May 22, 2024
Introduction
According to the Global Cancer Observatory (GLOBOCAN) data, there were 19.3 million incidence of cancer cases worldwide for the year 2020. India ranked third after China and the United States of America. Another article mentioned that in 2020, India reported an estimated 1.39 million cases of cancer which rose to 1.42 million and 1.46 million in the years 2021 and 2022, respectively. Studies have estimated a 12.8% increase in the number of annual cancer cases by the year 2025, which would be around 1.57 million. Although there is a worldwide variation in the incidence of gastric (stomach) cancer, a high incidence of gastric cancer has been reported from Southeast Asia, most commonly from Japan, China, and South Korea, and this has been attributed to the consumption of preserved food containing nitrates. The incidence of gastric cancer in India is overall less compared to the worldwide incidence. But gastric cancer is the fifth most common cancer among males and seventh most common cancer among females in India. The high incidence of local, distant recurrence and thereby mortality even in patients with completely operable gastric cancer indicates its aggressiveness and early metastatic spread of cancer, thus emphasizing the need for multimodality treatment including surgery, radiotherapy, and chemotherapy for treating the disease.
Anatomy:
Human digestive system begins from oral cavity into pharynx and then esophagus (food pipe) continues into stomach at about 32-50cms from the incisors teeth of an individual. Stomach later continues into intestine i.e. small and large intestine which later ends into rectum and anal canal.
The stomach has four main anatomical divisions; the cardia, fundus, body and pylorus: (Figure 1)
- Cardia – surrounds the superior opening of the stomach at the level of esophagus
- Fundus – the rounded, often gas filled portion superior to and left of the cardia.
- Body – the large central portion inferior to the fundus.
- Pylorus – This area connects the stomach to the duodenum. It is divided into the pyloric antrum, pyloric canal and pyloric sphincter.
Stomach has got rich blood supply and receives from left & right gastric arteries, short gastric artery and left & right gastroepiploic arteries (Figure 1). Likewise, the venous system drain the blood from the stomach. The left & right gastric vein drain into portal vein and the right & left gastro-epiploic vein drains into superior mesenteric & splenic vein respectively (Figure 2). The lymphatic supply from the stomach drains into 16 stations of lymph nodes (Figure 3). Anatomy of the stomach is important for the surgical aspect of the stomach. For the lesions in distal body, antrum and pylorus of the stomach; subtotal gastrectomy is done where the remnant stomach receives blood supply from short gastric arteries and station 1 to station 12 lymph nodes are cleared. Likewise, if the carcinomatous lesion in the proximal stomach. i.e. cardia, fundus and body of stomach; total gastrectomy is performed and esophago-jejunal anastomosis is done along with clearance of station 1 to 12 lymph nodes.
Etiology
Most of the common cause for stomach cancer is sporadic (non-genetic) related. However, 10% of cases have family predisposition or genetic causes like hereditary diffuse gastric cancer (HDGC), gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS), and familial intestinal gastric cancer (FIGC). Other syndrome related conditions leading to possibility of developing gastric cancer are Lynch syndrome (hereditary nonpolyposis colorectal cancer), Familial adenomatous polyposis (FAP), Li-Fraumeni syndrome, Peutz-Jeghers syndrome, Juvenile polyposis syndrome, hereditary breast and ovarian cancer syndrome, Cowden syndrome and Ataxia-telangiectasia.
Apart from genetic causes, nutritional factors such as high-salt (salt-preserved food), N-nitroso compounds (nitrates) consumption (dietary source), smoking, a low vitamin A and C diet, consuming large amounts of smoked or cured foods, a deficit of refrigerated foods, and contaminated drinking water. High body mass index (BMI) or obesity, increased calorie consumption, spicy food, lack of physical activity and smoking, all lead to gastroesophageal reflux disease, thereby, are associated with an increased risk of adenocarcinomas of the distal esophagus and proximal part of the stomach. Occupational exposure to rubber manufacturing, tin mining, metal processing, and coal also increases the risk. Helicobacter pylori infection has an attributable risk of 46% to 63%, while Epstein-Barr virus infection is an estimated 5% to 10% worldwide. Radiation exposure and prior gastric surgery also have been implicated as risk factors.
- Helicobacter. pylori Infection:H. pylori, a Gram-negative bacteria, is associated with gastric mucosal infection. In underdeveloped countries with poor hygienic conditions, 50-90% of the population is infected asymptomatically in childhood. H. pylori has been attributed to cause distal gastric cancers. H. pylori colonizes the gastric mucosa in 50% of the human population. It causes direct epigenetic effects by using certain toxins like cagA virulence factors and vacuolating cytotoxin A on gastric epithelial cells and the indirect inflammatory and infective response of H. pylori on the gastric mucosa. These chronic infection are associated with increased risk for developing both intense tissue responses leading to premalignant and malignant lesions in the stomach. These infections are seen certain individuals with long term problem of gastritis and in India, it can be detected after taking tissue biopsy through upper GI endoscopy and subjecting to rapid card test. There are other breathe tests done for the detection of the bacteria. However, the endoscopic method of detection has good detection rate. Once detected positive, the patient requires to take antibiotics and antacids (proton pump inhibitors) for some time to achieve cure and requires repeat check endoscopy after few months.
