3. UREDNI[TVO
Glavni i odgovorni urednik
Prim. dr Avdo ]erani}
Pomo}nici glavnog i odgovornog urednika
dr D`enana Detanac
dr D`email Detanac
Tehni~ki urednik
dr D`email Detanac
Nau~ni savet Me|unarodni nau~ni savet
Prof. dr Aleksandar Karamarkovi} (Srbija) Prof. dr Ivan Damjanov (SAD)
Prof. dr Branka Nikoli} (Srbija) Prof. dr Milan R. Kne`evi} ([panija)
Prof. dr Radivoj Koci} (Srbija) Prof. dr Ino Hused`inovi} (Hrvatska)
Prof. dr Ivan Dimitrijevi} (Srbija) Prof. dr Anastasika Poposka (Makedonija)
Prof. dr Stojan Sekuli} (Srbija) Prof. dr Sergio Zylbersztejn (Brazil)
Prof. dr Marina Savin (Srbija) Prof. dr Beniamino Palmieri (Italija)
Prof. dr Milica Berisavac (Srbija) Prof. dr Sahib H. Muminagi} (Bosna i Hercegovina)
Prof. dr Milan Kne`evi} (Srbija) Prof. dr Osman Sinanovi} (Bosna i Hercegovina)
Prof. dr Milo{ Jovanovi} (Srbija) Prof. dr Selma Uzunovi}-Kamberovi} (Bosna i Hercegovina)
Prof. dr Sne`ana Jan~i} (Srbija) Prof. dr Agima Ljaljevi} (Crna Gora)
Prof. dr ^edomir S. Vu~eti} (Srbija) Prof. dr Suada Helji} (Bosna i Hercegovina)
Prof. dr Slobodan Obradovi} (Srbija) Prof. dr Milica Martinovi} (Crna Gora)
Prof. dr Slobodan Grebeldinger (Srbija) Prof. dr Nermina Had`igrahi} (Bosna i Hercegovina)
Prof. dr Slobodan M. Jankovi} (Srbija) Prof. dr Miralem Musi} (Bosna i Hercegovina)
Prof. dr @ivan Maksimovi} (Srbija) Prof. dr Spase Jovkovski (Makedonija)
Prof. dr Zlata Janji} (Srbija) Prof. dr Evangelos J. Giamarellos-Bourboulis (Gr~ka)
Prof. dr Svetislav Milenkovi} (Srbija) Prof. dr Paolo Pelosi (Italija)
Prof. dr Radmilo Jankovi} (Srbija) Prof. dr Zsolt Molnar (Ma|arska)
Lektor za engleski jezik
Selma Mehovi}
Dizajn
Prim. dr Avdo ]erani}
Izdava~
Udru`enje lekara Sanamed, Novi Pazar
^ASOPIS IZLAZI TRI PUTA GODI[NJE
Adresa uredni{tva
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ISSN-1452-662X

4. EDITORIAL BOARD
Editor-in-chief
Prim. dr Avdo ]erani}
Associate Editors
dr D`enana Detanac
dr D`email Detanac
Technical Editor
dr D`email Detanac
Scientific council International scientific council
Prof. dr Aleksandar Karamarkovi} (Serbia) Prof. dr Ivan Damjanov (USA)
Prof. dr Branka Nikoli} (Serbia) Prof. dr Milan R. Kne`evi} (Spain)
Prof. dr Radivoj Koci} (Serbia) Prof. dr Ino Hused`inovi} (Croatia)
Prof. dr Ivan Dimitrijevi} (Serbia) Prof. dr Anastasika Poposka (R. Macedonia)
Prof. dr Stojan Sekuli} (Serbia) Prof. dr Sergio Zylbersztejn (Brazil)
Prof. dr Marina Savin (Serbia) Prof. dr Beniamino Palmieri (Italy)
Prof. dr Milica Berisavac (Serbia) Prof. dr Sahib H. Muminagi} (Bosnia and Herzegovina)
Prof. dr Milan Kne`evi} (Serbia) Prof. dr Osman Sinanovi} (Bosnia and Herzegovina)
Prof. dr Milo{ Jovanovi} (Serbia) Prof.drSelmaUzunovi}-Kamberovi}(BosniaandHerzegovina)
Prof. dr Sne`ana Jan~i} (Serbia) Prof. dr Agima Ljaljevi} (Montenegro)
Prof. dr ^edomir S. Vu~eti} (Serbia) Prof. dr Suada Helji} (Bosnia and Herzegovina)
Prof. dr Slobodan Obradovi} (Serbia) Prof. dr Milica Martinovi} (Montenegro)
Prof. dr Slobodan Grebeldinger (Serbia) Prof. dr Nermina Had`igrahi} (Bosnia and Herzegovina)
Prof. dr Slobodan M. Jankovi} (Serbia) Prof. dr Miralem Musi} (Bosnia and Herzegovina)
Prof. dr @ivan Maksimovi} (Serbia) Prof. dr Spase Jovkovski (R. Macedonia)
Prof. dr Zlata Janji} (Serbia) Prof. dr Evangelos J. Giamarellos-Bourboulis (Greece)
Prof. dr Svetislav Milenkovi} (Serbia) Prof. dr Paolo Pelosi (Italy)
Prof. dr Radmilo Jankovi} (Serbia) Prof. dr Zsolt Molnar (Hungary)
English language editor
Selma Mehovi}
Design
Prim. dr Avdo ]erani}
Publisher
Association of medical doctors “Sanamed”, Novi Pazar
ISSUED THREE TIMES A YEAR
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ISSN-1452-662X

5. CONTENTS
• AWORD FROM THE EDITOR ................................................................................................................. 98
• ORIGINAL ARTICLE
• THE IMPORTANCE OF ORAL HEALTH BEHAVIOUR OF CHILDREN
FOR THEIR ORALHEALTH..................................................................................................................... 101
Andjelic Ivana,
1
Matijevic Snezana,
2
Andjelic Jasminka
1
1
University of Montenegro, Faculty of Medicine Podgorica, Montenegro
2
Primary Heath Care Center Tivat, Montenegro
• SKIN TOXICITY OF TARGETED THERAPY: VEMURAFENIB,
FIRST EXPERIENCES FROM MONTENEGRO...................................................................................... 109
Todorovic Vladimir,
1
Martinovic Danilo
1
1
Oncology and Radiotherapy, Clinic Clinical Center of Montenegro, Podgorica, Montenegro
• CASE REPORT
• TREATMENT OF URACHALADENOCARCINOMA— CASE REPORT ............................................. 115
Mekic Abazovic Alma,
1
Sulejmanovic Samra,
1
Sehic-Kozica Erna,
1
Mehic Mirza,
2
Beculic Hakija,
3
Jakovljevic Branislava
4
1
Department of Oncology and Radiotherapy, Cantonal Hospital Zenica, Bosnia and Herzegovina
2
Department of Gynecology and Obstetrics, Cantonal Hospital Zenica, Bosnia and Herzegovina
3
Department of Neurosurgery, Cantonal Hospital Zenica, Bosnia and Herzegovina
4
Health Institution S. Tetik, Oncological Hospital Banjaluka, Bosnia and Herzegovina
• SEVERE COMMUNITY-ACQUIRED PNEUMONIA CAUSED BY MYCOPLASMA
PNEUMONIAE IN YOUNG FEMALE PATIENT..................................................................................... 119
Milacic Nena,
1
Djurovic Marija,
2
Hasanbegovic Mirha,
3
Milacic Bojan,
4
Stevanovic Dragana
5
1
Department of Internal Medicine, Clinical Centre od Montenegro, Podgorica, Montenegro
2
Department of Gastroenterology, Clinical Centre of Montenegro, Podgorica, Montenegro
3
Department of Internal Medicine, General Hospital Pljevlja, Montenegro
4
Department of Thoracic Surgery, Clinical Center of Montenegro, Podgorica, Montenegro
5
Department of Radiology, General Hospital Bar, Montenegro
• PEANUT AS ACAUSE OF TORSION MECKEL’S DIVERTICULUM................................................... 123
Sekulic Stojan,
1
Sekulic-Frkovic Aleksandra,
2
Milankov Andrijana
3
1
Surgical Clinic,C.H.C, Pristina-Gracanica, University of Pristina, Faculty of Medicine, Kosovska Mitrovica, Gracanica, Serbia
2
Pediatric Clinic, C.H.C, Pristina-Gracanica, University of Pristina, Faculty of Medicine, Kosovska Mitrovica, Gracanica, Serbia
3
Endocrinology Clinic, Clinical Centre of Vojvodine, Faculty of medicine Novi Sad, Serbia
• REVIEW PAPER
MicroRNAs AS BIOMARKERS FOR ACUTE MYOCARDIAL INFARCTION
—SMALLMOLECULES WITH AHUGE POTENTIAL.......................................................................... 127
Miskowiec Dawid,
1
Kasprzak Jaroslaw D.
1
1
Department of Cardiology, Medical University of Lodz, Poland
Broj 10(2)/2015

6. • CURRENT CONCEPTS IN THERAPYOF UVEALMELANOMA......................................................... 137
Detanac A. Dzenana,
1
Jancic Snezana,
2
Rakocevic Milena,
2
Ceranic Merima
3
1
Department of Ophthalmology, General hospital Novi Pazar, Novi Pazar, Serbia
2
Institute of Pathology, Faculty of Medicine, University of Kragujevac, Kragujevac, Serbia
3
School of Medicine, University of Belgrade, Belgrade, Serbia
• CORRECTIONS......................................................................................................................................... 143
• INSTRUCTIONS FOR AUTHORS............................................................................................................ 151

