Gastric Cancer

Overview

Epidemiology

• 3rd-most common cause of cancer-related death worldwide
• High incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency in Eastern Asia ASIA Spinal Cord Injuries, Eastern Europe, and South America
• Regional differences noted: ↓ incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency in the United States, but ↑ in Japan and South Korea
• Men > women
• Median age at the time of diagnosis: 70 years

Etiology

Endogenous risk factors:

• Chronic atrophic gastritis Atrophic gastritis Gastritis with atrophy of the gastric mucosa, the gastric parietal cells, and the mucosal glands leading to achlorhydria. Atrophic gastritis usually progresses from chronic gastritis. Gastritis 
• Pernicious anemia Pernicious anemia A megaloblastic anemia occurring in children but more commonly in later life, characterized by histamine-fast achlorhydria, in which the laboratory and clinical manifestations are based on malabsorption of vitamin B12 due to a failure of the gastric mucosa to secrete adequate and potent intrinsic factor. Megaloblastic Anemia
• Previous partial gastrectomy (antrectomy)
• Blood type A
• Menetrier’s disease (extreme hypertrophy Hypertrophy General increase in bulk of a part or organ due to cell enlargement and accumulation of fluids and secretions, not due to tumor formation, nor to an increase in the number of cells (hyperplasia). Cellular Adaptation of gastric rugal folds)
• Bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy reflux
• Genetic factors and hereditary syndromes:
  • Hereditary diffuse gastric cancer (associated with E-cadherin gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics or CDH1 mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations)
  • Gastric adenocarcinoma and proximal polyposis of the stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy (GAPPS)
  • Familial intestinal gastric cancer (FIGC)
  • Hereditary nonpolyposis colorectal cancer Colorectal cancer Colorectal cancer (CRC) is the 2nd leading cause of cancer-related deaths in the United States. Colorectal cancer is a heterogeneous disease that arises from genetic and epigenetic abnormalities, with influence from environmental factors. Colorectal Cancer ( HNPCC HNPCC Lynch syndrome, also called hereditary non-polyposis colorectal cancer (HNPCC), is the most common inherited colon cancer syndrome, and carries a significantly increased risk for endometrial cancer and other malignancies. Lynch syndrome has an autosomal dominant inheritance pattern involving pathogenic variants in one of the mismatch repair (MMR) genes or epithelial cell adhesion molecule (EpCAM). Lynch syndrome)
  • Peutz-Jeghers syndrome Peutz-Jeghers Syndrome Peutz-Jeghers syndrome (PJS) is an autosomal-dominant inherited disorder characterized by GI polyps and mucocutaneous-pigmented macules. Peutz-Jeghers syndrome is 1 of the polyposis syndromes, a group of inherited or acquired conditions characterized by the growth of polyps in the GI tract and associated with other extracolonic features. Peutz-Jeghers Syndrome
  • Familial adenomatous polyposis Familial Adenomatous Polyposis Familial adenomatous polyposis (FAP) is an autosomal dominant inherited genetic disorder that presents with numerous adenomatous polyps in the colon. Familial adenomatous polyposis is the most common of the polyposis syndromes, which is a group of inherited or acquired conditions characterized by the growth of polyps in the GI tract, associated with other extracolonic features. Familial Adenomatous Polyposis ( FAP FAP Familial adenomatous polyposis (FAP) is an autosomal dominant inherited genetic disorder that presents with numerous adenomatous polyps in the colon. Familial adenomatous polyposis is the most common of the polyposis syndromes, which is a group of inherited or acquired conditions characterized by the growth of polyps in the GI tract, associated with other extracolonic features. Familial Adenomatous Polyposis)
  • Li-Fraumeni syndrome

Exogenous risk factors:

