How we do it: regular infusion of local anaesthetic in the pedicle of pectoralis major myocutaneous flap to shorten hospitalization of surgically treated head and neck cancer patients.

Keypoints *Regular infusion of the flap with local anaesthetic for 6 days postoperative via an indwelling catheter is easy. *It does not cause any complications. *It shortens hospitalization by 7 days. *The necessary catheter is readily available.

Mechanisms dependent on tryptophan catabolism regulate immune responses in primary Sjögren's syndrome.

To investigate the possible role of tryptophan metabolism in immune regulation of primary Sjögren's syndrome (pSS) the serum concentrations of tryptophan and its metabolite kynurenine were measured by reverse-phase high-performance liquid chromatography (HPLC) in 103 patients with pSS, 56 patients with sicca symptoms and 309 healthy blood donors. The kynurenine per tryptophan ratio (kyn/trp), which reflects the activity of the indoleamine-pyrrole 2,3-dioxygenase (IDO) enzyme involved in tryptophan catabolism, was calculated. Both female and male patients with pSS had significantly higher serum kynurenine concentrations and kyn/trp than subjects with sicca symptoms or healthy blood donors. The median (quartile range) concentration of kynurenine in female patients with pSS was 2.41 micromol/l (1.86-3.26) compared with 1.85 micromol/l (1.58-2.38, P < 0.0001) in subjects with sicca symptoms and 1.96 micromol/l (1.65-2.27, P < 0.0001) in healthy blood donors. Their kyn/trp x 1000 was 34.0 (25.1-44.3) compared with 25.3 (21.1-31.5, P < 0.0001) in subjects with sicca symptoms and 24.3 (21.0-28.9, P < 0.0001) in healthy blood donors. Female pSS patients with high IDO activity (kyn/trp x 1000 > or = 34.0) had significantly higher ESR, serum C-reactive protein, serum IgA and serum beta-2 microglobulin concentrations as well as higher serum creatinine levels, and they had positive antinuclear antibodies more frequently and presented with more American-European consensus group criteria than those with low IDO activity (kyn/trp x 1000 < 34.0). These data suggest that mechanisms dependent on tryptophan catabolism regulate immune responses in pSS. Tryptophan degradation is enhanced in patients with pSS, and high IDO activity is associated with severity of pSS.

Endoscopic laser surgery for laryngeal cancer.

Endoscopic laser surgery is a novel treatment modality for laryngeal cancer. CO2 laser combined with an operating microscope is the most frequently used instrumentation. In Finland we started large-scale laser surgery in 1994 in all five university hospitals, covering a population of about five million people. By 1998 we had operated on 140 patients, of whom 11 were females. Eighty-three per cent of the lesions were glottic. Because of the low number of stage III-IV patients, the recurrence and survival analyses included 132 patients with in situ, stage I or stage II tumours, numbering 8, 96 and 28 respectively. The mean follow-up time was 38 months. The 2-year recurrence frequencies were 5% for stage I, 31% for stage II, and 11% altogether. No patients developed recurrences after 2 years. Seven patients underwent a salvage laryngectomy and the adjusted cumulative survival rate was 95%. After laser surgery the quality of voice was good or excellent in 70% and only three patients suffered from severe aphonia. This study showed that the results of endoscopic laser surgery are comparable with those of radiation therapy, but this type of treatment is more convenient for the patients and much cheaper for society.

Alteration of clinical picture and treatment of pediatric acute otitis media over the past two decades.

