non hodgkin's lymphoma prognosis | 4 ANALYSIS Non-hodgkiniens Lymphoma

4
ANALYSIS
Non-hodgkiniens Lymphoma



No-hodgkiniens (NHL) lymphomas constitute a heterogeneous group
of malignant proliferation of lymphoid cells (B or T) of origin
extra-medullaire. From a clinical point of view, these conditions are expressed by
the development of tumors in the lymphoid tissue, including the
lymph nodes. Due to the functional heterogeneity of cells
lymphoid and distribution of anatomical ubiquitous, these conditions
can develop in any organ and have an expression
the clinic is very heterogeneous. There is thus no clinical presentation type or
specific.

Classification
The classification of lymphomas is very complex and is constantly evolving
Depending on the State of knowledge. Several systems of classifications exist
and among them are the europeanno-American classification (REAL) (Harris
et al., 1994) which is largely based the classification of the Organization
World Health in present force in 2008 (Swerdlow et al., 2008).
This last includes more, unlike the REAL classification, the
lymphomas according to their grade of malignancy but classifies on the basis of criteria
cytological (large or small cells), histological (Nodular or diffuse).
immunophenotypiques (according to the surface antigenic markers), cytogenetic
and molecular (Douglas et al., 2010). In this last classification.
the NHL are divided into prognosis very clinico-biological entities
different. In a very simplified way, the NHL are listed in lymphomas
to B or T cells according to their histological type. The most common types being
the diffuse Lymphoma of type B large cells (30-40% of lymphomas in)
Western countries) and follicular lymphomas (20-30%) (Jaffe et al.,
(2001) the clinical aggressiveness of the NHL is correlated with the histological diagnosis.
For the aggressive NHL, the most frequent histological form is Lymphoma
diffuse large cell B (about 60% of the aggressive forms) so
for indolent NHL is follicular Lymphoma of type B (about
80% of the indolent forms) (Alexander et al., 2007). Very often the systems
classification have not been used in epidemiological studies
Although specific types of NHL have been studied in some studies.

Diagnostic criteria
Basically, the diagnosis of lymphoma is based on derivative
of a proliferation of cells, disrupting the normal architecture
lymphoid tissue in question and/or infiltrating non-lymphoid tissues. Them
detection on the basis of the morphological aspect, in the initial stages, is
problem because any normal lymphocyte can initiate a process of
dedifferentiation, proliferation, and differentiation during a response
immune physiological. Thus, the diagnosis can be evoked from a
cytological examination of the blood, bone marrow, of a liquid of effusion
or a suction of ganglionic juice but it must be confirmed on
a biopsy material of a undercover fabric.
The diagnosis is usually made following the discovery of Lymphadenopathy
often multiple who may serve in all areas of the ganglion
with a predominance in the cervical and axillary level. Extraganglionnaires attacks
are common and can affect all the tissues with a
special fondness for the bone marrow, spleen, digestive tract, the ORL sphere,
skin, lung, liver, pleura, bone, kidneys, central nervous system.
Extra-ganglionnaires preferential locations are dependent
The histological type of the NHL. The diagnosis of NHL is essentially
histological and rests on bioptic samples (ganglionic and/or)
tissue) (Douglas et al., 2010).Incidence and mortality
Data of incidence and mortality in France in general population
French epidemiological incidence data are estimated (since
1980) at the national level from departmental records which cover
about 20% of the population. Mortality data are from the file
National (Cépidc) which includes mortality data, available at the
national level since 1950.
In France, with almost 12,000 new cases per year (11 631 estimated in 2011
54.9% in humans), the NHL represent a little more than 3% of
all the incident cancers, and are, by their frequency, to the 7th
 rank
in humans, and on the 5th
 in women. In 2005, the standardized incidence
the age of the world population was 12.1 for 100,000 people-years
in humans and 8.2 for 100,000 people-years in women with
a sex‑ratio of 1,2. The impact which featured a sharp increase between
1980-2005 (annual average rates of change of 2.7% in men
and 2.9% for women) stagnates over the period 2000-2005, way
more tangible in men, and linked to a most important contribution non-hodgkiniens Lymphoma
ANALYSIS
young cohorts. This stagnation could lead to a reduction of
prevalence of exposure to factors of risk for younger cohorts
(Monnereau et al., 2008). NHL incidence increases with age. The age
way at diagnosis is around 65 years (although some)
types of NHL occur specifically in younger subjects)
(Douglas et al., 2010).
Projections of incidence and mortality from cancer in 201125 were
published recently (Inca, 2011). They rely on statistical modeling
observed data from impact from records of the period
1975-2006 and on the observed mortality data up to 2008 (table
4.I).
Table 4.I: Projection for the year 2011 of the impact of the NHL and the
mortality in France (according to Inca, 2011)
Incidence mortality
Staffing rate
impact
Rank staff rates
mortality
Rank
Man 6 381 12.5 7 1 991 3.1 8
Woman 5 250 08,3 5 1 684 1.7 6
Standardized rates the world 100 000 personnes‑annees
According to forecasts 2011, deaths due to the NHL are estimated at 3 675.
with a male excess of 1.13. The NHL represent 2.4 and 2.7%
of the total number of deaths by cancers respectively in humans and at the
woman with a standardised mortality rates of 3.1 and 1.7 (for 100,000
personnes-Annee). The evolution of mortality following the same trend as
of the impact but precedes it in time: after an increase
until about 1995 (Monnereau et al., 2008), mortality from NHL
decreases of 1.6 percent per year in men and 2.2 percent per year in women (Hill
(et al., 2009). This decline is probably due to therapeutic progress
(Monnereau et al., 2008). Comparison of changes in mortality
and the impact between 1980 and 2005 shows a stability of the impact
the NHL in recent years and a decrease of mortality both at
men and women (Hill et al., 2009).
Remember that the NHL are a group of very heterogeneous pathologies
each entity has an etiology and an own epidemiology.
The interpretation of recent evolutionary trends of incidence and mortality
These lymphomas can, moreover, be complicated by the evolution of

