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134 I. Mladenova
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Keywords
Epidemiology · Gastric carcinoma · Helicobacter pylori infection · MALT
lymphoma
1 Introduction
The discovery of Helicobacter pylori (H. pylori) by scientists Robin Warren and Barry
Marshall in 1982 fundamentally changed the understanding of chronic gastritis and
peptic ulcer disease as noncommunicable diseases (Warren and Marshall 1983).
B. Marshall self-infects and develops the clinic of acute gastritis. The biopsy after
examination of the gastric mucosa has been identified with a bacterial agent and
characteristic histological changes. C. Goodwin et al., in 1989, named it Helicobacter
pylori (in vivo helix, in vitro bacterium). Other known species of the new genus
Helicobacter are H. heilmannii, H. cinaedi, H. hepaticus, H. felis, H. mustelae,
H. muridarum, H. cynogastricus, H. fennelliae, H. acinonyx, H. equorum,
H. anseri, H. callitrichis, H. brantae, etc. (over 35 species) (Mladenova-Hristova
et al. 2017).
This is a revolution in the understanding of the development of chronic gastritis,
peptic ulcer disease, and gastric carcinoma. H. pylori is a microaerophilic bacterium
which colonizes the human stomach. It is one of the most common infections in
humans and infects more than 50% of the world’s population. H. pylori infection is
the biggest risk factor for gastric carcinoma. This bacterium was classified as a group
I carcinogen in 1994 by the International Agency for Research on Cancer (IARC)
and the World Health Organization (WHO). Helicobacter pylori is strongly
associated with gastric carcinoma and MALT lymphoma. The main characteristics
of H. pylori infection are predominant infection in childhood, high incidence and
prevalence in developing countries and in groups of people with low socioeconomic
status, reducing the incidence in developed countries in recent decades, and persistence of the infection in elderly people whose childhood was spent in poor sanitation.
In developed countries, the prevalence of H. pylori infection increases by 1% per
year after the age of 14. After the seventh decade, 50% ± 20% of all subjects are
infected. In underdeveloped countries, about 50% of children and 90% to 100% of
adults are infected. The discoverers R. Warren and B. Marshal received the Nobel
Prize in Medicine and Physiology in 2005 (Amieva and Peek 2016).
2 Incidence, Prevalence, and Mortality of Gastric Cancer:
Adenocarcinoma
Gastric cancer is the second cause of cancer mortality after lung cancer. More than
90% of the tumors are adenocarcinomas. Very few countries like Japan have
programs for its early detection, prevention, and eradication. Тhe highest incidence
rate is in China, Mongolia, Korea, and Japan – from 40 to 60/100,000 citizens. The
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incidence rate for men is twice more than in women. The risk of noncardiac gastric
cancer is six times higher in people infected with H. pylori than in uninfected people.
Globally, the incidence of gastric cancer has decreased in recent decades due to the
treatment of H. pylori infection (Correa 2013).
Approximately 5.5% of malignancies in the world are attributable to inflammation caused by H. pylori. H. pylori eradication has diminished the rate of gastric
carcinoma in some areas. Randomized controlled trials assay the influence of the
eradication on the development of gastric cancer. There is a link between the
eradication of H. pylori infection and the incidence of stomach carcinoma. The
benefits of therapy varied depending on the type of gastric cancer incidence area
(Lee et al. 2016; Lin et al. 2021; Mladenova 2021).
The incidence and fatality rate from gastric cancer are much higher in developing
countries. Around 2% of H. pylori-positive patients develop gastric carcinoma
(Plummer et al. 2015; Sukri et al. 2020).
Wong MCS et al. have analyzed in a population-based cohort study from 1980 to
2018, data from global and national cancer registries, about incidence and mortality
of gastric carcinoma and compare the global incidence trends between younger than
40 years and older populations in 48 countries. The data have been retrieved from the
National Cancer Institute, the Nordic Cancer Registries, and the World Health
Organization Mortality Database. The authors have discovered an increasing incidence of gastric cancer in younger than 40-year-old individuals than in older
patients, and there is a need to develop measures to prevent morbidity in younger
people (Wong et al. 2021).
