Christian Hjort Sørensen

Salivary gland carcinoma in Denmark 1990–2005: A national study of incidence, site and histology. Results of the Danish Head and Neck Cancer Group (DAHANCA)

To describe the incidence, site and histology (WHO 2005) of salivary gland carcinomas in Denmark. Nine hundred and eighty-three patients diagnosed from 1990 to 2005 were identified from three nation-wide registries. The associated clinical data were retrospectively retrieved from patient medical records. Histological revision was performed in 886 cases (90%). Based on histological revision, 31 patients (3%) were excluded from the study leaving 952 for epidemiological analysis. The mean crude incidence in Denmark was 1.1/100,000/year. The male vs. female ratio was 0.97 and the median age was 62 years. The parotid gland was the most common site (52.5%) followed by the minor salivary glands of the oral cavity (26.3%). The most frequent histological subtypes were adenoid cystic carcinoma (25.2%), mucoepidermoid carcinoma (16.9%), adenocarcinoma NOS (12.2%) and acinic cell carcinoma (10.2%). The revision process changed the histological diagnosis in 121 out of 886 cases (14%). The incidence of salivary gland carcinoma in Denmark is higher than previously reported. More than half of salivary gland carcinomas are located in the parotid gland with adenoid cystic carcinoma being the most frequent subtype. Histological classification of salivary gland carcinomas is difficult and evaluation by dedicated pathology specialists might be essential for optimal diagnosis and treatment.

Molecular Mapping to Species Level of the Tonsillar Crypt Microbiota Associated with Health and Recurrent Tonsillitis

The human palatine tonsils, which belong to the central antigen handling sites of the mucosal immune system, are frequently affected by acute and recurrent infections. This study compared the microbiota of the tonsillar crypts in children and adults affected by recurrent tonsillitis with that of healthy adults and children with tonsillar hyperplasia. An in-depth 16S rRNA gene based pyrosequencing approach combined with a novel strategy that included phylogenetic analysis and detection of species-specific sequence signatures enabled identification of the major part of the microbiota to species level. A complex microbiota consisting of between 42 and 110 taxa was demonstrated in both children and adults. This included a core microbiome of 12 abundant genera found in all samples regardless of age and health status. Yet, Haemophilus influenzae, Neisseria species, and Streptococcus pneumoniae were almost exclusively detected in children. In contrast, Streptococcus pseudopneumoniae was present in all samples. Obligate anaerobes like Porphyromonas, Prevotella, and Fusobacterium were abundantly present in children, but the species diversity of Porphyromonas and Prevotella was larger in adults and included species that are considered putative pathogens in periodontal diseases, i.e. Porphyromonas gingivalis, Porphyromonas endodontalis, and Tannerella forsythia. Unifrac analysis showed that recurrent tonsillitis is associated with a shift in the microbiota of the tonsillar crypts. Fusobacterium necrophorum, Streptococcus intermedius and Prevotella melaninogenica/histicola were associated with recurrent tonsillitis in adults, whereas species traditionally associated with acute tonsillitis like pyogenic streptococci and Staphylococcus aureus were scarce. The findings suggest that recurrent tonsillitis is a polymicrobial infection in which interactions within consortia of taxa play an etiologic role. The study contributes to the human microbiome data, to the understanding of the etiology of infections affecting the tonsils, and forms a basis for further insight into the consequences of the intense microbe-host interactions that take place in the tonsils.

Salivary gland carcinoma in Denmark 1990-2005: outcome and prognostic factors. Results of the Danish Head and Neck Cancer Group (DAHANCA).