Pesticides - Health effects

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classifications (the last of the who classification integrating codes of)

fiance and prolymphocytaires leukemias lymphomas), by a

best possible detection of the disease or by improving the quality

registration of cases (Monnereau et al., 2008).

Frequencies of the pathology at the global level:

variations spatio‑temporelles

At the global level, the NHL represent tenth malignant pathology.

According to the data Globocan26 2008 on 20 parts of the world, the

NHL incidence per 100,000 rate, standardized on age and on

the world's population, are estimated to be 5.1 for both sexes, 6.1 for the

4.2 for women and men respectively representing 2.8%; 3.0%

and 2.6 percent of all new cancer cases estimated (Harries et al.,

2010 (a). the highest incidence rates are observed in the regions of the

the most developed world (North America, Australia, New Zealand

(and Europe), with an estimate of the number of new cases of 95 000 men

and 64 000 women compared to 37 000 men and 33 000 women in the regions

developing (Globocan, 2008); the lowest rates were

reported for the Caribbean and Central Europe and the East (Globocan, 2008).

The 2008 estimates place the 10th

 rank in 40 European countries

studied (Harries et al., 2010b).

The geographical distribution of the different types of NHL is very variable: we

Note the predominance of follicular and diffuse lymphomas in large cellulesB

in Western countries, often aggressive T lymphomas in Asia and

Lymphoma Burkitt in Africa (Müller et al., 2005).

In 2008, the number of deaths by NHL globally was estimated to

191 000 (109 000 men and 81 000 women), or about 2.5 percent of all

mortality due to cancers. Mortality rates due to the NHL

per 100,000 population, standardized on the age and the world's population,

are estimated at 2.7 for both sexes, 3.3 for men and 2.1 for the

Women (Harries et al., 2010). The estimate of the number of deaths in the

the more developed regions is 37 000 men and 33 000 women against

71 000 men and 48 000 women in developing regions

(Harries et al., 2010 (a).

During the 1970s and 1980s, the worldwide incidence of NHL increased

steadily with an annual increase of the incidence rate of approximately

3 4% to the United States, which is practically a doubling

rates. This increase involved all age except groups

children under the age of 15 and appeared mainly among the older population. Non-hodgkiniens Lymphoma

ANALYSIS

and faster in rural areas than in urban areas. This

increase was higher among men than among women, at the

Caucasians than among African Americans, the rate of increase of these rates

incidence among these four groups are substantially identical (Reyes,

2001; Müller et al., 2005). Since the 1990s, the incidence rate

stagnating as well to the United States and Europe (Alexander et al., 2007).