3 Histologic Classification
The scheme approved by the International Gastric Cancer Association divides
gastric carcinomas into type I, type II, and type III to be tumors in the distal
esophagus, the cardia and stomach, and distal to the cardia, respectively (Siewert
and Stein 1998).
A retrospective study by Huang et al. showed that cardiac carcinoma involving
gastroesophageal junction or distal esophagus is more appropriately classified and
staged as gastric cancer than as esophageal cancer. Cardiac carcinomas are staged
according to the depth of invasion, status for positive lymph nodes, and distant
metastases. It is more appropriate to group and stage cardiac carcinomas as gastric by
origin (Huang et al. 2011). Early gastric cancer is defined as invasive cancer limited
to mucosa and/or submucosa, with or without lymph node metastases, regardless of
tumor size (Hamilton and Aatonen 2000).
The earliest gastric carcinomas are small, 2–5 cm in size, and often have a smaller
curvature around the angularis. Some early gastric cancers may be multifocal, which
has a worse prognosis (Murakami 1971). The most common forms of early gastric
cancer are well-differentiated, mostly with tubular and papillary architecture.
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The distinction between well-differentiated carcinoma and high-grade dysplasia or
carcinoma in situ can only be made when mucosal tissue is available for histological
evaluation. The prognosis for early gastric cancer is excellent, with a 5-year survival
rate of 90% of the cases (Everett and Axon 1997).
The distinction between early and advanced gastric cancer before resection is
clinically important because it helps to decide whether neoadjuvant (preoperative)
therapy, which has been shown to improve overall survival, is warranted (Ychou
et al. 2011 ).
Histological classification of gastric cancer was largely based on Laurén’s
criteria, where intestinal, approximately 54% (more commonly associated with
intestinal metaplasia and H. pylori infection), and diffuse adenocarcinoma 32%
(more common in women and young individuals) are the two main histological
subtypes, plus indeterminate type, 15%, as an unusual variant. The 2010 WHO
classification recognizes four main histological models of gastric cancer: tubular,
papillary, mucinous, and poorly cohesive (including signet ring cell carcinoma), plus
uncommon histologic variants.
Gastric Adenocarcinoma Classification Systems
Bosman et al. (2010) Laurén (1965)
Papillary adenocarcinoma
Tubular adenocarcinoma Intestinal type
Mucinous adenocarcinoma
Signet ring cell carcinoma
Other poorly cohesive carcinoma Diffuse type
Mixed carcinoma Indeterminate type
Adenosquamous carcinoma
Squamous cell carcinoma
Hepatoid adenocarcinoma
Carcinoma with lymphoid stroma
Choriocarcinoma
Carcinosarcoma
Parietal cell carcinoma
Malignant rhabdoid tumor
Mucoepidermoid carcinoma
Paneth cell carcinoma
Undifferentiated carcinoma
Mixed adeno-neuroendocrine carcinoma
Endodermal sinus tumor
Embryonal carcinoma
Pure gastric yolk sac tumor
Oncocytic adenocarcinoma (Hu et al. 2012)
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4 H. pylori as a Carcinogen and Gastric Cancer Pathogenesis
Helicobacter pylori has an original strategy to colonize the host and to induce
carcinogenesis. With development of cryogenic electron microscopy structures of
the main virulence factors, VacA and CagT4SS have been obtained. The key events
in the H. pylori-induced tumorigenesis are microRNA-mediated regulation
and epigenetic modifications, through DNA methylation (Denic et al. 2020).
Helicobacter pylori genotypes could define the clinical outcomes of preneoplastic
lesions in gastric cancer. There are geographic differences in the risk of H. pylorirelated cancer. High and low incidence areas of gastric cancer have shown
differences in transmission ecology, largely affecting the composition of H. pylori
populations. It is proposed that any high-risk population may have its own specific
H. pylori strains with national or regional gene pools (Bakhti et al. 2020). More than
700,000 people die each year from gastric cancer. It is an asymptomatic disease in
the early stages and is therefore often detected late; 5-year survival is only 20–30%
(Thiel and Ristimäki 2012). It is believed that the observed trend of declining
morbidity in developed countries is associated with a reduction in H. pylori infection, probably due to increased living standards (Parsonnet et al. 1992).
