Gastric Cancer and Helicobacter pylori

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Questions and Answers

What specific factors, associated with Helicobacter pylori infection, are believed to contribute to increased disease severity?

The Helicobacter pylori virulence factors CagA and VacAs1m1 are associated with increased disease severity.

How does Helicobacter pylori disrupt cell structure at the cellular level, potentially contributing to gastric cancer development?

It damages the apical-junctional complex, affecting the tight junction and adherens junction, leading to disruption of cell polarity.

What are some examples of host genetic factors that have been implicated in susceptibility to gastric cancer?

Polymorphisms within genes such as IL-1β, TNFα, IL-10, and IL-23, all involved in immune response, are linked to increased risk.

Besides bacterial factors and host genetics, what environmental factors can influence the development of gastric cancer?

Host iron and salt levels are mentioned as environmental factors influencing the virulence of Helicobacter pylori. Signup and view all the answers

What is the overall picture of how Helicobacter pylori is related to the development of gastric cancer?

It is a complex process involving bacterial virulence factors, host immune responses, and environmental factors working together to contribute to gastric cancer development. Signup and view all the answers

What are the major types of gastric cancer based on their appearance and how they infiltrate the stomach wall?

The major types of gastric cancer based on their appearance and infiltration are: Type I - Polypoid, Type II - Ulcerating, Type III - Ulcerating/Infiltrating, and Type IV - Diffuse infiltrating (linitis plastica). Signup and view all the answers

What is the significance of early gastric cancer diagnosis and what is prognosis of early gastric cancer?

Early gastric cancer diagnosis is crucial as it offers a very high chance of cure (>90%) through surgical resection. However, if left untreated, early gastric cancer progresses to the advanced stage over a few years. Signup and view all the answers

What are the key factors influencing prognosis in gastric cancer?

Prognostic factors in gastric cancer include the extent of local invasion, involvement of lymph nodes and distant metastasis, the histological subtype of the cancer (intestinal vs diffuse), and potential genetic mutations. Signup and view all the answers

How does the bacterium Helicobacter pylori contribute to the development of gastric cancer?

The bacterium Helicobacter pylori contributes to gastric cancer by inducing chronic inflammation in the stomach lining, leading to damage and alterations in the tissue. This inflammation can trigger a series of events that eventually increase the risk of developing malignant tumors. Signup and view all the answers

What is the difference between Early Gastric Cancer type II superficial (protruded, elevated) and Early Gastric Cancer type II superficial (depressed, excavated)?

Early Gastric Cancer type II superficial (protruded, elevated) has a tumor that grows outwards and creates a raised bump, whereas in Early Gastric Cancer type II superficial (depressed, excavated), the tumor grows inwards, creating a sunken or hollow area. Signup and view all the answers

Describe the relationship between Helicobacter pylori and MALT lymphoma.

Helicobacter pylori infection is a major risk factor for the development of MALT lymphoma. It is present in over 90% of cases, and eradication of the bacteria can lead to remission in a significant portion of patients. Signup and view all the answers

What is the most frequent symptom experienced by patients with gastric MALT lymphoma?

The most common symptom is non-specific upper gastrointestinal complaints. Signup and view all the answers

What percentage of all cancers worldwide are thought to be associated with Helicobacter pylori infection?

Helicobacter pylori infection is estimated to be associated with 5.5% of all cancers worldwide. Signup and view all the answers

What is the connection between gastric MALT lymphoma and the prevalence of Helicobacter pylori in the population?

The prevalence of Helicobacter pylori in a population can directly influence the incidence of gastric MALT lymphoma. In areas with a higher prevalence of H. pylori, gastric MALT lymphoma is more common. Signup and view all the answers

List two reasons why eradication of Helicobacter pylori is considered a potential treatment strategy for gastric MALT lymphoma.

First, Helicobacter pylori is directly implicated as a causative agent of the lymphoma in many cases. Second, studies have shown that eradication can lead to tumor regression in a significant percentage of patients. Signup and view all the answers

Study Notes

Gastric Cancer

Gastric cancer is a malignant disease known for thousands of years
It was the leading cause of cancer death until the 1980s, when it was overtaken by lung cancer.
Worldwide, incidence and mortality have declined dramatically over the past 70 years. Possible reasons include recognizing risk factors like H. pylori and dietary/environmental factors.
Refrigerators played a key role in the reduction of this malignant disease, allowing for better food preservation and availability of fresh foods rich in antioxidants.

Gastric Tumors

Malignant gastric tumors can originate from various segments of the stomach, but are mostly adenocarcinomas (>90%)
Benign tumors include polyps and intramural tumours. Malignant tumors include adenocarcinomas, lymphomas, GISTs, neuroendocrine tumours, and leiomyosarcomas.

Adenocarcinoma: Epidemiology

Stomach cancer is the fifth most common cancer worldwide and the third leading cause of cancer-related death.
About 90% of stomach tumors are adenocarcinomas.
Two main histological types: well-differentiated (intestinal type) and undifferentiated (diffuse type).
Intestinal type tumors are more common in males, older individuals, and high-risk geographic areas (e.g., East Asia).
Diffuse type is more common in younger individuals and has a more equal male-to-female ratio.
The incidence of intestinal type tumors in the gastric corpus has declined, contributing to the overall decrease in gastric cancer rates worldwide.