- Dietary Factors: The World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) concluded that vegetables and fruits probably protect against gastric cancer, whereas salt and salt-preserved foods as well as smoked foods, spicy foods, processed, grilled (broiled) and barbecued (charbroiled) animal meat are probably causes of gastric cancer. Food carcinogens can also interact directly with the gastric epithelial cells and cause gene mutation of epithelial cells. A high level of sodium chloride has been shown to damage the gastric mucosa, cause cell death and induce regenerative cell proliferation, resulting in inflammation and injury such as diffuse erosion and degeneration. High-salt diet has been found to be associated with colonization of H. pylori and together they act in a synergistic way to promote gastric cancer.
- N-nitroso compounds or nitrates are another dietary factor that might play a role in gastric carcinogenesis. Dietary or endogenous exposure to N-nitroso compounds has been demonstrated to significantly increase gastrointestinal cancer risk. Many processed meats contain high levels of salt and nitrite. Red meat has been shown to promote the formation of N-nitroso compounds through direct reaction between nitric oxide and haemoglobin and myoglobin of the meat product. Red meat also contains iron, which can lead to the production of free radicals causing further damage to gastric mucosa.
- Roles of Smoking and Alcohol Habits: Smokers exhibits an 80% increase in the risk of gastric cancer along with heavy drinkers. These cause continuous generation of free radicals leading to cascade of damage, inflammation and regeneration of gastric mucosa leading to gastric cancer.
- Epstein-Barr Virus Infection: Epstein-Barr virus (EBV), which has been associated with gastric cancer. EBV has been causally associated with the development of several malignancies, including nasopharyngeal carcinoma, Hodgkin's lymphoma, Burkitt's lymphoma and immunosuppression-related lymphoma. Around 8% of gastric cancers have been estimated to harbor EBV. This viral genome exists in the tumour cells in a monoclonal form, and transforming EBV proteins are expressed in the tumour cells leading to cancer.
In India, The incidence of gastric cancer in Mizoram has been reported to be the highest due to dietary and possibly some unknown genetic differences. The regional variation in incidence and presentation can be ascertained by the fact that gastric cancer in South Indian males has been reported to be more common and occurring a decade before their North Indian counterparts. This is due to the differences in some dietary pattern and use of tobacco and alcohol have been considered as potential risk factors. In a case–control study from Trivandrum and Hyderabad, a high consumption of rice and chili, and consumption of high-temperature food were found to be independent risk factors for gastric cancer. Likewise, in another report from Chennai, alcohol consumption and use of pickled food were found independent risk factors for gastric cancer.
Clinical Features:
The most common presenting symptoms for gastric cancers are non-specific weight loss, persistent abdominal pain, dysphagia (difficulty in swallowing), hematemesis (vomitus mixed with blood), anorexia (loss of appetite), nausea, early satiety (fullness and decreased hunger), and dyspepsia (gastritis symptoms). Patients presenting with a locally-advanced or metastatic disease usually present with significant abdominal pain, potential ascites, weight loss, fatigue, and have visceral metastasis on scans, and can have a gastric-outlet obstruction. Gastric outlet obstruction refers to the growth in the pylorus involving circumferential extent and thereby blocking the passage of food into duodenum. Sometimes patients might present with iron deficiency anemia or weakness due to prolonged obscure bleeding from the gastric malignant ulcer. These patients would also pass black coloured stools as well.
The most common physical examination finding is a palpable abdominal mass indicating advanced disease. The patient may also present with signs of metastatic lymphatic spread distribution, including Virchow’s node (left supraclavicular lymph node), Sister Mary Joseph node (peri-umbilical nodule), and Irish node (left axillary node). Direct metastasis to the peritoneum can present as Krukenberg’s tumour (ovary mass), ascites (peritoneal carcinomatosis), and hepatomegaly (often diffuse disease burden).
Investigations and evaluation:
Patients presenting with any symptoms suspicious for symptoms of gastritis, retrosternal burning pain, loss of appetite needs to undergo primarily two basic investigations. i.e. ultrasound abdomen and upper GI endoscopy. Ultrasound abdomen would be helpful in diagnosing if there are any gall stones causing flatulent dyspeptic symptoms or it could provide basic findings on gastric cancer. Endoscopy would provide visual interpretation of the ulcer as discussed below.
