Early stage gastric adenocarcinoma patients have nonspecific symptoms, that usually do not trigger a consultation until the disease has advanced, such as dyspepsia, anorexia, low intensity, diffuse abdominal pain and weight loss [1]. As the disease progresses and the tumor occupies a larger part of the stomach or causes stomach distention, other symptoms, such as early satiety, nausea, vomiting, dysphagia, postprandial fullness appear [2]. With increasing progression, bleeding occurs, and the blood is expelled as hematemesis, melena or hematochezia. With the development of complications, the patient may experience jaundice and peritoneal or pleural effusions, due to metastases or hypoalbuminemia caused by inanition. Pedal edema may also develop due to the same cause [3] [4].

The tumor may cause metastasis in the ovary, the peritoneum or lymph nodes (supraclavicular, left axilla or periumbilical).

Paraneoplastic syndromes, such as acanthosis nigricans and dermatomyositis have been described.

• Virchow's Node

  Several nodal metastases with eponymous names associated with gastric cancer have been described: sister Mary Joseph’s node Virchow’s node Krukenberg’s node Irish node Adenocarcinoma is by far the most common gastric malignancy, representing over 95% [radiopaedia.org]

  Node Microscopic (histologic) images Contributed by Andrey Bychkov, M.D., Ph.D. [pathologyoutlines.com]

  Signs may include a palpably enlarged stomach, a primary mass (rare), an enlarged liver, Virchow’s node (i.e., left supraclavicular), Sister Mary Joseph’s nodule (periumbilical), or Blumer’s shelf (metastatic tumor felt on rectal examination, with growth [aafp.org]

• Weight Loss

  A 56-year-old woman presented with epigastric pain and weight loss. Endoscopy showed an irregular depressed hyperemic lesion covered with a whitish plaque on the cardia. [ncbi.nlm.nih.gov]

  Early stage gastric adenocarcinoma patients have nonspecific symptoms, that usually do not trigger a consultation until the disease has advanced, such as dyspepsia, anorexia, low intensity, diffuse abdominal pain and weight loss. [symptoma.com]

  Left: 82 year-old woman who presented with early satiety and postprandial vomiting, suggestive of gastric outlet obstruction, along with weight loss and anemia. [endoatlas.com]

  Patients may present with anorexia and weight loss (95%) as well as abdominal pain that is vague and insidious in nature. [radiopaedia.org]

• Anemia

  A natural evolution can be traced back from gastric adenocarcinoma to megaloblastic anemia due to achlorhydria in the context of chronic infection; periodic endoscopy thus seems justified to detect and treat carcinoma in early stages. [ncbi.nlm.nih.gov]

  Initial studies revealed iron-deficiency anemia and blood in the stool. [endoatlas.com]

  Workup should begin with a complete blood count, that might show anemia, due to blood loss or insufficient food intake due to lack of appetite. [symptoma.com]

  The patient was admitted 1 month prior to presentation with abdominal pain, anemia, and increasing lower extremity edema. [acgcasereports.gi.org]

• Fatigue

  A 56-year-old Malaysian woman with a past medical history of iron deficiency anemia presented with lower extremity edema and progressive fatigue of 1 month's duration. [ncbi.nlm.nih.gov]

  […] symptoms of advanced stomach cancer are: nausea and vomiting frequent heartburn loss of appetite, sometimes accompanied by sudden weight loss constant bloating early satiety (feeling full after eating only a small amount) bloody stools jaundice excessive fatigue [healthline.com]

  The most frequently occurring treatment-related adverse events (AEs) of all grades were fatigue (18.9 percent), pruritus (8.9 percent), rash (8.5 percent), hypothyroidism (7.7 percent), decreased appetite (7.3 percent), anemia (6.9 percent), nausea (6.9 [curetoday.com]

• Familial Adenomatous Polyposis

  Familial adenomatous polyposis. Peutz-Jeghers syndrome. Lynch syndrome. Note: Possible association with tobacco use - dependent on the study. [2] Treatment: Surgical excision. [librepathology.org]

  adenomatous polyposis or hereditary nonpolyposis colorectal cancer. [cancer.org.au]

  They are generally regarded as being of no significance although multiple fundic gland polyps with evidence of dysplasia can occur in familial adenomatous polyposis (FAP). [atlasgeneticsoncology.org]

