Journal of Gastrointestinal Cancer

https://doi.org/10.1007/s12029-020-00382-3

ORIGINAL RESEARCH

Colorectal Cancer Trends of 2018 in Romania—an Important

Geographical Variation Between Northern and Southern Lands
and High Mortality Versus European Averages
Elena Mirela Ionescu 1,2 & Cristian George Tieranu 1 & Dana Maftei 1 & Adriana Grivei 1 & Andrei Ovidiu Olteanu 1 &
Tudor Arbanas 1,2 & Valentin Calu 1,2 & Simona Musat 3 & Constanta Mihaescu-Pintia 3 & Ionut Cristian Cucu 4

# Springer Science+Business Media, LLC, part of Springer Nature 2020

Abstract
Purpose In Romania, one of the highest rates for colorectal cancer (CRC) incidence and mortality in Europe was estimated based
on data available in 2008. Ever since, consistent data are missing. In this article, we tried to estimate the general burden of CRC in
our country.
Methods We collected data from all hospitalized recorded cases according to the ICD-10 revision (codes C18–C20), as both
primary and secondary diagnoses, as reported by all the hospitals to the DRG National System, between 2016 and 2018.
Results There were 50,890 persons hospitalized with CRC. The prevalence of hospitalized colorectal cancer was 108.24/100,000
inhabitants in 2016, 113.09/100,000 inhabitants in 2017, and 116.83/100,000 inhabitants in 2018. Distal localization prevailed.
We registered 34.13/100,000 deaths by CRC within the mentioned period of time, almost twofold higher than average European
range. There are significant geographical differences regarding CRC prevalence and mortality, with higher rates in the Northern
and Central Regions, and a very low prevalence and mortality in Bucharest and Southern provinces.
Conclusion We note a high colorectal mortality rate in Romania, especially in the Northern and Central Regions, nearly double
versus European ranges.

Keywords Colorectal cancer . Hospitalized morbidity . Mortality . Romania . Geographical variation

Introduction recorded in Central and Eastern Europe. Therefore, in the

The data available in 2012 have shown that worldwide, colo-
rectal cancer (CRC) was the third most commonly occurring
cancer in men (10% of all sites) and the second most com-
monly occurring cancer in women (9% of all sites), with an
estimated 1.4 million cases and 693,900 deaths in 2012. With
a significant geographical variation, the highest rates were
* Cristian George Tieranu
tieranucristian@gmail.com
1
Department of Gastroenterology, “Elias” Emergency University
Hospital, 17th Blvd. Marasti, 011461 Bucharest, Romania
2
Department of Gastroenterology, “Carol Davila” University of
Medicine and Pharmacy, Bucharest, Romania
3
The National School of Public Health, Management and Professional
Development, Bucharest, Romania
4
Medigate, Bucharest, Romania
European Region, colorectal cancer (CRC) was the first tumor
by incidence, with 471,000 new cases registered each year and
a mean mortality rate of 28.2 per 100,000 inhabitants [1, 2].
For comparison, in 1995, 334,000 new cases (30% less than
17 years later) were recorded in Europe, with 189,000 deaths
from colon and rectum cancers [3]. In 2010, Ferlay et al. and
Segnan et al. reported for Europe data concerning age-
standardized incidence and mortality rates for colorectal cancer
by country and gender. Therefore, they showed that CRC mor-
tality varied among the 27 EU Member States at that time, with
Hungary having the highest mortality rates and Cyprus having
the lowest ones. Hence, in 2008, when the data were collected,
Romania had similar rates with the Hungarian population—
43.8/100,000 inhabitants’ incidence and 25.2 mortality in fe-
males, and 93.8 incidence and 53.3 mortality in males, while in
Romania, we had 43.9 incidence and 20.2 mortality in females
and 88.6 incidence and 46.9 mortality in males [1, 4]. We can
easily observe that Hungary or Romania have higher rates than
most of the other European countries [4–7].