To describe outcome and prognostic factors in a national Danish series of patients treated for salivary gland carcinoma. From three Danish nation-wide registries and supplementary patient records, 871 patients diagnosed with primary major or minor salivary gland carcinoma in the period from 1990 to 2005 were identified. A total of 796 (91%) histological specimens were revised according to the WHO 2005 classification. The median follow-up time was 78 months. Three hundred and thirty-four patients (38%) experienced recurrence. Crude survival, disease-specific survival and recurrence-free survival after 5 and 10 years were 66%, 76%, 64% and 51%, 69%, 58%, respectively. In multivariate analysis age, latency, stage, microscopic margins, vascular invasion and histological grade were all independent prognostic factors with regards to crude and disease-specific survival. Stage, microscopic margins, vascular invasion and histological grade were independent prognostic factors for recurrence-free survival. Age over 61 years, latency under 8 months, stage 3+4 disease, involved or close microscopic margins, vascular invasion and high histological grade are all independent prognostic factors with a negative impact on survival in salivary gland carcinoma patients. This knowledge can be helpful in guiding clinicians in daily work and choice of treatment across the large variety of salivary gland carcinoma subtypes.

Bimodal ex vivo expansion of T cells from patients with head and neck squamous cell carcinoma: a prerequisite for adoptive cell transfer

BACKGROUND AIMS Adoptive transfer of tumor-infiltrating lymphocytes (TIL) has proven effective in metastatic melanoma and should therefore be explored in other types of cancer. The aim of this study was to examine the feasibility of potentially expanding clinically relevant quantities of tumor-specific T-cell cultures from TIL from patients with head and neck squamous cell carcinoma (HNSCC) using a more rapid expansion procedure compared with previous HNSCC studies. METHODS In a two-step expansion process, initially TIL bulk cultures were established from primary and recurrent HNSCC tumors in high-dose interleukin (IL)-2. Secondly, selected bulk cultures were rapidly expanded using anti-CD3 antibody, feeder cells and high-dose IL-2. T-cell subsets were phenotypically characterized using flow cytometry. T-cell receptor (TCR) clonotype mapping was applied to examine clonotype dynamics during culture. Interferon (INF)-γ detection by Elispot and Cr(51) release assay determined the specificity and functional capacity of selected TIL pre- and post-rapid expansion. RESULTS TIL bulk cultures were expanded in 80% of the patients included, showing tumor specificity in 60% of the patients. Rapid expansions generated up to 3500-fold expansion of selected TIL cultures within 17 days. The cultures mainly consisted of T-effector memory cells, with varying distributions of CD8(+) and CD4(+) subtypes both among cultures and patients. TCR clonotype mapping demonstrated oligoclonal expanded cultures, ranging from approximately 10 to 30 T-cell clonotypes. TIL from large-scale rapid expansions maintained functional capacity, and contained tumor-specific T cells. CONCLUSION The procedure is feasible for expansion of TIL from HNSCC, ensuring clinically relevant expansion folds within 7 weeks. The cell culture kinetics and phenotypes of the TIL resemble previously published results on TIL from melanoma, setting the stage for clinical testing of this promising treatment strategy for patients with HNSCC.

A Prospective Comparative Study of Parathyroid Dual-Phase Scintigraphy, Dual-Isotope Subtraction Scintigraphy, 4D-CT, and Ultrasonography in Primary Hyperparathyroidism.

Purpose Preoperative localization of the diseased parathyroid gland(s) in primary hyperparathyroidism allows for minimally invasive surgery. This study was designed to establish the optimal first-line preoperative imaging modality. Patients and Methods Ninety-one patients were studied consecutively in a prospective head-to-head comparison of dual isotope (99mTc-MIBI vs 123I) subtraction parathyroid scintigraphy (PS), dual-phase PS, 4-dimensional (4D) CT, and ultrasonography (US). Surgery, histological confirmation, and postoperative normalization of Ca++ and parathyroid hormone were the reference standard. Results Ninety-seven hyperfunctioning parathyroid glands (HPGs) were identified by the reference standard. Sensitivity and specificity for subtraction PS, dual-phase PS, 4D-CT, and US were 93%, 65%, 58%, and 57% as well as 99%, 99.6%, 86%, and 95%, respectively. Interrater agreement was excellent for subtraction PS (&kgr; = 0.96) while only fair for 4D-CT (&kgr; = 0.34). Pinhole imaging and subtraction of delayed images (the latter especially in case of a nodular thyroid gland) increased the sensitivity of subtraction PS. SPECT/low-dose CT did not increase sensitivity but aided in the exact localization of the HPGs. Of 7 negative subtraction PS studies, 4D-CT and US were able to locate 3 and 1 additional HPGs, respectively. Conclusions Dual isotope pinhole subtraction PS has higher diagnostic accuracy compared with dual-phase PS, 4D-CT, and US as a first-line imaging study in primary hyperparathyroidism. In case of a negative scintigraphy or suspicion of multiglandular disease, 4D-CT and/or US is recommended as a second-line modality. However, diagnostic algorithms should be adapted in accordance with local availability and expertise.

