Understanding Carcinoma of the Stomach

Introduction

Carcinoma of the stomach is most frequently found in the distal part, accounting for around 40% of cases, followed by the middle and proximal parts, each at approximately 30%. Oral/distal gastric cancer rates are on the decline, while the occurrence of GE junction tumors is on the rise.

• The antrum is the stomach's most commonly affected site.
• In the case of pernicious anemia, the most common site is fundus.
• The most common histological type is the adenocarcinoma. 
• The most common genetic abnormality is P53, followed by the Cox-II gene.
• For the adenocarcinoma, non-specific tumor markers include CEA, CA 19-9, CA-125, and CA 72-4.
• The most common site of metastasis is the liver. 
• The chemotherapy regimen for stomach carcinoma is ECF (Epirubicin, Cisplatin, 5- Fluorouracil).
• Carcinoma in the stomach is more common in males. The peak incidence occurs in the 7th decade.
• Higher geographic latitudes are associated with higher gastric cancer risk.
• The maximum incidence of carcinoma stomach is seen in Japan and Korea.
• Gastric cancer and stomach carcinoma are the most common cancers in Japan.

Risk factors for carcinoma stomach: 

1. Nutritional factors:
   • Reduced fat or protein intake, especially when consuming salted meat or fish, may result in stomach cancer.
   • Increased risk of stomach carcinoma can be associated with high nitrate and complex carbohydrate consumption.
   • Insufficient consumption of fruits and vegetables can contribute to the development of stomach carcinoma.
2. Social factors: 
   • Carcinoma in the stomach is most common in low socioeconomic status.
3. Environmental factors:
   • Poor food preparation (smoked, salted). 
   • Lack of refrigeration
   • Poor drinking water (contaminated well water)
   • Smoking & alcohol.
4. Medical factors: 
   • If there is prior gastric surgery, it may lead to the risk of carcinoma of the stomach.
   • H-pylori infection increases the risk of carcinoma in the stomach. 
   • Epstein Barr Virus infection may lead to stomach carcinoma. 
   • Prior abdominal irradiation and atrophic gastritis can lead to carcinoma stomach.
   • Adenomatous polyps: These are neoplastic polyps, and there’s an increased risk of malignancy if the patient has adenomatous polyps.
5. Occupational Risk Factors:
   •  There’s an increased risk of carcinoma stomach in rubber and coal workers. 
   • It’s more common in males.
   • Also, it is more common in people with  blood group “A.”
   • Pernicious anemia- MC site is fundus
   • Positive family history
   • Patients having Hereditary nonpolyposis colorectal cancer are at an increased risk.
   • In Le-Fraumeni syndrome, an autosomal dominant condition, there’s an increased risk of gastric cancer. 
6. Infections
   • H-pylori infection: 
     • It is the most common factor in the cause of infection-related cancers.
     • Patients with H-pylori seropositivity will have a 6-fold increased risk of gastric cancer.
     • The primary mechanism that causes the carcinoma stomach due to H.Pylori infection is chronic inflammation.
     • In the sequence of events, there is chronic gastritis, and further, there will be gastric atrophy, which leads to intestinal metaplasia.
     • Further, it leads to dysplasia, which increases the risk of intestinal type of adenocarcinoma.
7. Molecular alterations in intestinal metaplasia:  
   • There is overexpression of Cox-2 and Cyclin-D2.
   • There is a p53 mutation and instability of microsatellites.
   • There is a decrease in the P27 expression.
   • There will be an alteration in transcriptional factors, CDX-1 and CDX-2.
   • There’s an increased risk of gastric cancer due to intestinal metaplasia. 
8. Dietary factors:
   • Highly salted or smoked food contains a high level of nitrates, which increases the production of N-nitroso compounds. This compound is also present in tobacco smoke and increases the risk of gastric cancer.
   • Low intake of fruits and vegetables is also associated with an increased risk of gastric cancer. It’s because low intake of ascorbic acid leads to impaired removal of nitroso compounds and free radicals. 
   • After nitrate injection, there’s increased production of N-nitroso compounds, resulting in an increased risk of gastric cancer. 
   • H.pylori infection inhibits the secretion of ascorbic acid and prevents the effective scavenging of Oxygen free radicals and N-nitroso compounds. 
   • Refrigeration decreases the risk of gastric cancer. Earlier, only salting was done to preserve meat. Now, refrigeration is also done, reducing the amount of meat preserved by salting alone. Likewise, refrigeration allows increased storage of fruits and vegetables. 
