Pleomorphic adenoma in the nasal cavity: a clinicopathological study of ten cases in Finland.

The objective of the study was to investigate the nationwide occurrence of sinonasal pleomorphic adenoma in Finland. A retrospective study was conducted at The Departments of Otorhinolaryngology-Head and Neck Surgery, and Pathology at the five university hospitals in Finland. Data were obtained by searching for sinonasal pleomorphic adenoma cases in the clinical and histopathological registries at these institutions for the past two to four decades. All patients who had had a histologically proven pleomorphic adenoma in the sinonasal area were included as participants. Ten cases with pleomorphic adenoma of the nasal cavity were found. The majority of these tumours originated in the septum, and there were no malignant transformations. Pleomorphic adenomas of the nasal cavity were found to be extremely rare in this nationwide investigation.

Altered expression of ezrin, E-Cadherin and ß-Catenin in cervical neoplasia.

High-grade cervical squamous intraepithelial lesions (CIN) as well as squamous cell carcinoma and adenocarcinoma of the cervix are associated with persistent high-risk human papillomavirus (HPV) infection. A number of cellular events play a role in HPV pathogenesis and in the development of cervical lesions, including alterations in cell adhesion and motility. The crucial plasma membrane - cytoskeleton linker protein ezrin of the Ezrin-Radixin-Moesin (ERM) protein family is involved in the regulation of cell morphology, cell adhesion and invasion. Based on our previous work on ERM proteins we sought out to study the expression of ezrin in cervical premalignant lesions. We also studied the expression of E-cadherin and ß-catenin, which play an important role in epithelial cell adhesion. We observed intensifying expression of ezrin along with progressing grade of neoplasia. Ezrin staining was found to colocalize with p16 staining in high-risk HPV associated lesions. Expression of E-cadherin and ß-catenin was found to be altered along with the severity of the lesion, similar to ezrin. Enhanced expression of ezrin in cervical HPV associated lesions suggests a role in the development of cervical neoplasia and cancer. Further clinical evaluation should reveal the feasibility of ezrin as a biomarker for the progression of cervical lesions.

Large performance variation does not affect outcome in the Finnish cervical cancer screening programme.

OBJECTIVE: Cytology screening for prevention of cervical cancer can reduce incidence and mortality by more than 80% in settings with good organization and rigorous quality control. Audit studies are essential for reaching and maintaining a high quality of screening. The aim of this study was to evaluate variation in performance indicators by screening laboratory and assess the impact on the effectiveness of screening as indicated by cervical intraepithelial neoplasia grade 3 and above (CIN3+) rates after a negative screen. METHODS: Seven cytology screening laboratories operating during 1990-1999 with a total of 953 610 screening tests performed were included in the study. By linking screening and cancer register files, all cases of CIN3+ diagnosed in the screened population were identified. For 395 CIN3+ cases with a preceding negative screen and 787 controls, a re-evaluation of smears was undertaken to uncover false negative screening tests. Performance parameters and rates of CIN3+ after a negative screen were analysed for interlaboratory heterogeneity. RESULTS: The rates of follow-up recommendations and referrals varied by up to 3.6- (2.8-10.2%) and 4.0-fold (0.03-0.12%), respectively. CIN1, CIN2 and CIN3+ screen detection rates differed by up to 8.5- (0.02-0.17%), 5.4- (0.05-0.25%) and 3.3-fold (0.05-0.18%). False negative rates determined by re-evaluation showed up to 2.1-fold differences (29-62%). Rates of CIN3+ after a negative screen (0.023-0.048%) and as a proportion of total CIN3+ (15-31%) in the screened population were low and did not vary significantly. CONCLUSIONS: There were large variations in the sensitivity-specificity trade-off between laboratories, reflected in all performance indicators as well as in the test validity estimates of the re-evaluation phase, but not in screening effectiveness. Even though performance variations do not always have an impact on the effectiveness of screening, they lead to variations in cost, treatment and psychological burden, and should be addressed.

Epstein-Barr viral load and disease prediction in a large cohort of allogeneic stem cell transplant recipients.

