Carotid body tumors are not associated with an increased risk for sleep-disordered breathing.

PURPOSE: Tumors in the carotid bodies may interfere with their function as peripheral chemoreceptors. An altered control of ventilation may predispose to sleep-disordered breathing. This study aimed to assess whether patients with unilateral or bilateral carotid body tumors (uCBT or bCBT, respectively) or bilateral CBT resection (bCBR) display sleep-disordered breathing and to evaluate the global contribution of the peripheral chemoreceptor to the hypercapnic ventilatory response. METHODS: Eight uCBT, eight bCBT, and nine bCBR patients and matched controls underwent polysomnography. The peripheral chemoreflex drive was assessed using euoxic and hyperoxic CO2 rebreathing tests. Daytime sleepiness and fatigue were assessed with the Epworth Sleepiness Scale and the Multidimensional Fatigue Index. RESULTS: All patient groups reported significant fatigue-related complaints, but no differences in excessive daytime sleepiness (EDS) were found. The apnea/hypopnea index (AHI) did not differ significantly between patient groups and controls. Only in bCBT patients, a trend towards a higher AHI was observed, but this did not reach significance (p=0.06). No differences in the peripheral chemoreflex drive were found between patients and controls. CONCLUSIONS: Patients with (resection of) CBTs have more complaints of fatigue but are not at risk for EDS. The presence or resection of CBTs is neither associated with an altered peripheral chemoreflex drive nor with sleep-disordered breathing.

Short-term outpatient follow-up of COVID-19 patients: A multidisciplinary approach.

BACKGROUND: Short-term follow-up of COVID-19 patients reveals pulmonary dysfunction, myocardial damage and severe psychological distress. Little is known of the burden of these sequelae, and there are no clear recommendations for follow-up of COVID-19 patients.In this multi-disciplinary evaluation, cardiopulmonary function and psychological impairment after hospitalization for COVID-19 are mapped. METHODS: We evaluated patients at our outpatient clinic 6 weeks after discharge. Cardiopulmonary function was measured by echocardiography, 24-hours ECG monitoring and pulmonary function testing. Psychological adjustment was measured using questionnaires and semi-structured clinical interviews. A comparison was made between patients admitted to the general ward and Intensive care unit (ICU), and between patients with a high versus low functional status. FINDINGS: Eighty-one patients were included of whom 34 (41%) had been admitted to the ICU. New York Heart Association class II-III was present in 62% of the patients. Left ventricular function was normal in 78% of patients. ICU patients had a lower diffusion capacity (mean difference 12,5% P = 0.01), lower forced expiratory volume in one second and forced vital capacity (mean difference 14.9%; P<0.001; 15.4%; P<0.001; respectively). Risk of depression, anxiety and PTSD were 17%, 5% and 10% respectively and similar for both ICU and non-ICU patients. INTERPRETATION: Overall, most patients suffered from functional limitations. Dyspnea on exertion was most frequently reported, possibly related to decreased DLCOc. This could be caused by pulmonary fibrosis, which should be investigated in long-term follow-up. In addition, mechanical ventilation, deconditioning, or pulmonary embolism may play an important role.

Verrucous carcinoma of the larynx: determining the best treatment option.

BACKGROUND: Verrucous carcinoma (VC) of the larynx is a rare variant of well-differentiated squamous cell carcinoma, characterized by locally invasive, exophytic warty growth. The purpose of the present study was to evaluate the experience with this rare disease in Slovenia over a 23-year period and to weigh the potential for cure of different treatment options against the functional outcome. MATERIALS AND METHODS: The databases of the Cancer Registry of Slovenia as well as of the registries of all three departments licensed for the treatment of laryngeal cancer in the country were used for the identification of patients. Presentation, diagnosis, treatment and outcome were reviewed retrospectively. RESULTS: From 1980 to 2002, 30 patients were diagnosed with VC of the larynx, representing 1.23% of all laryngeal malignancies. The most frequent site of origin was the glottis. Twenty-three patients had surgery (functional 13; total laryngectomy 10), three patients had radiotherapy, and a combination of irradiation and concomitant chemotherapy was used in four patients. Only one tumor recurred, six months after primary radiation treatment, but was successfully salvaged with a total laryngectomy. The 5-year overall survival rate of 75% was not significantly different from an age- and sex-matched cohort from the Slovenian population (P=0.071). CONCLUSIONS: In VC of the larynx, determination of treatment options should be dictated by voice preservation strategies. Surgery remains the gold standard of treatment. However, concomitant radiochemotherapy emerges as an attractive alternative to mutilating surgical procedures.