  Other inherited forms of digestive system cancer include familial adenomatous polyposis (FAP) and hereditary non-polyposis colorectal cancer ( HNPCC ): Hereditary diffuse gastric cancer (HDGC) : HDGC is an autosomal dominant disorder and is caused by [cancerquest.org]

  Familial adenomatous polyposis involves developing multiple noncancerous polyps in the colon, stomach and intestines that may later progress to cancer. [cityofhope.org]

• Anorexia

  Early stage gastric adenocarcinoma patients have nonspecific symptoms, that usually do not trigger a consultation until the disease has advanced, such as dyspepsia, anorexia, low intensity, diffuse abdominal pain and weight loss. [symptoma.com]

  Patients may present with anorexia and weight loss (95%) as well as abdominal pain that is vague and insidious in nature. [radiopaedia.org]

  The dog presented with a history of diarrhea, weakness, lethargy, and anorexia of several months' duration. Hematologic and biochemical examinations, abdominal ultrasonography, computer tomography, and exploratory laparotomy were performed. [semanticscholar.org]

  This 67 year-old female presented with anorexia and weight loss of 10 pounds. The images as well as the video clips display a small size neoplasia at the greater curvature in the distal body and posterior wall limiting with the antrum. [gastrointestinalatlas.com]

• Pleural Effusion

  With the development of complications, the patient may experience jaundice and peritoneal or pleural effusions, due to metastases or hypoalbuminemia caused by inanition. Pedal edema may also develop due to the same cause. [symptoma.com]

  There were two treatment-related grade 5 AEs (acute kidney injury and pleural effusion). Keytruda is approved for several indications, including as a treatment for patients with lung cancer, melanoma, Hodgkin lymphoma, and other types of cancer. [curetoday.com]

  There were 2 treatment-related grade 5 AEs (acute kidney injury and pleural effusion). Pembrolizumab is approved for several indications, including as a treatment for patients with lung cancer, melanoma, Hodgkin lymphoma, and other types of cancer. [onclive.com]

  effusions Obstruction of the gastric outlet, gastroesophageal junction, or small bowel Bleeding in the stomach from esophageal varices or at the anastomosis after surgery Intrahepatic jaundice caused by hepatomegaly Extrahepatic jaundice Inanition from [emedicine.medscape.com]

• Nausea

  This 65-year-old patient was admitted with nausea, vomiting and abdominal pain, in addition to loss of weight (13 Kg in 3 months). [ncbi.nlm.nih.gov]

  As the disease progresses and the tumor occupies a larger part of the stomach or causes stomach distention, other symptoms, such as early satiety, nausea, vomiting, dysphagia, postprandial fullness appear. [symptoma.com]

  Right: 70 year-old man with melena as his only presenting symptom; no nausea, vomiting, early satiety or pain. Endoscopy revealed a partially obstructing adenocarcinoma, seen here from the antrum. [endoatlas.com]

  Nausea, vomiting, and early satiety may occur with bulky tumors that obstruct the gastrointestinal lumen or infiltrative lesions that impair stomach distension 2. [radiopaedia.org]

• Vomiting

  This 65-year-old patient was admitted with nausea, vomiting and abdominal pain, in addition to loss of weight (13 Kg in 3 months). [ncbi.nlm.nih.gov]

  Left: 82 year-old woman who presented with early satiety and postprandial vomiting, suggestive of gastric outlet obstruction, along with weight loss and anemia. [endoatlas.com]

  As the disease progresses and the tumor occupies a larger part of the stomach or causes stomach distention, other symptoms, such as early satiety, nausea, vomiting, dysphagia, postprandial fullness appear. [symptoma.com]

  Nausea, vomiting, and early satiety may occur with bulky tumors that obstruct the gastrointestinal lumen or infiltrative lesions that impair stomach distension 2. [radiopaedia.org]

• Abdominal Pain

  Abdominal pain is a frequent complaint in the pediatric emergency department. A 13-year-old boy presented with complaints of abdominal pain, hematemesis, headache, and leg pain. [ncbi.nlm.nih.gov]

  The tunor extended into the second portion of the duodenum. 51 year-old woman who had undergone EGD one month previously for symptoms of abdominal pain. [endoatlas.com]

• Loss of Appetite

  Some of the most common symptoms of advanced stomach cancer are: nausea and vomiting frequent heartburn loss of appetite, sometimes accompanied by sudden weight loss constant bloating early satiety (feeling full after eating only a small amount) bloody [healthline.com]

