Macroscopic and multiple metastases in sentinel lymph node biopsy are respectively associated with poor prognosis in early oral cancer.

BACKGROUND: A multicenter, randomized controlled phase III trial was conducted on sentinel lymph node biopsy (SLNB) and elective neck dissection for T1 (depth of invasion ≥ 4 mm)-T2N0M0 oral cavity squamous cell carcinoma. This study identified factors associated with poor prognosis in patients who underwent SLNB based on a subgroup analysis of this trial. METHODS: We analyzed 418 sentinel lymph nodes (SLNs) from 132 patients who underwent SLNB. The metastatic SLNs were classified into three categories based on size-isolated tumor cells: < 0.2 mm, micrometastasis: ≥ 0.2 mm and < 2 mm, and macrometastasis: ≥ 2 mm. Three groups were formed based on the number of metastatic SLNs: no metastasis, 1 metastatic node, and ≥ 2 metastatic nodes. The size and number of metastatic SLNs on survival were evaluated using Cox proportional hazard models. RESULTS: Patients with macrometastasis and ≥ 2 metastatic SLNs had worse overall survival (OS) and disease-free survival (DFS) after adjustment for potential confounders (HR for OS: macrometastasis, 4.85; 95% CI 1.34-17.60; ≥ 2 metastatic SLN, 3.63; 95% CI 1.02-12.89; HR for DFS: macrometastasis, 2.94; 95% CI 1.16-7.44; ≥ 2 metastatic SLN, 2.97; 95% CI 1.18-7.51). CONCLUSIONS: In patients who underwent SLNB, a poorer prognosis was associated with macrometastasis or having ≥ 2 metastatic SLNs.

Schlafen family member 11 indicates favorable prognosis of patients with head and neck cancer following platinum-based chemoradiotherapy.

Recently, Schlafen family member 11 (SLFN11) has been reported to increase the sensitivity of cancer cells to DNA-damaging agents, including platinum derivatives; thus, SLFN11 may be a predictive biomarker for platinum-based chemoradiotherapy (CRT). In this study, we examined whether SLFN11 expression was associated with the therapeutic outcome of platinum-based CRT in head and neck squamous cell carcinoma (HNSCC). We performed immunohistochemical analyses for SLFN11 expression in 161 HNSCC tissues from patients who had been administered cisplatin-based CRT and examined the correlation between SLFN11 expression and progression-free survival (PFS). Additionally, SLFN11 expression was examined in 10 paired samples obtained before and after CRT in patients with local failure. Furthermore, in vitro experiments were performed using several HNSCC cell lines and isogenic SLFN11-knockout cells to assess the association between SLFN11 expression and drug sensitivity. PFS was found to be significantly better in the SLFN11-positive group than in the SLFN11-negative group among the 161 patients (5-year PFS: 78.8% vs. 52.8%, respectively, p < 0.001). Similar results were observed for the PFS at each primary site. The percentage of SLFN11 positivity was lower in tumor samples from patients with local failure after CRT than that in the corresponding primary tumors before CRT in 8 of 10 cases. Results of the in vitro assay demonstrated that SLFN11-knockout cells exhibited reduced sensitivity to DNA-damaging agents but not to the non-DNA-damaging agent docetaxel. Our findings suggest that SLFN11 may serve as a potential biomarker for predicting the response of HNSCC patients to platinum-based CRT.

Multiparametric Analysis of Tumor Morphological and Functional MR Parameters Potentially Predicts Local Failure in Pharynx Squamous Cell Carcinoma Patients.