7. SADR@AJ
• RE^ UREDNIKA....................................................................................................................................... 97
• ORIGINALNI NAU^NI RAD
• ZNA^AJ PONA[ANJADECE ZASTANJE ORALNOG ZDRAVLJA..................................................... 101
An|eli} Ivana,
1
Matijevi} Sne`ana,
2
An|eli} Jasminka
1
1
University of Montenegro, Faculty of Medicine Podgorica, Montenegro
2
Primary Heath Care Center Tivat, Montenegro
• DERMATOLO[KA TOKSI^NOST CILJANE TERAPIJE: VEMURAFENIB,
PRVAISKUSTVAIZ CRNE GORE............................................................................................................ 109
Todorovi} Vladimir,
1
Martinovi} Danilo
1
1
Klinika za onkologiju i radioterapiju Klini~kog centra Crne Gore, Podgorica, Crna Gora
• PRIKAZ SLU^AJA
• TRETMAN URAHALNOG KARCINOMA— PRIKAZ SLU^AJA ........................................................ 115
Meki} Abazovi} Alma,
1
Sulejmanovi} Samra,
1
[ehi}-Kozica Erna,
1
Mehi} Mirza,
2
Be~uli} Hakija,
3
Jakovljevi} Branislava
4
1
Slu`ba za onkologiju i radioterapiju, Kantonalna bolnica Zenica, Bosna i Hercegovina
2
Slu`ba za ginekologiju i porodiljstvo, Kantonalna bolnica Zenica, Bosna i Hercegovina
3
Slu`ba za neurohirurgiju, Kantonalna bolnica Zenica, Bosna i Hercegovina
4
Zdravstvena ustanova S Tetik, Onkolo{ka bolnica Banjaluka
• TE[KA VANBOLNI^KI STE^ENA PNEUMONIJA UZROKOVANA MIKOPLAZMOM
PNEUMONIJE U MLADE PACIJENTKINJE ........................................................................................... 119
Mila~i} Nena,
1
urovi} Marija,
2
Hasanbegovi} Mirha,
3
Mila~i} Bojan,
4
Stevanovi} Dragana
5
1
Interna klinika, Odjeljenje pulmologije, Klini~ki centar Crne Gore, Podgorica, Crna Gora
2
Interna klinika, Odjeljenje gastroenterologije, Klini~ki centar Crne Gore, Podgorica, Crna Gora
3
Odjeljenje interne medicine,, Op{ta bolnica Pljevlja, Crna Gora
4
Hirur{ka klinika, Odjeljenje za grudnu hirurgiju, Klini~ki centar Crne Gore, Podgorica, Crna Gora
5
Odjeljenje radiologije, Op{ta bolnica Bar, Crna Gora
• KIKIRIKI KAO UZROK UVRTANJAMECKEL-OVOG DIVERTIKULUMA........................................ 123
Sekuli} Stojan,
1
Sekuli}-Frkovi} Aleksandra,
2
Milankov Andrijana
3
1
Hirur{ka klinika KBC Pri{tina-Gra~anica, Univerzitet u Pri{tini, Medicinski fakultet Kosovska Mitrovica, Gra~anica, Srbija
2
Pedijatrijska klinika, KBC Pri{tina-Gra~anica, Univerzitet u Pri{tini, Medicinski fakultet Kosovska Mitrovica, Gra~anica, Srbija
3
Klinika za endokrinologiju, Klini~ki centar Vojvodine, Medicinski fakultet Novi Sad, Srbija
• REVIJALNI RAD
• MicroRNA KAO BIOMARKERI AKUTNOG INFARKTA MIOKARDA
— MALI MOLEKULI SAVELIKIM POTENCIJALOM .......................................................................... 127
Miskowiec Dawid,
1
Kasprzak Jaroslaw D.
1
1
Department of Cardiology, Medical University of Lodz, Poland
Broj 10(2)/2015

8. • SAVREMENATERAPIJAUVEALNOG MELANOMA........................................................................... 137
Detanac A. D`enana,
1
Jan~i} Sne`ana,
2
Rako~evi} Milena,
2
]erani} Merima
3
1
Odeljenje za o~ne bolesti, Op{ta bolnica Novi Pazar, Novi Pazar, Srbija
2
Institut za Patologiju, Medicinski fakultet, Univerzitet u Kragujevcu, Kragujevac, Srbija
3
Medicinski fakultet, Univerzitet u Beogradu, Beograd, Srbija
• CORRECTIONS......................................................................................................................................... 143
• UPUTSTVO AUTORIMA.......................................................................................................................... 147

9. Rije~ urednika
Po{tovani,
Ovaj broj ~asopisa obradovat }e sve one koji sara|uju sa
nama, one koji pi{u i objavljuju u njemu, na{e uredni{tvo, a po-
sebno o~ekujem da }e obradovati one koji se dvoume gde da ob-
javesvojrad,kadaimsaop{tim dajeMinistarstvo Prosvete,nau-
ke i tehnolo{kog razvoja Srbije, na osnovu kvaliteta koji smo po-
stigli, na{em „SANAMED“-u dodijelilo kategoriju M52, ~ime je
uvr{tenu~asopiseodnacionalnogzna~aja.Samimtim,radobja-
vljen u ~asopisu ove kategorije ima ve}u vrijednost i presti`. [ta
ovo zna~i, znaju oni koji pi{u i objavljuju svoje radove.
Ukoliko nastavimo da radimo ovim tempom, za o~ekivat je
da se smjestimo u sam vrh spiska presti`nih ~asopisa.
U nauci i stvarala{tvu tradicionalno postoji stalna utakmi-
ca u kojoj pobje|uje samo onaj tim koji stalno trenira. Ukoliko se
malozastane,neminovnisupenalikojisenemogulakonadomje-
stiti novim poenima. Nije dovoljno da imate jak {ut da bi ste po-
stigli gol, ve} da ste dobar tehni~ar, da ste uigrani, i uvijek na gol
liniji za zgoditak. Takav trening uvijek donosi rezultate.
Na{e uredni{tvo se opredjelilo da nastavi sa ozbiljnim ra-
dom, i zna da vrijednuje podr{ku svojih saradnika koji imaju ve-
liko iskustvo u svojoj oblasti djelovanja i usmjeravaju nas ka za-
jedni~kom cilju i zato im se posebno zahvaljujemo.
Po{tovani ~itaoci, odavno ste primjetili da je na{ ~asopis
me|unarodnog karaktera i da smo otvoreni za sve stvaraoce {i-
rom svijeta.
Analizom dosada{njeg rada primjetio sam da uprkos svim
problemima koji prate ovakav rad, na prvo mjesto kao problem,
na`alost, isti~e se novac. Sa te strane mi smo relaksirani jer radi-
mo volonterski. Po logici stvari, inovacije u tehnici, otkri}a u na-
uci, obrazovanje u dru{tvu, skop~ani su sa potrebom za novcem
kao sto`erom kako bi se dobili neki rezultati. Postoji paradoks
poznat u svijetu, da su samo geniji stvarali primarno bez motiva-
cijezanovcem,kakobiunaprijedilisvjetskupopulaciju.Postojei
oni koji su neretko bili i gladni, u nema{tini, ali su ostavili svoj
zapis i otkri}a za pokoljenja i oni nikada ne}e umrijeti. Mi jesmo
veoma mali da bi se uporedili sa tim imenima, {to mi ni na kraj
pameti nije namjera, ali su sa nama velika imena iz oblasti medi-
cine, koji, onim {to ~ine su postali dio tog svijeta. Njihov entuzi-
jazam ih je nesvjesno svrstao u one ljude, bi}a bliskim Bogu, {to
}e svojim djelima dati doprinos nauci i boljem, zdravijem i ~isti-
jem `ivotu. Bog }e priznati samo te ~iste du{e koje ne mare za po-
hlepu i sebe su stavile u slu`bu ~ovjeka zarad o~uvanja zdravlja
kroz nauku, preno{enje znanja mla|im generacijama i podsticaj
drugih da stvaraju. Ubje|en sam u to, i nema razloga da sum-
njam ako se podsjetim prvih pet poruka, ajeta, upu}enih od Boga
Bo`jem Poslaniku da prenese ljudima:
1. ^itaj,u ime Gospodara tvoga koji stvara,
2. stvara ~ovjeka od ugru{ka!
3. ^itaj, plemenit je Gospodar tvoj,
4. koji pou~ava peru,
5. koji ~ovjeka pou~ava onome {to ne zna.
(SURA XCVI,Al’-Alaq,Mekka-19 ajeta, Kur’an)
Ovo je svojevrsna potvrda da nema ni{ta svetije i ~istije od
stvaranja i preno{enja znanja za dobrobit onih koji dolaze.
Bez preterane religioznosti i nimalo sujevjerja, ~ovjek ne-
svjesno sebe svrstava u bla`ena Bo`ja bi}a, kojima kao i svakom
`ivom bi}u do|e kraj na ovom svijetu i kad fizi~ki pre|u u materi-
ju od koje su nastali, njihov duh i ime ostaju da `ive srazmjerno
onome {to su stvarali.
Izvinite na ovome {to me je malo odvojilo od teme, ali mi je
u~vrstilo duh i duhovnost ~istote ljekara, ~ovjeka koji nije podlegao
novcu i kao dar od Boga bio je i ostao naklonjen obi~nom ~ovjeku.
S po{tovanjem,
Prim. dr Avdo ]erani}

10. A word from the editor
Respected,
This issue will be a pleasant surprise for our editorial, as-
sociates, and I think, especialy for those who hesitate to publish
their article, when I announce that Ministry of Education, based
onthequalitywehaveachieved,categorizedSANAMEDasM52,
and by that included our Journal among journals of national im-
portance. Therefore, articles published in Sanamed Journal will
have a higher value and prestige from now on.
If we continue at this pace, it is expected that we will reach
the top of the list of prestige medical journals.
In science and creativity there is traditionally a constant
game where the winner is only the one who trains all the time. If
you faltet, penalties which cannot be easily replaced with new
points, are inevitable. It is not enough to have strong shot in or-
der to achieve the goal. It is important to be a good technician
too, to bewellcoordinated, and alwayson the line for score.That
kind of training always brings good results.
Our editorial staff chose to continue with serious work and
we know the value of the support from our co-workers, experts in
their particular fields, who direct us towards the common goal
and to whom we are especially greatful.
Dear readers, long ago you have noticed that our journal
has international character and that we are open to all authors
worldwide. By analysis of the work so far, I have noticed that de-
spite all the problems that this kind of work follows, the problem
number one, unfortunately, is money. In this respect, we are rela-
xed, because we work voluntarily. Technical innovations, scienti-
fic discoveries, social education, are impossible without finan-
cial support. There is a paradox that only geniuses created pri-
marily without financial motivation in order to improve world
population. There are those who often were hungry, in poverty,
but they left their mark and discoveries and they will never be
dead. We are very small to be compared with such names, which
by far was not my intention, but we have great names in the field
of medicine, who, with what they do, became part of that world.
Their enthusiasm, by giving their part as contribution to science
and better, healthier and purer life, classified them within those
people, creatures close to God. God will admit those pure souls
who do not care for greed and who dedicated themselves to the
service of man and preservation of health through science, trans-
mitting knowledge to younger generations and encouraging oth-
ers to create.
I am convinced in that, without a shred of doubt, when I re-
member the first five messages God sent to the people via His
prophet:
1. Read, in the name of your Lord who creates,
2. Creates man from a clot!
3. Read, thy Lord is noble,
4. The One who taught by pen,
5. Who teaches a man what he did not know.
(SURAH XCVI, Al’-Alaq, Mekka-19 verses, Quran)
This is a confirmation that there is nothing more sacred
and pure than the learning and transmitting knowledge for the
sake of future generations.
I apologize from moving away from the topic, but this has
strengthen the spirit of the doctors who did not succumb to the
money and, as gifted by God, were and are sympathetic to the
common man.
With respect,
Prim. dr Avdo Ceranic