• Chronic Helicobacter pylori Helicobacter pylori A spiral bacterium active as a human gastric pathogen. It is a gram-negative, urease-positive, curved or slightly spiral organism initially isolated in 1982 from patients with lesions of gastritis or peptic ulcers in Western Australia. Helicobacter pylori was originally classified in the genus campylobacter, but RNA sequencing, cellular fatty acid profiles, growth patterns, and other taxonomic characteristics indicate that the micro-organism should be included in the genus Helicobacter. It has been officially transferred to Helicobacter gen. Helicobacter infection (associated with distal intestinal-type adenocarcinoma)
• Long-term diet rich in nitrates Nitrates Nitrates are a class of medications that cause systemic vasodilation (veins > arteries) by smooth muscle relaxation. Nitrates are primarily indicated for the treatment of angina, where preferential venodilation causes pooling of blood, decreased preload, and ultimately decreased myocardial O2 demand. Nitrates (found in dried, smoked, salted, and partially decayed foods) 
• Low vegetable consumption
• Smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases
• Epstein-Barr virus Epstein-Barr Virus Epstein-Barr virus (EBV) is a linear, double-stranded DNA virus belonging to the Herpesviridae family. This highly prevalent virus is mostly transmitted through contact with oropharyngeal secretions from an infected individual. The virus can infect epithelial cells and B lymphocytes, where it can undergo lytic replication or latency. Epstein-Barr Virus ( EBV EBV Epstein-barr virus (EBV) is a linear, double-stranded DNA virus belonging to the herpesviridae family. This highly prevalent virus is mostly transmitted through contact with oropharyngeal secretions from an infected individual. The virus can infect epithelial cells and B lymphocytes, where it can undergo lytic replication or latency. Epstein-Barr Virus) infection
• Abdominal irradiation in cancer survivors

Types of Gastric Cancer

Adenocarcinoma

• 85% of gastric cancers
• Main histologic types:
  • Intestinal type (70%):
    • Tumor Tumor Inflammation cells exhibit adhesion Adhesion The process whereby platelets adhere to something other than platelets, e.g., collagen; basement membrane; microfibrils; or other ‘foreign’ surfaces. Coagulation Studies and have glandular formations.
    • More common in men and older age groups
    • Associated with ↑ incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency in lower socioeconomic classes 
    • Better prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas
  • Diffuse type (30%):
    • Poorly cohesive histology, lacking intercellular adhesions (includes signet-ring cell carcinoma)
    • Tumor Tumor Inflammation cells with likelihood of infiltration and manifestation as stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy wall thickening instead of a mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast
    • Stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy loses distensibility.
    • Equal sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria distribution
    • More common in younger age groups
    • Overall, worse prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas

Primary gastric lymphoma Lymphoma A general term for various neoplastic diseases of the lymphoid tissue. Imaging of the Mediastinum

• 13% of gastric cancers
• Stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy: most common extranodal site of lymphoma Lymphoma A general term for various neoplastic diseases of the lymphoid tissue. Imaging of the Mediastinum
• Ranges from superficial mucosa-associated lymphoid tissue Mucosa-associated lymphoid tissue Colon, Cecum, and Appendix: Anatomy ( MALT MALT Colon, Cecum, and Appendix: Anatomy) to large cell lymphoma Lymphoma A general term for various neoplastic diseases of the lymphoid tissue. Imaging of the Mediastinum
• MALT MALT Colon, Cecum, and Appendix: Anatomy development is associated with H. pylori H. pylori A spiral bacterium active as a human gastric pathogen. It is a gram-negative, urease-positive, curved or slightly spiral organism initially isolated in 1982 from patients with lesions of gastritis or peptic ulcers in Western Australia. Helicobacter pylori was originally classified in the genus campylobacter, but RNA sequencing, cellular fatty acid profiles, growth patterns, and other taxonomic characteristics indicate that the micro-organism should be included in the genus Helicobacter. It has been officially transferred to Helicobacter gen. Helicobacter infection.