Purpose : To predict local control / failure by a multiparametric approach using magnetic resonance (MR)-derived tumor morphological and functional parameters in pharynx squamous cell carcinoma (SCC) patients. Materials and Methods : Twenty-eight patients with oropharyngeal and hypopharyngeal SCCs were included in this study. Quantitative morphological parameters and intratumoral characteristics on T2-weighted images, tumor blood flow from pseudo-continuous arterial spin labeling, and tumor diffusion parameters of three diffusion models from multi-b-value diffusion-weighted imaging as well as patients' characteristics were analyzed. The patients were divided into local control / failure groups. Univariate and multiparametric analysis were performed for the patient group division. Results : The value of morphological parameter of 'sphericity' and intratumoral characteristic of 'homogeneity' was revealed respectively significant for the prediction of the local control status in univariate analysis. Higher diagnostic performance was obtained with the sensitivity of 0.8, specificity of 0.75, positive predictive value of 0.89, negative predictive value of 0.6 and accuracy of 0.79 by multiparametric diagnostic model compared to results in the univariate analysis. Conclusion : A multiparametric analysis with MR-derived quantitative parameters may be useful to predict local control in pharynx SCC patients. J. Med. Invest. 68 : 354-361, August, 2021.

Analysis of acute-phase toxicities of intensity-modulated proton therapy using a model-based approach in pharyngeal cancer patients.

Pharyngeal cancer patients treated with intensity-modulated proton therapy (IMPT) using a model-based approach were retrospectively reviewed, and acute toxicities were analyzed. From June 2016 to March 2019, 15 pharyngeal (7 naso-, 5 oro- and 3 hypo-pharyngeal) cancer patients received IMPT with robust optimization. Simulation plans for IMPT and intensity-modulated X-ray therapy (IMXT) were generated before treatment. We also reviewed 127 pharyngeal cancer patients with IMXT in the same treatment period. In the simulation planning comparison, all of the normal-tissue complication probability values for dysphagia, dysgeusia, tube-feeding dependence and xerostomia were lower for IMPT than for IMXT in the 15 patients. After completing IMPT, 13 patients completed the evaluation, and 12 of these patients had a complete response. The proportions of patients who experienced grade 2 or worse acute toxicities in the IMPT and IMXT cohorts were 21.4 and 56.5% for dysphagia (P < 0.05), 46.7 and 76.3% for dysgeusia (P < 0.05), 73.3 and 62.8% for xerostomia (P = 0.43), 73.3 and 90.6% for mucositis (P = 0.08) and 66.7 and 76.4% for dermatitis (P = 0.42), respectively. Multivariate analysis revealed that IMPT was independently associated with a lower rate of grade 2 or worse dysphagia and dysgeusia. After propensity score matching, 12 pairs of IMPT and IMXT patients were selected. Dysphagia was also statistically lower in IMPT than in IMXT (P < 0.05). IMPT using a model-based approach may have clinical benefits for acute dysphagia.

The role of endoscopic resection for selected patients with sinonasal squamous cell carcinoma.

OBJECTIVE: Despite of rapid advances in endoscopic surgery, the gold standard for sinonasal squamous cell carcinoma (SNSCC) surgery has remained the open approach with en-block resection due to the aggressive nature of SNSCC, including frequent recurrence and high mortality rate. For that reason, few studies have focused on SNSCC treated by endoscopic surgery alone. The objective of this study was to evaluate the usefulness of endoscopic surgery for patients with SNSCC. METHODS: A retrospective analysis was performed for 15 consecutive SNSCC patients who underwent endoscopic surgery without an open approach. We carefully selected patients whose tumor attachment sites could be fully visualized and completely resected through an endonasal approach. RESULTS: Of the fifteen patients, 4 patients (27%) were diagnosed with T1, 7 (47%) with T2, 4 (27%) with T3, and no patients with T4a or T4b disease. Four of the 15 (27%) patients showed positive surgical margins. The 5-yr overall survival, disease-specific survival, and local control rate was 72.4%, 79.6%, and 92.9%, respectively. The 5-yr disease-specific survival for T1, T2, and T3 disease was 100% and 75% and 75%, respectively. Patients with negative surgical margins had a better disease-specific survival rate than did those with positive surgical margins (p = 0.0253). CONCLUSION: Endoscopic surgery for patients with SNSCC appears to afford an effective method in selected cases. The achievement of negative surgical margins with a good view of the tumor attachment site was considered to be critical to the management of SNSCC.

Phase II trial of combination treatment with S-1/cetuximab in patients with platinum-ineligible recurrent and/or metastatic squamous cell carcinoma of the head and neck.