13. THE IMPORTANCE OF ORALHEALTH BEHAVIOUR
OF CHILDREN FOR THEIR ORALHEALTH
Andjelic Ivana,
1
Matijevic Snezana,
2
Andjelic Jasminka
1
1
University of Montenegro, Faculty of Medicine Podgorica, Montenegro
2
Primary Heath Care Center Tivat, Montenegro
Primljen/Received 24. 05. 2015. god. Prihva}en/Accepted 24. 06. 2015. god.
Abstract: Introduction. Caries or tooth decay re-
gardless of the good knowledge of the nature of the dis-
ease and the possibility of its effective prevention is
still the most widespread disease in our population. It
also very often threatens the functions of organs and
even the entire organism. Health culture is an integral
part of general culture and health education plays an
important role in maintaining health of individuals.
Aim. The main objective of this study is to determine
the influence of oral health behaviour of schoolchil-
dren aged 12 to 14 on their oral health. The schoolchil-
dren attended the seventh and eight grade at Drago Mi-
lovic Elementary School in Tivat. Method. The survey
was conducted during the period from the end of Janu-
ary to April 2015 at Drago Milovic Elementary School
in Tivat. It comprised all seventh and eight-graders that
were at school those days. The survey instrument was a
questionnaire specially designed for this study and it
consisted of 36 closed-ended questions. Clinical exam-
ination of oral health in children was used as an additi-
onal research instrument. Assessment of oral health
was carried out under natural light with dental mirror
and probe according to WHO recommendations. The
parameter used to assess the state of oral health was
DMFT index — the number of carious, extracted and
filled teeth. In addition, the assessment of oral hygie-
ne was conducted using soft debris index according to
Green-Vermillion which determines absence or pres-
ence, quantity and distribution of dental plaque and
other soft deposits. Results. The majority of students
stated that they lack knowledge regarding the effecti-
veness of fluoride toothpaste (69.4%). It was found
that the lowest incidence of caries occurred among
those students who think that teeth should be brushed
after every meal, and the highest incidence of this di-
agnosis occurred in respondents who think that teeth
should be brushed once a day. Half of the surveyed
students believe that teeth should be brushed most of-
ten after every meal and more than half of excellent
students (55.6%) believe so. DMFT index for study
population was 1.87 while Green-Vermillion soft de-
bris score of oral hygiene was 2 in largest number of
students (49.5%). Conclusion. Looking at the results
it can be concluded that dental care in this area does
not significantly affect the improvement of oral health
in children. Therefore a greater attention should be
paid to continuous education programmes and gain-
ing knowledge about oral health and hygiene of the
mouth and teeth.
Key words: students, oral health, health education,
DMFT index, Green-Vermillion index.
INTRODUCTION
Caries or tooth decay regardless of the good
knowledge of the nature of the disease and the possi-
bility of its effective prevention is still the most wide-
spread disease in our population. It also very often
threatens the functions of organs and even the entire
organism. Even in ancient times it was known that
dental foci may be the cause of subsequent diseases
and thus for the treatment of arthritis the tooth extrac-
tion was advised (1). Different diseases such as infec-
tive endocarditis, an infection of head and neck, respi-
ratory infections, diseases of gastrointestinal tract,
skin diseases, bone disease, premature birth, can be
caused by microorganisms from odontogenic foci (2).
Health culture is an integral part of general culture
and health education plays an important role in main-
taining health of individuals. Special attention should
be paid to education of parents and children and im-
plementation of prevention programmes in order to
ensure not only adequate oral health of children, but
also a better quality of life (3).
DOI:10.5937/sanamed1502101A
UDK: 616.31-053.5(497.16)
2015; 10(2): 101–107 ID: 216795404
ISSN-1452-662X Original paper

14. ORAL HEATH BEHAVIOUR AS
DETERMINANT OF ORAL HEALTH
Parents have very important role in maintaining
oral health in children because children attitude forma-
tion is based on the opinions and actions of their par-
ents in preschool age. Studies have shown that the con-
trol of oral hygiene in children by their parents as well
as good oral hygiene habits of parents have a statisti-
cally significant impact on the dental health of a child
(4). However, even today it is not rare that among very
young children tooth decay occurs due to unhealthy di-
et and lack of oral hygiene (5). Children should be edu-
cated on the consequences of their risky behavior in or-
der to accept responsibility for their own health. Nu-
merous studies conducted so far confirmed the possibi-
lity of high preventability of oral diseases and therefo-
re it is very important to start with prevention and edu-
cation programmes at preschool age so that children
can get information about caries and periodontal disea-
ses as well as proper tooth brushing techniques and use
of assistive devices for oral hygiene (6). The main goal
of the implementation of health education programmes
is to reduce the incidence primarily of dental caries and
periodontal diseases but also of other diseases of the
oral cavity (7).
Apart from education, regular preventive dental
check-ups can also prevent oral diseases. Unfortuna-
tely, this fact is not fully appreciated by the parents of
a large number of school-age children (8). The study
conducted in Norway found that family characteris-
tics such as marital status and education level of par-
ents, ethnicity, parents lifestyle as well as the mot-
her’s diet during pregnancy are associated with the
development of caries in preschool children (9). Cor-
relation between dental health and socio-economic
status is higher at that age than in older children. A
higher prevalence of dental caries has been demon-
strated in children in families with low income, lower
education level of mothers and those from large fami-
lies (10). Also, one of the studies has shown that par-
ents with proper oral hygiene habits paid more atten-
tion to their children’s tooth brushing, prevention of
caries as well as diet rich in sugar compared to parents
with bad oral hygiene (11). A study conducted in Iran
showed a statistically significant difference between
plaque index of children and education level of their
mothers as well as between the toothbrushing frequ-
ency in parents and their children (12).
RESEARCH GOAL
The main objective of this study is to determine
the influence of oral health behaviour of school chil-
dren aged 12 to 14 on their oral health. The school-
children attended the seventh and eighth grade at Dra-
go Milovic Primary School in Tivat, Montenegro.
The specific objective is to identify habits, attitudes,
and behaviour of school children as well as the state
of their oral health that determines the occurrence of
oral diseases.
METHOD
The survey was conducted during the period from
the end of January to April 2015 at Drago Milovic Ele-
mentary School in Tivat. The survey comprised all sev-
enth and eighth-graders that were at school those day.
All children have voluntarily agreed to participate in
the study.
Coverage rate was about 95%, since total number
of students in above mentioned grades in this school is
432 which means that 20 students were absent on days
the survey was conducted.
The survey instrument was a questionnaire speci-
ally designed for this study and it consisted of 36 clo-
sed-ended questions. It had three parts which related to
children’s knowledge about oral health, behaviour of
children in relation to oral health and their attitudes to-
wards oral health. Clinical examination of oral health
in children was used as an additional research instru-
ment. Assessment of oral health was carried out under
natural light with dental mirror and probe according
to WHO recommendations. The parameter used to as-
sess the state of oral health was DMFT index — the
number of carious, extracted and filled teeth. In addi-
tion, assessment of oral hygiene was conducted using
soft debris index according to Green-Vermillion
which determines absence or presence, quantity and
distribution of dental plaque and other soft deposits.
Lesions with clearly formed cavity on the surface of
the tooth were marked as dental caries. Changes in
transparency and initial enamel demineralization
with intact surfaces which did not lead to discontinua-
tion of dental tissue were not registered. Clinical exa-
mination at school was done by the dentist trained to
use abovementioned indices. During the examination
children were advised how to maintain proper oral hy-
giene and that was demonstrated on a model as well.
They were also given advice on proper nutrition and
fluoride prophylaxis.
The survey data were presented using descriptive
statistics.
RESULTS
The study included a total of 412 seventh and
eighth-graders.
102 Andjelic Ivana, Matijevic Snezana, Andjelic Jasminka

15. Of all respondents 52.3% were boys (Figure 1).
The majority of pupils stated that they lack knowl-
edge regarding the effectiveness of fluoride toothpaste
(69.4%) while 5.4% of them believe that fluoride toot-
hpaste does not affect dental health. Almost one in four
respondents (24.5%) said that fluoride toothpaste is ef-
fective in maintaining oral health (Figure 2).
Slightly more than half of the respondents (53.2%)
change their toothbrush every six months, 10.7% of
them do so only once a year while more than a third of
respondents use a toothbrush while it lasts (Figure 3).
One-way analysis of variance (ANOVA) was used
to study the effects of attitudes of how often one should
brush the teeth on the values of diagnostic data regard-
ing occurrence of caries. Respondents were divided in-
to five groups based on their attitude to the frequency
of tooth brushing: at least once a day, twice a day, and
not every day, after every meal and not knowing how
often teeth should be brushed. It was found that the lo-
west incidence of caries occurred in group four i.e. tho-
se who believe that teeth should be brushed after every
meal. The highest incidence of caries occurred in gro-
THE IMPORTANCE OF ORAL HEALTH BEHAVIOUR OF CHILDREN FOR THEIR ORAL HEALTH 103
Figure 1. Distribution of respondents by gender
Figure 2. Knowledge about effectiveness
of fluoride toothpaste
ACHIEVEMENT
AT THE END
OF THE
PREVIOUS
SCHOOL YEAR
TOOTHBRUSHING FREQUENCY
At least
once a day
At least
twice a day
It is not
necessary to
brush your
teeth every
day
After each
meal
I don’t
know
Total
Unsatisfactory 0 3 1 2 0 6
Took makeup exam 2 3 0 1 2 8
Satisfactory 2 4 0 1 1 8
Good 8 28 0 29 3 68
Very good 11 51 2 69 2 135
Excellent 13 69 0 104 1 187
Total 36 158 3 206 9 412
X squared test = 65,579; p < 0,001
Table 2. Corelation between toothbrushing frequency and educational achievement
at the end of the previous school year
ATTITUD TOWARDS TOOTH BRUSHING MD SE Sig.
At least once a day 1,27 0,33 0,002
At least twice a day 1,31 0,39 0,001
It is not necessary to brush your teeth every day –1,27 –2,21 0,002
After each meal –1,36 –0,39 0,001
I do not know –1,44 –4,80 0,219
ANOVA: F = 6,530; p < 0,001
Table 1. The impact of students’attitude about toothbrushing frequency on occurrence of caries
Figure 3. Frequency of changing toothbrushes

16. up one i.e. those who think the teeth should be brushed
once a day (Table 1).
Data analysis showed that there was a statistically
significant difference between attitudes of children to-
wards frequency of tooth brushing and their educatio-
nal achievement. Half of the surveyed children think
that teeth should be brushed after every meal and
among excellent students more than half of them
(55.6%) think so, slightly less very good ones (51%),
followed by those who are good (42.6%) while it is less
present in children with bad grades (Table 2).
DMFT index for study population was 1.87 and the
most common identified change was caries (81.65%),
most frequently occurred in two teeth, then three, follo-
wed by one while there were students with eight or ten
carious teeth (Table 3). Filled teeth were also frequently
present (77.9%) while number of students with extrac-
ted teeth was the lowest (28.2%) (Table 3).
It was found that only one student had no deposits
(Figure 4) using Green-Vermillion soft debris index.
The largest number of students had debris score 2
(49.5%), followed by score 1 (25.7%) and score 3
(24.7%).
DISCUSSION
This study aims to investigate risk factors for oc-
currence of caries that are caused by certain health hab-
its, attitudes and behaviour and as such they can be
highly preventable with adequate health education ac-
tivities. Regular and proper oral hygiene, the use of flu-
oride and regular dental visits are of particular impor-
tance for maintaining good oral health.
The research has shown that nearly half of respon-
dents (45.9%) know that for a thorough cleaning of te-
eth besides toothbrush and toothpaste it is necessary to
use dental floss while more than a third of students
(36.2%) apply that in practice. In a study conducted in
Pancevo, 16.2% of children (4), and in Albania 21% of
children (13) stated that they regularly use dental floss.
The analysis of respondents responses showed that 182
students (44.2%) do not use anything else besides toot-
hbrush and toothpaste to maintain oral hygiene which
agrees with result of research conducted in a group of
teenage boys in Banja Luka (14).
Apart from regular and proper oral hygiene, every
prevention programme in dentistry must have for its
basis prevention of dental caries and application of flu-
oride both endogenous and exogenous (15). Data on
whether the students are informed about fluoride pro-
phylaxis showed that majority of children (87.4%) do
not know whether the toothpaste they used for brush-
104 Andjelic Ivana, Matijevic Snezana, Andjelic Jasminka
Table 3. Changes in teeth diagnosed in respondents
Number of Teeth
Type of change
CARIES EXTRACTION FILLING
No changes in teeth 80 296 91
Changes in one tooth 61 52 41
Changes in two teeth 96 41 63
Changes in three teeth 81 17 78
Changes in four teeth 47 6 76
Changes in five teeth 23 0 34
Changes in six teeth 10 0 19
Changes in seven teeth 9 0 3
Changes in eight teeth 3 0 5
Changes in nine teeth 0 0 2
Changes in ten teeth 1 0 0
Changes in eleven teeth 0 0 0
Changes in twelve teeth 1 0 0
TOTAL 412 412 412
DMF INDEX = 1,87
Figure 4. Green-Vermillion index soft plaque index
(oral hygiene index)