Environmental Risk Factors

Geographic and ethnic differences exist in gastric cancer incidence, following trends over time.
Emigrants from high-incidence to low-incidence countries often have a decreased risk, suggesting environmental factors play a role, and exposure to risk factors occurs early in life.
Helicobacter pylori infection is a significant risk factor. It's linked to a six-fold increase in distal gastric adenocarcinoma risk (intestinal and diffuse).
High salt and salt-preserved/smoked food intake increases risk for gastric cancer. Exposure to N-nitroso compounds from diet, tobacco smoke, and environmental sources is a significant factor.
Diets high in fried food, processed meat, fish, alcohol and low in vitamins (A, C, E and β-carotene) are associated with greater risk.
In 2015, the IARC classified processed meats as group 1 carcinogens.

Blood type A is associated with a higher risk of gastric cancer and pernicious anemia.
Family history is a significant risk factor (risk is about 6-7 times higher). A cluster of H. pylori infection in families further contributes to risk.
True hereditary gastric cancer accounts for 1-3% of cases and encompasses several syndromes, including hereditary diffuse gastric cancer (HDGC), and familial intestinal gastric cancer (FIGC).
Germline truncating mutations in CDH1 (encodes E-cadherin) gene is responsible for HDGC.

Gastric Adenocarcinoma Classification

Lauren (1965) classification is the oldest and most common: intestinal type (well-differentiated) and diffuse type (poorly differentiated).
Ming (1977) classification details growth patterns: intestinal type (expanding patterns) and diffuse type (infiltrating patterns).
WHO (2010) provides a comprehensive classification of gastric adenocarcinoma with numerous subtypes.

Early Gastric Cancer

Adenocarcinoma confined to gastric mucosa and/or submucosa, regardless of lymph node status, presents a high (often >90%) chance of cure with surgical resection.
Usually located in the lesser curvature of the stomach.
Histologically, well-differentiated tubular and papillary architectures are common in early stages.
Classification systems include superficial types (protruded, elevated, flat, depressed, excavated) based on endoscopic appearance and depth of invasion.

Gastric Cancer: Spread

Spread via lymphatic vessels to locoregional lymph nodes, liver hilum, splenic nodes, and along the curvature.
Haematogenous spread to liver, lungs, and bone and direct spread to pancreas, transverse colon, and colon mesentery.
In women, spreading to serosa leads to peritoneal carcinomatosis and ovarian metastasis (Krukenberg tumor).

Gastric Cancer: Staging

Two common staging systems: Japanese and Western (AJCC/UICC, TNM classification).
TNM Staging system uses Tumor (T) size, Lymph Node (N) involvement, and Metastases (M) to classify gastric cancer stage.
Imaging techniques (e.g., CT-scan, endoscopy, PET) are used to assist in staging.

Gastric Cancer: Treatment

Treatments differ depending on the stage of the disease. Locoregional stages (I - III) are potentially curable and may respond to surgery. Advanced stages (IV) often require palliative therapies (e.g., chemotherapy).
Complete surgical resection and targeted therapies may be components of treatment.

Gastric Cancer: Clinical Presentation

Initial stages are often asymptomatic or with vague symptoms.
Main symptoms in later stages include weight loss, anorexia, fatigue, dysphagia, vomiting, abdominal pain, and early satiety.
Clinical examination may reveal an abdominal mass, hepatomegaly, palpable left supraclavicular lymph node, ascites, or cachexia.
Laboratory tests might show microcytic hypochromic anaemia and liver function tests abnormalities.

Gastric Cancer: Precancerous Lesions

Chronic atrophic gastritis, often preceded by intestinal metaplasia and dysplasia.
Autoimmune gastritis.
Gastric resection.
Ménétrier disease.
Adenomatous polyps.
Some hereditary syndromes (e.g., familial adenomatous polyposis).

Gastric Cancer: Molecular Targeted Therapy

Multiple clinical studies are trying to establish the precise role and efficacy of molecular targeted therapy (e.g., drugs targeting EGFR, PI3K/AKT/mTOR, VEGF pathways).
Challenges include variability of tumor biology and specific factors in early stages in comparison to late stages.
The use of immunotherapy (e.g. anti PD-1 antibodies, CAR-T therapies) for treating advanced or metastatic disease remains under investigation.

Helicobacter Pylori and Gastric Adenocarcinoma

Helicobacter pylori infection is strongly associated with gastric adenocarcinoma development, characterized by chronic gastritis, intestinal metaplasia, and dysplasia.
The prevalence of this infection is very high in patients with intestinal type adenocarcinoma; in contrast, it's less strongly associated with non-cardia gastric cancer in certain patients' groups .
H. pylori eradication is a key component in the management and prevention of gastric cardia cancer.
H. Pylori damages the apical-junctional complex, affects cell polarity, alters gene transcription, leading to disease progression, and contributes to gastric cancer by various means.

Primary Gastric Lymphoma

MALT lymphoma is the most common type of gastric lymphoma and a type of non-Hodgkin lymphoma.
Typically related to H. pylori infection; eradication often leads to responses.
Can be characterized by non-specific symptoms, depending on the tumor's size and/or invasion extent.
Diagnosis requires endoscopic examination with biopsies for immunohistochemical analysis of B cells.

GIST

GIST is the most prevalent mesenchymal stomach tumor.
It can be malignant or benign.
It arises from interstitial cells of Cajal (ICCs).
It is most often detected only by accidental findings due to no obvious symptoms. Usually diagnosed with endoscopy, endoscopic ultrasound, CT scan, MRI, and PET.
80% of cases have mutations in the KIT oncogene.
Treatment often involves surgery or therapies that target the KIT protein.

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Description

Explore the complex relationship between Helicobacter pylori infection and gastric cancer. This quiz examines various factors including bacterial influence, host genetics, environmental impacts, and the overall disease progression. Test your knowledge on disease severity, cellular disruption, and prognosis in early gastric cancer.