migratory thrombosis in the veins finally if gastric cancer grows near the gastroesophageal junction it can cause a stricture that makes it difficult for foods and liquids to pass through from the esophagus into the stomach which is called pseudoakalasia syndrome generally speaking risk factors for gastric cancer include a family history of gastric cancer smoking alcohol consumption and being obese also the risk for gastric cancer increases with age specific risk factors for the intestinal type of adenocarcinoma include being male H pylori infection having blood type A a diet rich in nitrates nitrosamines highly salted Foods pickled or smoked foods and conditions such as autoimmune gastritis and pernicious anemia and acchlorhydria autoimmune gastritis is when the self-immune system attacks the parietal cells causing inflammation pernicious anemia is a condition where there's decreased production of red blood cells due to a deficiency of vitamin B12 and a chlorohydria means decreased or lack of gastric acid production on the other side there's protective factors to prevent gastric cancer and these include a high intake of fruits vegetables fiber and folate initially gastric cancer can be asymptomatic if there are symptoms they're usually vague like malaise loss of appetite and dyspepsia which is a burning sensation in the upper part of the abdomen once the disease progresses the main symptoms include epigastric pain nausea vomiting and weight loss in addition gastric cancer can ulcerate and bleed if there's significant blood loss this can cause anemia also the accumulation of blood in the stomach can cause hematemesis or vomiting of blood this can be bright red blood or have a darker color like coffee grounds when the red blood cells have been broken down by gastric acid finally there could be Molina where the discolored blood can also appear in stool making it black other signs and symptoms include those of perineoplastic syndromes laissez Trey law sign polyarteritis nodosa and trusso syndrome acanthosis cans is another sign that could be present and involves darkening of the skin at the axilla and other skin folds Sister Mary Joseph sign is a mass around the belly button caused by metastasis an enlargement of the lymph nodes in that area trocerosine refers to an enlarged hard Veer cow's node also caused by metastasis finally if gastric cancer grows near the gastroesophageal junction there might be dysphagia or difficulty swallowing diagnosis of gastric cancer is essentially made with endoscopy which is when a tube with a camera at the end of it is placed into the stomach to directly visualize the tumor and take a biopsy x-rays with barium contrast of the upper GI tract can be useful to identify complications like ulcers and finally abdominal pelvic CT can be used to evaluate if the cancer is spread to nearby organs or lymph nodes in order to determine the stage of the tumor treatment depends on the stage for initial stages surgery can be performed to treat the cancer for advanced stages surgery can only relieve the pain called palliative surgery chemo radiotherapy after surgery is used to increase the chance of survival unfortunately the overall survival rate is very low because gastric cancer is usually diagnosed at very Advanced stages alright as a quick recap gastric cancer is when malignant or cancerous cells arise in the stomach it's classified into adenocarcinoma lymphoma carcinoid tumor and lyomyosarcoma although the first one accounts for the majority of cases complications like metastasis and perineoplastic syndromes like laissez trilocine polyarteritis nodosa and trusso syndrome risk factors include family history of gastric cancer smoking alcohol consumption and being obese H pylori infection is the most important risk factor for the intestinal type of adenocarcinoma protective factors include a high intake of fruits vegetables fiber and folate early symptoms include malaise loss of appetite and dyspepsia epigastric pain nausea vomiting and weight loss are later symptoms diagnosis is made with endoscopy and biopsy x-rays with barium contrast of the upper GI and abdominopelvic CT are used for further evaluation the treatment depends on the stage for initial stages surgery can be sufficient for advanced stages there's palliative surgery combined with chemo radiotherapy