Early diagnosis of radiotherapy failure for patients with head and neck cancer: the role of biochemical markers.

PURPOSE: There is a lack of effective diagnostic tools for early assessment of radiotherapy (RT) outcome in patients with head and neck cancer (HNC). The timely diagnosis of treatment failure may facilitate use of salvage procedures to prevent disease progression. We assessed squamous cell carcinoma antigen and CYFRA 21-1 as early markers of radiotherapy failure in patients with HNC. METHODS: Between January 2009 and February 2012, 185 patients (median age 59 years) with squamous cell carcinoma were treated with curative intent with RT alone or combined with chemotherapy (ChT). Markers were estimated in the serum 2 times: before RT and after completion of treatment. RESULTS: The median of follow-up was 40 months. Locoregional control (LRC) was 53% and locoregional failure (LRF) was 31%. When comparing LRC and LRF, there were no significant differences between markers concentration obtained before RT. After RT, CYFRA 21-1 (p = 0.018) was significantly elevated in the LRF group. Patients with CYFRA 21-1 <1.79 ng/mL had a higher disease-free survival rate compared to patients with CYFRA 21-1 ≥1.79 ng/mL (74% vs 53%, respectively). After RT, CYFRA 21-1 was significantly related to the overall survival ratio in both univariate (p = 0.049) and multivariate analysis (p = 0.019). CONCLUSIONS: CYFRA 21-1 assessed at the end of RT or ChT seems to be a prognostic marker for tumor response. A high concentration of CYFRA 21-1 after treatment increases the risk of death. CYFRA 21-1 might be suggested in the monitoring of carcinomas of HNC.

Ionizing radiation affects profile of serum metabolites: increased level of 3-hydroxybutyric acid in serum of cancer patients treated with radiotherapy.

Radiotherapy causes molecular changes observed at the level of body fluids, which are potential biomarker candidates for assessment of radiation exposure. Here we analyzed radiotherapy-induced changes in a profile of small metabolites detected in sera of head and neck cancer patients using the gas chromatography coupled with mass spectrometry approach. There were about 20 compounds, including carboxylic acids, sugars, amines and amino acids, whose levels significantly differed between pre-treatment and post-treatment samples. Among metabolites upregulated by radiotherapy there was 3-hydroxybutyric acid, whose level increased about three times in post-treatment samples. Moreover, compounds affected by irradiation were associated with several metabolic pathways, including protein biosynthesis and amino acid metabolism.

Human papillomavirus DNA in pharyngeal scrapes as a marker of HPV-related squamous cell cancer of the oropharynx.

BACKGROUND: Recent studies have indicated that human papillomavirus is an etiologic agent for a subset of head and neck cancers associated with better prognosis, therefore, prompt confirmation of such etiology seems to be crucial for choosing the optimal therapeutic option. Standard HPV diagnosis is currently based on histopathological material. In the present study, the novel diagnostic method based on pharyngeal brush biopsy is proposed. OBJECTIVES: The aim of this study was to evaluate the usefulness of the Real-Time PCR-based (RT-PCR) test in detecting HPV-related cancer of the oropharynx using superficial scraps taken from the oropharyngeal region. STUDY DESIGN: Ninety patients with head and neck squamous cell cancer were enrolled in the study. The presence of HPV DNA in pharyngeal superficial scrapes assessed by RT-PCR was compared to the HPV status in the tumor tissue samples determined by a combined RT-PCR/P16(INK4A) expression algorithm. Analytical sensitivity and specificity were calculated and the clinical outcome was analyzed in correlation to the HPV status. RESULTS: HR-HPV DNA in pharyngeal swabs was revealed in 25 cases (28.4%) and simultaneously confirmed in all corresponding tissue samples. Sensitivity and specificity of the viral status assessment in the brush biopsies in respect to the RT-PCR/P16(INK4A) 20 were 100% and 96.2%, respectively. HR-HPV positive status was associated with an excellent clinical outcome and reduced hazard ratio of recurrence and disease-related death. CONCLUSIONS: The proposed novel method of HPV status assessment using RT-PCR and superficial scraps appeared to be highly sensitive, specific, and useful in predicting the clinical outcome.

[Assessment of retrocochlear hearing pathway activity in infants with central nervous system impairment occurring as an effect of perinatal asphyxia]. / Ocena funkcji pozaslimakowej czesci drogi sluchowej u niemowlat ze zmianami w obrebie osrodkowego ukladu nerwowego powstalymi na skutek asfiksji okoloporodowej.