BACKGROUND: We wanted to determine the clinical significance and predictability of Epstein-Barr virus (EBV) infections among a large cohort of recipients of allogeneic, unselected stem cell transplants. METHODS: During 1988-1999, a total of 5479 consecutive serum samples obtained during 406 transplantations performed in Helsinki, Finland, were retrospectively analyzed by quantitative polymerase chain reaction for the presence of EBV DNA. RESULTS: Overall, EBV DNA was noted in at least 1 serum sample for 57 patients (14.0%), of whom 22 (5.4%) were found to have progressively increasing and ultimately high (>50,000 copies/mL) EBV DNA levels (median level, 179,000 copies/mL). In addition, 16 patients (4.0%) had low EBV DNA levels (median level, 3260 copies/mL) in isolated sera before death. Among the transplant recipients who survived, transient EBV DNAemia (median level, 3110 copies/mL), which apparently corresponded to asymptomatic EBV infection, was noted in 19 patients (4.7%). CONCLUSIONS: Low-level EBV DNA positivity in serum occurs relatively frequently after stem cell transplantation and may subside without specific treatment. However, high EBV DNA levels (i.e., >50,000 copies/mL) are strong predictors for the development of posttransplantation lymphoproliferative disease, are not spontaneously reversible, and should be treated immediately. If the EBV DNA level is >or=50,000 copies/mL, the patient can be classified as having life-threatening EBV infection.

Analysis of risk factors for childhood persistent middle ear effusion.

Although exposure to infectious agents and parental smoking are known to influence the overall risk of otitis media, these risk factors do not appear to be linked with the tendency to develop chronic otitis media with effusion (COME) instead of recurrent acute otitis media (RAOM). The genetic inflammatory response type of the child appears to influence the risk of persistent middle ear effusion in COME. Two different clinical presentations of childhood otitis media are encountered: RAOM; and COME, which is associated with persistent effusion in the middle ear. The objective of this study was to assess putative factors that may regulate the development of persistent middle ear effusion in COME. In total, 159 children with RAOM and their parents (n=304), and 55 children with COME and their parents (n=110) were evaluated. All the children with COME or RAOM were aged <4 years. There was no difference in the frequency of attendance at day care outside the home, number of siblings or parental smoking between children with RAOM and those with COME. The frequency of parental allergy and asthma was lower among children with COME than those with RAOM.

B- and T-lymphocyte subpopulations in the adenoids of children with otitis media.

Adenoid hyperplasia is connected with the pathogenesis of otitis media in children, as implicated by the residence of pathogens causing otitis media in adenoids, and by the beneficial effect of adenoidectomy. We have quantitated the proportions of certain T- and B-lymphocyte subsets in the adenoids by three-color flow cytometry. Three groups were studied: 1) children with persistent effusion in the middle ear (pOME), 2) children with recurrent otitis media with no effusion in the middle ear at the time of surgery (rAOM), and 3) children with adenoid hyperplasia without otitis media (AH) presenting either with snoring or upper respiratory tract infections. B lymphocytes comprised on average 64, 66 and 58% of all mononuclear cells in the respective patient groups. The majority of the B lymphocytes were of the follicular mantle zone phenotype expressing surface IgD (on average 69, 67 and 70% of all B lymphocytes in the respective patient groups). Almost one third of the B lymphocytes were of the germinal center cell phenotype, expressing CD38 but negative for surface IgD (on average 29, 30 and 25% in the respective patient groups). CD3+ T lymphocytes comprised 33, 33 and 40%, respectively, of all mononuclear cells, and the average CD4+/CD8+ ratio was 5.2, 4.9 and 5.7, respectively. No statistically significant differences between the patient groups were seen in these T- and B-lymphocyte subpopulations. These results suggest that the relative sizes of the germinal center, follicular mantle and interfollicular compartments of the adenoids do not correlate with the disease status of the middle ear cavity.

High incidence of PTLD after non-T-cell-depleted allogeneic haematopoietic stem cell transplantation as a consequence of intensive immunosuppressive treatment.

The occurrence of post-transplant lymphoproliferative disorder (PTLD) in relation to immunosuppressive treatment was determined in 257 patients treated with non-T-cell-depleted allogeneic stem cell transplantation from an HLA-matched sibling (173 patients) or unrelated donor (84 patients). The conditioning consisted of total body irradiation and cyclophosphamide (myeloablative conditioning, 250 patients), or fludarabine combined with cyclophosphamide or a single 2 Gy dose of TBI (nonmyeloablative conditioning, seven patients). In transplantations from an unrelated donor, the patients also received antithymocyte globulin (ATG). The prophylaxis against graft-versus-host disease (GVHD) consisted of cyclosporine A, methotrexate, and methylprednisolone. The autopsy reports of deceased patients were systematically reviewed, and the autopsy materials of cases suggestive of PTLD were re-examined histologically for Epstein-Barr virus (EBV). Nineteen patients with EBV-positive PTLD were identified, of whom six had been transplanted from a sibling donor and 13 from an unrelated donor. All the patients who developed PTLD had been given ATG either for the treatment of steroid-resistant acute GVHD (all PTLD patients with a sibling donor and one with an unrelated donor), or as part of the conditioning (all patients with an unrelated donor). In conclusion, in transplantations from an HLA-identical donor with a non-T-cell-depleted graft, the risk of PTLD correlated strongly with the intensity of the immunosuppressive treatment.