Use of polarised equine endothelial cell cultures and an in vitro thrombosis model for potential characterisation of EHV-1 strain variation.

Equine herpesvirus-1 (EHV-1) is responsible for respiratory disease and abortion in pregnant mares. Some high virulence isolates of EHV-1 also cause neurological disease. The pathogenesis of both abortion and neurological disease relates in part, to thrombus formation occurring in the pregnant uterus and central nervous system. The differences in disease outcome may relate to differing abilities of high and low virulence EHV-1 isolates to cause cell-associated viraemia, infect endothelial cells and cause thrombosis at sites distant from the respiratory tract. This study attempted to identify in vitro assays, which could be used to characterise the interaction between these isolates, equine endothelial cells and clotting factors. No significant difference was found between the growth kinetics of high and low virulence isolates of EHV-1 in polarised endothelial cells. For both isolates, virus was released preferentially from the apical surface of the polarised cells. The functional effects of viral infection on endothelial cells, with reference to virally-induced thrombosis were then investigated. Endothelial cells were grown on microcarrier beads, infected with EHV-1 and assayed for procoagulant activity. No significant difference in clotting time was observed between mock and EHV-1 infected endothelial cells in microcarrier cultures. Thus the degree of thrombosis may reflect a more complex interaction between endothelial cells, circulating leucocytes and other factors in the microenvironment.

Prognostic significance of cysteine proteinases cathepsins B and L and their endogenous inhibitors stefins A and B in patients with squamous cell carcinoma of the head and neck.

Cysteine proteinases cathepsins (Cats) B and L and their endogenous inhibitors stefins (Stefs) A and B are implicated in the processes of local and metastatic tumor spread. They were identified as potential prognosticators in various malignant diseases, particularly in breast cancer. The aim of the present study was to determine the concentrations of Cats B and L and Stefs A and B in the tumor and adjacent normal tissue samples collected from 49 patients (the present group) with squamous cell carcinoma of the head and neck (SCCHN), using quantitative immunosorbent assays (ELISA; KRKA d.d., Novo mesto, Slovenia). Their clinical significance was compared with that from a previous study (the reference group, 45 patients; Budihna et al., Biol. Chem. Hoppe-Seyler, 377: 385-390, 1996). The follow-up of patients from the latter report was updated for this purpose. In the present group, significantly higher concentrations of Cat B (P < 0.0001), Cat L (P < 0.0001) and Stef A (P = 0.006) were found in tumors compared with concentrations in their normal tissue counterparts. Cat concentrations in normal laryngeal tissue were significantly/marginally elevated compared with nonlaryngeal tissue (Cat B, P = 0.02; Cat L, P = 0.06). The tumor concentration of Cat L was found to correlate with pT classification (P = 0.005) and tumor-node-metastasis stage (P = 0.05), whereas the concentrations of Stefs A and B correlated with pN classification (P = 0.007 and P = 0.03, respectively) and tumor-node-metastasis stage of the disease (P = 0.02 and P = 0.03, respectively). There was no statistically significant difference between low and high Cat B or Cat L groups, regarding either disease-free survival or disease-specific survival, using a minimum P approach to determine cutoff concentrations. The risk of disease recurrence and SCCHN-related death was significantly higher in patients with low Stef A (P = 0.0006 and P = 0.0005, respectively) and Stef B (P = 0.0009 and P = 0.0007, respectively) tumors, compared with those with high-Stef A and Stef B tumors. These results remained significant even after Ps were adjusted for a possible bias in the estimated effect on survival. The survival analysis in the reference group also confirmed these findings (Stef A: P = 0.0009 and P = 0.002, respectively; Stef B: P = 0.03 and P = 0.009, respectively). To avoid any possible bias arising from the differences between the laboratories that performed the biochemical analysis, the concentrations of both Stefs in the present group and in the reference group were standardized and coupled together to form a uniform group. In univariate survival analysis, standardized values of Stef A and Stef B correlated inversely with the rate of relapse (P = 0.0000) and mortality rate (P = 0.0000). Multivariate regression analysis showed that the standardized value of Stef A is the strongest independent prognostic factor for both disease-free survival and disease-specific survival. These findings show the specific role of Cats B and L and Stefs A and B in the invasive behavior of SCCHN. Furthermore, Stef A proved to be a reliable prognosticator of the risk of relapse and death in patients with this type of cancer.

