The National Swedish Lymphoma Register - a systematic validation of data quality.

BACKGROUND AND PURPOSE: The Swedish Lymphoma Register (SLR) was initiated in the year 2000 with the aim to monitor quality of care in diagnostics, treatment and outcome of all lymphomas diagnosed nationally among adults. Here, we present the first systematic validation of SLR records as a basis for improved register quality and patient care. PATIENTS AND METHODS: We evaluated timeliness and completeness of register records among patients diagnosed with lymphoma in the SLR (n = 16,905) compared with the National Cancer Register for the period 2013-2020. Comparability was assessed through evaluation of coding routines against national and international guidelines. Accuracy of 42 variables was evaluated through re-abstraction of data from medical records among 600 randomly selected patients diagnosed in 2016-2017 and treated across all six Swedish healthcare regions.  Results: Completeness was high, >95% per year for the period 2013-2018, and >89% for 2019-2020 compared to the National Cancer Register. One in four patients was registered within 3 months, and 89.9% within 2 years of diagnosis. Registration instructions and coding procedures followed the prespecified guidelines. Missingness was generally low (<5%), but high for occasional variables, for example, those describing maintenance and consolidative treatment. Exact agreement of categorical variables was high overall (>80% for 24/34 variables), especially for treatment-related data (>80% for 17/19 variables). INTERPRETATION: Completeness and accuracy are high in the SLR, while timeliness could be improved. Finetuning of variable registration guided by this validation can further improve reliability of register reports and advance service to lymphoma patients and health care in the future.

Nitric Oxide Is Locally Produced in the Human Middle Ear and Is Reduced by Acquired Cholesteatoma.

OBJECTIVE: To find out if nitric oxide (NO) can be locally produced in the middle ear and if chronic otitis media (COM) and acquired cholesteatoma affect the production. DESIGN: Case-control study. SETTING: Two tertiary-referral hospitals. PATIENTS: Gaseous NO from 11 patients with unilateral perforations or grommet openings was measured with chemiluminescence. Middle ear mucosa from 48 patients with COM and 26 patients with cholesteatoma was investigated. MAIN OUTCOME MEASURES: Detection of NO. Expression of nitric oxide synthase (NOS) mRNA, in mucosa from COM, cholesteatoma and healthy controls, quantified using polymerase chain reaction. RESULTS: The gaseous NO from ears with a unilateral tympanic membrane perforation or a grommet was higher (9 ±â€Š3 ppb, n = 11) than among the controls (4 ±â€Š1 ppb, n = 11, p = 0.04). Lower levels of eNOS (2.64 ±â€Š0.86 mol/100,000 mol ACTB) were detected in the pooled samples from the COM group (n = 48), compared with the control group (140.48 ±â€Š92 mol/100,000 mol ACTB, n = 45, p = 0.010). In the cholesteatoma group (n = 26), a lower expression of nNOS (5.78 × 10-6 ±â€Š1.13 × 10-6 ΔCt) was found in comparison with the controls (1.23 × 10-4 ±â€Š3.18 × 10-5 ΔCt, n = 15, p = 0.011). CONCLUSIONS: NO is likely a natural and permanent part of the gas mixture in the human middle ear. The presence of NOS enzymes in the middle ear mucosa indicates an ongoing NO production and the reduction of NOS in ears with cholesteatoma, and pooled samples from ears with COM, suggest a role for locally produced NO in middle ear disease.

JAK/STAT Dysregulation With SOCS1 Overexpression in Acquired Cholesteatoma-Adjacent Mucosa.

