Novel human lymph node-derived matrix supports the adhesion of metastatic oral carcinoma cells.

BACKGROUND: 3D culture is increasingly used in cancer research, as it allows the growth of cells in an environment that mimics in vivo conditions. Metastases are the primary cause of morbidity and mortality in cancer patients, and solid tumour metastases are mostly located in lymph nodes. Currently, there are no techniques that model the pre-metastatic lymph node microenvironment in vitro. In this study, we prepared a novel extracellular matrix, Lymphogel, which is derived from lymph nodes, mimicking the tumour microenvironment (TME) of metastatic carcinoma cells. We tested the suitability of the new matrix in various functional experiments and compared the results with those obtained using existing matrices. METHODS: We used both commercial and patient-derived primary and metastatic oral tongue squamous cell carcinoma (OTSCC) cell lines. We characterized the functional differences of these cells using three different matrices (human uterine leiomyoma-derived Myogel, human pre-metastatic neck lymph node-derived Lymphogel (h-LG), porcine normal neck lymph node-derived Lymphogel (p-LG) in proliferation, adhesion, migration and invasion assays. We also performed proteomic analyses to compare the different matrices in relation to their functional properties. RESULTS: OTSCC cells exhibited different adhesion and invasion patterns depending on the matrix. Metastatic cell lines showed improved ability to adhere to h-LG, but the effects of the matrices on cell invasion fluctuated non-significantly between the cell lines. Proteomic analyses showed that the protein composition between matrices was highly variable; Myogel contained 618, p-LG 1823 and h-LG 1520 different proteins. The comparison of all three matrices revealed only 120 common proteins. Analysis of cellular pathways and processes associated with proteomes of each matrix revealed similarities of Myogel with h-LG but less with p-LG. Similarly, p-LG contained the least adhesion-related proteins compared with Myogel and h-LG. The highest number of unique adhesion-related proteins was present in h-LG. CONCLUSIONS: We demonstrated that human pre-metastatic neck lymph node-derived matrix is suitable for studying metastatic OTSCC cells. As a whole-protein extract, h-LG provides new opportunities for in vitro carcinoma cell culture experiments.

Epidemiological and treatment-related factors contribute to improved outcome of oropharyngeal squamous cell carcinoma in Finland.

BACKGROUND: Treatment for oropharyngeal squamous cell carcinoma (OPSCC) has changed, as the proportion of human papilloma virus (HPV)-related disease has increased. We evaluated nationwide information on its management and outcome during the treatment paradigm change period. METHODS: We included all patients diagnosed and treated for OPSCC at the five Finnish university hospitals from 2000 to 2009. Patient records and pathology registries provided the clinicopathological data. p16 staining was performed on primary tumor samples of patients who had received treatment with curative intent. RESULTS: A total of 674 patients were diagnosed and treated for OPSCC and the incidence increased along the study period. Of the evaluable tumors 58.5% were p16-positive and the number of p16-positive tumors increased along the years. The treatment was given with curative intent for 600 patients and it was completed in 564. Of them, 47.9% underwent primary surgery and 52.1% received definitive oncological treatment. Also, the treatment protocol changed towards a more oncological approach. Among patients treated with curative intent the five-year overall, disease-specific and disease-free survival rates were 60.1, 71.5 and 57.0%. In multivariate analysis, p16-positivity seemed to relate to reduced disease mortality in lateral and anterior-wall disease. Depending on primary tumor localization, also sex, classes T3-4, presence of regional metastasis and radiotherapy modality had an association with disease mortality. CONCLUSION: The incidence of p16-positive OPSCC and delivery of definitive oncological treatment increased in Finland during the study period. An improved survival outcome compared with the previous nationwide investigation was observed in this subset of patients.

The feasibility of NBI in patients with suspected upper airway lesions: A multicenter study.

