Lojze Šmid

Autofluorescence imaging in the diagnosis of laryngeal cancer

Abstract Differences in autofluorescence (fluorescence without photodynamic drugs) between normal and malignant tissues offer new possibilities in detecting and localizing early laryngeal carcinoma. Autofluorescence imaging was performed using a modified fluorescence endoscopy system from Xillix Technologies (Richmond, Canada). Fluorescence was induced by blue light at 442 nm and captured by an image-intensified camera through a laryngeal telescope. The images were then processed by the system and displayed on a video monitor. Normal tissue appeared green while malignant sites appeared reddish-brown. The autofluorescence imaging technique was compared to standard microlaryngoscopy in 108 patients with laryngeal pathologies (in 74 of whom malignancy was suspected). The acquired reflectance and fluorescence images of each lesion were assessed independently as malignant or not malignant by three ENT specialists who were familiar with the procedure but were not provided with clinical data or histopathological information concerning the lesion. The assessments of pathology were determined from the two imaging modalities and were compared to histopathological findings of the biopsy specimens taken from the lesion. The present study showed that autofluorescence imaging can be a useful complementary method to microlaryngoscopy for detecting and delineating laryngeal malignancies. If in the future, the device can be developed for use in an outpatient office, a significant improvement can be made for the early detection of laryngeal malignancies.

Radiotherapy, combined with simulataneous 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/m 2 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/m 2 . 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 radiotherpy 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.

The music perception abilities of prelingually deaf children with cochlear implants

OBJECTIVE To investigate the music perception abilities of prelingually deaf children with cochlear implants, in comparison to a group of normal-hearing children, and to consider the factors that contribute to music perception. METHODS The music perception abilities of 39 prelingually deaf children with unilateral cochlear implants were compared to the abilities of 39 normal hearing children. To assess the music listening abilities, the MuSIC perception test was adopted. The influence of the childs age, age at implantation, device experience and type of sound-processing strategy on the music perception were evaluated. The effects of auditory performance, nonverbal intellectual abilities, as well as the childs additional musical education on music perception were also considered. RESULTS Children with cochlear implants and normal hearing children performed significantly differently with respect to rhythm discrimination (55% vs. 82%, p<0.001), instrument identification (57% vs. 88%, p<0.001) and emotion rating (p=0.022). However we found no significant difference in terms of melody discrimination and dissonance rating between the two groups. There was a positive correlation between auditory performance and melody discrimination (r=0.27; p=0.031), between auditory performance and instrument identification (r=0.20; p=0.059) and between the childs grade (mark) in school music classes and melody discrimination (r=0.34; p=0.030). In children with cochlear implant only, the music perception ability assessed by the emotion rating test was negatively correlated to the childs age (r(S)=-0.38; p=0.001), age at implantation (r(S)=-0.34; p=0.032), and device experience (r(S)=-0.38; p=0.019). The childs grade in school music classes showed a positive correlation to music perception abilities assessed by rhythm discrimination test (r(S)=0.46; p<0.001), melody discrimination test (r(S)=0.28; p=0.018), and instrument identification test (r(S)=0.23; p=0.05). CONCLUSIONS As expected, there was a marked difference in the music perception abilities of prelingually deaf children with cochlear implants in comparison to the group of normal hearing children, but not for all the tests of music perception. Additional multi-centre studies, including a larger number of participants and a broader spectrum of music subtests, considering as many as possible of the factors that may contribute to music perception, seem reasonable.

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.

Prognostic value of cathepsins B, D and stefins A and B in laryngeal carcinoma

Concentrations of cathepsins A, D and stefins A and B were measured in primary tumor and adjacent normal tissue of 25 patients with laryngeal carcinoma. Median concentrations of both cathepsins and that of stefin B were significantly higher in tumor tissue than in their normal counterparts (cathepsins B and D,P < 0.0001; stefin B,P = 0.01), indicating their possible involvement in the process of tumor spread. Early (T1 and T2) tumors had lower concentrations of stefins A and B than locally advanced (T3 and T4) tumors (P = 0.04). Disease-free and disease-specific survival rates at 45 months were significantly better in patients with tumor concentrations of stefins above or equal to the cut-off values (stefin A,P = 0.001 andP = 0.004; stefin B,P = 0.048 andP = 0.008), indicating that these might be of prognostic value. The concentrations of cathepsins B and D did not correlate with survival.

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.

Impairments of vestibular system in infants at risk of early brain damage

Children with early brain damage often present with balance disorders. We evaluated the vestibular apparatus function in 110 infants at risk of brain lesions. Our study confirmed a statistically significant correlation between vestibular apparatus dysfunction and the degree of neurological risk. Early recognition of vestibular disorders preconditions adequate rehabilatation and supports the acquisition of motor skills.

Prognostic value of some tumor markers in unresectable stage IV oropharyngeal carcinoma patients treated with concomitant radiochemotherapy

Abstract Background. The aim of the study was to investigate how the expression of tumor markers p21, p27, p53, cyclin D1, EGFR, Ki-67, and CD31 influenced the outcome of advanced inoperable oropharyngeal carcinoma patients, treated with concomitant radiochemotherapy. Patients and methods. The pretreatment biopsy specimens of 74 consecutive patients with inoperable stage IV oropharyngeal squamous cell carcinoma treated with concomitant radiochemotherapy were in retrospective study processed by immunochemistry for p21, p27, p53, cyclin D1, EGFR, Ki-67, and CD31. Disease-free survival (DFS) was assessed according to the expression of tumor markers. Results. Patients with a high expression of p21 (≥10%), p27 (>50%), Ki-67 (>50%), CD31 (>130 vessels/mm2) and low expression of p53 (<10%), cyclin D1 (<10%) and EGFR (<10%) (favorable levels - FL) had better DFS than patients with a low expression of p21 (<10%), p27 (≤50%), Ki-67 (≤50%), CD31 (<130 vessels/mm2) and high expression of p53 (≥10%), cyclin D1 (≥10%) and EGFR (≥10%) (unfavorable levels - UL). However, statistical significance in survival between FL and UL was achieved only for p27 and cyclin D1. DFS significantly decreased with an increasing number of markers with an unfavorable level per tumor (1–4 vs. 5–7) (78% vs. 32%, respectively; p = 0.004). The number of markers per tumor with UL of expression retained prognostic significance also in multivariate analysis. Conclusions. Statistical significance in survival between FL and UL emerged only for p27 and cyclin D1. The number of markers per tumor with UL of expression was an independent prognostic factor for an adverse outcome.