INTRODUCTION: The most often changes in the central nervous system (CNS) occurring as an effect of perinatal asphyxia are found to be hypoxic-ischemic encephalopathy (HIE) in term newborns, peri- (PVH) or intraventricular hemorrhages (IVH) and periventricular leukomalacia (PVL) in preterm neonates. Chronic hypoxia is considered to affect the brainstem in infants, especially nuclei of the hearing pathway are vulnerable to low oxygen level. The aim of the study was to carry out the objective assessment of the retrocochlear hearing pathway activity using ABR in infants with CNS impairment occurring as an effect of perinatal asphyxia, imaged during trans-fontanel ultrasonography. MATERIAL AND METHODS: To the investigation 36 infants with HIE, IVH or PVL were included, the control group encompassed 32 born at term, health children. ABR recordings were performed in 3 months old children using Nicolet Spirit System for clicks of 85 and 80 dB nHL. RESULTS: No differences were found between latencies of waves I and II. ABR latencies of waves III, IV, V and interpeak latencies I-III, III-V, I-V were significantly delayed in InvG when compared to control patients. In conclusion, the brainstem activity in infants with CNS involvement as an effect of perinatal asphyxia is lower comparing to health children. Subclinical abnormalities as prolonged synaptic transmission of electric signal in retrocochlear auditory pathway were revealed.

[Extramedullary plasmacytoma of the neck--case report]. / Szpiczak plazmocytowy odosobniony pozakostny w obrebie szyi--opis przypadku.

Extramedullary plasmacytoma (EMP) is a rare neoplasm which belongs to non-Hodgkin's lymphomas, which is characterized by monoclonal, neoplastic proliferation of B-type lymphocytes in the soft tissues. The most common location for EMP to occur is the nasopharynx and paranasal sinuses. Treatment is efficacious with surgery, radiotherapy or combination these two methods. This report presents a case of EMP of the neck in 63-year-old patient, diagnosed and treated in ENT Department of Medical University of Silesia in Zabrze. On the basis of physical examination and radiologic studies the extensiveness of the tumour was determined and the surgical procedures were undertaken. Diagnosis was established on the basis of histopatological and immunohistochemical postoperative examinations as well as radiologic studies and trepanobiopsy. Surgery was followed by radiotherapy. 6 months later because of progression and dissemination of the disease chemotherapy and hematological treatment were performed. Patient remains in laryngological, oncological and transplantological follow-up.

[Parapharyngeal oncocytoma of the parotid gland--case report]. / Przypadek gruczolaka kwasochlonnego slinianki przyusznej penetrujacego do przestrzeni przygardlowej.

Oncocytoma is a rare, benign salivary gland tumour with slowly course. It usually occurs in the parotid gland, seldom in submandibular gland. This report presents a case of parapharyngeal oncocytoma of the left parotid gland in 77-year-old patient, treated in 2nd ENT Department of Medical University of Silesia in Zabrze. On the basis of physical examination and preoperative radiologic studies (computed tomography scan of nasopharynx, magnetic resonance imaging, Doppler ultrasonography of carotid and vertebral arteries) the extensiveness of the tumour was determined and the surgical procedure was undertaken. The removal of a whole tumour was performed through a cervical--transpharyngeal approach with midline mandibulotomy. A follow-up of 30 months hasn't revealed any recurrence of the oncocytoma.

[Septal nasal chondroma--a case report]. / Chrzestniak przegrody nosa--opis przypadku.

INTRODUCTION: Cartilaginous tumors of the head and neck are rare. The most frequent site is larynx and spheno-ethmoidal area. Chondroma of the nasal septum is very rare. Since its first description in the literature in 1842, only about 140 cases have been reported. The symptoms of nasal septum chondroma are nasal obstruction, headache and epistaxis. The treatment of choice is wide surgical excision. AIM: The aim of our study was to show own, very rare case of septal nasal chondroma. MATERIAL AND METHODS: We described a case of septal nasal chondroma in the 39-year-old female. She reported nasal obstruction, headache of the frontal area for about 10 years. The CT examination showed the tumor mass in the right nasal cavity extending to the maxillary sinus and right orbit. The tumor was removed via the lateral rhinotomy. Histopathological examination revealed chondroma. No recurrence was noticed after 2 years of follow-up. CONCLUSIONS: Chondroma should be taken into consideration during the differential diagnosis of the septal nasal tumors.

[Otoacoustic emissions measurements in children during the chemotherapy because of the acute lymphoblastic leukemia]. / Badania emisji otoakustycznych u dzieci podczas chemioterapii z powodu ostrej bialaczki limfoblastycznej.