- Upper GI Endoscopy is an invasive investigation where upper GI tract from oral cavity, pharynx, esophagus, stomach and duodenum is visualised it. Apart from visualisation, biopsy of suspected lesions or gastric ulcer can be performed. Also biopsy for rapid card test diagnosis of H.pylori infection can be done. Gastric cancer screening by upper endoscopy has successfully detected early stages of cancer.
Based on the findings of the above investigations, further tests as done as mentioned below
- Endoscopic ultrasound – This is an endoscope with an inbuilt ultrasound done for early gastric cancers to assess the depth and staging of the cancer. If the lesion only penetrates superficial layers of the gastric wall with no lymph nodal or metastatic spread, then the lesion can be excised with the endoscopic techniques
- Positron Emission Tomography Combined With Computerized Tomography Imaging (PET-CT) – This is done to perform metastatic workup. To determine the resectability of gastric cancers, to assess the local lymph nodal spread, distant spread to other organs and to categorise cancer staging purposes.
- Abdominopelvic Computerized Tomography along with Chest Computerized Tomography instead of PET-CT Scan. However, PET-CT scan is preferred.
- Receptor studies like HER2, MSI testing and PDL1 receptor testing can be performed on the biopsied specimen to check for the role of possibility immunotherapy being combined with chemotherapy
- Referral for genetic testing — For genetic counselling and DNA testing for CDH1 mutations and large rearrangements in patients with diffuse gastric cancer who have one or more of the following criteria:
- Family history of two gastric cancers, at any age, with at least one confirmed diffuse gastric cancer
- Diffuse gastric cancer diagnosed at age <40 years, regardless of family history
- Personal or family history of diffuse gastric cancer and lobular breast cancer, with at least one diagnosed at <50 years of age
In addition, families in whom testing could be considered include the following:
- Bilateral lobular breast cancer or family history (first- or second-degree relative) of two or more cases of lobular breast cancer <50 years
- A personal or family history (first- or second-degree relative) of cleft lip/palate in a patient with diffuse gastric cancer
- An individual with in situ signet ring cells and/or pagetoid spread of signet ring cells on a gastric biopsy
Treatment: Surgery, Chemotherapy and immunotherapy play a major role in the treatment of gastric cancer. The role of radiotherapy is currently restricted to palliative and metastatic settings. Patients presenting with symptoms of gastric cancer and during staging investigations, presence of the lymph node and cancerous lesion involving submucosal layer of stomach requires to undergo neoadjuvant chemo and immunotherapy followed by surgery for the better response rates or cure rates. During surgery, patients would undergo subtotal or total gastrectomy with lymph node dissection upto station 12 (Figure 4). This can be done with open, laparoscopy or robotic surgery. Robotic approach would provide better results as manoeuvring instruments with 7 degrees freedom, 12x magnification and 3D vision provide superior dissection and minimal blood loss in four 8mm ports (Figure 5). After resection, gastro-jejunostomy anastomosis in done in subtotal gastrectomy while esophago-jejunostomy is done in total gastrectomy. Following are the conditions which are exception to the above.
- Patients with early stages of gastric cancer, with only mucosal involvement and no lymph nodes involved can undergo endoscopic resection techniques (Figure 6)
- Patients presenting with gastric outlet obstruction and actively bleeding gastric ulcer would require upfront surgery to avoid metabolic, electrolyte and hypovolemic complications respectively.
The Prevention Strategies for Gastric Cancer: Itincludes the intervention of gastric cancer etiology (such as H. pylori eradication and changes in lifestyle) and early detection and treatment of gastric cancer.
- H. pylori eradication: H. pylori infection is the main cause of gastritis and precancerous conditions (atrophic gastritis, intestinal metaplasia and dysplasia), its eradication is a reasonable strategy for gastric cancer prevention. There is significant decrease in gastric cancer risk following 2-week antibiotic treatment for H. pylori followed by surveillance endoscopy.
- Increased intake of fruits and vegetables: Sufficient fruit and vegetable intake has been demonstrated to reduce the prevalence of cancer in various organs, including gastrointestinal cancers together with reduced consumption of salt or salt-preserved foods. Studies have shown that Vitamin C may protect against H. pylori-associated gastric carcinogenesis by enhancing mucosal immune response, neutralizing free radicals, decreasing the formation of gastric N-nitroso compounds and influencing H. pylori growth. Pulses (legumes) and foods containing selenium can protect against gastric cancer.
- Lifestyle modification: Cessation of smoking, decreased alcohol intake, increased fruit and vegetable intake, reduced salt intake, increased physical activity and diet rich with fruits & vegetables may help reduce the risk of getting gastric cancer.
I have covered the gastric cancer topic briefly and I hope this basic information is sufficient to guide you on gastric cancer, you can approach me if there are any further queries.
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