Inoperable oropharyngeal carcinoma treated with concomitant irradiation, mitomycin C and bleomycin - long term results.

Patients with inoperable head and neck tumors were treated concomitantly with radiochemotherapy with mitomycin C and bleomycin in our prospective randomized clinical trial (1991- 1993). For the subgroup of patients with oropharyngeal carcinoma the results with radiochemotherapy were significantly superior to irradiation alone. Such scheme of treatment was then adopted as standard method. Here we present the long-term results and dose- response relationships in patients with inoperable oropharyngeal carcinoma treated by the same radiochemotherapy scheme till 1997. Ninety-five patients with stage III and IV inoperable oropharyngeal squamous cell carcinoma were treated with curative intent, concomitantly with supra-voltage irradiation 2 Gy/day 5 times weekly to 60-73 Gy, bleomycin 5 mg 2 times weekly and. one application of mitomycin C 15 mg/m(2) after 10 Gy. Logistic dose- response curve was calculated. Median follow-up was 85 months. The loco-regional control, disease- free survival and overall survival at 5 years were 55%, 51% and 32% (95% CI: 44-67%, 41-62%, 22-42%), respectively. The probability of new primary malignancy at 5 years was 23%. In multivariate analysis performance status, biological equivalent dose, dose of bleomycin, and stage were identified as independent prognostic factors for loco-regional control, disease-free, and overall survival. Th gamma-value of dose response curve was 2.86. The outcome of the disease was directly proportional to intensity of irradiation and chemotherapy. It appears that in our concomitant radiochemotherapy MiC increased radioresponsiveness of the tumor by its effect on hypoxic fraction.

Urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) in tissue and serum of head and neck squamous cell carcinoma patients.

The aim of this study was to determine urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) concentrations in tumour and adjacent normal tissue samples from 58 patients, and in serum samples from 40 of 58 patients with squamous cell carcinoma of the head and neck obtained at diagnosis and after completion of therapy. uPA and PAI-1 serum concentrations were also measured in 28 healthy volunteers who served as controls. Measurements were made using enzyme-linked immunosorbent assay (ELISA) techniques. For both uPA and PAI-1, significantly elevated concentrations were measured in tumour tissue as compared with normal tissue (uPA: 8.89 versus 0.41 ng/mg total protein (mgp), P < 0.0001; PAI-1: 23.9 versus 1.47 ng/mgp, P < 0.0001). A statistically significant difference in uPA concentrations was found between normal laryngeal and nonlaryngeal tissue (0.52 versus 0.3 ng/mgp, P = 0.008), and in PAI-1 concentrations between T1 + 2 and T3 + 4 stage of disease (17.32 versus 35.63 ng/mgp, P = 0.04). The uPA concentrations positively correlated with those of PAI-1 measured in both tumour (Rs = 0.62, P < 0.0001) and normal tissue (Rs = 0.30, P = 0.02). In serum samples, lower concentrations of PAI-1 were measured in the control group than in patients with cancer (412.0 versus 680.5 ng/ml serum (mls), P = 0.0006). The time of collection of the serum sample did not influence uPA and PAI-1 concentrations, and no association was observed between their concentrations and any clinical and histopathological prognostic factors tested. Our results indicate that both uPA and PAI-1 may play a specific role in the process of invasion and metastasis, and might also be of prognostic value in squamous cell carcinoma of the head and neck.

Early glottic cancer: the influence of primary treatment on voice preservation.

