High-risk human papilloma virus was not detected in a Norwegian cohort of oral squamous cell carcinoma of the mobile tongue.

OBJECTIVES: The presence of and the causative role of high-risk human papilloma virus (HPV) is a subject of controversy in oral squamous cell carcinoma (OSCC). The disagreement can be related to the misclassification of OSCC as oropharyngeal squamous cell carcinoma and/or lack of standard detection methods. This study aimed to examine the presence of transcriptionally active high-risk HPV in a homogenous Norwegian cohort of primary and second primary OSCC of the mobile tongue (oral tongue squamous cell carcinoma-OTSCC). METHODS: Tissue microarrays containing formalin-fixed and paraffin-embedded cores of 146 OTSCC from the anterior 2/3 of the tongue (n = 128 primary and n = 18 second primary) from a multicentric Norwegian cohort were examined for the presence of high-risk HPV by DNA- and RNA-in situ hybridization (ISH) assays and p16 immunohistochemistry. RESULTS: Transcriptionally active HPV (E6/E7 mRNA) was not identified in any of the OTSCC specimens. In parallel, no tumors were positive for HPV by DNA ISH. Although, 61 (42%) OTSCC demonstrated p16 positivity with varying staining intensity and subcellular localization, only two cases demonstrated strong and uniform p16-staining (both cytoplasmic and nuclear) in >70% of cancer cells. The absence of transcriptionally active high-risk HPV in this cohort of OTSCC indicates that high-risk HPV is an unlikely causative factor in the present material.

Tumor budding score predicts lymph node status in oral tongue squamous cell carcinoma and should be included in the pathology report.

BACKGROUND: The majority of oral cavity cancers arise in the oral tongue. The aim of this study was to evaluate the prognostic value of tumor budding in oral tongue squamous cell carcinoma, both as a separate variable and in combination with depth of invasion. We also assessed the prognostic impact of the 8th edition of the American Joint Committee on Cancer's TNM classification (TNM8), where depth of invasion (DOI) supplements diameter in the tumor size (T) categorization. METHODS: Patients diagnosed with primary oral tongue squamous cell carcinoma were evaluated retrospectively. Spearman bivariate correlation analyses with bootstrapping were used to identify correlation between variables. Prognostic value of clinical and histopathological variables was assessed by Log rank and Cox regression analyses with bootstrapping using 5-year disease specific survival as outcome. The significance level for the hypothesis test was 0.05. RESULTS: One-hundred and fifty patients had available material for microscopic evaluation on Hematoxylin and Eosin-stained slides and were included in the analyses. Reclassification of tumors according to TNM8 caused a shift towards a higher T status compared to the previous classification. The tumor budding score was associated with lymph node metastases where 23% of the patients with low-budding tumors had lymph node metastases, compared with 43% of those with high-budding tumors. T-status, lymph node status, tumor budding, depth of invasion, and the combined tumor budding/depth of invasion score were all significantly associated with survival in univariate analyses. In multivariate analyses only N-status was an independent prognosticator of survival. CONCLUSION: Reclassification according to TNM8 shifted many tumors to a higher T-status, and also increased the prognostic value of the T-status. This supports the implementation of depth of invasion to the T-categorization in TNM8. Tumor budding correlated with lymph node metastases and survival. Therefore, information on tumor budding can aid clinicians in treatment planning and should be included in pathology reports of oral tongue squamous cell carcinomas.

A combined histo-score based on tumor differentiation and lymphocytic infiltrate is a robust prognostic marker for mobile tongue cancer.

We wanted to evaluate the prognostic value of common histopathological variables in a large cohort of patients with cancer in the mobile tongue as such information can be important for treatment stratification of the individual patient, especially for patients with low-stage disease. In addition, we wanted to investigate whether an alternative scoring model with fewer options would compromise the prognostic value. One hundred fifty patients with oral tongue squamous cell carcinomas that were treated in curative intent and with available HE-stained tumor sections were included. We reclassified all tumors and performed univariate and multivariate survival analyses of histopathological and clinical variables. For the complete cohort, lymph node status, grade of differentiation, perineural infiltration, and lymphocytic infiltration were independent prognosticators. In the low-stage disease group, independent prognostic factors were tumor size, grade of differentiation, and lymphocytic infiltrate. For patients with low-stage disease, a histo-score combining the scores for tumor differentiation and lymphocytic infiltrate identified a group of patients with particularly low survival, as patients with moderately or poorly differentiated tumors and little lymphocytic infiltrate had a less favorable 5-year survival outcome than patients in the high-stage disease group. This study shows that a histo-score combining tumor differentiation and lymphocytic infiltration should be given special consideration in treatment planning. Our results also illustrate that many variables can be scored with fewer options than previously suggested to increase their reproducibility, and still maintain their prognostic value.