Based on the most recent GLOBOCAN 2018 estimations of
cancer incidence and mortality, made by the International
Agency for Research on Cancer, it seems that there are over
1.8 million new colorectal cancer cases estimated in 2018 (still
10% of all sites), meaning 29.5% more cases than 6 years ago,
and 881,000 deaths (also 9% of all sites), representing 27%
more deaths than 6 years ago. According to this report, in
2018, colorectal cancer ranked third worldwide in terms of
incidence but second in terms of mortality, with over
500,000 new cases diagnosed only in Europe, and 245,000
deaths. The highest colon cancer incidence rates are still found
in some European Regions (on the first position in 2018 was
again, Hungary). All Eastern Europe statistics report for an
incidence of 20.3 in men and 13.8 in women per 100,000
inhabitants [5–7], but data are inconsistent for some countries.
CRC incidence and mortality in a population are related to
changes in the prevalence of some modifiable risk factors such
as smoking, alcohol consumption, and diet. According to epi-
demiological evidence, the risk of developing CRC increases in
relation to lifestyle (such as higher consumption of red meat,
increased alcohol intake, decreased physical activity, obesity).
At least a part of the variations in CRC mortality can be ex-
plained by differences in lifestyle, but also by unequal screening
practices and a dissimilar treatment between countries [8].
In addition to primary prevention, potential factors contribut-
ing to decreasing CRC incidence and mortality are early detec-
tion, improved diagnosis, and treatment. It was clearly shown
that screening is associated with a reduction in mortality [9–13].
No screening program is currently set in Romania, al-
though aging population, demographic changes, and western-
ization of the Romanian lifestyle (including changes in the
prevalence and distribution of the main risk factors for CRC,
associated with socioeconomic development) could be pre-
mises for more increasing rates in the near future.
No National Cancer Register is set in Romania (except for
a Regional Register in Cluj-Napoca, with data from the
Transylvanian province); therefore, no pertinent statistics re-
garding colorectal cancer is available for this part of Europe
nowadays. We can only extrapolate the rates comparing with
our Hungarian or Bulgarian neighbors.
In Romania, one of the highest rates for CRC incidence and
mortality in Europe was estimated based on the data available
in 2008. Ever since, consistent data are missing. We can only
presume that these trends remain to be similar or worse than
10 years ago, if Hungary (who publishes valuable data) re-
ports the highest incidence in the world now (51.2/100,000
inhabitants) [14].
Moreover, since the data recorded in 2012, the scientists
believe that increases in mortality rates are still occurring in
countries that have more limited resources and increasing in-
cidence, including Romania in Eastern Europe [15, 16].
In this article, we estimated the general burden of CRC in
Romania, collecting data from all the CRC hospitalized
J Gastrointest Canc
recorded cases in our country, as reported to the DRG
National System, during the last 3 years.
Materials and Methods
According to Romanian law, all the cases admitted in the
hospitals are electronically reported as a minimum dataset
to the National School of Public Health, Management and
Professional Development (SNSPMPDSB), and registered
within a national database since 2007. We recorded all the
CRC hospitalized cases as reported between 2016 and 2018
for continuous hospitalization (no day-care), in respect to
personal data confidentiality by using a specific cryptic
system.
For this article, the data were extracted from the national
database at the level of hospitalization episode, by querying
the following: diagnosis—primary and secondary, localiza-
tion of the tumor, age, sex, domicile, the length of stay, and
discharge status. CRC cases were recorded according to the
ICD-10 revision (codes C18–C20). In order to avoid biases
related to secondary diagnosis of CRC persistence due to
DRG coding issues, we performed a stepwise querying of
the database, applying a double filtered search by diagnosis
code and the period of time between 2016 and 2018. So, we
initially found all the patients registered with CRC during the
study period, and thereafter, we applied the next filter to ex-
clude “carriers” of CRC diagnosis before 2016, using as pa-
rameters the identification code of the patients selected in the
previous step and the diagnosis code. Thus, we selected only
the recent diagnosed cases of CRC, coded as either primary or
secondary diagnosis, restricted to the aforementioned period.
In the national demographic reports, we searched for popu-
lation data (the number of Romanian inhabitants in each from
the 42 counties and the number of the whole Romanian popu-
lation in 2016, 2017, and 2018). Thus, we calculated the prev-
alence of hospitalized colorectal cancer, hospitalized mortality
by CRC in the general population and by sex, in male and
female patients in Romania and in each county, but also
grouped by the main administrative-territorial regions.
For personal data protection, a specific cryptic system was
used: each patient with a unique identification number
(Romanian CNP) received a unique alpha numeric identifica-
tion code (IC). By convention, for the patients with an un-
known CNP at the time of hospitalization, the cryptic system
attributed to such cases a code of 13 numbers of zero. All the
patients in this extremely rare situation have been given the
same IC, which represented a limitation of our study when we
calculated indicators regarding number of people.
So, excepting this situation, each patient was counted one
time with a number of hospitalizations till their death or till the
end of our study in 2018.
J Gastrointest Canc