9. Other factors:
   • There are increased levels of IL-1 beta and TNF alpha, and their expression is increasing, increasing the risk of gastric cancer. 
   • CAG-A (Cytotoxin Associated Gene - A) is present in the case of H.pylori infections. 
   • This gene upregulates cellular pro-inflammatory response, cellular migration, and elongation. It increases the risk of virulence and gastric cancer. 
10. Hereditary risk factors and cancer genetics: 
    • Hereditary Diffuse Gastric Cancer:
    • FAP (Familial adenomatous polyposis)
      • This condition is inherited in an autosomal dominant condition 
      • A majority of patients exhibit sessile polyps, which are primarily located in the fundus region. 
      • Furthermore, malignant duodenal polyps are more likely to occur in individuals with this condition, so upper GI surveillance is warranted. 
    • Li-Fraumeni Syndrome
      • It is an autosomal dominant condition caused by p53 mutation. It increases the risk of the following conditions:
        • Brain Tumor
        • Breast Cancer
        • Adrenocortical Carcinoma
        • Gastric Cancer
        • Sarcoma
    • Hereditary Non-polyposis Colorectal Cancer :
      • It is also known as Lynch syndrome. 
      • It is associated with mismatch repair gene abnormality and microsatellite instability.
      • There is an increased risk of endometrial, gastric, and ovarian cancer.
    • Other Factors
      • Overexpression of C-MET proto-oncogene, K-RAS, and HER-2-NEU oncogenes
      • Inactivation of P53 will increase the risk of diffuse and intestinal variety of gastric cancer.
      • Reduction or loss in e-cadherin is seen in 50% of diffuse variety of gastric cancer in patients.
      • Microsatellite instability is found in 20% to 30% of the intestinal variety of gastric cancer. 
11. Polyps: 
    • Most gastric polyps are asymptomatic. The risk of malignancy and the management of gastric polyps are dependent on polyp histopathology. 
    • If a patient has an isolated polyp of size more than 1 cm, there’s an increased risk of malignancy. So, go for a complete polypectomy. 
    • In the case of multiple polyps, the largest polyp should be removed endoscopically. The rest should be removed through a biopsy. A normal mucosa biopsy is needed to assess the underlying dysplasia and H. pylori infection. 
    • Adenomatous poly is a neoplastic polyp. There’s an increased risk of malignancy. Typically, these are solitary lesions. The risk of malignancy is more than 30 percent. The risk of malignancy is directly proportional to the size of the polyp. In the case of a pedunculated polyp, endoscopic removal is preferred. Endoscopic removal is sufficient if there are no foci of invasive cancer on histopathological examination. 
    • Sessile polyps with a size exceeding 2 cm are at higher risk of malignancy, and the proven focus is on invasive carcinoma. Operative excision is performed in these cases. 
    • Fundic gland polyps are benign lesions resulting from glandular hypoplasia and decreased luminal flow. They are strongly associated with proton pump inhibitor (PPI) use.
    • For the patient using PPI, it is going to occur in 1/3rd of patients by 1 year's use of PPI.
    • Hyperplastic polyps are associated with H. pylori infection, which can cause chronic gastritis. They are usually benign, and there is a low risk of malignancy.
    • Hyperplastic polyps (usually benign) are associated with H.pylori infection and chronic gastritis. The risk of malignancy is under 2%.
    • Peutz-Jeghers Syndrome patients also have gastric polyps. The risk of malignancy is low, 2-3%. 
    • For the patient with an H-pylori infection and taking PPI, there is a low-acid environment, and the organism colonizes the gastric body. Afterward, the bacteria cause corpus gastritis. ⅓rd of these patients are going to develop atrophic gastritis, which increases the risk of carcinoma stomach.
    • Atrophic gastritis is the major risk factor for gastric cancer. It’s a risk factor for invasive gastric cancer. 
    • Other risk factors include pernicious anemia, EBV, smoking, and prior abdominal irradiation.
      • Pernicious anemia: This is an autoimmune disorder, and antibodies are present mainly against parietal cells. The maximum concentration of parietal cells is in the proximal part of the stomach. So, an autoimmune reaction destroys parietal cells, increasing the risk of carcinoma stomach. The most common site is the fundus.
      • Epstein Barr Virus: It’s associated with gastric cardia cancer. 
      • Prior Abdominal Irradiation: It occurs in patients with testicular cancer, where radiotherapy is given, or patients with Hodgkin’s Lymphoma.  