Anyone who has H. pylori in their stomach develops a cellular infiltration in their
gastric mucosa called chronic gastritis. In most patients (80%), H. pylori does not
cause clinical symptoms and the infection can last a lifetime without causing
problems. A proportion (10–20%) of infec ted patients develop gastric hyperacidity
and peptic ulcer, but can be cured by antibiotic treatment. However, a small
percentage (0.1–4%) of infected patients develop distal gastric adenocarcinoma,
depending on the circumstances of the infection and the individual’s immune
response to the bacterium (Portal-Celhay and Perez-Perez 2006). Stomach cancer
is a multistage and multifactorial disease. H. pylori infection is the most important
factor in the pathogenesis of chronic gastritis and is a significant factor in 71–95% of
all gastric cancers (Ekstrom et al. 2001). Patients with corpus-dominant H. pylori
gastritis have a significantly increased risk of gastric cancer (Matsuhisa et al. 2004).
Intestinal metaplasia and atrophy are indicators of a high risk of malignant transformation and serve as precancerous markers (Hatto ri 1986). Some studies showed that
gastric atrophy can be reversible only in the corpus, but not in the antrum cavity.
There is a consensus that intestinal metaplasia is irreversible (Ito et al. 2002).
H. pylori infection is the most common proven risk factor for human noncardiac
gastric cancer. The evidence is based on epidemiological data and in vitro and
in vivo experimental models. There is biological plausibility from clinical observation and therapeutic studies. Epidemiological studies have shown that the risk is
20-fold or even higher (Forman 1995; Malfertheiner et al. 2010; Brenner et al. 2004).
H. pylori has been confirmed to be a risk factor if the lesion is gastric and originates
below the cardia (Bornschein et al. 2010). Hyperplasia and metaplasia of the gastric
epithelium significantly increase the risk of developing gastric cancer and MALT
lymphoma, especially when H. pylori infection was acquired in early childhood
(Kuipers 1999).
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The role of dietary factors (increased salt intake) in the development of gastric
cancer has been suggested (McColl et al. 1998) and that hypochlorhydria is involved
in gastric carcinogenesis, creating a favorable environment for the synthesis of
carcinogenic nitrosamines (Hill 1991). One of the “products” of H. pylori activity
for which there is experimental evidence that it increases the cell proliferation of the
gastric mucosa is ammonia (Tsujii et al. 1995). Intervention studies conducted in
Colombia (Mera et al. 2005), China (You et al. 2006), and Japan (Take et al. 2005)
all claim that H. pylori eradi cation is the most effective way to prevent stomach
cancer and that it is more effective in those who do not have atrophic gastritis.
Helicobacter pylori is associated with chronic atrophic gastritis, the precursor of
gastric adenocarcinoma. Parsonnet et al. have explored retrospectively the risk of
gastric carcinoma in а cohort of 128,992 persons with stored serum samples collected during the 1960s. Eighty-four percent of 109 patients with confirmed gastric
adenocarcinoma had been infected previously with H. pylori, as compared with 61%
of the matched control subjects. H. pylori has been proved as a strong risk factor for
stomach cancer in women and blacks (Parsonnet et al. 1991). Although there is
skepticism within a short period of time, many scientific teams have verified the
association of H. pylori with gastric carcinoma (Pandey et al. 2010). Around 75% of
the global gastric cancer prevalence and 5.5% of all malignancies in the world are
due to H. pylori-induced inflammation 2. There are many investigations focused on
mechanisms of gastric carcinogenesis as risk factors like H. pylori strain genotypes
and host and env ironmental influences (Amieva and Peek 2016).
Gunathilake, M et al. have observed the combined effects of Gaussian graphical
model derived dietary patterns and the gastric microbiome on the risk of gastric
cancer in a Korean population. They concluded that the vegetable and seafood
pattern network has been identified as the main dietary pattern in that population.
