What are the other Names for this Condition? (Also known as/Synonyms)

• Adenocarcinoma of Stomach
• Stomach Adenocarcinoma

What is Gastric Adenocarcinoma? (Definition/Background Information)

• Gastric Adenocarcinoma is a malignant epithelial tumor with glandular differentiation of the gastric mucosa (in the stomach). It is a common type of stomach cancer seen in adult men and women
• There are several subtypes of Gastric Adenocarcinoma, and these include:
  • Papillary adenocarcinoma
  • Poorly cohesive adenocarcinoma including signet ring cell carcinoma
  • Tubular adenocarcinoma
  • Mucinous adenocarcinoma
  • Hepatoid adenocarcinoma
  • Micropapillary adenocarcinoma
  • Mixed pattern adenocarcinoma
  • Medullary carcinoma
  • Adenocarcinoma of fundic gland type 
  • Parietal cell carcinoma
  • Paneth cell carcinoma
  • Mucoepidermoid carcinoma
• The Laurens classification of gastric carcinoma include:
  • Intestinal type 
  • Diffuse type

Who gets Gastric Adenocarcinoma? (Age and Sex Distribution)

• Gastric Adenocarcinoma is generally seen in adults over 30 years of age
• Both males and females are affected, although a greater number of cases are observed in males than females (male-female ratio is about 3:2, according to some studies)
• When children and young adults are affected, it is mostly seen in the background of a predisposing factor such as an inherited genetic disorder. In such cases, a greater number of females are affected
• Worldwide, gastric cancers are the third most cause of cancer related death. The location of the tumor varies according to geographical incidence (from one region to another)
  • It is located in antral-pyloric location in regions with high incidence of gastric cancer such as Asia, eastern Europe, and central and south America
  • And, in the cardia/fundus in northern Europe and USA

What are the Risk Factors for Gastric Adenocarcinoma? (Predisposing Factors)

• Environmental factors include tobacco smoking, EBV infection, Helicobacter pylori infection, and dietary factors
• In general, it is observed that Gastric Adenocarcinoma can also be associated with certain genetic syndromes/disorders such as:
  • Li-Fraumeni syndrome
  • Juvenile polyposis syndrome
  • Peutz-Jeghers syndrome
  • Cronkhite-Canada syndrome

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Gastric Adenocarcinoma? (Etiology)

• 90% cases are sporadic; 10% cases are hereditary 
• Germline mutations such as CDH1, APC exon 1B mutations can be seen
• Chronic H. pylori infection has been assumed to cause DNA mutations and epigenetic changes in epithelial cells of the stomach. This is called field cancerization

The following genetic abnormalities are noted:

• Damage to DNA is noted with Helicobacter pylori infection. It also interferes with the function of certain tumor-suppressing genes and oncogenes including CTNNB1, CCND1, TP73, and CDKN1B genes
• 12-30% malignancies show abnormalities on CDKN2A gene; this has a bearing on infiltration of the tumor and tumor metastasis
• Abnormalities in the RARB gene are noted in 60-65% of intestinal type Gastric Adenocarcinomas, but not in the diffuse type
• 45-65% show genetic aberration in the RUNX3 gene (reduced gene expression)
• Other gene mutations noted include CDKN1A, MAGE, and SNCG (seen in cancers showing lymph node metastasis)
• Microsatellite instability (MSI): It occurs due to abnormalities in DNA mismatch repair (MMR) system. High levels of MSI (MSI-H) are seen in Gastric Adenocarcinomas that involve the antral region of stomach (lower part, nearer to the duodenum)

What are the Signs and Symptoms of Gastric Adenocarcinoma?

• The signs and symptoms vary from individual to individual
• Gastric Adenocarcinomas in the early stages can be asymptomatic
• At advanced stages, weight loss, indigestion, vomiting, anemia, loss of appetite, and dysphagia (difficulty swallowing) can be seen

How is Gastric Adenocarcinoma Diagnosed?