17. ing their teeth contains fluoride, while results of rese-
arch conducted in Sweden showed that 20% of respon-
dents aged 15 to 16 years were also not familiar with
the fact whether the toothpaste contains fluoride or not
(16). The highest percentage of children (88.6%) does
not use fluoride tablets as their peers in Bosnia and
Herzegovina (17). Slightly more than a half of respon-
dents (52.2%) do not use mouth rinse with fluoride.
Low awareness of positive effects of fluoride among
children was observed in Serbia where only 21.33% re-
spondents were informed about impact of fluoride pro-
phylaxis on dental health (18). Similar results were ob-
tained in a study conducted in Pancevo which showed
that 35.4% of children knew that fluoride in toothpaste
helps prevent tooth decay while only 9.1% of respon-
dents used mouth rinse with fluoride (4).
All respondents stated that they have their own
oral hygiene kit which is consistent with research con-
ducted in six municipalities (Tivat, Kotor, Herceg No-
vi, Budva, Ulcinj and Bar) of coastal region of Monte-
negro. The results ranged from 76.5% in Ulcinj to
100% in Bar (19).
Slightly more than half of respondents brush their
teeth twice a day, in the morning and in the evening,
while 18.2% of twelve year olds in Bosnia and Herze-
govina (17), 81.8% of respondents in Pancevo (4),
58% of respondents in Croatia (6) and 42.5% of re-
spondents in Albania (13) also do it twice day. The re-
search conducted in the area of Banja Luka showed
that 53.37% of twelve year olds from urban areas brus-
hed their teeth twice a day and 33.76% after each meal
while in rural areas the corresponding percentages we-
re 59.23% and 17.93% (14). Our research has showed
that the lowest incidence of carries occurs among those
respondents who believe that the teeth should be brus-
hed after every meal and the highest incidence occurs
in children who think that teeth should be brushed once
a day. Also, students with excellent and very good gra-
des believe that the teeth should be brushed after every
meal while this attitude is less prevalent in schoolchil-
dren with bad grades in school.
In this study about half of respondent have oral
health index score 2 while research conducted in Monte-
negro showed that the average values of this index in
children of both sex in urban compared to rural areas is
1.084 : 1.142 (t = 1,517, p > 0,05) (20). Of the total
number of examined students only one respondent had
no deposits as opposed to 6.5% of respondents from re-
search conducted in Republic of Srpska (21).
DMFT index for study population was 1.87 while
caries occurred in 81.6% of examined children. The
value of this index was 3.43 in the research conducted
in 2006 in Montenegro while carries occurred in
88.35% of examined children (20). When the compari-
son with results from similar epidemiological studies
conducted in the neighbouring countries was made the
average value of the number of diseased permanent te-
eth per respondent ranged from 2.89 ± 0.37 in Romania
(22), 3.4 in Macedonia (23), 3.8 in Albania (13), 4.2 in
Bosnia and Herzegovina (24) to 4.8 in Croatia (25).
Significantly lower value of DMFT index were re-
corded in Italy (1.21), Austria (1.50), Germany (0.72),
Norway (1.2), Kenya (0.76 — urban areas, 0.36 — ru-
ral areas), Brazil (0.9%), Zimbabwe (1.29% — urban
area, 0.66% rural area), and slightly higher in Russia
(2.95), Lithuania (3.7), Qatar (4.62) and Saudi Arabia
(5.49) (26–36). The study conducted in 2010 in Nor-
way showed that the prevalence of dental caries in chil-
dren is low (8.78) and that most preschool children had
no experience with caries as a disease. This could beat-
tributed to the high level of education of the population
and free dental care for children from early years (37).
CONCLUSION
Taking into account the obtain results it can be
concluded that dental health care in this area does not
significantly affect the improvement of oral health in
children. Therefore, a greater attention should be paid
to continuous education programmes and gaining
knowledge about oral health and hygiene of the mouth
and teeth. Special emphasis should be placed on the de-
velopment of primary dental care that will be based on
preventive and prophylactic methods, promotion of
oral health and health education particularly of chil-
dren and then of their parents.
THE IMPORTANCE OF ORAL HEALTH BEHAVIOUR OF CHILDREN FOR THEIR ORAL HEALTH 105
SA@ETAK
ZNA^AJ PONA[ANJADECE ZASTANJE ORALNOG ZDRAVLJA
An|eli} Ivana,
1
Matijevi} Sne`ana,
2
An|eli} Jasminka
1
1
University of Montenegro, Faculty of Medicine Podgorica, Montenegro
2
Primary Heath Care Center Tivat, Montenegro
Uvod. Karijes ili zubni kvar je danas bez obzira na
dobro poznavanje prirode bolesti i mogu}nosti njene
efikasne prevencije, jo{ uvek najrasprostranjenije obo-
ljenje na{e populacije, koje ne retko ugro`ava funkcije

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aprila meseca 2015. godine u osnovnoj {koli “Drago
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`io je klini~ki pregled oralnog zdravlja dece. Procena
stanja oralnog zdravlja kod dece ra|ena je uz pomo}
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prema preporukama SZO. Parametar kori{}en za pro-
cenu stanja oralnog zdravlja bio je KEP indeks — broj
karijesnih, ekstrahovanih plombiranih zuba. Pored to-
ga, ra|ena je i procena stanja oralne higijene, za {ta je
kori{}en indeks mekih naslaga prema Green-Vermil-
lion-u kojim se odre|uje, odsustvo odnosno prisustvo,
koli~ina i rasprostranjenost dentalnog plaka i ostalih
mekih naslaga na zubima. Rezultati. Najve}i broj ispi-
tivanih u~enika je naveo da nema znanja u vezi sa delo-
tvorno{}u zubne paste sa fluorom (69,4%). Utvr|eno
je da se najmanja u~estalost dijagnoze karijesa javlja
kod onih u~enika koji smatraju da zube treba prati po-
sle svakog obroka, a najve}a u~estalost ove dijagnoze
javlja se kod ispitanika koji smatraju da zube treba pra-
ti jednom dnevno. Polovina od ukupnog broja ispitiva-
ne dece imaju stav da zube naj~e{}e treba prati posle
svakog jela i to vi{e od polovine odli~nih u~enika
(55,6%). U ispitivanoj populaciji KEP indeks je izno-
sio 1,87, dok je ispitivanjem Green-Vermillionovog in-
deksa mekih naslaga (oralne higijene) kod najve}eg
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THE IMPORTANCE OF ORAL HEALTH BEHAVIOUR OF CHILDREN FOR THEIR ORAL HEALTH 107
Correspondence to /Autor za korespondenciju
Ivana Andjelic
Email: ivaand89ªgmail.com
Tel: +382 69 883 801

21. SKIN TOXICITY OF TARGETED THERAPY: VEMURAFENIB,
FIRST EXPERIENCES FROM MONTENEGRO
Todorovic Vladimir,
1
Martinovic Danilo
1
1
Oncology and Radiotherapy, Clinic Clinical Center of Montenegro, Podgorica, Montenegro
Primljen/Received 20. 06. 2015. god. Prihva}en/Accepted 01. 08. 2015. god.
Abstract: Introduction: Data on melanoma inci-
dence and mortality in Montenegro is only partially
complete. GLOBOCAN and EUCAN reports estimate
melanoma incidence in Montenegro to be between
4.6–7.3 cases/100 000.
At least 50% of all metastatic melanoma cell lines
carry an activating mutation in the BRAF oncogene.
The treatment of advanced melanoma with the selecti-
ve BRAF inhibitors, such as vemurafenib demonstra-
ted improvement in progression free interval and over-
all survival when compared to conventional chemothe-
rapy treatment. Up to 95% of patients treated with ve-
murafenib experience skin toxicity.
Material and methods: Five patients with meta-
static melanoma have been treated with vemurafenib at
the Clinic for Oncology and Radiotherapy Podgorica,
Montenegro, during the period 2013–2014. They were
treated with standard dose (960 mg twice a day, per os).
Data about the occurrence and management of skin si-
de-effects in these patients were retrospectively collec-
ted from medical charts. Severity of side-effects was
graded using the National Cancer Institute’s Common
Terminology Criteria for Adverse Events, version 4.0.
Results: In 2013, 41 new cases of melanoma were
registered in Montenegro, 20 (48.7%) male and 21
(51.3%) female. In 2014, 49 new cases of melanoma
were registered, 27 (55.1%) male and 22 (44.9%) fe-
male. Two out of five (40%) vemurafenib treated pati-
ents experienced photosensitivity, three (60%) had
rash eruptions, four (80%) developed alopecia, and
two (40%) had dry skin problems. Alteration in nevus
color and size occurred in one (20%) patient, and two
(40%) patients developed new pigmented lesions.
Conclusion: Skin side effects associated with ve-
murafenib are plentiful, but generally manageable with
supportive care measures. In our experience, majority
of described side-effects were of grade 1 or 2, and none
required dose modifications, or discontinuation of the
therapy. Our experience suggests that patients taking
BRAF inhibitors should have regular full body skin as-
sessments, both prior to the beginning of the therapy
and periodically after its onset. Clinicians should be
aware of the skin related toxicities, in order to minimi-
ze their impact on treatment efficacy and patients’ qua-
lity of life.
Key words: Melanoma, vemurafenib, skin side ef-
fects.
INTRODUCTION
Melanoma accounts for less than 2% of all skin
malignancies, but it is responsible for majority of
skin-malignancy related deaths (1). Epidemiologic stu-
dies demonstrate that both the incidence and the preva-
lence of melanoma have increased steadily during last
30 years (1).
Data related to incidence and mortality of melano-
ma in Montenegro are still incomplete. GLOBOCAN
(2) and EUCAN (3) reports estimate the melanoma in-
cidence in Montenegro to be between 4.6–7.3 ca-
ses/100 000. According to the register data at the Clinic
for Oncology and Radiotherapy Podgorica in 2013, 41
new cases of melanoma were registered in Montene-
gro, 20 (48.7%) males and 21 (51.3%) females. In nine
(21.9%) patients, disease was initially metastatic. In
2014, 49 new cases of melanoma were registered, 27
(55.1%) males and 22 (44.9%) females. In 7 (14.3%)
patients disease was initially metastatic.
Activating mutation of BRAF oncogene is found
in more than 50% of all metastatic melanoma cell lines
(4, 5). Treatment of advanced melanoma with activat-
ing BRAF mutation with selective BRAF inhibitors,
such as vemurafenib, proved to be effective both in
terms of progression-free survival and overall survival,
when compared to conventional chemotherapy treat-
ment with dacarbazine (6, 7, 8).
DOI:10.5937/sanamed1502109T
UDK: 616.5-006.81-085.65(497.16)
2015; 10(2): 109–114 ID: 216794892
ISSN-1452-662X Original paper