Higher fruit pattern network scores resulted in a reduced risk of gastric cancer. The
microbial dysbiosis index has been positively associated with the risk of gastric
carcinoma in females. The higher vegetable and seafood pattern scores and a low
microbial dysbiosis index could attenuate the risk of gastric cancer in men. In
females, the interaction between high dairy pattern scores and a low microbial
dysbiosis index have reduced the risk of this cancer (Gunathilake et al. 2021; den
Hoed and Kuipers 2016).
Оther microbes in addition to H. pylori may influence the transformation of
epithelial cells in the stomach. Infection of C57BL/6 mice with H. bilis or
H. muridarum before challenge with H. pylori significantly reduced the severity of
H. pylori-induced gastric inflammation. In contrast, pre-colonization with a different
enterohepatic Helicobacter species, H. hepaticus, increases H. pylori-induced gastric injury. These results could help to define the associations between H. pylori and
the other members of the gastrointestinal microbiome for better understanding
gastric carcinogenesis (Amieva and Peek 2016).
Chronic H. pylori-induced inflammation can eventually lead to loss of the normal
architecture of the gastric mucosa, with destruction of the gastric glands and
replacement by fibrosis and intestinal epithelium. This process of atrophic gastritis
and intestinal metaplasia occurs in approximately half of the H. pylori-colonized
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population. The area of gland loss and intestinal metaplasia expands over time
multifocally, and although they do not lead to any specific symptoms, they increase
the risk of gastric cancer by 5- to 90-fold depending on the degree and severity of
atrophy (Engstrand and Graham 2020;Kaź mierczak-Siedlecka et al. 2020; Kuipers
et al. 1995a, b; Sipponen et al. 1985).
5 Routes of Transmission of H. pylori Infection
The acquisition of H. pylori infection is thought to be more common in early
childhood, presumably from close family members (Raymond et al. 2004; Taneike
et al. 2001). Factors such as overcrowding, bed sharing, and lack of running water
are associated with an increased risk of H. pylori infection (Perez-Perez et al. 2004).
The infection is acquired by ingestion of a bacterium, most often transmitted within
the family, where the main source of infection in most cases is the mother (Webb
et al. 1994 ).
H. pylori can be cultivated from vomit or diarrheal feces, suggesting the possibility of transmission of the infection between family members during periods of illness
(Parsonnet et al. 1999). Several studies have reported the presence of H. pylori DNA
in environmental water sources, but this includes sewage water contaminated with
feces (Enroth and Engstrand 1995; Queralt et al. 2005). The first successful attempt
to cultivate H. pylori from feces belonged to Thomas et al. (1992), who isolated it in
9 of 23 malnourished children from. Even flies have been suggested to be a vector
for the spread of H. pylori, as it can remain viable for up to 30 h in their digestive
tract (Osato et al. 1997).
H. pylori is present in the feces of children in endemic areas, which makes it
possible for fecal-contaminated food or water to be a factor in transmission. From
this point of view, uncooked vegetables irrigated with untreated sewage water could
also be a factor in the transmission of H. pylori (Hopkins et al. 1993). Primates could
be a reservoir for H. pylori infection. This is important for developing countries,
where monkeys live near rural areas and could contaminate food and water sources
with H. pylori (Sahay and Axon 1996).
The epidemiological features of H. pylori infection can best be explained by
fecal-oral and oral-oral (in other authors gastro-oral, due to return of some gastric
contents to the oral cavity during regurgitation, reflux, and vomiting) mechanism
of transmission of infection. After eradication of H. pylori, recolonization by
microorganisms under the dental plaque is possible. Saliva could be a factor of
transmission of H. pylori infection. A link between a positive biopsy and the
presence of H. pylori in dental plaque has been demonstrated. The specific etiological treatment leads to eradication of H. pylori from the gastric mucosa in 83% of
patients, but fails to destroy the microorganism from dental plaque. The high
prevalence is associated with the low socioeconomic status, as well as in older
people whose childhood was spent in poor sanitation. Nosocomial transmission
between patients with fibrogastroscopy has been reported by many authors
(Ferguson Jr. et al. 1999, 1993; Kabir 2004; Leung et al. 1999).
