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The effect of depth of tumor invasion on neck lymph node metastasis in patients with oral squamous cell carcinoma

dc.contributor.advisorKiralj, Aleksandar
dc.contributor.advisorVučković, Nada
dc.contributor.otherIlic, Miroslav P.
dc.contributor.otherLončarević, Slobodan
dc.contributor.otherJovančević, Ljiljana
dc.contributor.otherNikolić, Jelena
dc.contributor.otherFejsa-Levakov, Aleksandra
dc.creatorMijatov, Ivana
dc.date.accessioned2020-06-23T13:28:29Z
dc.date.available2020-06-23T13:28:29Z
dc.date.available2020-07-03T13:28:38Z
dc.date.issued2019-11-22
dc.identifier.urihttps://www.cris.uns.ac.rs/DownloadFileServlet/Disertacija155807616783928.pdf?controlNumber=(BISIS)110690&fileName=155807616783928.pdf&id=12873&source=NaRDuS&language=srsr
dc.identifier.urihttp://nardus.mpn.gov.rs/handle/123456789/12330
dc.identifier.urihttps://www.cris.uns.ac.rs/record.jsf?recordId=110690&source=NaRDuS&language=srsr
dc.identifier.urihttps://www.cris.uns.ac.rs/DownloadFileServlet/IzvestajKomisije155807619210436.pdf?controlNumber=(BISIS)110690&fileName=155807619210436.pdf&id=12874&source=NaRDuS&language=srsr
dc.description.abstractOralni karcinom je po učestalosti šesta najčešća maligna bolest u svetu čija incidenca varira u različitim geografskim područjima. Predstavlja 5% svih novootkrivenih malignih tumora godišnje i čini 14% svih malignih tumora glave i vrata. Pod oralnim karcinom podrazumevamo planocelularni karcinom obzirom na činjenicu da on čini preko 90% malignih tumora oralne lokalizacije, dok se u manjem procentu javljaju drugi tumori (maligni tumori malih pljuvačnih žlezda, limfomi, mezenhimni tumori). Oralni karcinom podrazumeva karcinome koji se javljaju u sledećim anatomskim regijama: sluznici prednje 2/3 jezika, poda usta, obraza, gingivi gornje i donje vilice, retromolarnom trouglu, kao i sluznici mekog i tvrdog nepca. Najčešća lokalizacija oralnog planocelularnog karcinoma je sluznica pokretnog dela jezika i poda usta. Oralni karcinom se češće javlja kod muškaraca (odnos muškarci:žene je 3:1) verovatno zbog većeg procenta rizičnog ponašanja kod muškaraca. Najčešće se javlja u šestoj i sedmoj deceniji života (medijana je 62 godine) iako se poslednjih godina sve češće javlja kod mlađih od 45 godina. Faktori rizika za oboljevanje su dobro poznati. Na prvom mestu se izdvaja pušenje duvana (značajna je dužina pušenja, da li pacijent puši lulu ili cigaretu, da li žvaće duvan, kao i dužina trajanja apstinencije). Smatra se da je smrtnost kod oralnog karcinoma direktno povezana sa brojem popušenih cigareta na dan. Preko 75% pacijenata sa oralnim karcinomom anamnestički daje podatak o prekomernoj upotrebi alkohola. Postoji sinergističko dejstvo alkohola i cigareta, dugotrajna ekspozicija ovim faktorima rizika dovodi do pojave “polja kancerizacije“, pojave genetske nestabilnosti i razvoja tumora. Kod oralnog planocelulranog karcinoma primećene su hromozomske abnormalnosti koje su rezultat oštećenja DNK i uključuju promene genetskog materijala na hromozomima.Jedna od najčešćih genetskih abnormalnosti kod oralnog planocelularnog karcinoma je mutacija r53 gena koji se nalazi na kratkom kraku hromozoma 17 i predstavlja tumor supresor gen. Planocelularni karcinom nije teško dijagnostikovati kada postane simptomatski. Pacijent se žali na bol, krvavljenje, otalgiju, otežano gutanje, smanjenje pokretljivosti jezika. Neretko je prvi simptom metastatski uvećan limfni čvor na vratu jer bolesnici ne primećuju ili ignorišu oralnu patologiju. Dijagnoza oralnog karcinoma se postavlja na osnovu detaljno uzete anamneze, kliničkog pregleda i patohistološke verifikacije. Oralni planocelularni karcinom se javlja u tri klinike forme: egzofitična, endofitična i infiltrativna. Zlatni standard za dijagnozu oralnog karcinoma je biopsija i patohistološka