BACKGROUND: The standard of care for first-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) in patients who cannot tolerate platinum-based regimens has not been clarified. We aimed to develop a new treatment regimen for patients with R/M SCCHN who are ineligible for platinum-based therapy, by evaluating the effects and safety of tegafur/gimeracil/oteracil (S-1) and cetuximab. METHODS: Platinum-ineligibility was defined as: elderly (aged ≥ 75 years), poor PS, comorbidity, platinum resistance and refusal to undergo platinum-based therapy. Patients received S-1 (80 mg/m2/day for 14 days followed by a seven-day break) and cetuximab (initial dose, 400 mg/m2, followed by 250 mg/m2 weekly) until disease progression or unacceptable toxicity. The primary endpoint was overall response rate (ORR). RESULTS: Between September 2014 and September 2018, we enrolled 23 patients. Among the 21 patients who were evaluable, 20 were male [median age, 69 years (range 49-82)]. The ORR was 9 (43%) of 21 patients [95% confidence interval (CI) 22-66]. One and eight patients achieved complete response (CR) and partial response (PR), respectively. The median overall survival (OS) was 13.7 months (95% CI 9.0-18.3) and progression-free survival (PFS) was 5.7 months (95% CI 3.1-8.2). Grade 3/4 adverse events included acneiform rash and skin reactions (33%), hypomagnesemia (19%), hand-foot syndrome (14%), fatigue (14%), mucositis (10%), and anorexia (10%). CONCLUSIONS: Combination treatment with S-1 and cetuximab was effective and tolerated well by patients with platinum-ineligible R/M SCCHN. Registered clinical trial number: UMIN000015123.

Optimization of therapeutic strategy for p16-positive oropharyngeal squamous cell carcinoma: Multi-institutional observational study based on the national Head and Neck Cancer Registry of Japan.

BACKGROUND: Although the American Joint Committee on Cancer TNM classification has been amended to include human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) as an independent entity, to the authors' knowledge the optimized de-escalating treatment modality has not been established to date. METHODS: The authors conducted a retrospective, nationwide, observational study in patients with HPV-related OPSCC who were treated from 2011 to 2014 in Japan to determine the best treatment modality. RESULTS: A total of 688 patients who were newly diagnosed with HPV-related OPSCC who were treated with curative intent at 35 institutions and had coherent clinical information and follow-up data available were included in the current study. In patients with T1-T2N0 disease (79 patients), both the 3-year recurrence-free survival and overall survival (OS) rates were 100% in the group treated with radiotherapy (RT) as well as the group receiving concurrent chemoradiotherapy (CCRT). The 3-year OS rates were 94.4% (for patients with T1N0 disease) and 92.9% (for patients with T2N0 disease) among the patients treated with upfront surgery. In patients with stage I to stage II HPV-related OPSCC, the 5-year recurrence-free survival and OS rates were 91.4% and 92%, respectively, in the patients treated with CCRT with relatively high-dose cisplatin (≥160 mg/m2 ; 114 patients) and 74.3% and 69.5%, respectively, in the patients treated with low-dose cisplatin (<160 mg/m2 ; 17 patients). CONCLUSIONS: Despite it being a retrospective observational trial with a lack of information regarding toxicity and morbidity, the results of the current study demonstrated that patients with T1-T2N0 HPV-related OPSCC could be treated with RT alone because of the equivalent outcomes of RT and CCRT, and patients with stage I to stage II HPV-related OPSCC other than those with T1-T2N0 disease could be treated with CCRT with cisplatin at a dose of ≥160 mg/m2 .

Enhanced Angiogenesis in Salivary Duct Carcinoma Ex-Pleomorphic Adenoma.