The clinical picture of acute otitis media (AOM) has changed greatly over the last few decades: serious complications have almost disappeared but more and more children suffer from recurrent middle ear infections and prolonged silent effusion. In this retrospective study we registered all AOM attacks among children under 10 in two rural municipal areas of Finland during 12-month-periods in 1978-79 and 1994-95. In addition to epidemiological data, the clinical picture and given treatments were recorded. Between study periods the number of children with recurrent AOM attacks increased heavily. The percentage of spontaneous otorrhea decreased from 6.0 to 3.3% (P=0.01) and the proportion of afebrile patients increased from 64.0 to 73.4% (P=0.002). In 1978-79 there were significantly more cases of diagnostic symptoms lasting over 24 h. Prescribing penicillin-V as a primary treatment decreased from 80.2 to 10.5% in favor of broad-spectrum antibiotics. The primary treatment with penicillin-V was associated with a decreased risk of recurrences. Acute tympanocentesis was performed less often and the incidence of surgical treatments (adenoidectomy and/or tympanostomy tube insertion) doubled from 6.2 to 12.4% of the acute cases. Although the clinical picture of AOM has become milder, children are treated with wider spectrum antibiotics. Nevertheless, a large number of children suffer from sequelae and there is a greater need for surgical treatments than 20 years ago.

Symptoms of laryngeal carcinoma and their prognostic significance.

Symptoms of 301 patients with laryngeal squamous cell carcinoma were evaluated. Tumour site affected the symptom profile significantly. Hoarseness was more common among patients with glottic and subglottic tumours, but was also the leading symptom in supraglottic patients. Other symptoms were mainly associated with supraglottic tumours and more advanced glottic lesions. There was a positive correlation between the number of symptoms and stage, regardless of tumour site. Patients with a supraglottic tumour had significantly more symptoms (median 2) than those with a glottic lesion (median 1). The median duration of the symptoms was significantly longer in stages III-IV (4.7 months) than in stages I-II (3.8 months). In the multivariate analysis, tumour stage was the only variable showing prognostic significance.

Radiotherapy outcome and prognostic factors in early glottic carcinoma.

OBJECTIVE: To evaluate radiotherapy outcome and prognostic factors in early glottic carcinoma. METHODS: The medical records of 76 patients with glottic T1N0 or T2N0 squamous cell carcinoma diagnosed at Tampere University Hospital from 1970 to 1991 and treated with primary radiotherapy were retrospectively reviewed. Except for three patients treated during the last years of the study period, radiotherapy was delivered by split-course technique with a pause of 1-3 weeks in the middle of the treatment. Primary locoregional control and disease-specific survival were analysed by the Kaplan-Meier method, and the log rank test was applied to compare the survival functions. Prognostic factors were evaluated by uni- and multivariate Cox regression analysis. RESULTS: The 10-year locoregional control rate after radiotherapy was 83 and 48% for patients with T1 and T2 tumours, respectively (P = 0.0005). The 10-year disease-specific survival was 91% for T1 and 69% for T2 disease (P = 0.0018). The larynx could be preserved in 87% of T1 and 44% of T2 cases. Tumour extent expressed by the number of vocal cord thirds involved was the only factor with significant prognostic value in the multivariate analysis of primary locoregional control (hazard ratio (HR) 3.2, 95%CI 1.8-5.8, P = 0.0001). Involvement of the posterior vocal cord third (HR 8.4, 95%CI 1.0-69.5, P = 0.04899) and T-category (HR 3.0, 95% CI 0.9-10.2, P = 0.0790) were connected with poorer prognosis in the multivariate analysis of disease-specific survival. In the multivariate analysis of T1 cases only, higher number of vocal cord thirds involved (HR 5.9, 95%CI 2.2 16.2, P = 0.0005) and longer treatment duration (HR 1.1, 95%CI 1.0-1.3, P = 0.0188) indicated worse locoregional control. Treatment duration (HR 1.2, 95%CI 1.0-1.3, P = 0.0384) together with posterior cord involvement (HR 9.9, 95% CI 1.1-92.7, P= 0.0437) signified poorer survival. CONCLUSION: Our findings indicate that the extent of the tumour is the most important predictor of radiotherapy outcome in early glottic carcinoma. This suggests that a classification based on the actual size of the tumour could be a better prognostic indicator than the conventional T-grouping. Although treatment duration was significant only in separate analysis of T1 cases, the split-course regimen resulting in long treatment times may be considered a major contributor to our relatively low local control rate also in T2 disease.

Speech articulation after subtotal glossectomy and reconstruction with a myocutaneous flap.