INTRODUCTION: Chemotherapy is associated with an increased risk of ototoxic changes. The predictive value of conventional pure-tone audiometry on early detection of ototoxicity has been questioned. Otoacoustic emissions (OAEs) appear to be more sensitive to cochlear insult than the conventional pure-audiometry. The purpose of our study was (a) investigation the clinical usefulness of Distortion Product Otoacoustic Emissions (DPOAEs) as early indicator of chemotherapy-induced ototoxicity, (b) determination which of the protocols of chemotherapy is most ototoxic as measured by DPOAEs, (c) comparison of the short-term and long-term effects of chemotherapy on DPOAEs. MATERIAL AND METHODS: Tonal audiometry (0,25-8 kHz), immitance audiometry and DPOAEs were measured in 10 children with acute lymphoblastic leukemia (ALL). Measurements were performed before and after each protocol of ALL IC-BFM 2002 chemotherapy: protocol I: vincristine (VCR), L-asparaginase (L-ASP), daunorubicin (DNR), cyclophosphamide (CPM), cytarabine (ARA-C), 6-mercaptopurine (6-MP), methotrexate (MTX); protocol mM: 6-MP, MTX; protocol II: VCR, doxorubicin (DOX), L-ASP, CMP, ARA-C, thioguasine (6-TG), MTX; protocol III: VCR, DOX, L-ASP, CMP, ARA-C, 6-TG, MTX. DPOAEs were measured using ILO2 92 Otodynamics Analyser. Cochlear activity was evaluated by recording 2f1-f2 DPOAEs with L1 = 65 and L2 = 60 dB SPL. Comparisons of the DP-grams amplitudes were performed between baseline measurements and those recorded before and after each chemotherapy course. RESULTS: Our results indicate that: a)DPOAE is a more sensitive technique for the assess of chemotherapy-induced ototoxicity than conventional audiometry, b) with DPOAE monitoring very subtle hearing changes can be detected, c) DPOAE amplitude was significantly decreased at all frequencies studied in 50% children with leukemia, d) depression of DPOAE amplitude was evident only during and after first protocol, e) long-term DPOAE monitoring reviled reversibility of ototoxicity in all children, f) a large individual variability in the DPOAE response following the chemotherapy was observed, g) in a few cases a transient increase in DPOAE amplitude had been observed before it was reduced. CONCLUSIONS: Distortion product otoacoustic emissions measurements are very sensitive on early detection of the changes in cochlear function and are recommended for monitor hearing in patients during chemotherapy.

[Hearing evaluation in chronic renal failure children]. / Ocena narzadu sluchu u dzieci z przewlekla niewydolnoscia nerek.

UNLABELLED: Chronic renal failure (CRF) causes a lot of systemic side-effects, among them: neurological and otological complications. In present study hearing evaluation was made in young patients, using distortion product otoacoustic emissions (DPOAEs) and auditory brainstem responses (ABR). THE AIM OF STUDY: (1) objective assessment of hearing organ activity in CRF children, (2) localization of hearing organ part involved in CRF, (3) establishing best parameters of ipsilateral stimulation in DPOAEs for clinical use. MATERIALS AND METHODS: Hearing acuity was assessed in 22 CRF children ranging in age from 9 to 17 years and 18 healthy children ranging in age from 10 to 18 years. At first pure tone audiometry and tympanometry were evaluate. Only patients with normal middle ear condition and hearing threshold better than 30 dB HL were put forward further investigations. Objective assessment of hearing condition included: (1) DPOAEs using DP-gram format. Two simultaneous pure-tone signals (primaries) were presented to the ear at two different frequencies (f1 and f2, where f2 > f1) and the 2f1-f2 were analyzed. Five pairs of non equal level and L2 were used L1 and L2: panel A1: L1 = 65 and L2 = 60 dB SPL, panel A2: L1 = 63 and L2 = 55 dB SPL, panel A3: L1 = 59 and L2 = 45 dB SPL, panel A4: L1 = 55 and L2 = 35 dB SPL, panel A5: L1 = 51 and L2 = 25 dB SPL; (2) ABR investigation using click stimulus, at 90 dB nHL level. Wave I, III, V latencies and intervals I-III, III-V, I-V were evaluated. Our results reviled significantly lower mean DPOAEs amplitudes in CRF children when compare to healthy children, at all frequencies measured. No differences in ABR evaluation were observed. Most optimal DPOAEs parameters in clinical use seem to be panel A1, A2 and A3 of level L1 and L2.

[Evaluation of the cochlear efferent system in patients with cerebello-pontine angle tumor]. / Ocena ukladu eferentnego slimaka u pacjentów z guzem kata mostowo-mózdkowego.

