Limfadenektomija kod karcinoma hipofarinksa - korelacija mikrometastatskog širenja sa prediktivnim molekularnim faktorima terapijskog odgovora

Abstract

Uvod: Skvamocelularni karcinom hipofarinksa (SKH) predstavlja jednu od najagresivnijih neoplazmi glave i vrata. Petogodišnje preţivljavanje kod ovog oboljenja u većini studija je ispod 30%. Zahvaćenost limfnih ţlezda prepoznata je kao nabitniji prognostiĉki faktor za SKH. Hirurško leĉenje SKH stoga treba orijentisati prema odstranjenju primarnog tumora, ali i adekvatnoj limfonodalnoj disekciji, ĉime bi se postigao potencijalni kurativni efekat, ali i odredio taĉan stadijum i prognoza oboljenja. Uniformno radikalno operisana grupa bolesnika i veliki broj odstranjenih limfnih nodusa omogućio nam je adekvatno odreĊivanje distribucije limfonodalnih metastaza, procene N stadijuma bolesti, ali i dodatnu imunohistohemijsku analizu na prisustvo mikrometastaza u odstranjenim limfnim nodusima. Dodatnim ispitivanjem pokušali smo da ustanovimo korelaciju ekspresije molekularnih markera p53 i EGFR sa preţivljavanjem, i stadijumom bolesti odraţenim prevashodno kroz N stadijum bolesti. Metodologija: U studiju je ukljuĉeno ukupno 55 bolesnika kod kojih je naĉinjena faringolaringoezofagektomija sa funkcionalnom disekcijom vrata i rekonstrukcija visceralnim transplantatom. Disekcija obe strane vrata je uĉinjena primenom lateralne selektivne disekcije koja je obuhvatala uklanjanje limfnih nodusa iz nivoa II, III, IV i VI . Prilikom patohistološke obrade preparata posebna paţnja je obraćena na sledeće parametre:1. Primarna lokalizacija tumora (mukozna distribucija i dubina infiltracije, diferencijacija, invazija vaskularnih, limfatiĉnih i neuralnih elemenata), 2. Nodalni status (ukupan broj odstranjenih nodusa, ukupan broj pozitivnih nodusa, prisustvo ektrakapsularnog rasta, veliĉina nodusa). Dodatnom imunohistohemijskom analizom ispitivani su limfni nodusi na prisustvo mikrometastaza i izolovanih tumorskih ćelija, odnosno uĉinjena je semikvantitativna procena ekspresija ispitivanih 6 markera (p53 i EGFR). Statistiĉkim analizama naĉinjena je korelacija gore navedenih parametara sa ukupnim preţivljavanjem i kliniĉkim ishodom pri završetku studije...

Introduction: Hypopharyngeal squamocellular carcinoma (HSCC) represents one of the most aggressive neoplastic diseases of head and neck. Most of the studies reports 5 year survival rate to be below 30%. Lymph node involvement in HSCC has been recognized as the most important prognostic factor. Surgical treatment of HSCC therefore should be oriented towards removal of the primary tumor, together with the adequate lymhonodal dissection, by which one accomplishes curative intent, both with the proper definite disease staging and prognosis. Uniformly radically operated group of patients and a large number of dissected lymph nodes provided us with a possibility of accurate estimation of lymph node distribution, accurate N staging and also allowed us additional immunohistochemical analyzes for presence of micrometastases in lymph nodes. With further investigation we will try to estimate the correlation between molecular expression of p53 and EGFR with the overall survival, and the disease stage. Methodology: Overall, in this study we included 55 patients in whom pharyngolaryngoesophagectomy with selective lymph node dissection and reconstruction with the visceral substituent was performed. We performed bilateral selective lymph node dissection, which included levels II, III, IV and VI. During the pathohistologic work up special emphasis was given upon: 1. primary tumor (mucosal distribution and the depth of infiltration, differentiation and invasion of vascular, lymphatic and neural elements), 2. nodal status (overall number of harvested lymh nodes, overall number of positive lymph nodes, size and presence of extracapsular growth). Immunohistochemistry was performed in order to determine presence of micrometastases and isolated tumor cels (ITC) in lymph nodes, and also to determine the expression of p53 and EGFR. Statistical analyzes were performed with the intent to determine the correlation of the aforementioned parameters with the overall survival rate. Results: In this study there was no intrahospital mortality. Overall survival median was 18.00 months (11,89 - 24,11). 42 (76%) patients died and 13 (24%) was alive when we ended the study. Two year survival was marked in 27 patients (46.5%). N0 stage was present in 17 patients, 8 9 patients had N1 stage while N2 stage was present in 30 patients...