Papillary microcarcinoma of the thyroid gland: Is the immunohistochemical expression of cyclin D1 or galectin-3 in primary tumour an indicator of metastatic disease?

Introduction. Papillary microcarcinomas (PMC) of the thyroid gland are defined according to The WHO Committee as papillary carcinomas measuring 10 mm or less in diameter. A large proportion of these tumours are found coincidentally in the treatment of symptomatic goitre and most cases follow an indolent course with an excellent prognosis. However, a more aggressive behaviour with regional and distant metastases does occur. The aim of this study was to evaluate if the immunohistochemical markers cyclin D1 or galectin-3 might indicate the presence of metastatic disease in patients with PMC at the time of diagnosis. Material and methods. From the 1st of January 1996 to 31st of December 2002 a total of 169 PMC patients were diagnosed and registered in the national Danish thyroid cancer database DATHYRCA and 131 of these were eligible for the study. Forty-three (33%) had histologically verified regional or distant metastases. Slides were cut from the primary tumour and immunostaining and quantification was subsequently performed. Results. The percentage of positive cells was examined for patients with and without metastases. For cyclin D1 the median values were 31% (range: 0–59) and 21% (range: 0–75), respectively, showing a statistically significant difference (p=0.02). For galectin-3 the medians were 87% (range: 6–96) and 85% (range: 0–99) and no significant difference was found. Conclusion. Cyclin D1 showed significantly higher median expression in patients with metastases compared to those without, indicating a correlation to tumour aggressiveness. However, both groups showed large variation in expression, which disqualify the marker as a discriminator for the detection of metastases. Galectin-3 was without any significant correlation to the presence of metastases from PMC.

Risk factors for postoperative complications after total laryngectomy following radiotherapy or chemoradiation: a 10-year retrospective longitudinal study in Eastern Denmark.

To determine the rates of and risk factors for postoperative complications following total laryngectomy in patients treated with radiotherapy or chemoradiation.

Harmonic focus in thyroidectomy for substernal goiter

OBJECTIVES No previous prospective study has evaluated harmonic scalpel in thyroidectomy for substernal goiter. The objective of this study was to evaluate the use of harmonic scalpel (FOCUS shear, Ethicon Endo-Surgery) in thyroidectomy for substernal goiter for blood loss, operative time, hospital stay and complications. MATERIALS AND METHODS Prospective non-randomised study of 242 consecutive patients with substernal goiter out of 2258 patients (11%) who underwent thyroidectomy. A total of 121 patients had thyroidectomy performed with bipolar electrocoagulation and knot-tying techniques and 121 patients had harmonic scalpel thyroidectomy. RESULTS The use of harmonic scalpel was associated with significant reduction in intraoperative blood loss (50 vs. 100mL, p=0.001), postoperative haemorrhage (4% vs. 12%, p=0.03) and length of hospital stay (2 vs. 3 days, p=0.001). The mean operative time was significantly longer in the harmonic group. CONCLUSION Harmonic scalpel is a safe tool for thyroidectomy for substernal goiter. Its utilisation is associated with reduced blood loss, lower incidence of postoperative haemorrhage and shorter hospital stay.

Prognostic factors for survival after salvage total laryngectomy following radiotherapy or chemoradiation failure: a 10-year retrospective longitudinal study in eastern Denmark.

The primary aims were to determine the rates of and prognostic factors for overall survival, disease‐specific survival and disease‐free survival following salvage total laryngectomy.

A nationwide registry-based cohort study of incidence of tonsillectomy in Denmark, 1991-2012

To update tonsillectomy incidence rates in Denmark and identify whether the incidence rates vary between geographical areas in the country during the period 1991‐2012.