Speech samples of 9 subjects (8 males, 1 female) were recorded before and 0.5-2 years after a partial glossectomy and reconstruction with a pectoralis major myocutaneous flap. A reading sample, a list of meaningful and nonsense words, and a list of sustained vowels were recorded. The speech samples were evaluated by pairs of naive listeners and using acoustic analysis of the vowel production. Each pair listened to the recordings of only one patient. Inter-rater agreement was satisfactory. The general impression of the speech outcome varied from normal to moderately impaired. The perceptually estimated impairments of speech articulation in the after/before comparisons were statistically significant. Only the first formant of the vowel /i/ (rise) and the second formant of the vowel /a/ (drop) changed significantly at the group level. There was a negative correlation (r = -0.79) between the extent of tongue resection and the drop of the second formant of the vowel /a/. The perceptual variables showed a relationship (r = 0.74-0.82) with the changes in the level of the second formant of the vowel /i/. The relationship that emerged between the perceptual estimates and the objective acoustic parameters suggests that it will be possible to develop clinically relevant test batteries for articulatory quality analysis.

Changing trends in the occurrence and subsite distribution of laryngeal cancer in Finland.

Cancer of the larynx represents worldwide approximately 1-2% of all cancers and generally occurs predominantly in males. Based upon many reports, the age-adjusted incidence of laryngeal cancer has been rising in recent years, especially among women. Squamous cell carcinomas arising in the glottic region are the most common of all laryngeal cancers and more prevalent than the supraglottic ones. Subglottic disease is still rare. The Finnish Head and Neck Oncology Group evaluated the present occurrence of laryngeal cancer by site and gender in Finland. The annual age-standardized incidence of laryngeal cancer is 3.2 per 100,000 for men and 0.3 per 100,000 for women. The proportion of females in the five university centers reviewed was 5%. During the 30-year time period from the early 1960s to the 1990s there has been a significant decrease in the laryngeal cancer incidence rates for males, but no change for females. Finland thus seems to be the only Western country with clearly declining occurrence rates in recent decades. In the same time period a clear decrease in the incidence of bronchial cancer has occurred in males and an increase in females. The results also show that in all five university hospital districts glottic cancer became more common (50-68%) in the late 1980s and 1990s, which is opposite to the situation in the 1960s when supraglottic localizations (65%) dominated in Finland.

Clinical follow up study of 87 patients with sicca symptoms (dryness of eyes or mouth, or both).

OBJECTIVE: To assess the prognosis of patients with sicca symptoms and to identify the clinical and immunological factors that most sensitively predict the later development of primary Sjögren's syndrome (SS) or other connective tissue diseases. METHODS: Eighty seven patients (72 female, 15 male) with sicca symptoms were re-evaluated after a median follow up time of 11 years (range 8-17). The clinical examination included ophthalmological examination (Schirmer's test, break up time and Rose-Bengal staining). Labial salivary gland biopsy was performed and histological findings graded according to the Chisholm-Mason scale. The immunoserological tests included determination of rheumatoid factor (RF), antinuclear antibodies (ANA), anti-extractable nuclear antigen-antibodies (ENA), serum immunoglobulins IgA, IgG, and IgM, and serum beta2-microglobulin (beta2m). RESULTS: At follow up 31 patients (36%) fulfilled modified Californian criteria (salivary flow measurements were not performed and Chisholm-Mason grades 3-4 were regarded as diagnostic histological findings) for possible or definite SS. Likewise, a significant progression of the histological findings was observed. Labial salivary gland re-biopsy was performed in 42 patients with grade 0-2 findings at baseline, progression to grades 3-4 being observed in 21 (50%) at follow up. The patients who later developed SS were at baseline significantly older (mean (SD) 52 (9) v 44 (14) years, p

Glottic and supraglottic laryngeal carcinoma: differences in epidemiology, clinical characteristics and prognosis.