PURPOSE: Retrospective analysis was performed to assess the influence of primary surgical or irradiation treatment on local control, survival, and final preservation of larynx in comparable groups of patients with T1N0 and T2N0 glottic cancer. METHODS AND MATERIALS: Two hundred sixty-three previously untreated patients with invasive squamous cell carcinoma of the glottis (187T1 and 76T2) were treated with primary radiotherapy (159T1 and 60T2) or primary surgery (28T1 and 16T2) between January 1976 and December 1990, at the University of Ljubljana, Slovenia. Conventional one daily fraction of 2 Gy to doses of 60-74 Gy (median: 65 Gy) were used in 98% of primarily irradiated patients through out the observed period. To enable better comparison between the two treatment groups, primarily irradiated patients were retrospectively stratified by the criteria of suitability for primary voice-sparing operation. Several host, tumor, and treatment parameters were analyzed. RESULTS: Only the stage of the disease significantly influenced both 10-year recurrence-free and disease-specific survival regardless primary treatment modality (p = 0.0002). In all primary irradiated patients local control was significantly better for those with overall treatment time of less than 48 days (p = 0.007). In patients suitable for voice-sparing operation, local control of primarily operated patients was similar to that of patients primarily irradiated with shorter overall treatment time, which was 93 and 88% for T1 and 67 and 64% for T2 tumors, respectively. Ultimate local control in primary surgery and radiotherapy group was 96 and 96% for T1 and 89 and 88% for T2 tumors, respectively. Equal larynx preservation of 100% in T1 and 90% in T2 patients was achieved in finally cured primarily operated patients and those patients primarily irradiated with a shorter overall treatment time. If treatment time was longer than 48 days, significantly worse final larynx preservation of 84% in T1 and 75% in T2 patients was observed (p = 0.003). In patients unsuitable for voice sparing operation, 87% of T1 and 50% of T2 patients in primary radiotherapy group finally had their larynx preserved. CONCLUSION: Stratification based on criteria of possibility for initial voice-sparing operation is important when comparing primary surgery with primary radiotherapy treatment in early glottic cancer. The detrimental effect of prolonged treatment time of irradiation resulted not only in inferior local control rate but also in worse final larynx preservation.

Concomitant radiotherapy with mitomycin C and bleomycin compared with radiotherapy alone in inoperable head and neck cancer: final report.

PURPOSE: To compare the efficacy of concomitant irradiation with mitomycin C and bleomycin in patients with inoperable head and neck carcinoma with radiotherapy alone. METHODS AND MATERIALS: Between March 1991 and December 1993, 64 patients with inoperable head and neck carcinoma (41 with oropharyngeal site) were randomized to radiotherapy alone (group A) or radiotherapy combined with simultaneous application of mitomycin C and bleomycin (group B). In both groups patients were irradiated five times weekly with 2 Gy to a total dose of 66-70 Gy. The planned concomitant treatment in group B was: bleomycin 5 units twice a week i.m., total dose 70 units, mitomycin C 15 mg/m2 i.v. after delivery of 10 Gy, and 10 mg/m2 i.v. on the last day of radiotherapy. To enhance the effect of these two drugs, patients received also nicotinamide, chlorpromazine, and dicoumarol. Because significantly better results were achieved in arm B for patients with inoperable oropharyngeal carcinoma, the study was closed and such patients were after December 1993 routinely treated with the combined therapy (as in arm B). Until October 1996, we treated and followed up 48 such consecutive patients. RESULTS: Median follow-up of our study patients is 42 months. Complete remission (CR) rate in group A was 31% and in group B 59% (p = 0.04); disease-free survival (DFS) in group A was 8% and in group B 37% (P = 0.01); and overall survival (OS) was 7% in group A and 26% in group B (p = 0.08). CR rate for patients with oropharyngeal carcinoma was 29% in group A (N = 21) and 75% in group B (N = 20) (p = 0.007); DFS in group A was 10% and in group B 48% (p = 0.001); and the OS was 10% in group A and 38% in group B (p = 0.019). In patients with inoperable oropharyngeal carcinoma treated after December 1993, complete remission was achieved in 32/48 (67%, 95% CI: 52%-80%). DFS at the median follow-up of 14 months was 60% (95% CI 43-77%) and OS 58% (95% CI 42-74%). CONCLUSION: From the results of our study it seems that the concomitant treatment significantly improves CR rate, DFS, and OS in patients with inoperable oropharyngeal carcinoma in comparison with radiotherapy alone.