verifikacija, pri čemu se može primeniti „punch“ biopsija, inciziona biopsija ili eksciziona biopsija kod manjih promena. TNM „staging“ sistem AJCC (American Joint Committee on Cancer) se danas standardno koristi za klinički „staging“ oralnog karcinoma i bazira se na podacima dobijenim kliničkim pregledom i „imaging“ metodama. Sam „staging“ je bitan kako zbog komunikacije među lekarima koji učestvuju u lečenju bolesnika tako i zbog standardizacije prognoze. T stadijum označava veličinu primarnog tumora, N stadijum označava regionalnu nodalnu zahvaćenost dok M stadijum prikazuje prisustvo udaljenih metastaza. Terapija patohistološki dokazanog oralnog karcinoma zahteva multidisciplinarni pristup. Osnova terapije oralnog planocelularnog karcinoma je hirurško lečenje koje podrazumeva ablativno i rekonstruktivno hirurško lečenje. Osnovni princip ablativne hirurgije kod oralnog karcinoma je resekcija primarnog tumora sa najmanje 1cm negativnim hirurškim marginama. Pored ablacije tumora hirurško lečenje podrazumeva i uklanjanje regionalnih limfnih čvorova vrata. Cilj disekcije vrata je da se kod klinički evidentnih metastaza iste uklone (terapijska disekcija) ili da se uklone okultne metastaze koje su klinički neevidentne (elektivna disekcija). Oralni planocelularni karcinom spada u tumore sa visokom stopom smrtnosti, većom nego što je kod limfoma, laringealnog karcinoma, karcinoma testisa i endokrinih karcinoma. Stopa petogodišnjeg preživljavanja je direktno povezana sa veličinom tumora, prisustvom metastaza u regionalnim limfnim čvorovima i prisutvom udaljenih metastaza. Prosečno trogodišnje preživljavanje bolesnika sa oralnim karcinomom je 52% dok je prosečno petogodišnje preživljavanje oko 39% i ove stope se nisu mnogo menjale tokom godina bez obzira na nova saznanja i nove pristupe lečenju oralnog planocelulanog karcinoma. Ciljevi istraživanja su da se utvrdi da li postoji korelacija debljine OPK izmerene kompjuterizovanom tomografijom i svetlosnim mikroskopom, da li dubina invazije OPK i volume tumora mogu biti prediktivni faktor za razvoj regionalnih cervikalnih metastaza kod oralnog planocelularnog karcinoma. Istraživanje je uključilo 65 konsekutivnih bolesnika oba pola lečenih od oralnog karcinoma na Klinici za maksilofacijalnu hirurgiju Kliničkog centra Vojvodine. Dijagnoza oralnog karcinoma je postavljena na osnovu anamneze, kliničkog pregleda i biopsije. U sklopu TNM „staging“-a bolesnika načinjen je pregled glave i vrata i grudnog koša kompjuterizovanom tomografijom (CT) na osnovu kog smo dobili podatak o dimenzijama tumora. Na osnovu kliničkog nalaza i analize CT nalaza planiralo se operativno lečenje u skladu sa bolesnikovim TNM statusom. Postoperatativni patohistoški preparati je pregledan od strane istog patologa. Parametri koji će su određivani su sledeći: 1. Veličina tumora (2 dimenzije) izmerene na osnovu CT pregleda izražene u cm 2. Debljina tumora izmerena na osnovu CT pregleda izražena u cm 3. Veličina tumora (2 dijametra) na makroskopskom preparatu izražena u cm 4. Debljina tumora na mikroskopskom preparatu izmerena svetlosnim mikroskopom izražena u cm 5. Dubina invazije tumora na mikroskopskom preparatu izmerena svetlosnim mikroskopom izražena u mm 6. Volumen tumora koji se izračunavao prema formuli: VT=π/6 x maksimalni dijametar tumora A x minimalni dijametar tumora B x dubina invazije tumora i izražava se u cm³ 7. Broj metastatski izmenjenih limfnih čvorova u disekatu vrata 8. Ukupan broj patohistološki ispitanih limfnih čvorova u disekatu vrata Nakon prikupljanja planiranog materijala urađena je statistička obrada podataka. Statistička analiza podataka je uključila metode deskriptivne statistike (srednja vrednost, standardna devijacija, učestalost), kao i standardne parametrijske i neparametrijske testove za komparacije dve grupe (Studentov T test, Mann–Whitney U test, hikvadrat test). U fazi statističke analize međusobnih uticaja i povezanosti prikupljenih podataka korišćen je Pearsonov test korelacije. Sva testiranja sprovedena su na nivou statističke značajnosti p<0,05. REZULTATI: Istraživanje je obuhvatilo 65 bolesnika, od kojih je 82% bilo muškog pola prosečne starosti 59 godina. 