Grading of oral squamous cell carcinomas - Intra and interrater agreeability: Simpler is better?

BACKGROUND: Numerous studies have been presented on histological grading of oral squamous cell carcinomas (OSCC) for predicting survival, but uncertainty of their usefulness rises due to discordances of results. A scoring system should be robust and well validated, and intra- and interrater agreement can be used as a tool to visualize the strength of reproducibility. METHODS: Here, we present an intra- and inter-observer study on evaluation of OSCC using some of the most common histopathological parameters. The observers were from different Norwegian university hospitals, and calibration to ensure accuracy was first performed. Percentage of the agreement was calculated for the score made by the individual observer at different times, as well as between pairs of observers. RESULTS: The evaluation made by the same observer at two different time points (intrarater) correlated better than observations made by different participants (interrater). In an attempt to increase the rate of agreement, many of the parameters were either dichotomized into simply low- and high grade, or to a three-tier system when more than three options in the original design. This increased the concurrence with 15.4% for the intrarater and with 23% for the interrater comparisons. CONCLUSION: High agreement for histopathological parameters can be difficult to obtain on hematoxylin and eosin staining in scoring systems with many options. A simpler system might be more advantageous to achieve higher degree of reproducibility.

CT imaging of the eustachian tube using focal contrast medium administration: a feasibility study.

OBJECTIVES: We aim to develop an imaging technique for visualization of the Eustachian tube (ET) lumen. STUDY DESIGN: A prospective, experimental study in an animal model and in human cadaver specimens. METHODS: Applying iodixanol to the middle ear in two human temporal bone specimens, followed by computed tomography (CT) examinations, we optimized contrast dilution, CT algorithm, and head positioning for visualization of contrast passage through the ET. Myringotomy was performed on eight rabbits. Based on the cadaver study, a 20% iodixanol solution was applied to the middle ear, and subsequent CT scans were performed to observe iodixanol in the epipharynx. For some animals, the procedure was repeated on the contralateral ear. We performed the procedure twice on four subjects. Twenty examinations were included. Iodixanol appearance in the ET and the epipharyngeal orifice was assessed qualitatively on CT scans. The tympanic membrane was inspected after 1 or 2 weeks, and histopathological examination of six contrast-exposed temporal bones was performed. RESULTS: The cadaver study provided information on imaging technique and contrast dosage. In rabbits, iodixanol passed through the ET in 19 of the 20 ears. Qualitatively, optimal visualization was seen after 9 to 12 minutes. Clinical inspection after 1 or 2 weeks revealed normal middle ear status. Histopathological samples showed no sign of inflammatory reaction in the tympanic membrane, middle ear, or ET. CONCLUSION: Iodixanol application to the middle ear is feasible, safe, and demonstrates patency of the ET. LEVEL OF EVIDENCE: N/A.

Cardiopulmonary response to reamed intramedullary nailing of the femur comparing traditional reaming with a one-step reamer-irrigator-aspirator reaming system: an experimental study in pigs.

BACKGROUND: Intramedullary reaming and nailing increases intramedullary pressure. This may cause intravasation of bone marrow contents, leading to bone marrow embolization and altered cardiopulmonary function. Possible beneficial effects of attenuation of the intramedullary pressure increase by the use of a reamer-irrigator-aspirator (RIA) system were studied with the hypothesis that the RIA technique would cause lower numbers of pulmonary embolisms (PEs) and lesser cardiopulmonary affection than traditional reaming (TR). MATERIAL AND METHODS: Intramedullary reaming and nailing was performed in intact femora of young Norwegian landrace pigs using either a standard intramedullary nailing technique (n = 8) or a RIA technique (n = 7). The hemodynamic and pulmonary effects were investigated during the reaming and nailing procedure and for 2 hours postoperatively. The animals were killed after 72 hours, and the lung/carcass weight ratio and the numbers of PEs were investigated. RESULTS AND CONCLUSION: The pattern of the procedure-related hemodynamic and pulmonary effects did not differ significantly between the RIA and the TR groups. The RIA group had lower numbers (ns) of embolisms per square centimeter lung area than the TR group. After reaming with the TR device, two animals died of PEs, the first postoperative day. The patients with femoral shaft fracture and additional cardiopulmonary injury or preexisting reduced cardiopulmonary function, however, need special attention, and the use of RIA may, in these cases, represent a better operative alternative with a lesser operative burden.