Gastrointestinal stromal tumors (GIST)

• Stromal or mesenchymal tumors, constituting approximately 1% of primary gastric cancers
• Found in other areas of the digestive tract, but most are in the stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy

Carcinoid tumors Carcinoid tumors Carcinoid tumors are small, well-differentiated, slow-growing neuroendocrine tumors (NET). Carcinoid syndrome describes the signs and symptoms associated with unregulated vasoactive hormone production by neuroendocrine tumors. Carcinoid tumors are most commonly found in the GI and bronchopulmonary tracts. Carcinoid Tumors and Syndrome

• Rare
• Slow-growing neuroendocrine tumors Neuroendocrine tumors Tumors whose cells possess secretory granules and originate from the neuroectoderm, i.e., the cells of the ectoblast or epiblast that program the neuroendocrine system. Common properties across most neuroendocrine tumors include ectopic hormone production (often via apud cells), the presence of tumor-associated antigens, and isozyme composition. Gastrinoma
• Originate from the hormone-producing (enterochromaffin) cells

Pathophysiology

Intestinal type

• Chronic infection with H. pylori H. pylori A spiral bacterium active as a human gastric pathogen. It is a gram-negative, urease-positive, curved or slightly spiral organism initially isolated in 1982 from patients with lesions of gastritis or peptic ulcers in Western Australia. Helicobacter pylori was originally classified in the genus campylobacter, but RNA sequencing, cellular fatty acid profiles, growth patterns, and other taxonomic characteristics indicate that the micro-organism should be included in the genus Helicobacter. It has been officially transferred to Helicobacter gen. Helicobacter: a primary risk factor for (intestinal-type) non-cardia gastric cancer
• Prolonged exposure to risk factor → atrophic gastritis Atrophic gastritis Gastritis with atrophy of the gastric mucosa, the gastric parietal cells, and the mucosal glands leading to achlorhydria. Atrophic gastritis usually progresses from chronic gastritis. Gastritis → achlorhydria Achlorhydria A lack of hydrochloric acid in gastric juice despite stimulation of gastric secretion. Gastritis or hypochlorhydria → ↑ stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy pH pH The quantitative measurement of the acidity or basicity of a solution. Acid-Base Balance → microbial colonization Colonization Bacteriology and loss of cells (which produce epidermal and transforming growth factors) needed to regenerate damaged tissue 
• Follows a pattern of stepwise progression (Correa’s cascade): chronic gastritis Gastritis Gastritis refers to inflammation of the gastric mucosa. Gastritis may occur suddenly (acute gastritis) or slowly over time (chronic gastritis). Gastritis may be asymptomatic or with symptoms, including burning abdominal pain (which either worsens or improves with eating), dyspepsia, nausea, and vomiting. Gastritis → chronic atrophic gastritis Atrophic gastritis Gastritis with atrophy of the gastric mucosa, the gastric parietal cells, and the mucosal glands leading to achlorhydria. Atrophic gastritis usually progresses from chronic gastritis. Gastritis → intestinal metaplasia Metaplasia A condition in which there is a change of one adult cell type to another similar adult cell type. Cellular Adaptation → dysplasia (direct precursor of cancer) → adenocarcinoma

Diffuse type

• Associated with loss-of-function mutations of CDH1 ( tumor Tumor Inflammation suppressor gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics that encodes E-cadherin, a cell-adhesion protein) 
• Neoplastic cells without intercellular adhesion (due to loss of expression of E-cadherin) → infiltration of neoplastic cells within the gastric wall → diffuse thickening of the gastric wall → loss of distensibility (known as linitis plastica, or “leather-bottle” appearance)

Clinical Presentation

Symptoms

• Asymptomatic in early stages when the cancer is more curable
• By the time symptoms start, the cancer is already advanced.