The hospital practitioner that registered and reported to the Table 1 The prevalence of CRC in the main 8 regions of Romania
national database was also specifically encrypted, in respect to Region Prevalence/100,000 inhabitants Male Female
the law of personal data protection.
Data were collected and processed in an Access database. Crisana 164.6 196.1 148.4
For the statistical work, we used R Program version 3.5.3/ Central Region 147.7 174.2 121.3
Platform x86_64-pc-linux-gnu. Muntenia 145.8 173.3 122.8
This study had a retrospective, observational design, with North Moldavia 139.1 163.7 117.8
approval for data usage from the owner and with specific en- South Moldavia 130.2 155.6 110.8
cryption of the data regarding the patient and the practitioner to Oltenia 78.4 92.9 64.8
protect identities. The study design was approved by the local Banat 68.4 80.2 58.6
ethics committee from the National School of Public Health, Bucharest and Ilfov 40.8 47.9 34.2
Management and Professional Development, Bucharest, with
registration number 2625 of 18 June 2019. This study was
performed in line with the principles of the Declaration of but the system recognizes the new patients registered in 2017
Helsinki. All the patients had previously signed a standardized (10,813) and 2018 (14,085), so we calculated the incidence of
written informed consent for hospitalization implying possible new CRC hospitalized in 2017 (55.05/100,000 inhabitants)
research use of their data, according to Romanian laws. The and in 2018 (72.15/100,000 inhabitants).
study protocol conforms to the ethical guidelines of 1975 A male predominance was observed, with a male/female
Declaration of Helsinki and its later amendments. ratio of 1.32/1 in CRC population within the 3 years studied.
The mean age of the CRC patients was nearly equal, with
68.23 years old in men and 68.83 years in women. In our
Results study population, only 6.24% of CRC people aged less than
50 years old.
Between 2016 and 2018, in Romania, there were 50,890 per- 44.2% of our patients had rectal, recto-sigmoid or sigmoid
sons hospitalized with colorectal cancer. Based on demo- as tumor site, so distal localization prevailed.
graphic reports, we estimated a prevalence of hospitalized Regarding geographical distribution of CRC in our coun-
colorectal cancer of 108.24/100,000 inhabitants in 2016, try, we note down some important differences in the preva-
113.09/100,000 inhabitants in 2017, and 116.83/100,000 in- lence of the disease. We mention that we considered the home-
habitants in 2018 (Fig. 1). Since we started our registration in county of the patients as the provenience region and not the
2016, we cannot know the number of new cases in that year, place where the patient was treated.