Signs and Symptoms of Stomach Cancer

• The most common site of carcinoma in the stomach is the antrum.
• Abdominal pain followed by weight loss is the most common symptom of carcinoma stomach.
• The most common symptom of GE junction tumor is dysphagia. 
• In linitis plastica, an extensive proliferation of fibrous tissue causes the stomach to lose its distensibility, causing early satiety. This stomach is known as a leather bottle stomach. For patients with epigastric cancer, there is non-radiating and continuous pain. It is not relieved by eating.

• For the patient having advanced lesions located at the antrum at the distal part of the stomach, there will be gastric outlet obstruction, and if located at the proximal part of the stomach, there’ll be dysphagia. Anemia is observed in 40% of patients, and fatigue is observed as well. 
• In some patients with carcinoma stomach, there will be a palpable abdominal mass.
  • These are palpable left axillary lymph nodes, which are called Irish nodes. 
  • There’s palpable left supraclavicular lymph node known as Virchow’s node. The sign is known as Troisier sign.
  • Most of the patients have cutaneous metastatic deposits around the umbilicus. This is known as Sister Mary Joseph node.
  • For patients having palpable peritoneal metastasis on a firm shelf during a digital rectal examination, it is called Blumer's shelf.
  • There is drop metastasis to the palpable bilateral ovary on pelvic examination, which is called the Krukenberg tumor. 
  • The most common route is retrograde lymphatic spread, but it can also occur because of hematogenous, transcoelomic, or transperitoneal spread. 

Screening in Gastric Cancer

• Gastric cancer screening is implemented in countries with a high incidence, such as Japan, Korea, or Chile.
• Primary modalities used for gastric cancer screening include upper GI endoscopic and Barium study.
• Upper GI endoscopic has better sensitivity.

• Minimum number of lymph nodes evaluated for accurate staging- 16
• Number of lymph nodes removed for proper staging: 
  • In carcinoma gall bladder, it is 6.
  • In carcinoma breast, it is around 10.
  • In carcinoma, the colon and rectum it is 12.
  • In carcinoma esophagus, it is 15
  • In carcinoma stomach, it is 16.
  • The mnemonic for this is GB CREST. 

SIEWERT CLASSIFICATION

• The Siewert-Stein classification, sometimes colloquially referred to as the Siewert classification in casual language, is a categorization system employed to classify adenocarcinomas occurring at the esophagogastric junction based on their anatomical characteristics.
  • Type I
    • Adenocarcinoma of the distal part of the esophagus. The tumor center is located 1–5 cm above the gastric cardia.
  • Type II
    • Adenocarcinoma is situated within the true cardia, with the tumor centre positioned either 1 cm above or 2 cm below the gastroesophageal junction.
  • Type III
    • Adenocarcinoma of the subcardial stomach. The tumor center is located 2–5 cm below the gastroesophageal junction.
• Type 1 & 2 are treated like esophageal adenocarcinoma.
• Type 3 is treated like gastric adenocarcinoma.

R-STATUS in Carcinoma Stomach

• It was given by Harmanek
• It is used to describe tumor status after resection.
• R0- Microscopically negative margins: best prognosis, or we can say that the patient has long-term survival
• R1- microscopically positive margins
• R2- macroscopically positive margins suggest there is a Gross residual disease.

Also Read:

Biliary Tree Pathophysiology & Investigations

Colorectal Polyps : Types, Neoplastic Polyps

Hope you found this blog helpful for your GIT, Hepatobiliary and Pancreatic Surgery preparation. For more informative and interesting posts like these, keep reading PrepLadder’s blogs.