• Initial symptoms occur with insidious onset:
  • Epigastric discomfort (postprandial fullness, steady pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways)
  • Anorexia Anorexia The lack or loss of appetite accompanied by an aversion to food and the inability to eat. It is the defining characteristic of the disorder anorexia nervosa. Anorexia Nervosa
  • Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics 
• Later symptoms as disease progresses:
  • Weight loss Weight loss Decrease in existing body weight. Bariatric Surgery
  • Increased nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics and early satiety Early Satiety Bariatric Surgery (noted in linitis plastica as the stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy is unable to distend)
  • Vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia or gastric outlet obstruction Gastric Outlet Obstruction Hypertrophic Pyloric Stenosis (especially with pyloric tumors)
  • Dysphagia Dysphagia Dysphagia is the subjective sensation of difficulty swallowing. Symptoms can range from a complete inability to swallow, to the sensation of solids or liquids becoming “stuck.” Dysphagia is classified as either oropharyngeal or esophageal, with esophageal dysphagia having 2 sub-types: functional and mechanical. Dysphagia (especially with diffuse-type, esophagogastric and cardiac tumors)
  • Melena Melena The black, tarry, foul-smelling feces that contain degraded blood. Gastrointestinal Bleeding or hematemesis Hematemesis Vomiting of blood that is either fresh bright red, or older ‘coffee-ground’ in character. It generally indicates bleeding of the upper gastrointestinal tract. Mallory-Weiss Syndrome (Mallory-Weiss Tear)

Signs

• Normal physical exam early in the disease 
• Epigastric mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast indicates long-standing growth.
• Signs of metastatic gastric carcinoma:
  • Hepatomegaly or palpable liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast
  • Virchow’s node: palpable node in the left supraclavicular region
  • Irish node: palpable nodes in the left axillary
  • Blumer’s shelf ( mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast in the pouch of Douglas Pouch of Douglas A sac or recess formed by a fold of the peritoneum. Ovaries: Anatomy): palpable on digital rectal or vaginal examination
  • Sister Mary Joseph’s nodule Nodule Chalazion: periumbilical nodule Nodule Chalazion 
  • Krukenberg tumor Tumor Inflammation: malignancy Malignancy Hemothorax in the ovaries Ovaries Ovaries are the paired gonads of the female reproductive system that contain haploid gametes known as oocytes. The ovaries are located intraperitoneally in the pelvis, just posterior to the broad ligament, and are connected to the pelvic sidewall and to the uterus by ligaments. These organs function to secrete hormones (estrogen and progesterone) and to produce the female germ cells (oocytes). Ovaries: Anatomy representing metastasis Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Grading, Staging, and Metastasis from another site (gastrointestinal source most often)
  • Ascites Ascites Ascites is the pathologic accumulation of fluid within the peritoneal cavity that occurs due to an osmotic and/or hydrostatic pressure imbalance secondary to portal hypertension (cirrhosis, heart failure) or non-portal hypertension (hypoalbuminemia, malignancy, infection). Ascites: can indicate peritoneal carcinomatosis

Paraneoplastic findings

• Malignant acanthosis nigricans Acanthosis nigricans A circumscribed melanosis consisting of a brown-pigmented, velvety verrucosity or fine papillomatosis appearing in the axillae and other body folds. It occurs in association with endocrine disorders, underlying malignancy, administration of certain drugs, or as in inherited disorder. Diabetes Mellitus: rapid appearance/growth of dark and velvety patches Patches Vitiligo (usually on skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions folds) 
• Diffuse seborrheic keratoses (Leser-Trélat syndrome)
• Dermatomyositis Dermatomyositis A subacute or chronic inflammatory disease of muscle and skin, marked by proximal muscle weakness and a characteristic skin rash. The illness occurs with approximately equal frequency in children and adults. The skin lesions usually take the form of a purplish rash (or less often an exfoliative dermatitis) involving the nose, cheeks, forehead, upper trunk, and arms. The disease is associated with a complement mediated intramuscular microangiopathy, leading to loss of capillaries, muscle ischemia, muscle-fiber necrosis, and perifascicular atrophy. The childhood form of this disease tends to evolve into a systemic vasculitis. Dermatomyositis may occur in association with malignant neoplasms. Paraneoplastic Syndromes
• Hypercoagulable Hypercoagulable Hypercoagulable states (also referred to as thrombophilias) are a group of hematologic diseases defined by an increased risk of clot formation (i.e., thrombosis) due to either an increase in procoagulants, a decrease in anticoagulants, or a decrease in fibrinolysis. Hypercoagulable States state
• Membranous nephropathy