Fig. 1 Prevalence of hospitalized

CRC in the main Romanian
provinces

CRISANA
164.6/100.000 NORTH
196.1 (M); 148.4 (F)
MOLDAVIA

139.1/100.000
163.7 (M); 117.8 (F)

CENTER

BANAT 147.7/100.000
174.2 (M); 121.3 (F)

68.4/100.000
80.2 (M); 58.6 (F)

SOUTH
MOLDAVIA
78.4/100.000 130.2/100.000
92.9 (M); 64.8 (F) 145.8/100.000
155.6 (M); 110.8 (F)
173.3 (M); 122.8 (F)

40.8/100.000
47.9 (M); 34.2 (F)

OLTENIA MUNTENIA

BUCHAREST,
ILFOV

Fig. 2 Geographical distribution of hospitalized CRC prevalence in the
main Romanian provinces
Therefore, there are considerable differences between
administrative-territorial regions of Romania as we see below
(Table 1, Fig. 2), with the highest prevalence of CRC in
Crisana Region, followed by Central Region, Muntenia, and
North Moldavia (the Northern and the Central part of the
country), and a significant lower prevalence in the Southern
part of the country (South Moldavia, Oltenia, Banat).
A total number of 6705 patients died of CRC from 2016 to
2018 in Romanian hospitals, meaning 34.13/100,000 deaths
by CRC in the mentioned period of time. 11.05% of the new
cases diagnosed in 2017 died in hospital during that year, and
8.45% of newly diagnosed cases in 2018 died in the same
year. The most fatal localization was rectal cancer (Fig. 3) with
989 death cases (14.7% of all deaths), followed by sigmoid
and recto-sigmoid junction (9.35% and 6.54% of deaths).
The highest hospitalized mortality is in the 2 regions where
the disease is the most prevalent (Crisana and Central Region).
After that, although in Muntenia CRC is more prevalent, the
mortality is higher in South and North Moldavia despite of a
lower prevalence here. The number of deaths caused by CRC
is the lowest in Bucharest and Ilfov in concordance with the
lowest prevalence in the same areas. The mortality is also very
low in Oltenia and Banat, as well as the prevalence. Another
observation is that the difference between the number of
deaths in men and women is more faded in Southern lands
(Muntenia, Bucharest-Ilfov, Banat, Oltenia), then in Northern
and Central provinces (Table 2, Figs. 4 and 5).
Fig. 3 Number of deaths by
tumor localization
J Gastrointest Canc
The mean number of hospitalizations per CRC patients was
2.92/year (2.88–2.95).
In 2016, the average length of stay (ALOS) was 8.86 days
per patient, with a total of 189.507 days of hospitalization for
CRC. In 2017, the ALOS increased to 9.66 days per patient,
with a total of 214.568 days of hospitalization for CRC for all
patients, while in 2018, the ALOS was 9.7 days with a total of
221.227 days of hospitalization for CRC.
The ALOS was higher for rectal cancer (C20) (9.96 days)
than for recto-sigmoid junction (C19) (7.96 days) or other
colonic localizations (C18) (8.84 days).
The highest discharge rate for CRC in-patients was in
2018, with 341.17 hospital discharges for CRC, followed by
330.23 cases in 2017 and 316.07 in 2016.
Discussions
Globally, CRC is among the cancers with an incidence expect-
ed to increase in the near future [14] despite the indisputable
fact that substantial progresses in CRC management and treat-
ment have been developed. Appropriate screening is very ef-
fective in reducing colorectal cancer mortality and incidence
[17]. In countries like the USA, where screening was intro-
duced by a number of decades and treatment has been consid-
erably improved, the prevalence and the overall death rate have
continued to drop [18]. Otherwise, in cancer registries from all
over the world, especially in economically transitioning coun-
tries including the Eastern European Region, rates are signifi-
cantly increasing [19, 20]. Many studies pointed out that CRC
prevalence and mortality tends to vary more rapidly than other
cancer localizations due to lifestyle changes like alcohol and
tobacco consumption, obesity and diabetes, sedentary life, and
unhealthy dietary patterns [21].