Radiotherapy, combined with simultaneous chemotherapy with mitomycin C and bleomycin for inoperable head and neck cancer--preliminary report.

PURPOSE: Prospectively designed randomized clinical study was undertaken to assess the efficacy of simultaneous application of irradiation, Mitomycin C, and Bleomycin in treatment of patients with inoperable head and neck carcinoma. METHODS AND MATERIALS: Between March 1991 and October 1993, 49 patients with inoperable head and neck carcinoma were randomly assigned to receive either radiation therapy alone (group A) or radiotherapy combined with simultaneous application of Mitomycin C and Bleomycin (group B). Patients in both groups were irradiated five times weekly with 2 Gy to the total dose of 66-70 Gy. Chemotherapy regimen included intramuscular application of Bleomycin 5 units twice a week, with the planned dose being 70 units and Mitomycin C 15 mg/m2 applied intravenously after delivery of 9-10 Gy of irradiation. The application of Mitomycin C was planned to be repeated on last day of radiotherapy in the dose of 10 mg/m2. In attempt to enhance the effect of chemotherapeutic drugs, patients in group B received also Nicotinamide, Chlorpromazine, and Dicoumarol. RESULTS: The difference in complete response rate between both treatment groups (24% in group A and 63% in group B) was statistically significant (p = 0.015). The difference in response rate was much more pronounced in patients with oropharyngeal carcinoma only (18% in group A compared to 81% in group B; p = 0.0003), while for all other subgroups added together, there was observed no benefit of multidrug therapy. Median follow-up was 18 months. Disease-free survival of patients in group A (9%) was significantly lower then in group B (48%) (p = 0.001). The difference between both treatment groups was even greater in patients with oropharyngeal carcinoma only: disease-free survival of these patients in group B was 66%, while in group A, all recurred (p = 0.00001). CONCLUSION: From results of our prospective randomized study it seems that the group of patients that received multidrug treatment with Mytomycin C, Bleomycin, Nicotinamide, Chlorpromazine, and Dicoumarol as enhancers of radiotherapy fared better than patients treated by radiotherapy alone.

The effect of pilocarpine and biperiden on salivary secretion during and after radiotherapy in head and neck cancer patients.

PURPOSE: The influence of parasympathicomimetic pilocarpine and anticholinergic biperiden on salivation in patients irradiated for malignant tumors of the head and neck region was assessed in a prospectively designed clinical study. METHODS AND MATERIALS: Sixty-nine patients, irradiated for head and neck cancer with salivary glands included in the irradiation fields, were randomly assigned into three groups (A, B, and C). Group A consisted of patients receiving pilocarpine, group B of those who were receiving biperiden during radiotherapy and pilocarpine for 6 weeks after its completion, while group C comprised patients not receiving any xerostomy prevention therapy during or after radiotherapy. The quantity of secreted unstimulated saliva was measured before the beginning of radiotherapy, after 30 Gy of irradiation, on completed irradiation, and 3, 6, and 12 months after completion of radiotherapy. RESULTS: Saliva secretion has been found to be the least affected by irradiation treatment in the group of patients receiving biperiden throughout the course of radiotherapy. Six months after completed irradiation, the differences in the quantity of secreted saliva between groups C and B as well as between groups A and B were statistically significant (P = 0.002 and 0.05 respectively). In patients receiving pilocarpine during radiotherapy, and those in the control group, further decrease in saliva secretion was observed. One year after completed therapy, the quantity of secreted saliva could only be measured in the patients receiving biperiden during radiotherapy: it amounted to 16% of the average quantity of saliva secreted before the beginning of irradiation. CONCLUSION: It seems that the inhibition of saliva production during irradiation treatment and the stimulation after completed radiotherapy may contribute to the preservation of salivary gland function after therapy.

Cathepsin D in tissue and serum of patients with squamous cell carcinoma of the head and neck.