83% bolesnika su se izjašnjavali kao pušači, dok je 69% bolesnika navelo da redovno koristi alkohol. Svim pacijentima je tokom hirurškog lečenja OPK rađena disekcija vrata i to najčeščće selektivna disekcija vrata (91%). Kod 30 bolesnika je utvrđeno postojanje cervikalnih regionalnih metastaza na operativnom preparatu te su bolesnici podeljeni u dve grupe: sa prisustvom i bez prisustva metastaza u limfnim čvorovima vrata. Utvrđeno je da se ove dve grupe statistički značajno razlikuju u dubini invazije tumora i volumenu tumora. Utvrđeno je takođe da postoji statistički značajna korelacija između debljine tumora izmerene CT pregledom i debljine tumora izmerene svetlosnim mikroskopom. Dokazano je da dubina invazije tumora veća od 7mm i zapremina tumora veća od 4cm³ predstavljaju prediktivni faktor za pojavu regionalnih cervikalnih metastaza. ZAKLjUČAK: Na osnovu istraživanja izvedeni su zaključci koji ukazuju na to da postoji statistički značajna korelacija između debljine tumora OPK izmerene CTpregledom i svetlosnim mikroskopom te se debljina tumora izmerena CT pregledom može koristiti za planiranje operativnog zahvata prilikom lečenja OPK. Dubina invazije tumora veća od 7mm i volumen tumora veći od 4 cm³ predstavljaju prediktivni faktor za pojavu nodalnih cervikalnih metastaza te su značajni za određivanje stadijuma bolesti.sr
dc.description.abstractOral cancer is the sixth most common malignant disease in the world which incidence varies based on geographic area. It represents 5% of all newly discovered malignant tumors annually and constitutes 14 % of all malignant tumors of head and neck. Squamous cell carcinoma is considered to be a type of oral cancer because more than 90 % of malignant tumors that occur in oral cavity are squamous cell carcinomas while other tumors (malignant tumor of minor salivary gland, lymphoma, sarcoma) rarely occur. Oral cancer is the cancer found in the following anatomic regions: mucosa of front two-thirds of the tongue, the floor of the mouth, cheeks, upper and lower gingiva, retromolar trigone as well as  mucosa of soft and hard palates. Oral squamous cell carcinoma is most commonly localized in mucous membrane of the movable part of the tongue and floor of the mouth. Men are more affected than women (male to female ratio is 3:1) probably because of men’s riskier behavior. It is most commonly diagnosed in the sixth and seventh decade of life (the median is 62 years old) although it has been diagnosed in patents younger than 45 in recent years. Risk factors of oral squamous cell carcinoma are well known. The major factor is tobacco smoking (the period of smoking is significant, it is also important to consider whether a patient smokes a pipe or cigarette, whether he/she chews tobacco as well as the period of abstinence). The mortality rate is believed to be directly related to the number of cigarettes smoked a day. An excessive use of alcohol has been reported in over 75% of patients with oral cancer. There is a synergistic effect of alcohol and cigarette consumption and long-term exposure to these risk factors results in ‘field of cancerization’, genetic instability and tumor development. Chromosome abnormalities, which are caused by DNA damage and include the change in genetic material of chromosomes, have been reported in patients with oral squamous cell carcinoma. One of the most common genetic abnormalities in patients with oral squamous cell carcinoma is a mutation of р53 gene which is located on a short arm of chromosome 