In the same way that the incidence, mortality rates have increased

until the beginning of the 1990s. According to data from the who covering the

1990-2006 period to 11 countries from different parts of the world, the rate of

mortality decreased in 10 countries since the second half of the years

1990, with the exception of the Russia that, with the lowest rate, shows an increase

during the last years (Saika and Zhang, 2011). This decrease

is more marked for the United States and the Australia who presented the

highest rates: these are similar to those observed in Europe. Them

rate the highest in Europe were observed for the United Kingdom and the

lower for the Spain and Germany (Saika and Zhang, 2011). Between 2000

and 2004, increases the survival of patients with NHL between 37% and 62%

among the European countries. The increase in rates until the Middle

1990s can partially be attributed to the HIV epidemic and to the

NHL associated with AIDS. However these viral infections alone, as

better diagnosis of NHL and definitions which would have favoured

the inclusion of more cases, cannot explain the magnitude of this

increase (for review see Alexander et al., 2007). Although no factor

specific could not be identified, some authors consider that important

changes in exposure to risk factors may have

contributed to the observed increases (Liu et al., 2003).

Etiology, known risk factors

The etiology of the NHL remains largely unknown. If a number of

risk factors have been established (some specific to particular types)

NHL), they account for only a small proportion of the total number

case. These include some viral infections (immunodeficiency virus

human, the virus of human Lymphoma T-cell in type 1, the virus

Epstein-Barr (virus responsible for herpes around 8% of deaths) (Hill and)

Al., 2009), the virus of hepatitis C, bacterial infections (Helicobacter

pillory, Campylobacter jejuni) as well as the weakening of the immune system

(immunosuppression resulting from a viral infection, taking medication

immunosuppressants, yet disorders or autoimmune diseases

hereditary). These last decades, research on the etiology

the NHL more turned to exposures to agents of

environmental (exposure to ionizing radiation or UV) to the

chemical agents resulting from occupational exposures (solvents, benzene, Pesticides - health effects

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pesticides...) or other (hair dye), but the results of these

studies are often contradictory. A more limited number of studies have

door on eating habits, family factors and polymorphisms

Genetics (journals in Müller et al., 2005, Eriksson et al.,

2008; Alexander et al., 2007).

Pesticides have been suggested as risk factors for the NHL to go

results of studies conducted on farmers, applicators of pesticides.

workers in industry synthesis of pesticides, workers

on chemical production sites and military veterans who served in the

Viet Nam. A synthesis of these data is the subject of the following paragraphs.

Occupational exposure to pesticides

and lymphomas non‑hodgkiniens

Epidemiological data concerning the link between pesticides and lymphomas

non-hodgkiniens are very numerous and constantly accumulate.

The analysis of these data is structured in the following way: a first

part summarises the results of the meta-analyses on the topic.

followed by a presentation of the results of the large prospective cohort

American (the Agricultural Health Study) and finally presented the results

obtained by chemical families from the studies of cohorts and studies

case-control.

Meta‑analyses

Between 1992 and 2009, seven meta-analyses have been published (table 4.II) (Blair

et al., 1992; Keller-Byrne et al., 1997; Khuder et al., 1998; Acquavella

et al., 1998; Boffetta and dash, 2007; Mehri et al., 2007; Jones and

Al., 2009). Among them, three were the NHL, one specifically on

the hematopoietic cancers and three on all cancers. The number

included in these meta-analyses epidemiological investigations varies from 6 to 47,

published between 1980 and 2005 (table 4.II). According to professional activities

considered, five of the seven meta-analyses are on exhibition in the

agricultural sector, one relates to the exposure of workers in manufacturing industry

products (Jones et al., 2009) and one is

related to occupational exposure in agriculture and injunctions

(Mehri et al., 2007).

Overall, the 5 meta-analyses covering professional agriculture

highlight an excess risk of NHL ranging from 3% to

34% in these populations compared to the general population. This increase

a threshold of statistical significance in 3-meta-analyses