| Abstract | Uvod i cilj istraživanja
Traheoezofagealni govor pomoću GP danas je zlatni standard u govornoj rehabilitaciji laringektomiranih bolesnika. Međutim, kvalitetu glasa kao i kvalitetu života značajno narušavaju komplikacije GP koje mogu biti posljedica pojedinih kirurških postupaka tijekom laringektomije i formiranja TEF ili su vezane uz TEF i samu GP. Nekoliko je rizičnih čimbenika koji pridonose razvoju komplikacija GP, a posljednjih pet godina mali broj studija proučavalo je utjecaj EER na komplikacije GP, prvenstveno atrofiju traheoezofagealnog zida, povećanje dijametra TEF i granulacije sluznice dušnika, te na kvalitetu glasa laringektomiranih bolesnika. Iako je donedavno zlatni standard u dijagnosticiranju EER bila višekanalna 24-satna pH-metrija, dokazano je da je pepsin najosjetljiviji i specifičniji marker EER, a mjerenje koncentracije pepsina u slini pouzdana, jeftina, jednostavna i neinvazivna metoda. ----- Ispitanici i metode
U istraživanje je uključeno 60 laringektomiranih bolesnika s GP i 30 kontrolnih zdravih ispitanika kojima su određene vrijednosti koncentracije pepsina u uzorcima sline ELISA metodom. Svakom bolesniku kliničkim je pregledom utvrđeno postojanje komplikacije GP i određena uspješnost govorne rehabilitacije Harrison-Robillard-Schultzovom skalom (HRS). U bolesnika s komplikacijama GP randomizirano je provedena terapija pantoprazolom u dozi od 40 mg ujutro kroz šest mjeseci. Za statističku analizu upotrijebljen je Mann-Whitneyjev test, Studentov t-test, Spearmannov test korelacije, chi kvadrat test i linearna regresijska analiza. Razina značajnosti P podešena je na 0.05. ----- Rezultati
U ovom istraživanju prvi je put istražen utjecaj EER na komplikacije GP i kvalitetu glasa određivanjem vrijednosti koncentracije pepsina u slini. U svim uzorcima sline svih ispitanika, i laringektomiranih bolesnika i zdravih kontrolnih ispitanika, dokazana je prisutnost pepsina. Pomoću rezultata vrijednosti koncentracije kontrolnih zdravih ispitanika koje su imale normalnu raspodjelu izračunat je raspon normalnih vrijednosti koncentracije pepsina u slini kao srednja vrijednost pepsina zdravih kontrolnih ispitanika ±3 standardne devijacije, čime je obuhvaćeno 95% rezultata zdravih kontrolnih ispitanika. Vrijednosti preko 0,884 pg/ml, 95 percentile, smatrane su povišenima, odnosno abnormalnima te je tako u svih bolesnika s vrijednostima pepsina iznad 0,884 pg/ml dijagnosticiran EER. Na taj je način u 1/4 laringektomiranih bolesnika s GP dijagnosticiran EER. Medijani vrijednosti koncentracije pepsina nisu se razlikovali između laringektomiranih bolesnika i zdravih kontrolnih ispitanika. Također, medijani vrijednosti koncentracije pepsina i učestalost EER nisu se značajno razlikovali između bolesnika sa i bez komplikacije GP, kao niti među bolesnicima s različitim vrstama komplikacija GP, iako su bolesnici s formiranim biofilmom na GP, odnosno kandidijazom GP imali više vrijednosti pepsina ali ta razlika nije bila statistički značajna. Utjecaj EER na atrofiju traheoezofagealnog zida i povećanje promjera TEF u ovom istraživanju nije se mogao istražiti jer je u istraživanje bio uključen samo jedan bolesnik s ovom vrstom komplikacije GP. U ovom istraživanju dokazana je visoka uspješnost govorne rehabilitacije no nije nađena statistički značajna povezanost između vrijednosti koncentracije pepsina u slini i kvalitete glasa bolesnika s GP. Učestalost komplikacija govorne proteze, analiza kvalitete glasa i vrijednost koncentracije pepsina uspoređene su i među bolesnicima u kojih je i u kojih nije provedena RT, te nije nađen značajan utjecaj RT na učestalost niti vrstu komplikacija GP, kvalitetu glasa niti na vrijednost koncentracije pepsina. Iako je nađena manja učestalost komplikacija GP nakon tri i šest mjeseci terapije pantoprazolom, ta razlika nije bila statistički značajna. Također nije dokazano ni značajano poboljšanje kvalitete glasa ni smanjenje vrijednosti koncentracije pepsina nakon terapije. ----- Zaključak
Ovim istraživanjem dokazano je da EER, dijagnosticiran jednostavnom i neinvazivnom metodom određivanja vrijednosti koncentracije pepsina u slini, ne utječe značajno na učestalost svih komplikacija GP, te da nije potrebno provoditi profilaktičku terapiju IPP u svih bolesnika s komplikacijama govorne proteze. S obzirom na to da je u ovom istraživanju sudjelovao samo jedan bolesnik s atrofijom traheoezofagealnog zida i povećanjem promjera TEF, buduća istraživanja trebala bi uključivati veći broj bolesnika s ovim vrstama komplikacija GP kako bi dobiveni rezultati bili usporedivi s većinom prethodno objavljenih istraživanja. |