The aim of the study was to estimate a cochlear efferent system in the group of patents with cerebello-pontine angle tumor (CPA). The size of an efferent effect was defined as the difference of the amplitudes in click evoked otoacoustic emissions (CEOAEs) during without contralateral acoustic stimulation (CAS) and with broad-bond noise (BBN) was estimated. The research was also conducted on the influence of tumor dimensions, age, sex, and the hearing level in tonal audiometry on the size of the efferent effect. The research was carried out on a group of 14 patients with cerebello-pontine angle tumor and on an appropriate fourteen-person test group. Having our results analyzed we were able to state that, compared with the test group, in the group of patients with CPA tumor significant reduce suppressions of otoacoustic emission response during CAS occurred both in an ear on the tumor side and in an ear on the healthy side. However, the tumor dimensions, sex, and the hearing level in tonal audiometry seemed not to affect significantly the size of the efferent effect.

[Evaluation of cochlear function in children with chronic renal failure]. / Ocena funkcji slimaka u dzieci z przewlekla niewydolnoscia nerek.

UNLABELLED: In present study cochlear function was evaluate in young chronic renal failure (CRF) patients using distortion product otoacoustic emissions (DPOAEs). THE AIM OF STUDY: (a) objective assessment of cochlear function in CRF children, (b) establishing best parameters of ipsilateral stimulation in DPOAEs (DP-gram format) for clinical use. Hearing acuity was assessed in 19 CRF children and 18 healthy children. At first pure tone audiometry and tympanometry were evaluate. Only patients with normal middle ear condition and hearing threshold better than 30 dB HL were put forward further investigations. Objective assessment of cochlear function included DPOAEs using DP-gram format. Our results reviled significantly lower mean DPOAE amplitudes in CRF children when compare to healthy children, at all frequencies measured. Most optimal DP-gram parameters in clinical use seems to be level L1 and L2 equal respectively: 65 and 60 dB SPL; 63 and 55 dB SPL; 59 and 45 dB SPL.

[Assessment of cochlea activity in a group of newborns with central nervous system impairment as an effect of perinatal asphyxia using click-evoked otoacoustic emissions (CEOAEs)]. / Ocena funkcji slimaka za pomocq emisji otoakustycznej wywolanej trzaskiem (CEOAEs) u noworodków z niedotlenienienem oklporodowym i nastepowymi zmianami w obrebie osrodkowego ukladu nerwowego.

During adaptation of newborn to extra-uterine environment dramatic changes in functioning in the inner organs and the entire human body is observed. Complicated or premature birth as well as complicated course of a perinatal period may cause reversible or irreversible damage of various tissues, organs or systems, and, consequently, their dysfunction. The most often changes in the central nervous system (CNS) in newborns occurring as an effect of perinatal asphyxia are found to be ischemic-hypoxic encephalopathy (IHE), periventricular leucomalacia (PVL) and intraventricular hemorrhages (IVH). Chronic hypoxia is considered to affect the hearing organ in newborns. Reversible or irreversible changes within the cochlea, brainstem or cortex may result in perceptive hearing losses. The aim of the study was to carry out the objective assessment of the cochlea activity using CEOAEs in neonates with CNS impairment occurring following perinatal asphyxia. To the investigation 16 newborns with IHE, PVL or IVH were included. The control group encompassed the health newborns matched as to the age. Perinatal anamnesis, general pediatric status, results of trans-fontanel ultrasonography and biochemical test results were taken into account in statistical analyses. In all newborns otoscopic examination and CEOAEs after birth and 3 months later were performed. CEOAEs in session 1 were significantly reduced in the investigated group comparing to control babies but 3 months later no differences between groups were observed. The outer hair cells activity in first days of life is reduced in newborns with asphyxia in anamnesis but with time no differences in cochlea development are observed.

[Hearing evaluation in children during chemotherapy]. / Ocena sluchu u dzieci podczas chemioterapii.

Chemotherapy is associated with an increased risk of ototoxic changes. The purpose of our study was to investigate the clinical usefulness of Distortion Product Otoacoustic Emissions (DPOAEs) as early indicator of chemotherapy-induced ototoxicity. Tonal audiometry, emission audiometry and DPOAEs were measured in 7 children with acute lymphoblastic leukemia (ALL). Measurements were performed before and after each protocol of chemotherapy. Cochlear activity was evaluated by recording 2f1-f2 DPOAEs with L1=65 and L2=60 dB SPL. Comparisons of the DP-grams amplitudes were performed between baseline measurements and those recorded before and after each chemotherapy course. Our results indicate that DPOAEs measurements are very sensitive on early detection of the changes in cochlear function and are recommended for monitor hearing in patients during chemotherapy.