17 and represents a tumor suppressor gene. Oral squamous cell carcinoma is not difficult to diagnose when it becomes symptomatic. The patient complains of pain, bleeding, otalgia, swallowing difficulties, decreased tongue mobility. The first symptom is rarely metastatic lymph node on the neck because patients either do not notice or ignore oral pathology. The oral cancer is diagnosed based on the detailed anamnesis, physical examination and pathohistological verification. The oral squamous cell carcinoma occurs in three clinical forms: exophytic, endophytic and infiltrative form. The gold standard for diagnosis of oral cancer is biopsy and pathohistological verification. However, in case of smaller changes, punch biopsy, incisional and excisional biopsies can also be applied. ТNМ staging system of AJCC (American Joint Committee on Cancer) is nowadays used for clinical staging of oral cancer and it is based on the data acquired by clinical examination and imaging methods. Not only is the staging itself important for communication between the doctors involved in treatment, but it is also important for standardization of prognosis. Т describes the size of primary tumor, N describes regional nodal spread and М describes distant metastasis. The treatment of histopathologically proven oral cancer requires multidisciplinary approach. The main treatment of oral squamous cell carcinoma is surgical treatment which involves ablative and reconstructive surgical treatment. The basic principle of ablative surgery for oral cancer is the resection of primary tumor with at least 1 cm negative surgical margins. Apart from tumor ablation surgical treatment also involves removal of regional lymph nodes on the neck. The aim of neck dissection is to remove clinically evident metastasis (therapeutic dissection) or to remove occult metastasis that are not clinically evident (elective dissection). The oral squamous cell carcinoma is the cancer with high mortality rate. The mortality rate is higher than the mortality rate for lymphoma, laryngeal cancer, testicular cancer and endocrine cancer. The five-year survival rate is directly related to the size of the tumor, presence of metastasis in regional lymph nodes and distant metastasis. The average three-year survival rate of the patients with oral cancer is 52% and the average five-year survival rate is 39%. These rates have not changed a lot over the years regardless of new knowledge and approaches in treatment of oral squamous cell carcinoma. The aims of the study are to determine whether there is a correlation between the depth of invasion of oral squamous cell carcinoma determined by computed tomography and light microscope and whether the invasion depth of OSCC and tumor volume can be predictive factors of development of regional cervical metastases in case of oral squamous cell carcinoma. The study covered 65 consecutive patients of both sexes who received treatment for oral cancer at the Clinic for Maxillofacial Surgery of the Clinical Center of Vojvodina. The diagnosis of oral cancer was established based on the anamnesis, physical examination and biopsies. The TNM ‘staging’ of the cancer involved the examination of the patient’s head and thorax by computed tomography (CT) which enabled us to obtain reliable data about the tumor size. After obtaining clinical findings and CT results, the patients’ treatment was planned based on their TNM status. A postoperative histopathological examination was performed by the same pathologist and the following parameters were determined: 1. Tumor size (2 dimensions) measured by CT and expressed in cm 2. Tumor thickness measured by CT and expressed in cm 3. Tumor size (2 diameters) on microscopic device and expressed in cm 4. Tumor thickness on microscopic device measured by light microscope and expressed in