Salivary duct carcinoma (SDC) is morphologically similar to breast cancer, with HER2-overexpression reported. With regard to the pattern of disease onset, SDC can arise from de novo or carcinoma ex-pleomorphic adenoma (Ca-ex-PA). Recently, multiple molecular profiles of SDC as well as breast cancer have been reported, with significant differences in HER2 expression between Ca-ex-PA and de novo. We assessed the differences in gene expression between onset classifications. We conducted immunohistochemical analysis and HER2-DISH for 23 patients and classified SDCs into three subtypes as follows: "HER2-positive" (HER2+/any AR), "Luminal-AR" (HER2-/AR+), and "Basal-like" (HER2-/AR-). We assessed the expression levels of 84 functional genes for 19 patients by using a qRT-PCR array. Ten cases were classified as HER2-positive, seven cases as Luminal-AR, and six cases as Basal-like. The gene expression pattern was generally consistent with the corresponding immunostaining classification. The expression levels of VEGFA, ERBB2(HER2), IGF1R, RB1, and XBP1 were higher, while those of SLIT2 and PTEN were lower in Ca-ex-PA than in de novo. The functions of those genes were concentrated in angiogenesis and AKT/PI3K signaling pathway (Fisher's test: p-value = 0.025 and 0.004, respectively). Multiple machine learning methods, OPLS-DA, LASSO, and RandomForest, also show that VEGFA can be a candidate for the characteristic differences between Ca-ex-PA and de novo. In conclusion, the AKT/PI3K signaling pathway leading to angiogenesis was hyper-activated in all SDCs, particularly in those classified into the Ca-ex-PAs. VEGFA was over-expressed significantly in the Ca-ex-PA, which can be a crucial factor in the malignant conversion to SDC.

Machine-Learning-Based Prediction of Treatment Outcomes Using MR Imaging-Derived Quantitative Tumor Information in Patients with Sinonasal Squamous Cell Carcinomas: A Preliminary Study.

The purpose of this study was to determine the predictive power for treatment outcome of a machine-learning algorithm combining magnetic resonance imaging (MRI)-derived data in patients with sinonasal squamous cell carcinomas (SCCs). Thirty-six primary lesions in 36 patients were evaluated. Quantitative morphological parameters and intratumoral characteristics from T2-weighted images, tumor perfusion parameters from arterial spin labeling (ASL) and tumor diffusion parameters of five diffusion models from multi-b-value diffusion-weighted imaging (DWI) were obtained. Machine learning by a non-linear support vector machine (SVM) was used to construct the best diagnostic algorithm for the prediction of local control and failure. The diagnostic accuracy was evaluated using a 9-fold cross-validation scheme, dividing patients into training and validation sets. Classification criteria for the division of local control and failure in nine training sets could be constructed with a mean sensitivity of 0.98, specificity of 0.91, positive predictive value (PPV) of 0.94, negative predictive value (NPV) of 0.97, and accuracy of 0.96. The nine validation data sets showed a mean sensitivity of 1.0, specificity of 0.82, PPV of 0.86, NPV of 1.0, and accuracy of 0.92. In conclusion, a machine-learning algorithm using various MR imaging-derived data can be helpful for the prediction of treatment outcomes in patients with sinonasal SCCs.

[A Nutritional Supplement with a High Blend Ratio of ω-3 Fatty Acids(Prosure®) Reduces Severe Oral Mucositis and Body Weight Loss for Head and Neck Cancer Patients Treated with Chemoradiotherapy].

BACKGROUND: Oral mucositis and body weight loss are the most critical conditions known to lead to the discontinuation of chemoradiotherapy for head and neck cancer. We investigated the effect of a nutritional supplement with a high blend ratio of w-3 fatty acids(Prosure®)on body weight loss, oral mucositis, and the completion rate of chemoradiotherapy in patients with oropharyngeal and hypopharyngeal cancer. PATIENTS AND METHODS: The study group comprised patients with oropharyngeal and hypopharyngeal cancer who were treated with concomitant cisplatin and 70 Gy of radiotherapy. These patients received 2 packs of Prosure®per day during chemoradiotherapy. RESULTS: A total of 17 patients were included in this study. The reduction in body weight was significantly improved compared with that in the historical control group that did not receive Prosure®(7.3% vs 10.3%, p<0.01), and the rate of Grade 3-4 oral mucositis was significantly reduced for the patient groups that received Prosure®(CTCAE v3.0 GradeB3; 24% vs 58%, p<0.05). The completion rate of chemoradiotherapy was not significantly different between both groups(77% vs 60%, NS). CONCLUSIONS: A nutritional supplement with a high blend ratio of w-3 fatty acids(Prosure®)had effects on oral mucositis and body weight loss in head and neck cancer patients treated with chemoradiotherapy.