Aspartic proteinase cathepsin D (CD) is believed to be associated with proteolytic processes leading to local invasion and seeding of tumour cells. To estimate a potential prognostic value of cathepsin D in squamous cell carcinoma of the head and neck, its total concentration was measured immunoradiometrically (ELSA-CATH-D kit, CIS bio international) in cytosols of tumour and adjacent normal tissue samples from 111 patients; in 42/111 patients, the CD concentration was determined in serum samples obtained at diagnosis (serum no. 1) and after the therapy (serum no. 2) from each of these patients. Sera of 15 healthy volunteers served as controls. A significantly elevated concentration of CD was measured in tumour cytosols as compared to normal tissue cytosols (31.1 versus 12.6 pmol/mgp, P < 0.0001) and in cytosols of normal laryngeal tissue than of the oral cavity or pharynx (13.3 versus 11.2 pmol/mgp, P = 0.03). The higher CD tumour concentration correlated with the age of the patients (< or =60 versus >60 years, 28.8 versus 32.8 pmol/mgp, P = 0.045) and histopathological tumour grade (G1+2 versus G3, 32.6 versus 24.4 pmol/mgp, P = 0.02). In serum samples, a lower concentration of CD was measured in the control group than in the patients (3.6 versus 4.1 pmol/mls, P = 0.045) and in serum no. 1 than in serum no. 2 (4.1 versus 5.1 pmol/ mls. P = 0.05). The CD concentration in sera obtained at diagnosis was stage-dependent (S(I-III) versus S(IV), 3.9 versus 4.7 pmol/ mls. P = 0.09); there was a trend towards lower CD concentrations with an increasing time delay in serum no. 2 sampling (Rs = -0.20, P = 0.21). No correlation was observed between cytosolic and serum concentrations of CD. We conclude that our results confirm a specific role of CD in the process of invasion and metastasis of squamous cell carcinoma of the head and neck, which might also be of prognostic value in this particular cancer type.

Carcinoma of the nasopharynx: results of radiation treatment and some prognostic factors.

Seventy-four patients treated for squamous cell carcinoma (SCC) of the nasopharynx were evaluated for the 5-year survival rate. The influence of stage, age, histological differentiation, total tumour dose and irradiation treatment technique (continuous vs. split-course) upon the survival was evaluated in 64 patients (palliations and histologically unclassified SCC were excluded). The 5-year survival rate in the whole group was 28/74 (38%), and in the group without palliations and unclassified SCC 26/64 (41%). The 5-year survival of patients with T1 carcinoma was better (8/9 = 89%) than of patients with T2 (4/14 = 29%), T3 (7/17 = 41%) and T4 (7/24 = 29%) carcinoma. In the group of 55 patients with T2, T3 and T4 carcinoma, those up to 50 years old had better survival (11/21 = 52%) than patients older than 50 years (7/34 = 21%) (p less than 0.01), patients treated with the tumour dose greater than 65 Gy had better survival (16/38 = 42%) than those treated with 50-65 Gy (2/17 = 12%) (p less than 0.05), and patients older than 50 years, with poorly differentiated carcinoma had better survival (7/20 = 35%) than those of the same age, with well-differentiated carcinoma (0/14 = 0%) (p less than 0.005). The split-course irradiation technique did not improved the 5-year survival rate, although on average the total tumour dose in this type of treatment was for 7.9 Gy higher than in the continuous irradiation.

Urokinase-type plasminogen activator, plasminogen activator inhibitor type 1 and cathepsin D: analysis of their prognostic significance in squamous cell carcinoma of the head and neck.

BACKGROUND: The aim of the study was to evaluate the prognostic significance of tumour and serum concentrations of urokinase-type plasminogen activator (uPA), its type 1 inhibitor (PAI-1) and cathepsin D (Cath D) in patients with squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Determinations of uPA and PAI-1 were made using enzyme-linked immunosorbent assays in tumour and serum samples of 47 and 32/47 patients, respectively. For the determination of tumour (94 patients) and serum (34/94 patients) Cath D concentrations, an immunoradiometric assay was used. RESULTS: In an univariate survival analysis, the risk of disease recurrence and SCCHN-related death was significantly higher in the patients with high uPA (P = 0.046, P = 0.010) tumours, compared to those with low uPA tumours. In addition, the high serum levels of uPA correlated positively with the rate of relapse (P = 0.007), but not with the mortality rate (P = 0.200). There was no statistically significant difference between low and high PAI-1 groups, regarding either tumour or serum concentration of the inhibitor, and between low and high Cath D tumours. Low Cath D serum levels appeared to be related to longer disease-free interval (P = 0.055), but not to disease-specific survival (P = 0.120). CONCLUSIONS: The tumour levels of uPA, as well as serum levels of uPA and Cath D could potentially predict the survival probability of patients with SCCHN. However, the strength of this association remains to be investigated on a larger and more homogeneous group of patients.