cm 5. Depth of tumor invasion on microscopic device measured by light microscope and expressed in cm 6. Tumor volume calculated based on the following formula: VT=π/6 x maximum tumor diameter А x minimum tumor diameter B x depth of tumor invasion and expressed in cm³ 7. The number of metastatic lymph nodes in the neck dissection 8. Total number of pathohistologically tested lymph nodes in the neck dissection. Upon collecting the planned material, statistical analysis of all data was carried out. The statistical analysis included the methods of descriptive statistics (mean value, standard deviation, frequency) and standard parametric and nonparametric tests for comparison of two groups (Student’s T test, Whitney U test, chi-square test). The Pearson’s Test of Correlation was used in the phase of statistical analysis of interaction effects and correlation of obtained data. All tests were performed at the level of statistical significance of p<0.05. RESULTS: The study covered 65 patients, out of which 82% were male patients aged 59. 83% of patients said they smoked and 69% of patients stated that they consumed alcohol regularly. A neck dissection was performed in all patients during surgical treatment of OSCC and it was selective neck dissection (91%). Cervical regional metastasis was found in 30 patients so they were divided into two groups: the group of patients who had metastasis in the lymph nodes and the group of patients with no metastasis in lymph nodes of the neck. It was determined that there was a statistically significant difference in depth of invasion and tumor volume between these two groups. The statistically significant difference was also determined between the thickness of tumor measured by CT and thickness of tumor measured by light microscope. Moreover, the depth of invasion of tumor greater than 7mm and volume of tumor greater than 4cm³ were proven to represent a predictive factor of development of regional cervical metastasis. The study results show that there is a statistically significant correlation between the thickness of OSCC tumor measured by CT and the thickness measured by light microscope, so the thickness of tumor measured by CT can be used for planning the surgery during the treatment of OSCC. The depth of tumor invasion greater than 7 mm and tumor volume greater than 4 cm³ represent a predictive factor of development of cervical metastasis, which means that they are significant for determining the stage of disease.en
dc.languagesr (latin script)
dc.publisherУниверзитет у Новом Саду, Медицински факултетsr
dc.rightsopenAccessen
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.sourceУниверзитет у Новом Садуsr
dc.subjectoralne neoplazmesr
dc.subjectMouth Neoplasmsen
dc.subjectplanocelularni karcinomsr
dc.subjectinvazivnost neoplazmisr
dc.subjectvolumen tumorasr
dc.subjectpušenjesr
dc.subjectkonzumiranje alkoholasr
dc.subjectbiopsijasr
dc.subjectmetastazesr
dc.subjectlimfni čvorovisr
dc.subjectkompjuterizovana tomografijasr
dc.subjectCarcinoma, Squamous Cellen
dc.subjectNeoplasm Invasivenessen
dc.subjectTumor Burdenen
dc.subjectSmokingen
dc.subjectAlcohol Drinkingen
dc.subjectBiopsyen
dc.subjectNeoplasm Metastasisen
dc.subjectLymph Nodesen
dc.subjectTomography, X-Ray Computeden
dc.titleUticaj dubine invazije oralnog planocelularnog karcinoma na pojavu metastaza u limfnim čvorovima vratasr
dc.title.alternativeThe effect of depth of tumor invasion on neck lymph node metastasis in patients with oral squamous cell carcinomaen
dc.typedoctoralThesisen
dc.rights.licenseBY-NC-ND
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/35508/IzvestajKomisije.pdf
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/35507/Disertacija.pdf
dc.identifier.rcubhttps://hdl.handle.net/21.15107/rcub_nardus_12330


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