Diagnosis

Surveillance Surveillance Developmental Milestones and Normal Growth

• No recommendations for the general population
• High-risk patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship for whom upper endoscopy Endoscopy Procedures of applying endoscopes for disease diagnosis and treatment. Endoscopy involves passing an optical instrument through a small incision in the skin i.e., percutaneous; or through a natural orifice and along natural body pathways such as the digestive tract; and/or through an incision in the wall of a tubular structure or organ, i.e. Transluminal, to examine or perform surgery on the interior parts of the body. Gastroesophageal Reflux Disease (GERD) may be of benefit:
  • Familial adenomatous polyposis Familial Adenomatous Polyposis Familial adenomatous polyposis (FAP) is an autosomal dominant inherited genetic disorder that presents with numerous adenomatous polyps in the colon. Familial adenomatous polyposis is the most common of the polyposis syndromes, which is a group of inherited or acquired conditions characterized by the growth of polyps in the GI tract, associated with other extracolonic features. Familial Adenomatous Polyposis
  • Gastric adenomas
  • Elderly with atrophic gastritis Atrophic gastritis Gastritis with atrophy of the gastric mucosa, the gastric parietal cells, and the mucosal glands leading to achlorhydria. Atrophic gastritis usually progresses from chronic gastritis. Gastritis or pernicious anemia Pernicious anemia A megaloblastic anemia occurring in children but more commonly in later life, characterized by histamine-fast achlorhydria, in which the laboratory and clinical manifestations are based on malabsorption of vitamin B12 due to a failure of the gastric mucosa to secrete adequate and potent intrinsic factor. Megaloblastic Anemia
  • Hereditary nonpolyposis colorectal cancer Colorectal cancer Colorectal cancer (CRC) is the 2nd leading cause of cancer-related deaths in the United States. Colorectal cancer is a heterogeneous disease that arises from genetic and epigenetic abnormalities, with influence from environmental factors. Colorectal Cancer 
  • History of partial gastrectomy
  • High risk immigrant ethnic population

Diagnosis

• Esophagogastroduodenoscopy (EGD):
  • Diagnostic imaging procedure of choice
  • Evaluates gastric mucosa Gastric mucosa Lining of the stomach, consisting of an inner epithelium, a middle lamina propria, and an outer muscularis mucosae. The surface cells produce mucus that protects the stomach from attack by digestive acid and enzymes. When the epithelium invaginates into the lamina propria at various region of the stomach (cardia; gastric fundus; and pylorus), different tubular gastric glands are formed. These glands consist of cells that secrete mucus, enzymes, hydrochloric acid, or hormones. Stomach: Anatomy and lymph Lymph The interstitial fluid that is in the lymphatic system. Secondary Lymphatic Organs node involvement
  • Allows deep mucosal/ulcer biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma (to distinguish benign Benign Fibroadenoma from malignant ulcers)
  • Possible findings suggesting gastric cancer:
    • Friable ulcerated mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast
    • Gastric ulcer Gastric ulcer Ulceration of the gastric mucosa due to contact with gastric juice. It is often associated with Helicobacter pylori infection or consumption of nonsteroidal anti-inflammatory drugs (NSAIDS). Peptic Ulcer Disease with irregular or thickened margins 
    • In linitis plastica, normal mucosa is noted but with poor stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy distensibility.
• Double-contrast barium swallow Barium Swallow Imaging of the Intestines study:
  • Low sensitivity 
  • Useful in evaluating linitis plastica, which has a leather-bottle appearance