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6 Virulence Factors
The pathogenesis caused by H. pylori is mainly attributed to its virulence factors,
including urease, flagella, VacA, and CagA. The last two factors, i.e., VacA and
CagA, play a key role. Infection with VacA-positive strains of H. pylori can lead to
vacuolation and apoptosis in the stomach mucosa, while infection with CagApositive strains can result in severe gastritis and gastric cancer. Studies focused on
gastric carcinogenesis divide risk factors into categories such as host responses,
genotypes, strain variation, and environmental factors. By assessing the interactions
between these factors, we could understand the risk and progression of the disease in
people with persistent colonization (Amieva and Peek 2016). Among the bacterial
pathogenetic factors that have a high risk of gastric cancer, CagA and VacA are by
far the most important. The oncogenic potential of bacterial virulence factors refers
to different polymorphisms of CagA and VacA (Basso et al. 2008; Jang et al. 2010).
CagA protein is a highly immunogenic protein encoded by the CagA gene. This
gene is present in approximately 50–70% of H. pylori strains. Patients infected with
CagA + strains tend to have a stronger inflammatory response and a significantly
higher risk of developing peptic ulcer or gastric cance r (Cover et al. 1995; Ching
et al. 1996; Kuipers et al. 1995a, b). The CagA protein is an oncoprotein that can
induce malignancies in mammals. On delivery, CagA disrupts multiple host
pathways by acting as a scaffold. CagA-induced g astric carcinogenesis progresses
through a shock-triggering mechanism in which the prooncogenic actions of CagA
are followed by a series of genetic or epigenetic changes composed of cancer-prone
cells during long-term infection with CagA-positive H. pylori (Hatakeyama 2014).
VacA protein plays an important role in the pathogenesis of peptic ulcer and
gastric cancer. VacA activities include membrane channel formation, disruption of
endosomal and lysosomal activity, effects on integrin receptor-induced cellular
signaling, disruption of cytoskeleton-dependent cellular functions, induction of
apoptosis, and immune modulation. There is a strong association between toxin
activity and the pathogenesis of H. pylori, with VacA s1/m1 type. It is the most
virulent genotype among the western population (Wada et al. 2004; Cover and
Blanke 2005; Atherton et al. 1997; Gunn et al. 1998).
The oncogenic potential of bacterial virulence factors refers to different
polymorphisms of CagA and VacA. EPIYA (Glu-Pro-Ile-Tyr-Ala) repeat variants
of CagA make it possible to differentiate between eastern and western CagA +
strains. Eastern strains have much higher virulence than western strains. The first
observation of a polymorphism leading to a high risk of atrophy and gastric cancer
was IL-1, tumor necrosis factor α, IL-10, interferon γ, and IL-8. The main factor
related to the pathogenicity of the strain includes the presence of membrane proteins
such as BabA, SabA, OipA, AlpA, AlpB, HopQ, vacuolating cytotoxin, and cagPAI
products (cytotoxin-associated gene indicating the island of pathogenicity). The
scientists have demonstrated the ability of H. pylori to penetrate normal, metaplastic,
and neoplastic gastric epithelium in vivo, intracellularly and interstitially, causing an
immune inflammatory response that promotes gastric carcinogenesis. Another
important factor in carcinogenesis is the genetic mutations that H. pylori infection
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can lead to, regardless of the inflammatory response (Basso et al. 2008; Jang et al.
2010; Yamaoka et al. 2008; Hou et al. 2007; Amieva and El-Omar 2008; Ansari and
Yamaoka 2019; Jeyamani et al. 2018).
H. pylori colonize and persist in a very unfavorable environment, the stomach,
which is bactericidal to the other species. By urease production, delivering of
bacterial products, and other mechanisms, H. pylori adapt to the acidic surroundings.