The utility of MRI histogram and texture analysis for the prediction of histological diagnosis in head and neck malignancies.

BACKGROUND: To assess the utility of histogram and texture analysis of magnetic resonance (MR) fat-suppressed T2-weighted imaging (Fs-T2WI) for the prediction of histological diagnosis of head and neck squamous cell carcinoma (SCC) and malignant lymphoma (ML). METHODS: The cases of 57 patients with SCC (45 well/moderately and 12 poorly differentiated SCC) and 10 patients with ML were retrospectively analyzed. Quantitative parameters with histogram features (relative mean signal, coefficient of variation, kurtosis and skewness) and gray-level co-occurrence matrix (GLCM) features (contrast, correlation, energy and homogeneity) were calculated using Fs-T2WI data with a manual tumor region of interest (ROI). RESULTS: The following significantly different values were obtained for the total SCC versus ML groups: relative mean signal (3.65 ± 0.86 vs. 2.61 ± 0.49), contrast (72.9 ± 16.2 vs. 49.3 ± 8.7) and homogeneity (2.22 ± 0.25 × 10- 1 vs. 2.53 ± 0.12 × 10- 1). In the comparison of the SCC histological grades, the relative mean signal and contrast were significantly lower in the poorly differentiated SCC (2.89 ± 0.63, 56.2 ± 12.9) compared to the well/moderately SCC (3.85 ± 0.81, 77.5 ± 13.9). The homogeneity in poorly differentiated SCC (2.56 ± 0.15 × 10- 1) was higher than that of the well/moderately SCC (2.1 ± 0.18 × 10- 1). CONCLUSIONS: Parameters obtained by histogram and texture analysis of Fs-T2WI may be useful for noninvasive prediction of histological type and grade in head and neck malignancy.

Safety and efficacy of concurrent carboplatin or cetuximab plus radiotherapy for locally advanced head and neck cancer patients ineligible for treatment with cisplatin.

BACKGROUND: Locally advanced squamous cell carcinoma of the head and neck (LASCCHN) is usually treated with cisplatin (CDDP)-based chemoradiotherapy, except when patients are elderly or have renal, cardiac, or neurogenic dysfunction. This study compared the safety and efficacy of concurrent carboplatin (CBDCA) to cetuximab (Cmab) plus radiotherapy (RT) in patients ineligible for CDDP treatment. METHODS: We retrospectively analyzed LASCCHN patients who received CBDCA plus RT (n = 29) or Cmab plus RT (n = 18) due to ineligibility for CDDP treatment at two Japanese institutions between August 2006 and December 2015. RESULTS: Patients characteristics for CBDCA plus RT and Cmab plus RT were: median age, 74 and 75 years; 0-1 performance status, 90% and 100%; main primary tumor site, hypopharynx 52% (n = 15) and oropharynx 39% (n = 7); and stage IV, 90% (n = 26) and 50% (n = 9), respectively. With a median follow-up time of 60.0 months for CBDCA plus RT and 53.6 months for Cmab plus RT, 3-year locoregional control rates were 56% versus 58%, and median progression-free survival was 42.7 versus 11.6 months. CBDCA plus RT was associated with more grade 3/4 hematologic toxicities, including neutropenia and thrombocytopenia, whereas Cmab plus RT was associated with more grade 3/4 oral mucositis and radiation dermatitis. CONCLUSIONS: CBDCA or Cmab as a concurrent systemic therapy with RT is a possible treatment option for LASCCHN patients ineligible for CDDP treatment, although attention to hematological toxicity should be paid.

Semi-quantitative analysis of pre-treatment morphological and intratumoral characteristics using 18F-fluorodeoxyglucose positron-emission tomography as predictors of treatment outcome in nasal and paranasal squamous cell carcinoma.