A diagnosis of Gastric Adenocarcinoma may involve the following tests and procedures:

• Complete physical exam with evaluation of medical history
• Ultrasound scan of the stomach/abdomen: It is a non-invasive procedure that uses high frequency sound waves to produce real-time images
• Abdominal CT scan: It is a noninvasive procedure that provides more details of soft tissues, blood vessels, and internal organs
• Stool sample analysis
• In high-risk patients, blood test for pepsinogen may be used as screening measure for early detection
• Upper GI endoscopy: An endoscopic procedure is performed using an instrument, called an endoscope, which consists of a thin tube and a camera. Using this technique, the radiologist can have a thorough examination of the insides of the gastrointestinal tract. The endoscopic procedure is a sensitive and specific diagnostic tool for Gastric Adenocarcinoma
  • Gastric Adenocarcinoma presents as mass lesion or a non-healing gastric ulcer on endoscopy
  • Linitis plastica is a term used to describe thickened wall of the stomach due to abundant fibrous stroma caused by the tumor
• Chromoendoscopy can help detect small-sized tumors; small tumors can also be detected using narrow band imaging technique
• Esophagogastroduodenoscopy (EGD): It is a procedure to check the linings of the esophagus, stomach, and duodenum. Through this procedure, biopsies may be performed at the same time. It is generally preferred for evaluating individuals with suspected stomach cancer
• Vascular angiographic studies of the tumor
• Exploratory laparoscopy (diagnostic laparoscopy) may be required, if gastrointestinal symptoms are present. In this procedure, the abdomen is examined using a minimally-invasive technique, and a tissue biopsy and tissue for culture obtained
• Although the above modalities can be used to make an initial diagnosis, a tissue biopsy of the tumor is necessary to make a definitive diagnosis to begin treatment. The tissue for diagnosis can be procured in multiple different ways which include:
  • Endoscopic fine needle aspiration (FNA) biopsy of the tumor: An endoscopic FNA biopsy may not be helpful, because one may not be able to visualize the different morphological areas of the tumor. Hence, a FNA biopsy as a diagnostic tool has certain limitations, and an open surgical biopsy is preferred
  • Core biopsy of the tumor
  • Open biopsy of the tumor
• Tissue biopsy: A tissue biopsy of the tumor is performed and sent to a laboratory for a pathological examination. A pathologist examines the biopsy under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis. Examination of the biopsy under a microscope by a pathologist is considered to be gold standard in arriving at a conclusive diagnosis
  • Biopsy specimens are studied initially using Hematoxylin and Eosin staining. The pathologist then decides on additional studies depending on the clinical situation
  • The tumors may have varying proportions of blood vessels, smooth muscle, and fat cells, when examined by a pathologist under a microscope
  • Sometimes, the pathologist may perform special studies, which may include immunohistochemical stains, molecular testing, and very rarely, electron microscopic studies to assist in the diagnosis

A differential diagnosis to eliminate other tumor types is considered before arriving at a definitive diagnosis.

• Staging is performed by contrast enhanced CT, MRI or FDG PET-CT, and staging laparoscopy
• Pathology microscopic features: Five histological subtypes are recognized by Pathologists under a microscope. They include:
  • Tubular
  •  Papillary 
  •  Poorly cohesive (signet-ring and others)
  •  Mucinous
  •  Mixed 
• Immunohistochemistry staining can show positivity for ERBB2(HER2)
• Other predictive biomarkers are ERBB2(HER2), receptor tyrosine kinases

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Gastric Adenocarcinoma?

The complications of Gastric Carcinoma are dependent upon the size of the tumor and may include:

• Large tumor masses may get secondarily infected with bacteria or fungus
• Bowel obstruction 
• Ascites(accumulation of fluid in the abdomen)
• Obstructive jaundice(yellowing of skin/eyes)
• Thrombosis(blood clot)
• Hydronephrosis(swelling of kidney due to fluid accumulation)
• Perforation of the stomach due to presence of infiltrative tumors
• Involvement of local and distant lymph nodes
• Metastasis: Spread of the cancer can occur to the peritoneal cavity (termed peritoneal dissemination), or to other organs nearby such as the lung and liver. In some cancer types, the ovaries may be affected
• Complications due to an underlying genetic disorder, if any present, may be noted
• Side effects of chemotherapy (such as toxicity) and radiation
• Recurrence of the tumor following treatment
• Damage to the muscles, vital nerves, and blood vessels, during surgery
• Post-surgical infection at the wound site is a potential complication

How is Gastric Adenocarcinoma Treated?