The most important factors linked with a higher risk of gastric pathology are CagA,
with type IV secretion system (T4SS), and the VacA (Amieva and Peek 2016). The
genes encoding CagA and the T4SS are located in a so-called Cag pathogenicity
island (cagPAI), in more virulent strains of H. pylori. CagA alters epithelial cell
polarity through direct interactions with the microtubule affinity polarity protein,
disrupts the cell junctions, and leads to the development of gastric cancer. CagA
induces cellular transformation by inducing accumulation of multiple genetic
variants and could promote the reprogramming of epithelial cells into stemlike
cells prone to transformation. VacA has the possibility to change the permeability
of the plasma membrane. The more pathogenic alleles of the VacA genes cause
formation of endosomal vacuoles and induce apoptosis and act as an immunosuppressant by inhibition of T-cells. Patients infected with H. pylori with CagA
antibodies are five- to eightfold more likely to develop gastric cancer than uninfected
patients. CagA-negative subjects are significantly less associated with gastric carcinoma incidence (Parsonnet and Orentreich 1997). Some results indicate that a highsalt diet potentiates the carcinogenic effect s of CagA+ H. pylori strains (Gaddy et al.
2013). The link of anti-CagA antibodies with a high grade of gastric atrophy sustains
the hypothesis that Helicobacter pylori CagA (+) strains could promote the precancerous cascade of gastric carcinogenesis (Bonvicini et al. 1997).
7 Can H. pylori Treatment Reduce the Risk of Gastric Cancer?
With the increase of the eradication therapy, the mortality from gastric cancer is
decreasing by degrees. Many meta-analyses show that eradication of H. pylori
reduces the incidence of gastric cancer. As stomach cancer is one of the leading
causes of cancer-related deaths worldwide, the approach to preventing this malignancy is a very important public health problem. Gastric cancer is associated with an
inflammatory tumor with multistage and multifactorial carcinogenesis. The process
includes a series of steps with development of metaplastic epithelium, dysplasia, and
gastric cancer. H. pylori infection is critical for the development of the disease,
and studies have consistently shown that bacterial eradication reduces inflammation
of the gastric mucosa, stopping the progression of the atrophy, metaplasia, and
dysplasia and lowering the risk of peptic ulcer disease onset and carcinogenesis
development. The screening and eradication of H. pylori have recently begun only
in high-risk populations. Elimination of gastric cancer requires information for
implementing effective H. pylori screening and treatment programs, taking into
account other health priorities in each particular population. The eradication therapy
has another important outcome, so-called the problem of gastric cancer after
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eradication therapy (GCAE). There is a hypothesis for the influence to carcinogenesis by other factors, such as gut microbiota and intestinal helminths (Watari et al.
2014; Ito et al. 2021; Kumar et al. 2021; Wen et al. 2021; Yang et al. 2021; Wu et al.
2019).
Gastric cancer develops slowly over the years, and cancer biomarkers are very
important to identify asymptomatic individuals where H. pylori eradication therapy
could prevent preneoplastic cascade (Cooke et al. 2013). There are some consensuses
about the first-line therapy, second-line therapy, etc. for H. pylori infection. The last is
the Maastricht V/Florence Consensus Report (Malfertheiner et al. 2017).
The triple clarithromycin-based therapy must be confined to patients without
prior exposure to macrolides living in areas with a low resistance to clarithromycin.
At present, bismuth quadruple therapy or concomitant non-bismuth quadruple
therapy (PPI, amoxicillin, clarithromycin, and nitroimidazole) should be the preferred regimen. This has been shown to be most effective in overcoming antibiotic
resistance. After the failure of the first-line therapy, the rescue regimen should avoid
antibiotics that have been used before. It is recommended to adopt classification
systems for stratification of gastric cancer risk and modern endoscopy to improve the
image for the diagnosis of gastritis. Eradication therapy against H. pylori prior to the
development of preneoplastic changes has been recommended to minimize the risk
of severe complications of this infection. These changes could be an important factor
in identifying the high-risk individuals for gastric cancer. Patients undergoing
endoscopic treatment for gastric cancer are at high risk of developing metachronous
gastric cancer. Patients with precancerous lesions who do not reverse after treatment
with H. pylori are the “point of no return” and may be at high risk of developing
stomach cancer. An earlier eradication of H. pylori should be preventable for the
development of gastric cancer before the onset of precancerous lesions (Ribaldone
et al. 2019 ; Li and Yu 2019; Venerito et al. 2018, 2020; Wong 2004).
Identifying high-risk individuals is important for monitoring and preventing
stomach cancer. The presence of first-degree relatives diagnosed with gastric cancer
is a strong risk factor for gastric cancer. Тhe pathogenic mechanisms are unclear.