  Symptoms of stomach cancer are often vague, such as loss of appetite and weight. Gastric cancer is diagnosed via a biopsy of stomach tissue during an endoscopy. Also called stomach cancer. [medicinenet.com]

  They include: persistent indigestion and heartburn trapped wind and frequent burping feeling very full or bloated after meals persistent stomach pain Symptoms of advanced stomach cancer can include: blood in your poo, or black poo loss of appetite weight [nhs.uk]

  […] of appetite Nausea Vomiting blood Weakness or fatigue Weight loss Diagnosis is often delayed because symptoms may not occur in the early stages of the disease. [nlm.nih.gov]

• Early Satiety

  Left: 82 year-old woman who presented with early satiety and postprandial vomiting, suggestive of gastric outlet obstruction, along with weight loss and anemia. [endoatlas.com]

  As the disease progresses and the tumor occupies a larger part of the stomach or causes stomach distention, other symptoms, such as early satiety, nausea, vomiting, dysphagia, postprandial fullness appear. [symptoma.com]

  Nausea, vomiting, and early satiety may occur with bulky tumors that obstruct the gastrointestinal lumen or infiltrative lesions that impair stomach distension 2. [radiopaedia.org]

  Some of the most common symptoms of advanced stomach cancer are: nausea and vomiting frequent heartburn loss of appetite, sometimes accompanied by sudden weight loss constant bloating early satiety (feeling full after eating only a small amount) bloody [healthline.com]

• Peripheral Neuropathy

  neuropathy grade 2 Inability to tolerate intravenous hydration e.g due to cardiac disease Co-morbidities (based on clinical judgement by the investigator) that in the view of the investigator would preclude the safe administration of cisplatin. [clinicaltrials.gov]

  Side effects may include: tiredness nausea and vomiting nerve damage ( peripheral neuropathy ) hair loss diarrhoea anaemia (a lack of red blood cells) weight loss skin changes – such as redness, swelling and a tingling sensation in the palms of the hands [nhs.uk]

  Grade III/IV neutropenia occurred in 33%, and grade III peripheral neuropathy in 7.4% of patients [ 79 ]. [annonc.oxfordjournals.org]

The clinician taking patient history should inquire about previous Helicobacter pylori infection or autoimmune gastritis, knowing that these conditions are predisposing factors for gastric adenocarcinoma.

Workup should begin with a complete blood count, that might show anemia, due to blood loss or insufficient food intake due to lack of appetite. The clinician should also recommend liver function tests (keeping in mind that gastric adenocarcinoma may cause hepatic metastasis) and tumor markers such as carcinoembryonic antigen and cancer antigen 19-9. Even if these antigens are absent, the diagnosis cannot be excluded.

Imaging studies in association with histologic findings confirm or disprove the diagnosis. Upper digestive endoscopy is at this time the gold standard for gastric adenocarcinoma diagnosis [5], as it allows tumor detection and biopsy. Endoscopic methods even allow tumor excision if found in the early stages. Classical endoscopy limitation resides in incomplete staging evaluation, but this can be overcome with endoscopic ultrasonography [6].

Mucosal aspect can also be evaluated using upper gastrointestinal barium study, that involves a lower amount of irradiation than a computer tomogram. The latter can also evaluate invasion of neighboring structures and lymphadenopathy [7]. Liver, bone and peritoneal metastasis are better defined by magnetic resonance, so if symptoms dictate, this should be the method of choice [8]. However, MRI is not as useful in describing gastric lesions per se, because a contrast agent is unavailable [8]. Barium study accuracy can be improved by using double contrast or compressive views.

Once a lesion has been documented, it is important to evaluate the histologic aspect. Adenocarcinomas (tubular, mucinous, papillary, signet-ring cells or undifferentiated) are far more frequent than lymphomas, stromal tumors, carcinoids, adenoacantomas, and squamous cell carcinomas, and account for more than 90% of gastric cancers [9].

Recent studies have described the importance of certain serum glycan patterns as markers for the risk of gastric cancer development [10].