Staging Staging Methods which attempt to express in replicable terms the extent of the neoplasm in the patient. Grading, Staging, and Metastasis procedures

• Computed tomography (CT) of the chest, abdomen, and pelvis Pelvis The pelvis consists of the bony pelvic girdle, the muscular and ligamentous pelvic floor, and the pelvic cavity, which contains viscera, vessels, and multiple nerves and muscles. The pelvic girdle, composed of 2 “hip” bones and the sacrum, is a ring-like bony structure of the axial skeleton that links the vertebral column with the lower extremities. Pelvis: Anatomy:
  • Provides information on the primary tumor Tumor Inflammation and the local extent of the disease
  • Evaluates areas for distant metastasis Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Grading, Staging, and Metastasis 
• Endoscopic ultrasonography (EUS):
  • Most reliable in evaluating depth of tumor Tumor Inflammation invasion 
  • Detects regional nodal involvement and allows fine-needle aspiration of lymph Lymph The interstitial fluid that is in the lymphatic system. Secondary Lymphatic Organs node
• 18-fluorodeoxyglucose (FDG)-positron emission tomography ( PET PET An imaging technique that combines a positron-emission tomography (PET) scanner and a ct X ray scanner. This establishes a precise anatomic localization in the same session. Nuclear Imaging) scan:
  • Detection of occult metastatic lesions (especially in ≥ T2N0 disease)
  • More sensitive than CT in detecting distant metastases
• Staging Staging Methods which attempt to express in replicable terms the extent of the neoplasm in the patient. Grading, Staging, and Metastasis laparoscopy Laparoscopy Laparoscopy is surgical exploration and interventions performed through small incisions with a camera and long instruments. Laparotomy and Laparoscopy:
  • As peritoneal metastases can be missed by CT, laparoscopy Laparoscopy Laparoscopy is surgical exploration and interventions performed through small incisions with a camera and long instruments. Laparotomy and Laparoscopy helps determine occult peritoneal dissemination. 
  • Allows peritoneal washings and cytology