22. Although the superior efficacy when compared to
conventional chemotherapy, treatment with vemurafe-
nib is often associated with numerous adverse effects
(6, 9, 10). Most common side effects of selective BRAF
inhibitors are skin side effects that occur in 92–95%
of all patients (9, 10, 11). Vemurafenib causes rush
and erythema eruptions, photosensitivity, hand foot
syndrome, squamous cell skin carcinoma, keratoa-
canthoma, and some less common adverse effects
such as erythema nodosum and toxic epidermal nec-
rolysis (9, 10, 11). Although these side effects do not
lead to the abruption of treatment, they can cause its
discontinuation, or require doses reduction. In addi-
tion, quality of life in these patients can be decreased
due to side effects. Literature shows that dose modifi-
cations or treatment discontinuation were required in
less than 10% of all vemurafenib treated patients (12).
Better understanding of skin related toxicities helps to
minimize their impact on treatment efficacy and pati-
ents’ quality of life.
AIM
Aim of this study is to analyze profile of vemura-
fenib treatment induced skin toxicity in patients with
BRAF mutation positive metastatic melanoma at the
Clinic for Oncology and Radiotherapy, Clinical Center
of Montenegro, during the period of 2013 and 2014.
MATERIALS AND METHODS
For each patient with metastatic melanoma, who-
se performance status was 0-1, BRAF mutation analy-
sis was suggested by the Clinic for Oncology and Radi-
otherapy Board for Skin Malignant Diseases. Analyses
were performed at Institute of Pathology, University of
Ljubljana, Slovenia. Patients with negative BRAF mu-
tation status were not eligible for vemurafenib treat-
ment. Medical documentation of all the patients with
confirmed BRAF V600E mutation was reexamined by
the Board of Health Insurance of Montenegro, whose
confirmation was required to initiate the treatment.
Total of five (BRAF mutation positive) metastatic
melanoma patients were treated with vemurafenib in
2013 and 2014. All of them were given standard dose
(960 mg twice a day, orally). All patients were exami-
ned by an oncologist (full body skin exam included)
prior to the onset of the BRAF inhibitor treatment, fol-
lowed by reevaluations conducted every four weeks.
We gathered data related to the occurrence and mana-
gement of skin side-effects in these patients. Severity
of side-effects was graded using the National Cancer
Institute’s Common Terminology Criteria for Adverse
Events, version 4.0 (13). Skin lesions with suspected
malignant potential were excised and submitted to pat-
hologist for examination. Treatment was interrupted in
patients with grade 3 or higher adverse effects. Vemu-
rafenib treatment was resumed after improvement of
toxicity to grade 1. For patients who experienced same
side effects more than once during the course of treat-
ment the highest recorded grade of toxicity was selec-
ted for this review.
RESULTS
Total of five metastatic melanoma patients were
treated with vemurafenib in 2013 and 2014 at the Cli-
nic for Oncology and Radiotherapy, Clinical Center
of Montenegro. Two of them were male and three fe-
male, average age 39.6 years. Treatment with vemu-
rafenib was recommended by the Board for Skin Ma-
lignancies.
Two (40%) patients experienced photosensiti-
vity. In one case, photosensitivity was mild (grade 1);
it required no treatment discontinuation. Symptoma-
tic therapy was not administered. Another patient ex-
perienced grade 3 photosensitivity, painful, burning
sensation after being exposed to UVA rays (patient
did not apply protective sun-screen). The reaction
was accompanied by face swelling. Vemurafenib had
to be discontinued for a period of seven days, with ad-
equate symptomatic treatment based on corticostero-
ids and non-steroid anti-inflammatory drugs. After
full resolution of symptoms, vemurafenib was contin-
ued in full dose. Astricter UVAprotection regime was
conducted.
In three (60%) of our patients, we have noticed
rash and erythema eruptions, all appearing within the
first three months after the treatment onset. All of the
rash eruptions were of grade 1 and grade 2. These requ-
ired neither treatment interruption, nor doses modifica-
tion, only a symptomatic treatment was prescribed by
dermatologist.
Four patients (80%) acquired grade 1 and grade 2
alopecia. Two (40%) reported dry skin problems, which
were treated with topical agents.
Alteration in nevus color and size occurred in
one (20%) patient. Lesion proved to be a dysplastic
nevus in pathological examination. In two (40%) pati-
ents, new pigmented lesions appeared on healthy loo-
king skin, both compound nevi by the report of patho-
logist.
We have encountered neither keratoacanthoma,
nor squamous cell carcinoma, although literature sug-
gests they appear in more than 20% of all the patients
treated with vemurafenib, which makes them most
common de novo skin malignancies in these patients.
Results are summarized in Table 1.
110 Todorovic Vladimir, Martinovic Danilo

23. DISCUSSION
Rash and erythema
Rash and erythema occur in nearly three quarters
of all vemurafenib treated patients, which makes them
the most common side effects of this therapy (8, 11,
12). There is no known correlation of vemurafenib in-
duced rush severity with treatment efficacy; this is un-
like the acneiform skin eruptions seen in EGFR inhibi-
tor treated patients that correlate positively with the
treatment outcome (14). For example, in BRIM-2 (8)
and BRIM-3 (11) trials, incidence of rash was similarly
distributed between the responders and the non-re-
sponders. Development of grade 3 rash was slightly
higher in the group of responders. This was, however
without statistical significance. Rash (that is pruritic
and maculopapular) is most likely caused by hypersen-
sitivity reaction (12). Literature shows that in most ca-
ses rash and erythema are of grade 1 and 2. Therefore,
there is no need for dose reduction or treatment discon-
tinuation (12). We have observed rash eruptions in three
of five patients treated at the Clinic for Oncology and
Radiotherapy, Clinical Center of Montenegro. In all of
the cases rush was of grade 1 or grade 2. Patients were
referred to a dermatologist, who prescribed symptoma-
tic treatment. In none of the patients dose reduction or
treatment abruption were required. Our experience is si-
milar to the findings of previous investigators, suggest-
ing that although a cautious approach is needed, major-
ity of rash outbursts are of lower to moderate severity
and are usually well tolerated by patients.
Photosensitivity
Photosensitivity is a frequent side effect in vemu-
rafenib treated patients (12). In BRIM studies 35–63%
of patients experienced photosensitivity, in majority of
cases of mild severity. Other studies on side effects of
BRAF inhibitors treatment report similar findings (15).
Taking into consideration the nature and evolution of
skin lesions, it can be concluded that BRAF inhibition
treatment is associated with UVA dependent photosen-
sitivity (16). Patients should therefore strictly follow
protection schedule and stay away from direct sun ex-
posure as much as possible. Broad spectrum sunscre-
ens, ultraviolet dense clothes and protective sunglasses
are highly recommended. It has been demonstrated
that these measures could largely help to prevent ve-
murafenib induced photosensitivity (17).
In our series of cases, two patients had photosensi-
tivity reaction. One patient experienced grade 1 pho-
to-toxicity. In this case, there was no need for sympto-
matic treatment and protection schedule was reintrodu-
ced. Other patient experienced grade 3 photosensiti-
vity, burning sensations and pain, followed by face
swelling (he did not apply sunscreen). Vemurafenib
treatment was paused until the resolution of symptoms
and corticosteroids and non-steroid anti-inflammatory
drugs were introduced. Seven days after the event, fol-
lowing another full body exam, vemurafenib treatment
(full doses) was continued and denser reexaminations
schedule and follow up was introduced. Vemurafenib
induced photosensitivity in one male patient was the
only grade 3 event we have encountered. No reduction
of doses was needed and our experience was compara-
ble to the results of previous studies.
Kerathoacantoma and squamous
cell skin carcinoma
Potential of BRAF inhibitors to cause secondary
malignancies is concerning. Literature data suggests
SKIN TOXICITY OF TARGETED THERAPY: VEMURAFENIB, FIRST EXPERIENCES FROM MONTENEGRO 111
Table 1: Vemurafenib associated skin toxicities graded using the National Cancer Institute’s
Common Terminology Criteria for Adverse Events, version 4.0.
M45yo F28yo F49yo F37yo M39yo
Photosensitivity Grade 3 – – – Grade 1
Rash Grade 2 Grade 1 Grade 1 – –
Erythema – Grade 2 Grade 2 – –
Alopecia Grade 2 Grade 1 Grade 2 – Grade 1
Dry skin – – Grade 1 – Grade 1
• New melanocytic lesions were found in one patient (female, 37 years old).
• In two patients (both male, 45 and 39 years old) alteration of existing nevi occured
• Other skin toxicities associated with vemurafenib treatment (kerathoacantoma, squamous cell skin carcinoma, basal cell
skin carcinoma, erythema nodosum, toxic epidermolysis and Stivens Jonson syndrome) did not occur in our five patients.

24. that up to one third of patients treated with vemurafe-
nib develop de novo skin malignancy, kerathoacanto-
mas and squamous cell skin carcinoma in majority of
cases (6–8, 18). Squamous cell skin carcinoma was ob-
served in 79 patients (23.5%) in BRIM 3 trial (11) and
in 25.8% in BRIM 2 trial (8). These lesions usually ap-
peared between the eight and the twelfth week after the
therapy onset.
Kerathoacanthoma is a common skin lesion of
low malignant potential, which usually appears on
sun-exposed parts of the skin (19). It is considered to
be a precursor lesion of squamous cell skin carcinoma,
which develops in about 10% of all the cases (20).
Genetic and histological analysis of keratoacant-
homas and squamous cell skin carcinomas suggest
they are more aggressive in BRAF inhibitor treated pa-
tients when compared to spontaneously developed le-
sions (6). Numerous genetic alterations are deemed to
be associated with appearance of skin malignancies,
including p53 mutation (21) that was found in about
50% of all secondary squamous cell skin carcinomas in
patients treated with vemurafenib (22). Furthermore,
RAS protooncogen mutation was identified in about
40% of lesions (23). Other drugs that lead to the inhibi-
tion of RAF signaling pathway, such as sorafenib or
dabrafenib, can also cause squamous cell skin carcino-
ma in up to 10% of all treated patients (24, 25). There-
fore it has been suggested that RAF inhibition has a di-
rect role in secondary malignancy development in the-
se patients. There is no significant change in risk fac-
tors for primary squamous cell skin malignancies and
vemurafenib-induced malignant lesions; chronic sun
exposure is believed to be the most important risk fac-
tor (12). We believe that lack of chronic sun exposure
could explain lack of secondary malignancies in pati-
ents treated at the Clinic of Oncology and Radiother-
apy in Podgorica. Namely, average age of our patients
was just above 39, compared to 54 in BRIM studies (8,
11), so preexisting sun induced skin toxicity was most
probably of a lesser grade. Taking into consideration
that de novo malignancies appear in the first three
months of treatment (12), it is possible that already de-
veloped precursor lesions are of greater significance,
while BRAF inhibition plays the role of a trigger. Nu-
merous studies also show that BRAF inhibition leads
to pathologic activation of MAPK signaling pathway
in cells without BRAF mutation (26–28), which leads
to assumption that MAPK pathway is also of importan-
ce in development of secondary skin malignancies du-
ring vemurafenib treatment.
Suggested therapeutic approach for keratoacantho-
mas is criotherapy and surgical excision for squamous
cell carcinomas. Secondary skin malignancies are not
considered a reason for dose reduction of vemurafenib.
Alopecia, dry skin, hyperkeratosis
and pruritus
Up to 45% of vemurafenib treated patients deve-
lop grade 1 or grade 2 alopecia (8, 11). Four out of five
patients treated at our Clinic developed alopecia, two
of them grade 2 (complete alopecia). Other common
skin side effects associated with BRAF inhibition are
pruritus (10–32% of cases), hyperkeratosis (23–30%)
and dry skin (8, 11). Two out of five of our patients ex-
perienced problems with dry skin. Following recom-
mendation of dermatologist, symptomatic treatment
with topical agents was administered. In our experien-
ce, none of the mentioned adverse effects influenced
vemurafenib treatment to any degree. Experiences of
other researchers also show that melanoma treatment is
not influenced in major degree by these side effects
(11, 12, 15). Consultation of a dermatologist was nee-
ded in selected cases.
Less common side effects associated with BRAF
inhibition such as basal cell skin carcinoma, hand foot
syndrome, erythema nodosum were not observed in
any of our patients.
Melanocytic lesions
De novo melanoma and benign melanocytic lesi-
ons were observed in a number of patients treated with
vemurafenib in BRIM-2 and BRIM-3 trials. Recom-
mended approach was a surgical removal and histolo-
gical assessment. Secondary malignant melanomas
were not considered as a progression of a disease;mod-
ification of specific BRAF inhibition treatment was not
required. In our case series, we have detected changes
in size and color of melanocytic nevi in a single pati-
ent, which were further evaluated by a pathologist after
surgical excision and demonstrated to be dysplastic ne-
vi. In two patients, de novo benign pigmentations ap-
peared on the healthy looking skin. Pathological exam-
ination in these two patients verified compound nevi.
No secondary melanomas were observed.
CONCLUSION
Skin side effects associated with vemurafenib tre-
atment are plentiful, but generally manageable with
supportive care measures. In our experience, majority
of described side-effects were of grade 1 or 2 and none
required dose modifications or abruption of the treat-
ment. Our experience suggests that patients taking
BRAF inhibitors such as vemurafenib should have reg-
ular full body skin assessments, both prior to the begin-
ning of the therapy and periodically after its onset. Cli-
nicians should be aware of the skin related toxicities, in
112 Todorovic Vladimir, Martinovic Danilo