BACKGROUND: To investigate the utility of quantitative morphological and intratumoral characteristics obtained by 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (FDG-PET/CT) for the prediction of treatment outcome in patients with nasal or paranasal cavity squamous cell carcinoma (SCC). METHODS: Twenty-four patients with nasal or paranasal cavity SCC who received curative non-surgical therapy (a combination of super-selective arterial cisplatin infusion and radiotherapy) were retrospectively analyzed. From pre-treatment FDG-PET data, a total of 13 parameters of quantitative morphological characteristics (tumor volume, surface area and sphericity), intratumoral characteristics (the maximum and mean standard uptake value, three intratumoral histogram and four textural parameters) and total lesion glycolysis (TLG) were respectively calculated. Information regarding the treatment outcome was determined from the histological diagnosis or clinical follow-up. Each of the 13 quantitative parameters as well as T- and N-stage was assessed for its relation to treatment outcome of local control or failure. RESULTS: In univariate analysis, significant differences in surface area and sphericity between the local control and failure groups were observed. The receiver operating characteristic (ROC) curve analysis showed that sphericity had the highest accuracy of 0.88. In the multivariate analysis, sphericity was revealed as an independent predictor of the local control or failure. CONCLUSIONS: The quantitative parameters of sphericity are useful to predict the treatment outcome in patients with nasal or paranasal SCC.

Comparison of the University of Pittsburgh staging system and the eighth edition of the American Joint Committee on Cancer TNM classification for the prognostic evaluation of external auditory canal cancer.

BACKGROUND: The purpose was to compare survival differences between patients with external auditory canal (EAC) cancer treated according to the University of Pittsburgh modified TNM staging system and those treated in accordance with the 8th edition of the American Joint Committee on Cancer (AJCC) staging manual on the TNM staging system for cutaneous cancers of the head and neck. METHODS: We performed a retrospective, single-institution review of 60 patients with EAC cancer treated with curative intent between September 2002 and March 2018. Survival outcomes were measured on the basis of the two staging systems. RESULTS: The C-index values for the overall survival (OS) rate revealed that the University of Pittsburgh staging system had higher prognostic accuracy than the 8th edition of the AJCC staging system. Univariable and multivariable analysis showed that T classification according to the University of Pittsburgh staging system was an independent predictor of the OS rate (hazard ratio 5.25; 95% confidence interval 1.38-24.9; P = 0.015). Meanwhile, the AJCC staging system could not differentiate T2 from T3-4 cancers. CONCLUSION: The University of Pittsburgh staging system for patients with EAC cancer is a valuable tool for use in clinical decision-making and predicting survival outcome.

Genetic mutation analysis of the malignant transformation of sinonasal inverted papilloma by targeted amplicon sequencing.

BACKGROUND: The mechanism underlying the malignant transformation of inverted papilloma (IP) has not yet been elucidated. METHODS: To clarify the genes responsible for the malignant transformation, we analyzed 10 cases of IP, 8 of IP with dysplasia, and 11 of squamous cell carcinoma (SCC) by targeted amplicon sequencing. RESULTS: The number of mutant genes increased in the order of IP < dysplasia < SCC. Significant differences were observed in the mutation rates of three genes (KRAS, APC and STK11) in particular. TP53 was altered frequently in each group and might be involved in malignant transformation based on to the site of the mutation. A comparison of the genetic variants by region of IP tissue among patients with IP alone, and those with dysplasia or SCC revealed significant differences in the mutation rate of the KRAS gene. CONCLUSION: Identification of genetic mutations in KRAS is effective for predicting the malignant transformation of IP.

Validation of the 8th edition of the AJCC/UICC TNM staging system for tongue squamous cell carcinoma.