Treatment varies from one individual to individual and depends on stage of the tumor:

• Surgical resection of tumor is important
• New advances are endoscopic resection and minimally invasive access for early gastric carcinoma
• Neoadjuvant chemotherapy for gastric cancer aims to downstage disease
• Immune checkpoint blockade inhibitors are approved recently for gastric cancer treatment
• Periodic screenings and follow-up are mandatory

How can Gastric Adenocarcinoma be Prevented?

Current medical research has not established a method of preventing both syndromic and non-syndromic forms of Gastric Adenocarcinoma. However, in case it is associated with genetic disorders, then the following may be considered:

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

In general, the following measures may be taken to lower the risk for Gastric Adenocarcinomas:

• Early and appropriate treatment of Helicobacter pylori infection
• Bringing about certain lifestyle changes, such as diet adjustments, to reduce fatty food and caffeine intake, reduction of alcohol intake, and cessation of smoking
• Consuming a diet that is rich in whole grains, vegetables, and fruits
• Correcting any nutritional imbalances through adequate vitamin and mineral supplementation
• Physical activities and regular exercising
• In order to avoid a relapse or be prepared for a recurrence, the entire diagnosis, treatment process, drugs administered, etc. should be well-documented and follow-up measures initiated
• Regular medical screening at periodic intervals with blood tests, scans, and physical examinations are mandatory due to its metastasizing potential and possibility of recurrence. Often, several years of active vigilance is necessary

Antioxidant supplements: A reduction in mortality rates (by over 10%) was noted in a study in nutritionally-deficient population (age below 55 years), when certain antioxidant supplements, such as minerals (selenium) and vitamins A, C, and E, were prescribed. However, such a reduction was not noted in healthy population subsets.

What is the Prognosis of Gastric Adenocarcinoma? (Outcomes/Resolutions)

• Early-stage Gastric Adenocarcinomas have good prognosis with treatment. The 10-year survival rate is about 90%. In such cases, lymph node metastasis and invasion of the cancer into deeper layers are reduced
• If the inner layers are invaded, then the prognosis reduces drastically; the 5-year prognosis is 60-80%, reducing further as the cancer invades deeper into the stomach layers
• The prognosis is poor when advanced-stage tumors with metastasis to the lymph nodes and involvement of the vascular system is noted. When 1-6 lymph nodes are affected, the 5-year survival is 46%; with 7-15 nodes, it falls to 30%. In such cases, aggressive treatment measures are recommended and necessitated
• The prognosis of Gastric Adenocarcinomas depend upon a set of several factors that include: 
  • Stage of tumor: With lower-stage tumors, when the tumor is confined to site of origin, the prognosis is usually excellent with appropriate therapy. In higher-stage tumors, such as tumors with metastasis, the prognosis is poor
  • Histological subtype and grade of the tumor; some variants are known to have better prognosis (on an equal stage-by-stage comparison basis)
  • Overall health of the individual: Individuals with overall excellent health have better prognosis compared with those with poor health
  • Age of the individual: Older individuals generally have poorer prognosis than younger individuals
  • The size of the tumor: Individuals with small-sized tumors fare better than those with large-sized tumors
  • Individuals with bulky disease may have a poorer prognosis
  • Involvement of vital organs may complicate the condition
  • The surgical resectability of the tumor (meaning if the tumor can be removed completely)
  • Whether the tumor is occurring for the first time or is a recurrent tumor. Recurring tumors have worse prognosis compared to tumors that do not recur
  • Response to treatment: Tumors that respond to treatment have better prognosis compared to tumors that do not respond to treatment
  • Progression of the condition makes the outcome worse
• An early diagnosis and prompt treatment of the tumor generally yields better outcomes than a late diagnosis and delayed treatment
• The combination chemotherapy drugs used, may have some severe side effects (such as cardio-toxicity). These chiefly impacts the elderly adults, or those who are already affected by other medical conditions. Tolerance to the chemotherapy sessions is a positive influencing factor

Additional and Relevant Useful Information for Gastric Adenocarcinoma:

The following DoveMed website link is a useful resource for additional information:

https://www.dovemed.com/healthy-living/digestive-center/