25. order to minimize their impact on treatment efficacy
and patients’ quality of life.
Abbreviations
GLOBOCAN — Global Burden Of Cancer Study
EUCAN — European Union Cancer Database
UVA — Ultraviolet A
EGFR — Epidermal Growth Factor Receptor
BRIM — BRAF Inhibitor In Melanoma
RAS — Rat Sarcoma
RAF — Rapidly Accelerated Fibrosarcoma
MAPK — Mitogen-Activated Protein Kinase
CONFLICTOFINTERESTSTATEMENT
The authors declare no conflict of interest.
SKIN TOXICITY OF TARGETED THERAPY: VEMURAFENIB, FIRST EXPERIENCES FROM MONTENEGRO 113
Sa`etak
DERMATOLO[KATOKSI^NOST CILJANE TERAPIJE:
VEMURAFENIB, PRVAISKUSTVAIZ CRNE GORE
Todorovi} Vladimir,
1
Martinovi} Danilo
1
1
Klinika za onkologiju i radioterapiju Klini~kog centra Crne Gore, Podgorica, Crna Gora
Uvod: Jo{ uvek nema sveobuhvatnih podataka o
incidenci i mortalitetu melanoma u Crnoj Gori. Izve-
{taji GLOBOCAN-a i EUCAN-a procenjuju incidencu
melanoma u Crnoj Gori na 4.6–7.3 na 100 000.
Aktiviraju}a mutacija BRAF onkogena postoji u
preko 50% }elijskih linija metastatskog melanoma.
Le~enjem BRAF pozitivnog, neresektabilnog melano-
ma selektivnim BRAF inhibitorima (poput vemurafe-
niba) posti`e se du`e ukupno pre`ivljavanje u pore|e-
nju sa konvencionalnim hemoterapijskim re`imom.
Tretman vemurafenibom je pra}en brojnim ne`eljenim
efektima, naj~e{}e dermatolo{kim, koji se javljaju u
skoro 95% obolelih.
Materijal i metode: Petoro obolelih od metastat-
skog melanoma su le~eni Vemurafenibom na Klinici za
onkologiju Klini~kog centra Crne Gore 2013. i 2014.
godine, po shemi: 960 mg dva puta dnevno, per os. Po-
daci o ne`eljenim efektima su retrospektivno sakuplje-
ni iz medicinske dokumentacije. Za gradiranje ne`elje-
nih efekata su kori{}eni kriterijumi National Cancer
Institute’s - Common Terminology Criteria for Adver-
se Events.
Rezultati: Prema podacima intrahospitalnog re-
gistra Klinike za onkologiju i radioterapiju Klini~kog
centra Crne Gore, u 2013. godini registrovan je 41 no-
vooboleli, 20 (48.7%) mu{karaca i 21 (51.3%) `ena. U
2014. godini registrovano je 49 novoobolelih, 27 mu-
{karaca (55.1%) i 22 `ene (44.9%). Kod 2/5 (40%) pa-
cijenata le~enih vemurafenibom su se javile fotosenzi-
tivne reakcije, kod 3/5 (60%) su se javile erupcije osi-
pa, kod 4/5 (80%) alopecija, a kod 2/5 (40%) suvo}a
ko`e. Promene veli~ine i boje postoje}ih nevusa su
uo~ene kod jednog (20%) pacijenta, dok su se kod 2/5
(40%) javile de novo pigmentne promene.
Zaklju~ak: Ko`ni ne`eljeni efekti povezani sa le-
~enjem vemurafenibom su brojni, ali se u najve}em bro-
ju slu~ajeva mogu kupirati simptomatskom terapijom.
Kod obolelih tretiranih na Klinici za onkologiju Kli-
ni~kog centra Crne Gore, najve}i broj ne`eljenih efekata
je bio gradusa 1 i 2, bez potrebe za prekidom terapije ili
za smanjivanjem doze leka. Oboleli na terapiji BRAF
inhibitorom bi trebalo da pro|u kroz redovne preglede
ko`e, kako pre zapo~injanja terapije, tako i periodi~no u
toku iste. Dobro poznavanje ne`eljenih efekata omogu-
}ava da se u praksi u {to ve}oj meri ograni~i njihov uti-
caj na uspe{nost le~enja i na kvalitet `ivota obolelih.
Klju~ne re~i: Melanom, vemurafenib, ne`eljeni
efekti na ko`i.
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Oncology and Radiotherapy Clinic,
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Clinical Center of Montenegro
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27. TREATMENT OF URACHALADENOCARCINOMA— CASE REPORT
Mekic Abazovic Alma,
1
Sulejmanovic Samra,
1
Sehic-Kozica Erna,
1
Mehic Mirza,
2
Beculic Hakija,
3
Jakovljevic Branislava
4
1
Department of Oncology and Radiotherapy, Cantonal Hospital Zenica, Bosnia and Herzegovina
2
Department of Gynecology and Obstetrics, Cantonal Hospital Zenica, Bosnia and Herzegovina
3
Department of Neurosurgery, Cantonal Hospital Zenica, Bosnia and Herzegovina
4
Health Institution S. Tetik, Oncological Hospital Banjaluka, Bosnia and Herzegovina
Primljen/Received 28. 05. 2015. god. Prihva}en/Accepted 10. 07. 2015. god.
Abstract: We report the case of a urachal adeno-
carcinoma diagnosed in a 55-year-old patient — pre-
senting with dysuria and bloody urine. After admission
to hospital, urethrocystoscopy showed large bleeding
mass in prostatic part of urethra. He underwent transu-
rethral resection of prostate and cystectomy, with im-
plantations of JJ stents. Immunohistochemistry revea-
led urachal adenocarcinoma, a rare type of urogenital
carcinoma, presented only in 5% of all cancer types.
The patient was treated with dual modality, chemother-
apy and radiotherapy.
Keywords: urachal adenocarcinoma, urethrocysto-
scopy, percutaneous nephrostomia, adjuvant chemora-
diotherapy, PET CT.
INTRODUCTION
Urachal adenocarcinomas are rare tumors that li-
kely arise from metaplasia of mucosal surface of pros-
tatic part of urethra or from periurethral glands (1, 2).
Other anatomic locations include pseudomembraneo-
us, but also penile part of urethra (3). Anatomic loca-
tion largely determines the hystological type of cancer.
The incidence of adenocarcinoma is 5%, squamous cell
carcinoma 80%, and transitional cell carcinoma 15%
(4). Causes include chronic inflammation and venereal
infections, most likely human papillomavirus. The rare-
ness of these carcinomas represents a formidable diag-
nostic challenge because of a poor therapeutic benefit in
advanced stages even with aggressive treatment.
CASE REPORT
A 55-year-old patient has been examined by urol-
ogist on July of 2012. due to pain in pubic area, dysuria
and bloody urine, occasionally followed by urine re-
tention. A clinical diagnosis of hypertrophic neoplasia
of prostate was made. Within two weeks, patient was
hospitalized because of the obstructive uropathy. The
urethrocystoscopy was scheduled and it confirmed lar-
ge, excessively bleeding mass in prostatic part of uret-
hra that is prominent to the urinary bladder lumen. Du-
ring hospitalization urgent CT scan was made, and it
showed homogenous diverticulous area of 54 x 28 mm
in the right lateral wall of the bladder and one on the
left wall sized 20 x 14 mm, and enlarged prostate of 60
x 60 mm, with unclear differentiation to the seminal
vesicles. Because of the massive haemorrhage, transu-
rethral resection of prostate and cystectomy was made
with implantations of JJ stents afterwards. On the first
pathohistological review, the suspicion for prostate
adenocarcinoma was made, but immunohistochemi-
stry revision was requested, and it confirmed that it
was urachal adenocarcinoma deriving from prostatic
part of urethra. On the tenth postoperative day, MRI
scan (Figure 1 and 2) was performed and showed earli-
er described areas on CT scan, but also neoplastic infil-
trating area of 40 mm in the base of prostatic gland go-
ing through the right wall of the bladder, pointing at the
rest of the tumor. In addition, right stent was removed,
and percutaneous nephrostomy was placed due to right
kidney hydronephrosis.
The case was presented to the multidisciplinary
team, also Rete Oncologica of Italy-Torrino was con-
sulted, and adjuvant chemotherapy (gemcitabin 2100
mg/D1, D8 Cisplatin 150 mg/D1 and 5-FU 2100 mg,
Cisplatin 210 mg after progression) and radiotherapy
(50 Gy/25 fr) were initiated, during which suprapubi-
cal cystostomy was done, resulting in significant clini-
cal improvement within two months and patient’s
symptoms completely resolved. The patient remained
DOI:10.5937/sanamed1502115M
UDK: 616.62-006.6-08
2015; 10(2): 115–117 ID: 216786956
ISSN-1452-662X Case report