Tumor, Nodes, Metastases (TNM) Classification and Stages

Management and Prognosis

Management

• H. pylori H. pylori A spiral bacterium active as a human gastric pathogen. It is a gram-negative, urease-positive, curved or slightly spiral organism initially isolated in 1982 from patients with lesions of gastritis or peptic ulcers in Western Australia. Helicobacter pylori was originally classified in the genus campylobacter, but RNA sequencing, cellular fatty acid profiles, growth patterns, and other taxonomic characteristics indicate that the micro-organism should be included in the genus Helicobacter. It has been officially transferred to Helicobacter gen. Helicobacter eradication therapy for those with positive infection
• Clinical staging Staging Methods which attempt to express in replicable terms the extent of the neoplasm in the patient. Grading, Staging, and Metastasis dictates initial therapy. 
• Locoregional disease (stage I–III):
  • Preoperative (neoadjuvant) chemotherapy Chemotherapy Osteosarcoma for downstaging
  • Surgery for proximal tumors: total gastrectomy and resection of adjacent lymph nodes Lymph Nodes They are oval or bean shaped bodies (1 – 30 mm in diameter) located along the lymphatic system. Lymphatic Drainage System: Anatomy 
  • Surgery for distal (lower ⅔) tumors: subtotal gastrectomy and resection of adjacent lymph nodes Lymph Nodes They are oval or bean shaped bodies (1 – 30 mm in diameter) located along the lymphatic system. Lymphatic Drainage System: Anatomy
  • Postoperative ( adjuvant Adjuvant Substances that augment, stimulate, activate, potentiate, or modulate the immune response at either the cellular or humoral level. The classical agents (freund’s adjuvant, bcg, corynebacterium parvum, et al.) contain bacterial antigens. Some are endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Their mode of action is either non-specific, resulting in increased immune responsiveness to a wide variety of antigens, or antigen-specific, i.e., affecting a restricted type of immune response to a narrow group of antigens. The therapeutic efficacy of many biological response modifiers is related to their antigen-specific immunoadjuvanticity. Vaccination) combination chemotherapy Chemotherapy Osteosarcoma ± chemoradiotherapy (depending on the stage)
• Locally advanced unresectable or metastatic (stage IV):
  • Limited palliative gastric resection 
  • Palliative chemotherapy Chemotherapy Osteosarcoma
  • Radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma therapy 
  • Trastuzumab Trastuzumab A humanized monoclonal antibody against the ErbB-2 receptor (HER2). As an antineoplastic agent, it is used to treat breast cancer where HER2 is overexpressed. Targeted and Other Nontraditional Antineoplastic Therapy if human epidermal growth factor receptor 2 Human epidermal growth factor receptor 2 A cell surface protein-tyrosine kinase receptor that is overexpressed in a variety of adenocarcinomas. It has extensive homology to and heterodimerizes with the EGF receptor, the ERBB-3 receptor, and the ERBB-4 receptor. Activation of the erbB-2 receptor occurs through heterodimer formation with a ligand-bound erbB receptor family member. Targeted and Other Nontraditional Antineoplastic Therapy ( HER2 HER2 A cell surface protein-tyrosine kinase receptor that is overexpressed in a variety of adenocarcinomas. It has extensive homology to and heterodimerizes with the EGF receptor, the ERBB-3 receptor, and the ERBB-4 receptor. Activation of the erbB-2 receptor occurs through heterodimer formation with a ligand-bound erbB receptor family member. Targeted and Other Nontraditional Antineoplastic Therapy)–positive tumor Tumor Inflammation
  • Endoscopic stenting
• Other: prophylactic gastrectomy considered in those with E-cadherin gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics or CDH1 mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations

Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas

• 5-year survival of gastric adenocarcinoma is 30%.
• 5-year survival for those who undergo curative surgical resection is > 45%.
• Main factors determining prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas after resection:
  • Staging Staging Methods which attempt to express in replicable terms the extent of the neoplasm in the patient. Grading, Staging, and Metastasis 
  • Histologic type
  • Resection margins

Postgastrectomy Complications

Small intestinal bacterial overgrowth Bacterial overgrowth Lactose Intolerance (SIBO)

• The normally low amount of bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology in the small intestine Small intestine The small intestine is the longest part of the GI tract, extending from the pyloric orifice of the stomach to the ileocecal junction. The small intestine is the major organ responsible for chemical digestion and absorption of nutrients. It is divided into 3 segments: the duodenum, the jejunum, and the ileum. Small Intestine: Anatomy increases or other pathogens have significant growth.
• Bacterial overgrowth Bacterial overgrowth Lactose Intolerance facilitated by decreased gastric acid Gastric acid Hydrochloric acid present in gastric juice. Gastroesophageal Reflux Disease (GERD) secretion Secretion Coagulation Studies and blind loops
• Clinical features:
  • Diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea, bloating Bloating Constipation
  • Malabsorption Malabsorption General term for a group of malnutrition syndromes caused by failure of normal intestinal absorption of nutrients. Malabsorption and Maldigestion that leads to weight loss Weight loss Decrease in existing body weight. Bariatric Surgery
  • Steatorrhea Steatorrhea A condition that is characterized by chronic fatty diarrhea, a result of abnormal digestion and/or intestinal absorption of fats. Diarrhea and osmotic diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea
• Diagnosis:
  • Jejunal aspirate cultures
  • Carbohydrate ( lactulose Lactulose A synthetic disaccharide used in the treatment of constipation and hepatic encephalopathy. It has also been used in the diagnosis of gastrointestinal disorders. Laxatives) breath test 
• Management: antibiotics and nutrient supplementation