Hemoglobin as a factor influencing the outcome in inoperable oropharyngeal carcinoma treated by concomitant radiochemotherapy.

The aim of the study was to analyze the prognostic significance of hemoglobin (Hb) concentration for loco-regional control and survival of patients with inoperable carcinoma of the oropharynx. Seventy patients with inoperable squamous cell carcinoma of the oropharynx were prospectively treated by concomitant regimen of conventional radiotherapy and chemotherapy with Mitomycin C and Bleomycin. The prognostic value of Hb concentration before the therapy (Hb-S) and at the end of the therapy (Hb-E), the difference between both (DHb), and the average Hb concentration (Hb-Av) were analyzed. Hb concentration was falling significantly (median values, from 139 g/L to p<0.0001) during the first three weeks of the therapy; after that, it reached a plateau. In the last week of therapy, a slight increase (p=0.08) in Hb concentration was recorded. Significant correlation (p<0.0001) was found between Hb-S and other Hb-related parameters. The median follow-up of the patients alive on close-out date was 5.7 years (range 4-10.5 years). Longer disease-free survival (DFS) and disease-specific survival (DSS) correlated with higher values of Hb-S (p=0.0005, p=0.008) and Hb-E (p=0.02, p=0.02), while the Hb-Av was predictive for DFS only (p=0.004). The most significant difference between low- and high-Hb groups was calculated at cut-off concentrations of 122 (Hb-S), 116 (Hb-E), and 120 (Hb-Av) g/L. Only Hb-S was tested in multi- variate model where its independent value for predicting both, DFS (p=0.002; RR 3.6) and DSS (p=0.01; RR 2.9), was confirmed. In our patients, Hb-Swas proved to bean independent prognostic factor in predicting DFS and DSS. We believe that the concentration of Hb > or =120 g/L should be maintained during radiotherapy course.

Cathepsin B and L and stefin A and B levels as serum tumor markers in squamous cell carcinoma of the head and neck.

Cysteine proteinases cathepsin (Cath) B and L and their endogenous inhibitors stefin (Stef) A and B concentrations were measured using a quantitative immunosorbent assay (ELISA; KRKA d.d., Novo mesto, Slovenia) in serum samples from 35 patients with primary and 7 patients with recurrent squamous cell carcinoma of the head and neck (SCCHN), obtained at diagnosis (Serum no.1) and after therapy (Serum no. 2), and compared to sera from 30 (Stef B, 90) healthy volunteers. A significantly higher Stef A (P = 0.005) and lower Stef B (P < 0.001) concentrations were measured in patients' Serum no.1 than in controls, and the levels of Caths B and L and Stef A were found to be significantly elevated in Serum no.1 as compared to Serum no. 2 (P = 0.045, P = 0.041 and P = 0.024, respectively). The time of Serum no.2 collection did not influence the concentration of either Caths or Stefs in these samples, and no correlation was observed with the established prognostic factors for any of the parameters studied. Patients with subsequently diagnosed recurrent disease had a significantly lower Cath L concentration than those without evidence of relapse during follow up (P = 0.05). The risk of disease recurrence and SCCHN-related death correlated significantly with low Cath L serum levels (P = 0.012, P = 0.006). The serum levels of Cath B, Stef A and Stef B did not influence significantly the probability of survival.

The influence of pilocarpine and biperiden on pH value and calcium, phosphate, and bicarbonate concentrations in saliva during and after radiotherapy for head and neck cancer.