In order to evaluate differences in epidemiology, clinical characteristics and prognosis, 166 glottic and 127 supraglottic cases of laryngeal squamous cell carcinoma diagnosed between 1962 and 1991 at Tampere University Hospital, Finland, were reviewed. The annual age-adjusted incidence in males decreased from 6.7/100,000 to 2.6/100,000 and the proportion of glottic tumours increased from one-third to two-thirds during the study period. The proportion of early stage lesions was greater among glottic tumours, and patients with a supraglottic tumour presented more often with neck node metastases. Hoarseness was the most common symptom, being more prevalent in patients with a glottic tumour. The symptom pattern of supraglottic carcinoma was altogether more diffuse. The 5-year disease-specific survival was 81% in glottic and 70% in supraglottic disease, but the difference in survival was not statistically significant. In the multivariate Cox regression analysis, higher T-category and presence of neck node metastases had adverse prognostic effect, while location of the tumour did not significantly affect the prognosis. Favourable changes in smoking habits seem to be the main reason for the incidence decrease and obviously also for the decrease in the proportion of supraglottic tumours.

Increase in paediatric acute otitis media diagnosed by primary care in two Finnish municipalities--1994-5 versus 1978-9.

In recent decades, several epidemiological studies have been published on acute otitis media (AOM), indicating that the occurrence of AOM is increasing. However, the comparison between the surveys is complicated and biased by several factors, e.g. variable study demography and design and dissimilar diagnostic criteria. The present study was performed with an identical set-up in 1978-9 and 1994-5 to find out potential changes in the occurrence of AOM. All the attacks of AOM among children under 10 years diagnosed by a physician during the 12-month periods 1 June, 1978 to 31 May 1979 and 1 June 1994 to 31 May 1995 were registered retrospectively in two Finnish municipalities. The incidence rate (total number of AOM attacks per 100 child years) was 19 (95% CI 18-21) in 1978-9 and 32 (95% CI 30-34) in 1994-5. The increase in the occurrence of AOM was 68% (95% CI 53-79%, P < 0001).

p53 expression and cell proliferation as prognostic factors in laryngeal squamous cell carcinoma.

PURPOSE: To investigate the prognostic significance of p53 expression and proliferation markers in primary laryngeal squamous cell carcinoma. PATIENTS AND METHODS: Primary tumors for analyses were obtained from 103 patients, with complete follow-up data. All patients were treated between the years 1975 and 1990. The expression of p53 was analyzed with monoclonal D07 antibody and proliferative activity with Ki-67 (MIB-1) and PCNA (monoclonal 19A2) antibodies. Volume corrected mitotic (M/V) index and histological grade were determined in hematoxylin and cosin-stained slides. RESULTS: Sixty-eight percent of the tumors overexpressed p53. During a median follow-up of 62 months, 41 (40%) of patients relapsed. In univariate analysis site of the primary tumor, stage, p53 expression, histologic grade, and M/V index were significant predictors of disease-free survival. In multivariate analysis, only M/V index was a statistically significant predictor of disease-free survival. Overall survival was significantly better for those overexpressing p53 (10-year cumulative survival rate 68% v 44%, P = .004). In multivariate analysis, M/ V index (P = .02), p53 (P = .02), and stage (P = .007) were statistically significant predictors of overall survival. When this analysis includes stratification according to the type of treatment received, M/V index (P = .007), stage (P = .0002), and p53 (P = .006) were even more significant predictors of overall survival. No association between p53 status and proliferative activity was found. CONCLUSION: Overexpression of p53 is associated with favorable disease-free and overall survival in laryngeal squamous cell carcinoma. It may also have an independent prognostic value in laryngeal cancer. M/V index, p53 overexpression, and stage predict with significant accuracy the 10-year overall survival.

Functional vs. radical maxillary surgery. Failures after functional endoscopic sinus surgery.