Dumping syndrome Dumping syndrome Gastrointestinal symptoms resulting from an absent or nonfunctioning pylorus. Bariatric Surgery

• Related to motility Motility The motor activity of the gastrointestinal tract. Gastrointestinal Motility (rapid gastric emptying Gastric emptying The evacuation of food from the stomach into the duodenum. Gastrointestinal Motility)
• Due to bypass of pyloric sphincter
• Early dumping type:
  • Impaired pyloric sphincter leads to rapid emptying of hyperosmolar chyme Chyme Small Intestine: Anatomy.
  • Vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia, diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea, abdominal cramps Cramps Ion Channel Myopathy
  • Vasomotor symptoms (sweating, flushing, and palpitations Palpitations Ebstein’s Anomaly) occur after ingestion of a meal.
• Late dumping type:
  • Rapid glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption causes hyperinsulinemic response.
  • Postprandial hypoglycemia Hypoglycemia Hypoglycemia is an emergency condition defined as a serum glucose level ≤ 70 mg/dL (≤ 3.9 mmol/L) in diabetic patients. In nondiabetic patients, there is no specific or defined limit for normal serum glucose levels, and hypoglycemia is defined mainly by its clinical features. Hypoglycemia 
  • Tremor Tremor Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of parkinson disease. Myotonic Dystrophies and faintness occurring 1 hour after the meal
• Management:
  • Dietary modifications (more fiber); frequent small meals that are rich in protein and fat
  • Consider octreotide Octreotide A potent, long-acting synthetic somatostatin octapeptide analog that inhibits secretion of growth hormone and is used to treat hormone-secreting tumors; diabetes mellitus; hypotension, orthostatic; hyperinsulinism; hypergastrinemia; and small bowel fistula. Antidiarrheal Drugs; reoperation in certain cases

Gastric stasis

• Related to motility Motility The motor activity of the gastrointestinal tract. Gastrointestinal Motility (slow transit)
• Due to vagal denervation, small stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy remnant, or postsurgical atony
• Clinical features: early satiety Early Satiety Bariatric Surgery, vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia, abdominal pain Abdominal Pain Acute Abdomen
• Management:
  • Use of prokinetic agents
  • If severe, total gastrectomy considered

Other long-term effects

• Reduced iron absorption Iron absorption Digestion and Absorption: anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types 
• Reduced B₁₂ absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption (no intrinsic factor Intrinsic factor A glycoprotein secreted by the cells of the gastric glands that is required for the absorption of vitamin B 12 (cyanocobalamin). Deficiency of intrinsic factor leads to vitamin B12 deficiency and anemia, pernicious. Gastritis): B₁₂ deficiency 
• Reduced calcium absorption Calcium absorption Digestion and Absorption: osteoporosis Osteoporosis Osteoporosis refers to a decrease in bone mass and density leading to an increased number of fractures. There are 2 forms of osteoporosis: primary, which is commonly postmenopausal or senile; and secondary, which is a manifestation of immobilization, underlying medical disorders, or long-term use of certain medications. Osteoporosis 
• Gallstones Gallstones Cholelithiasis (gallstones) is the presence of stones in the gallbladder. Most gallstones are cholesterol stones, while the rest are composed of bilirubin (pigment stones) and other mixed components. Patients are commonly asymptomatic but may present with biliary colic (intermittent pain in the right upper quadrant). Cholelithiasis
• Peptic ulcer Peptic ulcer Peptic ulcer disease (PUD) refers to the full-thickness ulcerations of duodenal or gastric mucosa. The ulcerations form when exposure to acid and digestive enzymes overcomes mucosal defense mechanisms. The most common etiologies include Helicobacter pylori (H. pylori) infection and prolonged use of non-steroidal anti-inflammatory drugs (NSAIDs). Peptic Ulcer Disease
• Partial gastrectomy is a risk for remnant cancer.