Effect of Alloiococcus otitidis and three pathogens of otitis media in production of interleukin-12 by human monocyte cell line.

Alloiococcus otitidis is detected in middle ear effusion of otitis media with effusion (OME). Only a limited number of studies are available concerning the immunological profile of A. otitidis. We have studied the ability of A. otitidis and three other representative pathogens of otitis media to stimulate the production of interleukin-12 (IL-12) from a monocytic cell line THP-1. Viable A. otitidis induced the production of IL-12 in THP-1 cells but IL-12 production was reduced if glutaraldehyde-fixed bacteria were used as stimulants. When viable bacteria were physically separated from THP-1 cells during the stimulation period, remarkable reductions of IL-12 secretion were shown after challenge with gram-positive bacteria A. otitidis and S. pneumoniae. When stimulated with soluble extracts of A. otitidis, THP-1 secreted IL-12 in a dose-dependent manner. The subfraction with a molecular mass over 100 kDa showed a strong ability to induce IL-12 production. Our results show that A. otitidis has immunostimulatory capacity with regard to IL-12 production. We also show that soluble antigen(s) of A. otitidis can modulate the immune response in OME.

Caldwell-Luc operation in the treatment of childhood bronchial asthma.

A follow-up study was carried out in 15 children with severe bronchial asthma. Chronic infection of the paranasal sinuses was connected with the unfavorable course of their bronchial asthma. As adenoidectomy and intranasal antrostomy had failed to cure the sinusitis, the Caldwell-Luc operation was performed at the age of 6-16 years. The follow-up examination was done 3-12 years after the radical operation of the maxillary sinuses. The majority of the patients had normal working capacity, and the need of medical treatment was reasonable. It is concluded that the Caldwell-Luc operation is indicated in children with severe bronchial asthma, when repeated respiratory infections are associated with asthmatic attacks and adenoidectomy and intranasal antrostomy have proved ineffective.

Influence of Caldwell-Luc operation on developing permanent teeth.

The influence of Caldwell-Luc operation on the permanent teeth of school children was studied in a material of 21 six to 14-year-old children, who had undergone, altogether, 30 Caldwell-Luc operations. Ten of the children had also undergone 23 endonasal antrostomies. The control material consisted of a class of 27 healthy school children, their mean age being 10.2 years. Total anesthesia was found in five teeth on the operated side and in one tooth on the non-operated side. Additionally, the operation had caused slight hypesthesia in part of the teeth, mostly in the first incisors. All sensory disturbances were caused by nerve lesion only, and no tooth had died as a result of the operation. The operation could not be shown to be conducive to caries. Correctly performed, Caldwell-Luc operation does not cause serious dental injuries in school children, and is indicated especially in chronic sinobronchitis when conservative methods of treatment fail.

Causes of tonsillar disease and frequency of tonsillectomy operations.

OBJECTIVE: To characterize the factors that influence the frequency of tonsillectomy and adenoidectomy operations. DESIGN AND SETTING: Nationwide questionnaire. Analysis of patients undergoing tonsillectomy or adenoidectomy at Helsinki University Central Hospital, Helsinki, Finland. PARTICIPANTS: Four hundred eighty-three of 819 individuals randomly selected from the Finnish National Public Registry. Two thousand two hundred thirty-one individuals younger than 30 years who underwent tonsillectomy (888 patients), adenotonsillectomy (294 patients), or adenoidectomy (1049 patients) at Helsinki University Central Hospital from January 1, 1997, through December 31, 1998. MAIN OUTCOME MEASURES: Age of the individual at the time of operation. Indication for the operation. RESULTS: The frequency of adenoidectomies was 24% (116 persons) and that of tonsillectomies 8% (39 persons) among the 483 individuals who returned the questionnaire. The frequency of tonsillectomy operations by age was multimodal; the frequency of tonsillectomies increased in preschool-aged children, declined thereafter, and increased again in teenagers. Tonsillar hyperplasia was the most frequent among children younger than 10 years, peritonsillar abscesses among teenagers, and chronic tonsillitis among individuals older than 20 years. The proportion of females was higher than males among teenaged patients. However, the cause and sex distribution could not explain the multimodality in the age-specific frequency. The age-specific frequency of tonsillectomies performed because of peritonsillar abscesses still followed a multimodal distribution. CONCLUSIONS: Factors relating to respiratory tract infections, maturation of the immune system, and the onset of puberty contribute to the cause of tonsillar disease. Distinct indications for tonsillectomy should be defined for preschool-aged children, teenagers, and individuals older than 20 years.