• Hypochlorhydria

  Hypochlorhydria: This condition occurs in gastric atrophy and promotes bacterial colonization of the stomach. It leads to increased nitrite formation, which may have a mutagenic effect on the atrophic gastric mucosa. [gastrointestinalatlas.com]

  Thus, a high-risk IL-1 genotype increases the likelihood of non-cardia GC, a disease that is characterized by hypochlorhydria, while it has no effect on cancers associated with high-level acid exposure, such as esophageal adenocarcinoma and certain gastric [spandidos-publications.com]

• Thrombocytosis

  glucose-6-phosphatase) and inhibition of glucose uptake in peripheral tissue Hyperlipidemia (hypercholesterolemia and hypertriglyceridemia) Leukocytosis (predominantly neutrophilic), eosinopenia, thrombocytosis Screening for hypercortisolism Any one [amboss.com]

• Helicobacter Pylori

  The rapid urease test, histological examination, and serum anti-Helicobacter pylori antibody indicated that the patient was Helicobacter pylori negative. Gastric mucosal atrophy was not evident on esophagogastroduodenoscopy. [ncbi.nlm.nih.gov]

• Gastric Lesion

  Two cycles of chemotherapy consisted of oral S-1 and intravenous cisplatin (SPIRITS regimen); this was markedly effective to reduce the primary gastric lesion and almost all the metastatic lesions. [ncbi.nlm.nih.gov]

  However, MRI is not as useful in describing gastric lesions per se, because a contrast agent is unavailable. Barium study accuracy can be improved by using double contrast or compressive views. [symptoma.com]

  Therefore, in early gastric lesions it is important for pathologists to recognize a phenotype consisting of patchy intramucosal signet ring cells often associated with pagetoid spread. [spandidos-publications.com]

• Pleural Effusion

  With the development of complications, the patient may experience jaundice and peritoneal or pleural effusions, due to metastases or hypoalbuminemia caused by inanition. Pedal edema may also develop due to the same cause. [symptoma.com]

  There were two treatment-related grade 5 AEs (acute kidney injury and pleural effusion). Keytruda is approved for several indications, including as a treatment for patients with lung cancer, melanoma, Hodgkin lymphoma, and other types of cancer. [curetoday.com]

  There were 2 treatment-related grade 5 AEs (acute kidney injury and pleural effusion). Pembrolizumab is approved for several indications, including as a treatment for patients with lung cancer, melanoma, Hodgkin lymphoma, and other types of cancer. [onclive.com]

  effusions Obstruction of the gastric outlet, gastroesophageal junction, or small bowel Bleeding in the stomach from esophageal varices or at the anastomosis after surgery Intrahepatic jaundice caused by hepatomegaly Extrahepatic jaundice Inanition from [emedicine.medscape.com]

1. Fenogilo-Preiser C, Carneiro F, Correa P, et al. Gastric carcinoma. In: Hamilton S, Aaltonin L, eds. Pathology and Genetics. Tumors of the Digestive System, vol 1. Lyon, France: Lyon Press; 2000;37–52.
2. Gore R. Gastrointestinal cancer. Radiol Clin North Am. 1997;35:295–310.
3. Albert C. Clinical Aspects of Gastric Cancer. Gastrointestinal Cancers: Biology, Diagnosis, and Therapy. Philadelphia: Lippincott-Raven. 1995;197–216.
4. Livingston E. Stomach and duodenum. In: Norton J, Bollinger R, Chang A, et al., eds. Surgery. Basic Science and Clinical Evidence. New York: Springer-Verlag; 2001;489–515.
5. Karpeh M, Brennan M. Gastric carcinoma. Ann Surg Oncol. 1998;5:650–656.
6. Willis S, Truong S, Gribnitz S, et al. Endoscopic ultrasonography in the preoperative staging of gastric cancer: accuracy and impact on surgical therapy. Surg Endosc. 2000;14:951–954.
7. Kuntz C, Herfarth C. Imaging diagnosis for staging of gastric cancer. Semin Surg Oncol. 1999;17:96–102.
8. Motohara T, Semelka RC. MRI in staging of gastric cancer. Abdom Imaging. 2002;27:376–383.
9. Avital I, Pisters PWT, Kelsen DP, Willett CG. Cancer of the Stomach. DeVita VT, Lawrence TS, Rosenberg SA. DeVita, Hellman, and Rosenberg’s Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia: Lippincott Williams & Wilkins; 2011; 924-54.
10. Waknine Y. Researchers Discover 'Glycan Fingerprint' for Gastric Cancer. Medscape. http://www.medscape.com/viewarticle/818637. Published January 03, 2014. Accessed January 30, 2017