In Romania, we had incidences of 43.9/100,000 population
in females and 88.6/100,000 in males in 2008 [1, 4]. By com-
parison, in our study, we note the general incidence of new
CRC hospitalized in 2017 of 55.05/100,000 and 72.15/
100,000 inhabitants in 2018 in both gender, and a prevalence
J Gastrointest Canc
Table 2 Hospitalized mortality
caused by colorectal cancer in the Administrative and territorial
main Romanian regions regions
Crisana
Central Region
North Moldavia
South Moldavia
Muntenia
Bucharest and Ilfov
Oltenia
Banat
of hospitalized CRC that slowly grows from 108.24/100,000
in 2016 to 116.83/100,000 in 2018.
Nowadays, colorectal cancer is responsible for the second
highest number of cancer deaths (after lung cancer) in the
European Union in 2018, with rates of 15.8/100,000 men and
9.2/100,000 women, declining since 2012 by 6.7% in men and
7.5% in women. Observed ASR (age-standardized mortality
rates per 100,000 persons using the world standard population)
in 2012 is 9.98, and predicted ASR in 2018 is 9.23 [22].
In Romania, the mortality arises in men from 12.33/
100,000 in 1997 to 16.99 in 2007, and in women from 8.50
in 1997 to 9.79 in 2007 [23]. According to our study data, in
2016–2018, we had a general mortality of 34.13/100,000 in-
habitants demonstrating a huge increase of CRC mortality in
our country. This observation might be explained by a better
healthcare availability in different regions contributing to bet-
ter diagnosis. Still, a limitation of the current study resides in
the fact that we did not have information about treatment
methods in different areas of our country, limitation induced
by the technique used in the data collection process. It is also
obvious that the mortality in our country is above twofold
higher than the mean mortality in the European Union, possi-
bly caused by a delayed diagnosis due to the lack of a screen-
ing program. In the Northern-Central Regions of Romania,
which are very developed and westernized areas, with a spe-
cific diet rich in fats, red and processed spicy meat, mortality
Fig. 4 Geographical distribution
of hospitalized mortality caused
by CRC in the main Romanian
provinces
Number of hospitalized CRC deaths/100,000 Males Females
inhabitants
31 29.8 19.1
22 24.2 13.5
16.6 16.3 10.5
13.4 18.6 11.1
12.8 12.5 7.5
3 9.2 5.2
4.8 7.2 3.4
4 7.6 3.7
in men is up to 29.8/100,000 and in women up to 19.1/
100,000, which is by far much higher than the EU averages.
However, there are regions like South-West provinces
(Oltenia and Banat), more rural, with lacto-vegetarian and cereal
preferences as plain specific regions, where mortality is very
low, with 3.4–5.2/100,000 in women and 7.2–9.2/100,000 in
men, sensible below mortality rates in the European Union.
For Bucharest and Ilfov County, there is an atypical situa-
tion, with a significantly lower prevalence of hospitalized CRC
and a very low mortality (5.2/100,000 in women and 9.2/
100,000 in men, practically similar with the general rates in
the EU population). The possible reasons are as follows: a more
educated population in comparison with the rural zones, cov-
ered by many medical centers including endoscopy, opportu-
nistic screening programs, a facile access to a gastroenterolo-
gist, with an easier diagnostic and treatment of colonic polyps.
We should also take into account the heterogeneity of the pop-
ulation that migrates here from all the country. All this factors
were shown to influence dramatically the risk of CRC [24–28].
The majority of colorectal cancers occur in people older
than 50. The median age at diagnosis for colon cancer is 68
in men and 72 in women; for rectal cancer, it is 63 years of age
in both men and women [29, 30]. According to our study, we
found that the mean age of hospitalized CRC was 68.49, near-
ly equal for both sexes and for rectal cancer in particular was
67.9 in our population.