28. symptom-free after an adjuvant treatment and was dis-
charged from the hospital. Scheduled reevaluation af-
ter two and half months was done and PET CT scan re-
vealed mass of 47 mm infiltrating prostatic part of uret-
hra in width of 28 mm, with diverticulous lesions on
the right wall of the urinary bladder of 8 mm, signifi-
cant retroperitoneal lymphadenomegaly and cystic le-
sion in 5th liver segment, with rectal abdominal muscle
infiltration. Two years after the initial symptoms oc-
curred, patient is in a great amount of pain, on daily
opioid patches, has bilateral nephrostomies and on clo-
se follow-up protocol because there are no further tre-
atment recommendations.
DISCUSSION
This case illustrates a potential of early recogni-
tion of this rare pathology which is critical to institu-
tion of appropriate therapy and prevention. Luckily, no
missteps were taken, although there was a clinical mis-
lead to prostate cancer because of symptom presenta-
tion. Eventhough right and aggressive treatment mea-
sures were taken, clinical and imaging techniques were
all indicating aggressive disease and progression over
such short period of time, but patient still has ecog of
2/3, two years after; in comparison to the median survi-
val without treatment or with palliation, which is ap-
proximately 3 months.
Treatment recommendations for superfitial lesi-
ons (Tis, T1) is to be managed by transurethral resec-
tion, but such are rare (5, 6, 7). Invasive T2 tumours
carries a poor prognosis in spite of radical cystoprosta-
tectomy and total urethrectomy. A recent report strati-
fied that extravesical involvement had much worse
prognosis than intraurethral disease, with a higher
chance of nodal involvement and 5-year survival of
only 32%. Advanced carcinomas (T3T4N1-N3) is best
treated with a combination of neoadjuvant chemother-
apy (MVAC) followed by surgery and irradiation, but
those data are consistent only for transitional cell tu-
mours (7, 8). Preoperative MVAC against nontransitio-
nal types turned out to be ineffective. Radiotherapy
yield poor results. Most common approach is exter-
nal-beam radiotherapy of 50-60Gy over 6 weeks pe-
riod. Patients who receive radiation therapy followed
by salvage surgery seem to fare worse than if surgery
was performed in an integrated fashion. Multimodal
therapy with chemoradiation has shown the efficacy of
5-FU, mitomycin C, and cisplatin along with exter-
nal-beam radiotherapy for squamous cell carcinomas
but not for other histologic types (6–10).
CONCLUSION
Combining both modalities is expected to lead to
a better outcome in treating urachal adenocarcinomas.
In NCCN (National Comprehensive Cancer Network)
guidelines there is no recommendation for further tre-
atment because of a poor therapeutic benefit documen-
ted in clinical trial after adjuvant chemoradiation for
advanced urachal adenocarcinomas.
There is no conflict of interests
Abreviations
PET — Positron Cmission Tomography
CT — Computed Tomography
MRI — Magnetic Resonance Imaging
5-FU — 5-fluorouracil
NCCN — National Comprehensive Cancer Net-
work
MVAC — Methotrexate, vinblastine, doxorubi-
cin, and cisplatin
116 Mekic Abazovic Alma, Sulejmanovic Samra, Sehic-Kozica Erna, Mehic Mirza, Beculic Hakija, Jakovljevic Branislava
Figure 1 and 2. Postoperative Magnetic Resonance
Imaging of Pelvis (sagital and axial scans)
(Department of Oncology and Radiotherapy
Cantonal Hospital Zenica, BH)

29. Sa`etak
TRETMAN URAHALNOG KARCINOMA— PRIKAZ SLU^AJA
Meki} Abazovi} Alma,
1
Sulejmanovi} Samra,
1
[ehi}-Kozica Erna,
1
Mehi} Mirza,
2
Be~uli} Hakija,
3
Jakovljeviæ Branislava
4
1
Slu`ba za onkologiju i radioterapiju, Kantonalna bolnica Zenica, Bosna i Hercegovina
2
Slu`ba za ginekologiju i porodiljstvo, Kantonalna bolnica Zenica, Bosna i Hercegovina
3
Slu`ba za neurohirurgiju, Kantonalna bolnica Zenica, Bosna i Hercegovina
4
Zdravstvena ustanova S Tetik, Onkolo{ka bolnica Banja Luka, Bosna i Hercegovina
Prikazali smo slu~aj urahalnog karcinoma dijag-
nostikovanog kod 55-godi{njeg pacijenta koji se mani-
festovao dizurijom i pojavom krvi u mokra}i. Nakon
hospitalizacije ureterocistoskopija je pokazala veliku
krvare}u masu i prostati~nom delu uretre. Na~injena je
transuretralna resekcija prostate i cistektomija sa im-
plantacijom JJ stenta. Imunohistohemija je pokazala
urahalni adenokarcinom, redak tip urogenitalnog kar-
cinoma, koji ~ini samo oko 5% svih tipova karcinoma.
Pacijent je le~en dualnim modalitetom, hemoterapijom
i radioterapijom.
Klju~ne re~i: urahalni adenokarcinom, uretroci-
stoskopija, perkutana nefrostomija, adjuvantna hemo-
radioterapija, PET CT.
TREATMENT OF URACHAL ADENOCARCINOMA — CASE REPORT 117
REFERENCES
1. Bosset JF, Roelofsen F, Morgan DA, et al. Shortened irra-
diation scheme, continuous infusion of 5-fluorouracil and fractio-
nation of mitomycin C in locally advanced anal carcinomas. Re-
sults of a phase II study of the European Organization for Rese-
arch and Treatment of Cancer. Radiotherapy and Gastrointestinal
Cooperative Groups. Eur J Cancer 2003; 39(1): 45–51.
2. Klimant E, Amrkman M. Management of Two Cases of
Recurrent Anal Carcinoma. Case Rep Oncol. 2013; 6(3): 456–61.
3. Chaux A, Amin M, Cubilla AL, Young RH. Metastatic
tumors to the penis: a report of 17 cases and review of the litera-
ture. Int J Surg Pathol. 2011; 19(5): 597–606.
4. Neuzillet Y. Urothelial prostatic and urethral carcino-
mas. Rev Prat. 2014; 64(10): 1367–8.
5. Chalya PL, Rambau PF, Masalu N, Simbila S. Ten-year
surgical experiences with penile cancer at a tertiary care hospital
in northwestern Tanzania: a retrospective study of 236 patients.
World J Surg Oncol. 2015: 13–71.
6. Russel AH, Dalbagni G. Cancer of the urethra. In: Vo-
gelzang Nj, Scardino PT, Shipley WU, Debruyne FMJ, Linehan
WM, eds. Comprehensive textbook on genitourinary oncology.
Philadelphia: Lippincott Williams and Wilkins, 2006.
7. Ikeda Y, Yasuda M, Kato T, Yano Y, Kurosaki A, Hase-
gawa K. Synchronous mucinous metaplasia and neoplasia of the
female genital tract with external urethral meatus neoplasm: A
case report. Gynecol Oncol Rep. 2015; 12: 27–30.
8. Corbishley CM, Rajab RM, Watkin NA. Clinicopatho-
logical features of carcinoma of the distal penile urethra. Semin
Diagn Pathol. 2015; 32(3): 238–44.
9. Gaya JM, Matulay J, Badalato GM, Holder DD, Hruby
G, McKiernan J. The role of preoperative prostatic urethral bi-
opsy in clinical decision-making at the time of radical cystec-
tomy. Can J Urol. 2014; 21(2): 7228–33.
10. Hu B, Djaladat H. Lymphadenectomy for testicular, pe-
nile, upper tract urothelial and urethral cancers. Curr Opin Urol.
2015; 25(2): 129–35.
Correspondence to /Autor za korespondenciju
Alma Meki}-Abazovi}
Department of Oncology and Radiotherapy
Cantonal Hospital Zenica, Crkvice 67
72000 Zenica, Bosnia and Herzegovina;
Phone: +387 32 405 133; +387 32 405 534;
E-mail: dr.alma.kbzªgmail.com

31. SEVERE COMMUNITY-ACQUIRED PNEUMONIACAUSED
BY MYCOPLASMAPNEUMONIAE IN YOUNG FEMALE PATIENT
Milacic Nena,
1
Djurovic Marija,
2
Hasanbegovic Mirha,
3
Milacic Bojan,
4
Stevanovic Dragana
5
1
Department of Internal Medicine, Clinical Centre od Montenegro, Podgorica, Montenegro
2
Department of Gastroenterology, Clinical Centre of Montenegro, Podgorica, Montenegro
3
Department of Internal Medicine, General Hospital Pljevlja, Montenegro
4
Department of Thoracic Surgery, Clinical Center of Montenegro, Podgorica, Montenegro
5
Department of Radiology, General Hospital Bar, Montenegro
Primljen/Received 23. 06. 2015. god. Prihva}en/Accepted 18. 07. 2015. god.
Abstract: Mycoplasma pneumonia is common
agent causing community acquired pneumonia in youn-
ger population. However, the course of illness is usu-
ally benign and is rarely associated with pulmonary
complications. We report a 27 years old female patient
with unilateral pneumonia followed by pleural effu-
sion and adhesions on the same side. This potential so-
urce of infection should be considered in young pati-
ents where resolution of symptoms from pneumonia is
delayed.
Key words: Mycoplasma pneumoniae, commu-
nity acquired pneumonia, pleural effusion, pleural ad-
hesions.
INTRODUCTION
M. pneumoniae infection is one of the most com-
mon causes of atypical community acquired pneumo-
nia (1). Pneumonia due to M. pneumoniae is usually
mild and it is not infrequently that infection itself is
asymptomatic. M. pneumoniae accounts for up 35% of
cases of pneumonia in outpatients and is responsible
for 3–18% of cases in patients who require hospitaliza-
tion (2). It has not real cellular wall, but three layer
membrane, so penicillin can not be effective against
this agent.
Infection is mostly spread by droplet transmis-
sion, being spread aerogenically in smaller closed spa-
ces. Incubation time from Mycoplasma infection to
first symptoms appearance takes from 14 to 21 days.
The most common affected individuals are adolescents
and younger persons by age of 30 years (3).
It is uncommon for M. pneumoniae to present in a
fulminant and fatal manner (2, 3, 4). The fatal compli-
cations of M. pneumonia infection are not well estab-
lished but include acute respiratory distress syndrome,
acute disseminated encephalomyelitis (ADEM), DIC,
hemophagocytic syndrome and Stevens Johnsons
syndrom. Rare cases of fatal myocarditis have been re-
ported.
This infective agent has two very expressed pat-
hogenic mechanisms: the first one reffers to strong affi-
nity to respiratory tract cells (damages ciliary activity),
the second one is capability of hydrogen peroxide pro-
duction which initially damages respiratory tract lining
cells, but also erythrocite membranes.
Initiation is almost obscure followed by symp-
toms originating from upper respiratory tract, subfebri-
le temperatures, shivering, headaches. After few days
attacks of dry irritating cough appear, which lead to
choking. Physical examination of lungs is most com-
monly normal. Symptoms appear only a week after, so-
metimes even latter, when inspiratory or expiratory
crackles can be heard on lung auscultation.
Diagnostics consists of standard laboratory blood
tests, serological testing, chest X-ray.
Radiological finding may manifest multiform pat-
terns: unilaterally bronchopneumonic band-forming,
blotchy infiltrates in lower pulmonary fields followed
by plate atelectases, nodular shadows, hillary adeno-
pathy, unilateral pleural effusions too.
Treatment is based on use of macrolides, te-
tracyclines and chinolones (5).
CASE PRESENTATION
A27 years old female with no significant past me-
dical history, smoker, working as hairdresser, was ad-
DOI:10.5937/sanamed1502119M
UDK: 616.24-002-008.87; 616.98:579.887
2015; 10(2): 119–122 ID: 216794124
ISSN-1452-662X Case report