There is an increased risk of developing stomach cancer among the patients having
two or more affected first-degree relatives with a family history of H. pylori infection. Eradication of H. pylori is the most important strategy to prevent stomach
cancer in first-degree relatives of patients with stomach cancer. Early eradication of
H. pylori can prevent progression to intestinal metaplasia and reduce the possibility
of developing gastric carcinogenesis in these individuals (Choi and Kim 2016; Wei
et al. 2010 ;. Wu et al. 2019).
8 Gastric Mucosa-Associated Lymphoid Tissue (MALT)
Lymphoma
H. pylori also develops another neoplastic process in the stom ach, primary lymphoma, which has a significantly better prognosis than carcinoma. The stomach is
the most common site for primary extranodal lymphoma (Isaacson and Wright
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1984). Almost all patients with MALT lymphoma are H. pylori-positive and
H. pylori-positive individuals are significantly more likely to develop gastric
MALT lymphoma. The high incidence of concomitant chronic H. pylori infection
reaches 98% in patients with low-grade MALT lymphoma and 71% in patients with
high-grade MALT lymphoma (Eidt et al. 1994; Parsonnet et al. 1994). Lymphoid
follicles are never found in the normal gastric mucosa, and their occurrence in
H. pylori-associated gastritis is significant evidence that these are precursors of
MALT lymphoma (Kuipers 1999; Chen et al. 2002; Fischbach et al. 2000).
Most patients with MALT lymphomas are over 50 years of age. The symptoms
are nonspecific – non-ulcer dyspepsia. In MALT lymphomas with a high degree of
malignancy, weight loss (67%) and palpable tumor mass (20%) were significantly
more common than in those with a low degree of malignancy (37% and 7%,
respectively) (Montalbán et al. 1995a). Most are associated with H. pylori infection,
and in the early stages, low-grade MALT lymphomas can be treated with H. pylori
eradication in 60–80% of cases (Wotherspoon et al. 1993; Stathis et al. 2009).
The effect of treat ment is directly related to the stage of MALT lymphoma and the
histological type. The best treatment results are for MALT lymphomas with low
malignancy, stage 1, and small lesions. Confirmation of this thesis is the complete or
partial remission of low-grade MALT lymphoma after eradication of H. pylori
(Montalbán et al. 1995b; Chan et al. 1990). All patients should be monitored closely
after H. pylori treatment, and alternative treatment (chemotherapy or radiation
therapy) should be instituted if MALT lymphoma does not respond or progress
(Ruskone-Fourmestraux et al. 2011).
There is a link between H. pylori infection and MALT lymphoma. Eradication
therapy of H. pylori in patients with low-grade MALT lymphoma is related with
tumor regression (Wotherspoon 1996).
In 460 patients of a population-based study, H. pylori was detected in 57% of the
cases. Eradication has been achieved in 76% but complete remission in 70% of
patients (Matysiak-Budnik et al. 2019). Eradication therapy of H. pylori is the
treatment of MALT lymphoma in all stages of this neoplastic disease (Gong and
Choi 2019).
The authors of one study recommended, for previous cases of atrophic gastritis
caused by H. pylori, endoscopic monitoring every 3 years for high-risk patients,
including those with endoscopic severe atrophy or intestinal metaplasia (Lee et al.
2016). Japan introduced a strategy for H. pylori
number of new cases of gastric cancer and deaths caused by this malignancy and
respectively the medical costs. It was estimated that the number of deaths from
stomach cancer could be reduced to 30,000 per year by 2020, but the annual number
of deaths in 2017 remained above 45,000. The effect of the strategy may appear until
2023. The risk of gastric cancer is likely to increase in some populations due to the
widespread use of PPIs and dysbiosis in the stomach mucosa. In one study, a
combined therapy with PPI s and aspirin has been proposed after the eradication of
H. pylori. To reduce the incidence of stomach cancer, health promotion, adequate
physical activity, low alcohol intake dietary nutrition, and quitting smoking have to
be included (Resende et al. 2020; Uno 2019; Na and Lee 2017; den Hoed and
eradication in 2013 to reduce the
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