Thoracic duct cyst: a case report and review of 29 cases.

Cysts of the thoracic duct are rare. We report a case of a cervical thoracic duct cyst and review 29 thoracic duct cysts reported previously (19 mediastinal, 9 cervical, and 1 abdominal). The mean age of the patients was 47.6 years (range 17 to 86 years). Fourteen (46.7%) of the patients were asymptomatic. When symptoms were present, they ranged from retrosternal pain, dysphagia, and dyspnea to respiratory insufficiency and superior vena cava compression. Diagnosis of the cyst can be made after computed tomography or ultrasonography. The cystic fluid contains T lymphocytes and triglycerides in excess. The symptoms in a patient with a thoracic duct cyst are related to compression of adjacent structures. The most profound symptoms are likely to be produced by mediastinal cysts above the aortic arch. Treatment consists of surgical removal of the cyst and ligation of all lymphatics connected to the cyst.

Stimulation of adenoidal lymphocytes by Alloiococcus otitidis.

Otitis media with effusion (OME) is characterized by persistent effusion in the middle ear cavity and by chronic inflammation in the middle ear mucosa. Alloiococcus otitidis, a gram-positive aerobic bacterium, has been isolated in middle ear effusion, and by means of sensitive polymerase chain reaction detection assays it has been detected in as many as 20% of middle ear aspirates of patients with OME. Because A otitidis may freely interact with leukocytes in the middle ear effusion, it may potentially modulate the inflammatory reaction in OME. To study the nature of these interactions, we applied an in vitro assay in which killed A otitidis bacteria were incubated with peripheral blood and adenoidal mononuclear cells. The expression of the proliferation-associated surface marker CD69 was then measured in B lymphocytes and in CD4+ helper and CD8+ cytotoxic-suppressor T lymphocytes by means of multicolor flow cytometry. Alloiococcus otitidis induced the expression of CD69 in both peripheral blood and adenoidal T and B cells. Among the T cells, the cytotoxic-suppressor T lymphocytes were preferentially activated. It was also tested whether A otitidis would have an effect in another cytotoxic and immunoregulatory system, namely, the induction of natural killer cell activity in peripheral blood mononuclear cells. However, the effect was minimal compared with that of Salmonella minnesota or Staphylococcus aureus. The results show that A otitidis has a unique immunostimulatory capacity in vitro that is mainly confined to CD8+ T lymphocytes.

Colposcopy referral rate can be reduced by high-risk human papillomavirus triage in the management of recurrent atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion cytology in Finland.

The aim of this study was to establish whether a combination of high-risk human papillomavirus (hrHPV) testing and cervical cytology could reduce colposcopy referral among women with atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion cytology. We randomized 598 women in the Helsinki area, Finland into three study groups. Different strategies of hrHPV testing, cytology and colposcopy with biopsy were used; subsequent hrHPV test results and cytological findings were compared with histology. The rates of hrHPV positivity and CIN2+ were compared. In total, 62.5% of all samples were hrHPV-positive. Altogether 45 (12.7%) CIN2 or worse (CIN2+) lesions were found in study groups A and B. Among hrHPV-positive women the rate of CIN2+ was 19.0% (n = 43), in contrast with 1.6% (n = 2) among hrHPV-negative women (relative risk = 12.2, 95% confidence interval [CI] 3.6-81.1, P < 0.001). Among all hrHPV-negative women whose cytological findings were normal or ASCUS, dysplastic lesions were uncommon (n = 4/119, 3.4%), and all were CIN1. If these women had not been referred to colposcopy, the number of colposcopies would have been reduced by 33.6%. We conclude that hrHPV testing combined with repeat cervical cytology had a high negative predictive value in patients with recurrent low-grade cervical cytology. This could reduce the referral rate to colposcopy without jeopardizing patient safety.