Fig. 5 Hospitalized deaths by
CRC/100,000 inhabitants in the
main Romanian regions
CRISANA
31/100.000
29.8 (M); 19.1 (F)
BANAT
4/100.000
7.6 (M); 3.7 (F)
4.8/100.000
7.2 (M); 3.4 (F)
OLTENIA
We found a high proportion of patients with distal locali-
zation (rectum and sigmoid) of above 44%, and rectal site was
the most fatal. Despite of this Romanian trend, in many
Western countries, a transition to more proximal tumor site
was observed [31–35] due to several factors like the use of
sigmoidoscopy (and associated polypectomy) as a screening
tool, changes in diet (more important reducing the consume of
red meat), and maybe the use of some medications such as
aspirin in principal for cardiovascular prevention, and the hor-
mone replacement therapy in women.
We had the highest discharge rate for colorectal cancer in
Europe for the last 3 years since in Romania, there were
316.07 CRC in-patients/100,000 inhabitants in 2016. In the
same year, in Croatia, where there were 276 discharges per
100,000 inhabitants in 2016, and in Hungary (2015 data),
Austria, Lithuania, Latvia, and Germany, this rate was of ap-
proximately 200 discharges per 100,000 inhabitants. The low-
est discharge rates for colorectal cancer were reported for the
UK and Ireland (68 and 59 discharges per 100,000 inhabi-
tants, respectively) [22]. The average length of stay for colo-
rectal cancer ranged from 6.1 days in Cyprus to 13.6 days in
Luxembourg. In Romania, these indicators varied from
8.86 days in 2016 to 9.7 days in 2018, showing a more severe
stage of the disease by the time.
Conclusion
Despite decreases in colorectal mortality rates due to oppor-
tunistic screening, early diagnosis, or better treatment, as
J Gastrointest Canc
NORTH
MOLDAVIA
16.6/100.000
16.3 (M); 10.5 (F)
CENTER
22/100.000
24.2 (M); 13.5 (F)
SOUTH
MOLDAVIA
13.4/100.000
12.8/100.000
18.6 (M); 11.1 (F)
12.5 (M); 7.5 (F)
3/100.000
9.2 (M); 5.2 (F)
MUNTENIA
BUCHAREST,
ILFOV
well as to the improvements in dietary and lifestyle observed
in most European countries over the last decade, in Romania,
we note a high colorectal mortality rate, especially in the
Northern and Central Regions. Our rates are nearly double
in comparison with the general EU region rates. DRG data
analysis together with results of other specific studies should
document tailored CRC Romanian programs in the near fu-
ture, in order to better respond to our population needs for
prevention, early detection, appropriate treatment, and dis-
ease management.
Author Contributions Mirela Ionescu contributed to the conceptualiza-
tion, literature search, and writing of the article, and performed the inter-
pretation and analysis of the data. Ionut Cristian Cucu performed the
statistical analysis, data interpretation, and drafting of the manuscript.
Dana Maftei performed the literature search and drafting of the manu-
script. Adriana Grivei helped in the literature search and revised the man-
uscript. Cristian Tieranu helped in the data interpretation and revised the
manuscript. Andrei Olteanu performed the literature search and drafting
of the manuscript. Tudor Arbanas assisted in the interpretation of study
findings and revised the manuscript. Valentin Calu oversaw the study,
including the study design, and revised the manuscript. Simona Musat
participated in the study design, database query, and electronic data link-
age. Constanta Mihaescu-Pintia contributed to the conceptualization, data
analysis, and manuscript revision.
Compliance with Ethical Standards
Conflict of Interest The authors declare that they no conflict of interest.
Disclaimer None
Ethics Approval The present study has received approval from the local
ethics committee of the National School of Public Health, Management
J Gastrointest Canc
and Professional Development, Bucharest, with registration number 2625
of 18 June 2019.
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