OBJECTIVE: The purpose of the present study was to investigate the influence of parasympathomimetic pilocarpine and anticholinergic biperiden on salivation, pH value, and calcium, phosphate, and bicarbonate concentrations in saliva in patients irradiated for malignant tumors of the head and neck region. STUDY DESIGN: Sixty-nine patients were randomly assigned into 3 groups. Group A consisted of patients receiving pilocarpine, group B of those who were receiving biperiden during radiotherapy and pilocarpine for 6 weeks after its completion, and group C comprised patients receiving neither of the mentioned drugs. The quantity of secreted unstimulated saliva, its pH value, as well as calcium, phosphate, and bicarbonate concentrations in saliva were measured before the beginning of radiotherapy, after 30 Gy of irradiation, at completed irradiation, and 3, 6, and 12 months after completion of radiotherapy. RESULTS: Saliva secretion was found to be the least affected in the group of patients receiving biperiden throughout the course of radiotherapy. One year after completion of therapy, the quantity of secreted saliva could only be measured in the patients receiving biperiden during radiotherapy; it amounted to 16% of the average initial quantity of saliva secreted before the beginning of irradiation. In all 3 groups of patients, mean pH value decreased during radiotherapy and started to increase again after completion of irradiation. In group B the decrease in pH value after radiotherapy was statistically significantly smaller than that in group C (P =.01). During and after irradiation, calcium concentration was increased in all 3 groups of patients. Phosphate concentration decreased during radiotherapy in all 3 groups. In group B it started to increase again 3 months after completion of radiotherapy. Bicarbonate concentration showed a slight increase during radiotherapy and started to decrease again after completion of irradiation. CONCLUSION: The results of our study indicate that the inhibition of saliva secretion during radiotherapy and its stimulation after completion of treatment can contribute not only to some preservation of the quantity of saliva but also to at least partial preservation of its quality in terms of pH value and calcium, phosphate, and bicarbonate concentrations.

Otoacoustic emissions and auditory assessment in infants at risk for early brain damage.

The importance of early hearing screening has long been recognized, as the prognosis for the hearing impaired child is improved when the diagnosis is made as early as possible, and the intervention is begun immediately. For clinical screening of hearing impairment, the recording of otoacoustic emissions was recommended. As some risk factors for early brain damage are at the same time also risk factors for dysfunction of auditory system, we presumed that infants at risk for brain damage have hearing impairment more frequently than the rest of the population of the same age. We were interested in the role of otoacoustic emission testing during the assessment of auditory function in these infants. There were 110 infants at risk for brain damage included in the study. After thorough otorhinolaryngological examination, auditory function was estimated by recording of otoacoustic emissions, tympanometry, pure tone audiometry and, when necessary, auditory brainstem responses. Otoacoustic emissions were recorded by Madsen-Electronics Celesta 503 in an acoustically treated sound room. We registered spontaneous as well as transient and distortion product otoacoustic emissions. The neurologist formed two groups with different degrees of neurological risk. The collected results of auditory function were compared with the degree of neurological risk. For the statistical analysis, the procedure chi(2) and Fischer test were used. Spontaneous otoacoustic emission was detected in 38.2% of examinees. Evoked otoacoustic emissions were registered in 87.3% of infants. The testing had to be repeated in 32.7% of infants. We observed evoked otoacoustic emissions to be present also in a child with sensorineural hearing impairment and no auditory brainstem responses. Up to 32.7% of infants at risk for brain damage were hard of hearing. Conductive hearing loss was discovered with 25.4% of infants, and eight (7.3%) had sensorineural hearing impairment. In the group of examinees with only risk factors 3.6% had sensorineural impairment and in a group with abnormal motor development, there were 18.5% with that kind of hearing loss. Fischer test confirmed a statistically significant difference between the groups. Infants at risk for brain damage have more frequently impaired auditory function than their peers. For this reason, it is especially important to focus attention on the hearing condition when dealing with this population. Recording of evoked otoacoustic emissions is very helpful in pediatric audiometry, but any interpretation of the results should consider the possibility of auditory neuropathy.

Cowden's disease--its importance for otolaryngologists.

Cowden's disease is a rare predominantly inherited disease, characterized by mucocutaneous lesions, gastrointestinal polyposis and benign or malignant thyroid and breast tumours. The report deals with a typical case of this disease with emphasis on its importance for otolaryngologists.

Laryngo-tracheo-bronchopathia chondro-osteoplastica.

Two cases of laryngo-tracheo-bronchopathia chondro-osteoplastica (LTBCOP) are discussed regarding the pathogenesis of the disease. Our observations support the belief that chronic irritation of the perichondrium in the region of subglottis, trachea and bronchi plays an important role in the aetiology of this disease.