| Abstract (english) | Introduction and aim
Tracheoesophageal speech with voice prosthesis (VP) is the gold standard in speech rehabilitation of laryngectomized patients. However, the voice quality and quality of life may be notably impaired by VP complications that may be related to certain surgical procedures during laryngectomy and the formation of tracheoesophageal fistula (TEF) or related to the TEF and the VP itself. There are several risk factors that contribute to the development of VP complications. In the last five years a small number of studies have examined the impact of extraesophageal reflux (EER) on several VP complications: tracheoesophageal wall atrophy, increasing diameter of TEF, and tracheal granulation and on the voice quality in laryngectomized patients. Until recently, multichannel 24-hour pH - metry was the gold standard in the diagnosis of EER. However, several studies identified pepsin as a sensitive and specific marker of EER, and showed that measurement of concentration of pepsin in saliva was a reliable, cheap, simple and non-invasive method to diagnoze EER. ----- Patients and methods
The study included 60 laryngectomees with VP and 30 healthy control subjects in whom concentrations of pepsin in saliva samples were analyzed with ELISA method. Clinical examination in the studied group evaluated the presence of VP complications and speech rehabilitation performance score with Harrison-Robillard-Schultz scale (HRS). Patients with VP complications were randomized in two groups: therapy with pantoprazole at a dose of 40 mg in the morning for 6 months or no medication. Statistical analysis was performed using Mann - Whitney test, Student's t-test, Spearmann's correlation test, chi square test and linear regression analysis. Significance level P was set to 0.05. ----- Results
This study is the first to show the effect of EER on VP complications and voice quality by measuring the concentration of pepsin in saliva. Saliva samples of all subjects, laryngectomees and healthy controls, demonstrated the presence of pepsin. Using the results of normally distributed pepsin concentration values of control healthy subjects, normal range of pepsin concentrations in saliva were determined as: mean pepsin concentration in healthy controls ± 3 standard deviations, which covered 95% of all healthy controls. Values above 0.884 pg/ml, (within 95th percentile) were considered increased or abnormal. Finally, in all patients with pepsin values above 0.884 pg/ml EER was diagnozed. Using this method, in 25% of laryngectomized patients with VP EER was diagnozed.
Median pepsin concentrations did not differ significantly between laryngectomized patients and controls. Also, median concentrations of pepsin and frequency of EER did not differ significantly between patients with and without VP complications, nor among patients with different types of VP complications. However, patients with biofilm formed on the GP or GP candidiasis had higher values of pepsin, but this difference was not statistically significant. Impact of EER on tracheoesophageal wall atrophy and TEF diameter increase could not be investigated in this study because there was only one patient with this kind of VP complication.
This study demonstrated a high performance of speech rehabilitation but did not find any significant correlation between the concentration of pepsin in saliva and voice quality in patients with VP. Incidence of VP complications, analysis of voice quality and concentration of pepsin in saliva did not differ significantly among patients regarding radiotherapy. Although the incidence of VP complications after 3 and 6 months of treatment with pantoprazole was lower, this difference was not statistically significant. In addittion, pantoprazole therapy did not significantly reduce pepsin in saliva, or show any significant improvement of voice quality. ----- Conclusion
This study demonstrated that EER, diagnozed non-invasively by concentration of pepsin in saliva, did not significantly affect the incidence of VP complications. Therefore, there are no data to support prophylactic protein pump inhibitor therapy in all patients with VP complications. Given that this study involved only one patient with tracheoesophageal wall atrophy and increasing TEF diameter, future research should include a larger number of patients with these kinds of VP complications in order to obtain results comparable with majority of previously published studies. |