32. mitted to Pulmology Department through Urgent cen-
tre for increased body temperature, dry irritating co-
ugh, dyspnea, general feeling unwell and malaise.
Symptoms appeared eight days before, in much less
expressed form. Initially increased body temperature,
by 37,5 degrees, nasal secretion and pain in region of
frontal sinuses, shiver and trembling were present. Du-
ring the course of disease patient has been normally
doing her daily activities. Consequently, symptoms be-
come more intensive with very intensive persisting co-
ugh, severe dyspnea, general malaise and exhaustion,
due to which patient was initially observed and diagno-
tically investigated in Urgent centre. C-reactive pro-
tein 227, hemoglobin 53 g/l. Chest X-ray verified infil-
trative change in projection of lung on left in lower pul-
monary lobe with pleural effusion. In personal history
she denied diseases of hereditary significance, but she
told she was ambulatory treated 15 days prior to admis-
sion due to bronchitis.
On admission she was conscious, oriented, easily
dispnoic, febrile (38,3), hypotensive, adinamic, had
pale skin, many herpetic changes on the upper lip, with
no signs of active haemorrhagic syndrome and signifi-
cant peripheral lymphadenopathy. At the lung base on
left decreased breath sound without pathological ac-
companied sounds. Cardiac action was rhythmic, so-
unds clear, without murmur. Her blood pressure was
110/70 mmHg, pulse 130 bpm, oxygen saturation 88%.
EKG showed sinus rhythm, frequency of 75 in minute,
without significant changes on ST segment. Remain-
ing of physical examination was regular.
During hospitalization she remains easily dispno-
ic, febrile (37,5), adinamic. Significant findings in her
hospital course are as follows: SR 54, WBC 6,2, RBC
3,59, MCV 52,6, HGB 53, TR 186, CRP 227,7, IL-6
28,0, D DIMER 4,99. Arterial blood gas showed pH
7,43, pC02 3,89 kPa, pO2 7,3 kPa, oxygen saturation
88,8%. GGT 364, remaining laboratory findings in re-
ferral frame values. Patient was sampled for Influenza
viruses A and B. Immunoserological analyses were
performed for Chlamydia trachomatis, Mycoplasma
pneumonia, Coxiella burnetti and Legionella pneu-
mophila. Sputum was taken for cultivation. Combining
parenteral antibiotic therapy was initiated (3
rd
genera-
tion cephalosporin and amynoglicoside), yet remain-
ing symptomatic and supportive therapy. On abdomen
ultrasound pathological changes were not detected, as
on ultrasound of thyroid gland. Gastroenterologist
consulted, indicated EGDS and screening on celiakia.
Normal finding on gynecological examination. Co-
ombs tests negative, vitamin B12, beta 2 microglobuli-
ne, hemostasis parameters level in referral values. Iron
serum level decreased — 3,9, TIBC 37,1, UIBC 33,2,
transferin 1,58, s-transferin 10, sTIR 4,23, FRT 197,0,
haptoglobin 5,42. Peripheral blood smear revealed
hypochromic neutrophilia with toxic granulations.
Hormonal status and tumor markers in normal range.
She received two doses of deplasmated erythrocytes.
However, symptoms of the same intensity persisted
followed by pain in region of rib arches on left side.
Control CRP did not show significant decline (CRP
218), control chest X-ray showed persisting paren-
chyma consolidation in projection of lower pulmonary
lappet with same side pleural effusion on left.
MSCT of chest confirmed infiltrative change in
pulmonary parenchyma on left in projection of lower
lobe anterobasically accompanied by pleural adhesi-
ons and small amount of pleural effusion on the same
side. Due to all the above mentioned, change in anti-
microbial therapy was indicated (combination of car-
bapenems and chinolons).
Three days after this therapy was administered,
subjective improvement was achieved, as the same of
inflammatory markers level decreasement (Se 50, CRP
120 Milacic Nena, Djurovic Marija, Hasanbegovic Mirha, Milacic Bojan, Stevanovic Dragana
Figure 1. The first patient’s chest X-ray
Figure 2. The second patient chest X-ray

33. 90, fibrinogen 5,2), control D-dimer 1,59. Immunose-
rological tests verrified IgM antibodies against Myco-
plasma pneumonia. Sputum culture showed unspeci-
fied result. Tests on Influenza Aand B negative, the sa-
me of celiakia screening. Patient refused to perform
suggested esophagogastroscopy. Same antimicrobial
therapy was continued. On control chest X-ray earlier
described condensation of pulmonary parenchyma was
verrified on left in projection of lower pulmonary lobe
in significant regression. Control inflammatory mark-
ers showed decline (CRP 4,5, fibrinogen 4,3). During
hospitalization increasement in platelet count was fo-
und in blood count (Tr 186… 255… 827… 935), possi-
bly reactive phenomenon regarding existing anemia
and mentioned pleuropnemonia on left. Patient was
physically examined in ambulance one week after dis-
charge. She denied any discomfort, while control chest
X-ray showed complete regression of earlier described
change in lung on left.
DISCUSSION AND CONCLUSIONS
The most common cause of community acquired
pneumonia in population by years of 30 is Mycopla-
sma pneumoniae. It runs often mild course and those
patients are usually treated as outpatients. However,
MP pneumonia can lead to complications, among them
the most often are unilateral small amount parapneu-
monic effusions, but also bilateral pneumonia, ARDS,
respiratory insufficiency. Pleural effusion, if it occurs,
is usually a small amount of effusion which is self limi-
ting(1, 2, 3).
The demonstration of elevated IgM antibodies by
either indirect immunoflorescence or EIA is required
for the diagnosis. Alternatively, a fourfold increase in
IgG antibodies by Complement Fixation Test or EIA
can also provide the diagnosis (4). The recommended
therapy for mycoplasma infection is a 10 day course of
clarithromycin or five day course of Azithromycin. Ot-
her drugs which can be effective include tetracyclines
and chinolons (5).
In our patient the symptoms did not resolve and
inflammatory markers did not decline despite initial in-
tervention (5, 6, 7), which was not appropriate one, lea-
ding to further examination and differential diagnosis
which indicated MP as the cause of the patient’s symp-
toms. After introducing of appropriate antibiotic treta-
ment, general patient state improves, inflammatory
markers decline, radiological chest finding shows re-
gression of changes.
Clinicians should be aware of potential pneumo-
nia in younger patients due to atypical pathogens,
which are resistant to initial empirical antibiotic ther-
apy (cephalosporines, penicillins). Without adecquate
antibiotic treatment in such a case, parapneumonic ef-
fusions, which can further lead to other respiratory
complications, occur. Early diagnosis and appropriate
therapy (macrolides, chinolons, tetracyclines) can pre-
vent bad patient’s outcome.
Abbreviations:
DIC — disseminated intravascular coagulation
ADEM — acute disseminated encephalomyelitis
mmHg — millimetres of mercury
bpm — beats per minute
SR — sedimentation rate
WBC — white blood cells
RBC — red blood cells
MCV — mean corpuscular volume
HGB — hemoglobin
PLT — platelets
CRP — C-reactive protein
SEVERE COMMUNITY-ACQUIRED PNEUMONIA CAUSED BY MYCOPLASMA PNEUMONIAE IN YOUNG FEMALE... 121
Figure 3. MCST of patients’s chest
Figure 4. Control chest X-ray

34. IL-6 — interleukin 6
pH — potential hydrogen
pO2 — partial pressure of oxygen
pCO2 — partial pressure of carbon dioxide
GGT — gamma-glutamyl transferase
EGDS — esophagogastroduodenoscopy
TIBC — total iron binding capacity
UIBC — unbound iron binding capacity
sTIR — short inversion time recovery
EIA — enzyme immunoassay
122 Milacic Nena, Djurovic Marija, Hasanbegovic Mirha, Milacic Bojan, Stevanovic Dragana
Sa`etak
TE[KAVANBOLNI^KI STE^ENAPNEUMONIJAUZROKOVANA
MIKOPLAZMOM PNEUMONIJE U MLADE PACIJENTKINJE
Mila~i} Nena,
1
urovi} Marija,
2
Hasanbegovi} Mirha,
3
Mila~i} Bojan,
4
Stevanovi} Dragana
5
1
Interna klinika, Odjeljenje pulmologije, Klini~ki centar Crne Gore, Podgorica, Crna Gora
2
Interna klinika, Odjeljenje gastroenterologije, Klini~ki centar Crne Gore, Podgorica, Crna Gora
3
Odjeljenje interne medicine, Op{ta bolnica Pljevlja, Crna Gora
4
Hirur{ka klinika, Odjeljenje za grudnu hirurgiju, Klini~ki centar Crne Gore, Podgorica, Crna Gora
5
Odjeljenje radiologije, Op{ta bolnica Bar, Crna Gora
Mycoplasma pneumoniae je ~est agens koji uzro-
kuje pneumoniju ste~enu u zajednici kod mla|e popu-
lacije. Me|utim, tok bolesti je obi~no benigan i retko
udru`en sa plu}nim komplikacijama. Mi prikazujemo
slu~aj 27-ogodi{nje pacijentkinje sa unilateralnom
pneumonijom pra}enom pleuralnom efuzijom i adhe-
zijama na istoj strani. Ovaj potencijalni uzrok infekcije
bi trebalo biti razmatran u mla|ih pacijenata gde je re-
zolucija simptoma od pneumonije odlo`ena.
Klju~ne re~i: Mycoplasma pneumoniae, pneu-
monija ste~ena u zajednici, pleuralni izliv, pleuralne
adhezije.
REFERENCES
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2. Powel DA. Nelson Textbook of Pediatrics. 19th ed. Phi-
ladelphia, Saunders, 2010; 1029–32.
3. Nastasijevi} Borovac D. Definicija, epidemiologija i
klasifikacija pneumonija. In: Pej~i} T, editor. Pneumonije da-
nas, 1st ed. Ni{: Grafika Galeb-Ni{; 2013. p. 5–12.
4. Nastasijevi} Borovac D. Biomarkeri inflamacije kod
bolesnika sa pneumonijama. In: Pej~i} T, editor. Pneumonije da-
nas. 1st ed. Ni{: Grafika Galeb-Ni{; 2013. p. 185–210.
5. Kashyap S, Sarkar M. Mycoplasma pneumonia: Clini-
cal features and management. Lung India. 2010; 7(2): 75–85.
6. Youn YS, Lee KY. Mycoplasma pneumoniae pneumo-
nia in children. Korean J Pediatr. 2012; 55(2): 42–7.
7. Kong MX, Newman K, Goldenberg R, Tierno PM, Mi-
kolaenko I, Rapkiewicz A. Fatal Mycoplasma Pneumoniae In-
fection: Case Report and Review of the Literature. NAJ Med
Sci. 2012; 5(2): 126–30.
Correspondence to/Autor za korespondenciju
Nena Mila~i}
Depatment of Internal medicine, Clinical Centre of Montenegro
Moskovska bb, 81000 Podgorica, Montenegro
Email: nena.milacic75ªgmail.com