OBJECTIVE: Narrow band imaging (NBI) improves diagnosis of laryngopharyngeal cancer, but most reported NBI studies are from experienced centers. Feasibility reports on use at everyday outpatient departments are needed. STUDY DESIGN: Researcher-initiated, prospective, multicenter. METHODS: Participating physicians were instructed in NBI technique during a 4-hour meeting. Patients underwent an examination that included endoscopy with white light (WL) high-definition (HD) TV and NBI filter in the selected time period. All suspicious lesions were biopsied. The medical records of patients with NBI negative findings were evaluated 6 months after the visit to detect all possible malignant lesions coming into view at mucosal sites. These were considered as false-negative cases, enabling long-term assess to the positive predictive value (NPV) of the protocol. RESULTS: We enrolled 125 patients. Of those, 84 (67.2%) were males and the median age was 65 years (range, 35-91). In analysis of the accuracy of WL HD TV and NBI against biopsy, the sensitivity and specificity of WL HD TV were 62% and 81%, respectively; and the sensitivity and specificity of NBI were 100% and 84%, respectively. The diagnostic accuracy of NBI was significantly better (P < 0.05). When analyzing medical records 6 months after the initial examination, we found three patients who had been diagnosed with a malignant lesion (NPV of NBI of 96.8%). CONCLUSION: Narrow band imaging is readily implemented in an everyday outpatient practice, and there seems to be better detection rates of dysplastic/carcinoma lesions with HD NBI compared to HD WL. LEVEL OF EVIDENCE: 2b. Laryngoscope, 127:1821-1825, 2017.

Acoustic rhinometry and rhinomanometry in the preoperative screening of septal surgery patients.

BACKGROUND: The preoperative assessment of septal surgery patients with acoustic rhinometry (AR) or rhinomanometry (RMM) is still a controversial subject. This study was designed to apply AR and RMM in preoperative screening of septal surgery patients. METHODS: The gold standard is postoperative satisfaction expressed by patients as "very high," "high," "moderate," or "low" subjective total benefit from the operation to the nasal obstruction 1 year after surgery. One hundred fifty-seven consecutive patients presenting for septal surgery because of an obstructing septum deviation in anterior rhinoscopy, sufficient pre- and postoperative data were available in 110 patients. Anterior rhinoscopy, AR, and RMM were performed before and 1 year after surgery. RESULTS: The preoperative AR and RMM had a statistically significant impact (p < 0.01) in predicting the postoperative satisfaction. The best single preoperative parameter for predicting postoperative satisfaction was the postdecongestion overall minimum cross-sectional area on the deviation side in AR; the estimated optimal cutoff value was 0.40 cm(2). The most predictive preoperative RMM parameter was the postdecongestion intercavital flow ratio (the flow on the deviation side divided by the flow on the wide side); the estimated optimal cutoff value was 1:2. For both parameters the sensitivity/specificity for the cutoff values was around 65/60% in finding patients with high or very high postoperative satisfaction. For anterior rhinoscopy the optimal cutoff was a deviation between severe and moderate with sensitivity/specificity around 55/55%. CONCLUSION: In patients with a very severe deviation, anterior rhinoscopy was sufficient for preoperative screening but in milder deviations AR and RMM significantly predicted postoperative success.

Effects of the Cottle's maneuver on the nasal valve as assessed by acoustic rhinometry.

BACKGROUND: The nasal valve is the narrowest segment of the nasal cavity and plays an essential role in breathing. There has been plenty of discussion in the literature concerning the location and function of the nasal valve. The Cottle's maneuver (CM) is a test in which the cheek on the side to be evaluated is gently pulled laterally with one to two fingers to open the valve. This test is used to determine if the most significant site of nasal obstruction is at the valve or farther inside the nasal cavity. The aim of this study was to determine the dimensional changes caused by the CM in the nose as measured by acoustic rhinometry (AR). METHODS: Eight adult volunteers with no nasal symptoms were recruited and their nasal cavities were measured by AR. The measurements were done with and without the CM both before and after decongestion with a mixture of 1:1000 epinephrine and 4% lidocaine in cotton pledgets. The MCA1 and MCA2 and their distances from the nostril, as well as the volume-measured from the zero point to the MCA2 point--were determined. RESULTS: The main effect of the CM was a mean increase in MCA1 by 33% (p = 0.001) and 44% (p < 0.001) before and after decongestion, respectively. The distance of MCA1 increased significantly, because of the CM, by 12% (p = 0.006) before and 7% (p = 0.008) after decongestion. The percentage increases in volume were 33% (p = 0.001) and 44% (p < 0.001), respectively. Decongestion of the nasal mucosa induced a statistically significant (p = 0.001) increase in both MCA1 (by 21%) and MCA2 (by 28%). CONCLUSION: The CM significantly increased MCA1 in AR, and the increase was more evident after decongestion of the nasal mucosa. The changes in MCA2 were nonsignificant. We conclude that the value of the CM in investigating a possible valve insufficiency may be greater if the nose is studied both before and after decongestion of the nasal mucosa.