Randomized FES or Caldwell-Luc (C-L) operations were performed in 150 patients suffering from chronic maxillary sinusitis during 1987-1989. Follow-up examination was done for 143 patients (95%) 1 year postoperatively. Although 15 patients had already deceased, questionnaires were obtained from 128 patients (85%) 5-9 years after operation. One year after surgery 51% of the C-L patients and 77% of the FES patients reported no symptoms or distinct improvement in their global symptoms, whereas 5-9 years postoperatively 82% of the C-L and 76% of the FES patients reported this outcome, respectively. Thirteen C-L operated patients (18%) and 14 FES patients (20%) have been reoperated during 7-9 years follow-up. In most cases revision surgery was done for polyposis or maxillary sinusitis. In the long term, altogether 21 patients (28%), including 14 reoperated patients, were failures after FES. These included also 4 patients with global symptoms unchanged at late inquiry and 3 other patients, though getting better, reported unwillingness for FES operation if they had known the result beforehand.

Immediate histological changes in soft palate after uvulopalatopharyngoplasty with CO2, contact Nd:YAG or combined CO2 and Nd:YAG laser beams.

CO2, contact Nd:YAG and Combolaser (combined, simultaneous and coaxial CO2 + Nd:YAG laser beam) were used for uvulopalatopharyngoplasty (UPPP). It has been proposed that the combined beam geometry diminishes thermal damage to surrounding tissues when compared with single laser radiation. To study the extent of thermal tissue damage produced by the lasers, tissue samples for light (LM) and transmission electron microscopy (TEM) were taken from the surface of the resected area and 2 and 4 mm below the resection plane. The depth of tissue damage and coagulation was measured. The results showed no consistent differences in the inflammatory reactions or the amount and depth of tissue coagulation observed in samples taken immediately after the operation. The CO2 laser typically produced a carbonized and coagulated wound edge. Combolaser and contact Nd:YAG lasers generated slightly less charring but otherwise resembled each other with coagulated and vacuolized resecate margins. These results indicate that the beam geometry in Combolaser does not diminish thermal damage to surrounding tissues.

Etiological factors of laryngeal cancer.

In order to evaluate the etiological factors, all 318 cases of laryngeal cancer diagnosed during the period of 1962-91 in the Tampere University Hospital area with a population of 400,000 were reviewed. Among males the annual age-adjusted incidence decreased significantly from 7.1 to 2.3 per 100,000. No significant difference in the occurrence was found between urban and rural areas. In males the relative risk (RR) was significantly higher in the lower socio-economic groups. In both sexes smokers had significantly higher risk compared to non-smokers. For male smokers RR was 15.5 (95% CI 10.0-25.4) and for female smokers 12.4 (95% CI 3.9-39.5). Changes in smoking habits seem to be the most important factor contributing to the decreasing incidence of laryngeal cancer in Finland, but other factors like changes in dietary and sauna habits may also have some significance.

Microvascular free flaps in head and neck cancer surgery in Finland 1986-1995.

Microvascular free tissue transfer has in many cases replaced classic flap techniques and is now an established workhorse for head and neck reconstructions. In this retrospective study the over 300 patients, who had microvascular free flap reconstructions in head and neck cancer surgery in Finland during a 10-year period (1986-1995) were reviewed. The operations were performed in the University Hospitals by plastic surgeons, ENT specialists or maxillofacial surgeons. The cases consisted of defects resulting from resection of oral cavity tumors (63%), mid- or upper-face and skullbase tumors (20%) and hypopharyngo-esophageal tumors (17%). The series includes a wide range of flap types and analyses flap outcome and complications. A total of 313 cases was reconstructed by 317 flaps (forearm flaps 47%, latissimus dorsi flaps 19%, free jejunum or colon transfers 15%, free iliaca crest flaps 8% and other flaps 11%). Thrombosis of one of the vessels and haematoma were the most frequent causes of failure in microvascular free tissue transfer. A total flap necrosis occurred in 27 (8.5%) and a partial necrosis in 12 (4%) patients. The most reliable flap in terms of survival was the radial forearm flap. The ever-improving success of microvascular free tissue transfer has made it a useful procedure for head and neck reconstructions. There is also a growing need for microvascular team surgery in the field of head and neck cancer therapy.