IMPORTANCE: Surgery remains the gold standard in cholesteatoma treatment. However, the rate of recurrence is significant and the development of new nonsurgical treatment alternatives is warranted. One of the possible molecular pathways to target is the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. OBJECTIVE: To investigate the JAK/STAT pathway in the middle ear mucosa in patients with acquired cholesteatoma compared with middle ear mucosa from healthy controls. DESIGN: Case-control study. SETTING: Linköping University Hospital, Sweden, and Karolinska Institutet, Stockholm, Sweden. Sampling period: February 2011 to December 2016. PARTICIPANTS: Middle ear mucosa from 26 patients with acquired cholesteatoma undergoing tympanoplasty and mastoidectomy, and 27 healthy controls undergoing translabyrinthine surgery for vestibular schwannoma or cochlear implantation was investigated. MAIN OUTCOMES/MEASURES: The expression of Interleukin-7 receptor alpha, JAK1, JAK2, JAK3, STAT5A, STAT5B, and suppressor of cytokine signaling-1 (SOCS1) were quantified using quantitative polymerase chain reaction. In addition, expression level of cyclin D2, transforming growth factor beta 1, thymic stromal lymphopoietin, CD3, and CD19 was evaluated. RESULTS: In cholesteatoma-adjacent mucosa, SOCS1 was significantly upregulated (p= 0.0003) compared with healthy controls, whereas STAT5B was significantly downregulated (p = 0.0006). The expression of JAK1, JAK2, JAK3, and STAT5A did not differ significantly between groups. CONCLUSIONS AND RELEVANCE: To the best of our knowledge, this is the first article reporting dysregulation of the JAK/STAT pathway in cholesteatoma-adjacent mucosa. The main finding is that important players of the aforementioned pathway are significantly altered, namely SOCS1 is upregulated and STAT5B is downregulated compared with healthy controls.

Extensive qPCR analysis reveals altered gene expression in middle ear mucosa from cholesteatoma patients.

The middle ear is a small and hard to reach compartment, limiting the amount of tissue that can be extracted and the possibilities for studying the molecular mechanisms behind diseases like cholesteatoma. In this paper 14 reference gene candidates were evaluated in the middle ear mucosa of cholesteatoma patients and two different control tissues. ACTB and GAPDH were shown to be the optimal genes for the normalisation of target gene expression when investigating middle ear mucosa in multiplex qPCR analysis. Validation of reference genes using c-MYC expression confirmed the suitability of ACTB and GAPDH as reference genes and showed an upregulation of c-MYC in middle ear mucosa during cholesteatoma. The occurrence of participants of the innate immunity, TLR2 and TLR4, were analysed in order to compare healthy middle ear mucosa to cholesteatoma. Analysis of TLR2 and TLR4 showed variable results depending on control tissue used, highlighting the importance of selecting relevant control tissue when investigating causes for disease. It is our belief that a consensus regarding reference genes and control tissue will contribute to the comparability and reproducibility of studies within the field.

The evaluation of canal wall up cholesteatoma surgery with the Glasgow Benefit Inventory.

PURPOSE: The aim of the study was to investigate the change in health-related quality of life (HRQoL) after canal wall up cholesteatoma surgery, using the Glasgow Benefit Inventory (GBI). METHODS: Data from a consecutive group of 47 adults scheduled for primary cholesteatoma surgery using canal wall up (CWU) with obliteration, from January 2005 to December 2009, were analysed. Information was extracted from a medical database, and complementary data from patient files and audiograms were collected and recorded retrospectively. The GBI questionnaire was used for the assessment of HRQoL after surgery. RESULTS: There was no finding of residual or recurrent cholesteatomas in the study group. Hearing was improved at 1 and 3 years postoperatively. No patient suffered a total hearing loss. The overall GBI scores showed an improved HRQoL after surgery. Twenty-nine (85%) patients benefitted from surgery, 1 (3%) had no change, and 4 (12%) expressed deterioration. CONCLUSIONS: Cholesteatoma surgery using CWU with obliteration gives an improved HRQoL for the majority of patients. The GBI questionnaire provides complementary information to hearing and healing results after cholesteatoma surgery.

Cholesteatoma surgery with the canal wall up technique combined with mastoid obliteration: results from primary surgery in 230 consecutive cases.

OBJECTIVE: To evaluate the canal wall up (CWU) technique combined with mastoid obliteration used in cholesteatoma surgery from the aspects of safety and function. STUDY DESIGN: Retrospective chart review. Information was extracted from a medical database and complementary data from patient files and audiograms were collected and recorded retrospectively. SETTING: A tertiary-stage hospital and a secondary-stage hospital. Surgeons of various levels of experience. METHOD: Data from a consecutive group of 230 primary operations for cholesteatoma surgery using CWU with obliteration employing the combined approach tympanoplasty (CAT) technique, from January 1994 to December 2009 were analyzed. RESULTS: In 90% of the ears, the anatomy was normalized with an intact ear drum. The frequency of residual cholesteatoma was 1% and the frequency of recurrent cholesteatoma 8%. Hearing was improved one year postoperatively and remained improved three years postoperatively. No patient suffered a total hearing loss. CONCLUSIONS: CWU procedure comprising CAT with obliteration of the mastoid is a safe surgical method with a low frequency of residual and recurrent disease and a good hearing preservation.