BACKGROUND: The revised 8th edition of the AJCC/UICC staging system was released in January 2017, and depth of invasion (DOI) was added to the new criteria for T classification in oral cavity cancer. In this study, we evaluated whether the 8th edition presents the prognosis and risk of nodal metastasis in patients with squamous cell carcinoma of tongue more accurately than did the 7th edition. METHODS: The data for 112 patients were obtained and reclassified based on the criteria presented in the 8th edition. RESULTS: Seven patients previously staged as T1 based on the criteria in the 7th edition were reclassified as T2 based on the 8th edition, while 19 T2 patients were reclassified as T3, and 9 T4a patients were reclassified as T3. T3 in the 8th edition represents a homogenous population showing the same prognosis, while T2 in the 8th edition represents a heterogenous population. Nodal metastasis was significantly correlated with T classification in both editions and DOI. However, neither the T classification in the 7th or 8th edition, nor DOI could predict the probability of potential nodal metastasis in patients with cN0 disease. CONCLUSIONS: The classification on T3 in the 8th edition can be seen as reasonable with regard to prognosis. Nodal metastasis was significantly correlated with T classification and DOI; however, the probability of subsequent nodal metastasis in patients with T2N0 was almost same for the criteria in the 7th and 8th editions, therefore, the same careful management as before is required for patients with N0 disease.

Osteoradionecrosis of the hyoid bone after intra-arterial chemoradiotherapy for oropharyngeal cancer: MR imaging findings.

BACKGROUND: Osteoradionecrosis (ORN) of the hyoid bone sometimes induces severe front neck infection and can cause laryngeal stenosis and carotid rupture. Although ORN of the hyoid bone is known to be a complication of chemoradiotherapy for head and neck cancer, there has been no basis for its evaluation. Our purpose is to present the clinical and MR imaging features of ORN of the hyoid bone. METHODS: The study group comprised patients with advanced oropharyngeal cancer treated with targeted intra-arterial cisplatin infusion with concomitant radiotherapy. ORN of the hyoid bone was identified on the basis of decreased signal intensity of the bone marrow on T1WI images. Signal intensity on T2WI images was used to distinguish between inflammation and fibrosis. RESULTS: A total of 39 pre-treatment MR images and follow-up MR images were reviewed. ORN of the hyoid bone were detected in 30% of patients after treatment, with 23% of them showing inflammation and 7.7% fibrosis. Two patients developed severe neck infection and received antibiotics and underwent surgical intervention by tracheostomy and resection of the hyoid bone. CONCLUSION: Our MR imaging study showed that ORN of the hyoid bone is not particularly rare in patients with oropharyngeal cancer treated with chemoradiotherapy. Clinicians should evaluate images carefully to prevent the development of severe complication due to infection associated with ORN of the hyoid bone.

Role of microRNA-296-3p in the malignant transformation of sinonasal inverted papilloma.

Inverted papilloma (IP) is a benign tumor occurring in the nasal cavity and paranasal sinuses. It is reported that 5-15% of IPs undergo malignant transformation into squamous cell carcinoma (SCC), and the role of microRNAs (miRNA/miR) in this process remains to be elucidated. In the present study, whole miRNA profiles using samples of IP and SCC were investigated, in order to detect the function of miRNA in the carcinogenesis of IP. Samples from IPs (n=5) and SCC lesions (n=5), which arose from IPs, were used for miRNA analysis. A total of 200 miRNAs exhibited a >2-fold differential expression between IP and SCC. miR-296-3p was markedly upregulated in SCC with a 23-fold difference. Computational analysis indicated that miR-296-3p targeted PTEN, which regulates the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway and PTEN is involved in the carcinogenesis of SCC. miR-296-3p directly regulated PTEN expression in head and neck cancer cells, with PTEN protein levels decreased in 4/19 the SCCs (21.0%), as compared with those in the IPs (76.4%). Positive p21 staining was observed in 64.7% of IPs; this was a significantly increased rate compared with that for SCCs (26.3%, P=0.0086). The results of the present study indicated that there were marked changes in the miRNA expression signature during the malignant transition. miR-296-3p may serve an important role in the malignant transformation of IPs via the regulation of PTEN, combined with the subsequent inhibition of the PI3K/Akt signaling pathway, and may be a novel agent for cancer prevention.

Atypical adenoma of the thyroid diagnosed as anaplastic cancer by cytopathology.

Atypical adenoma of the thyroid is a rare form of tumor, and its accurate diagnosis prior to surgical resection is difficult as the histological and pathological morphologies are very similar to those of anaplastic thyroid carcinoma (ATC), and its anaplastic transformation remains to be elucidated. We reported a case of a 75-year-old female with a thyroid isthmus nodule diagnosed repeatedly by FNAC as anaplastic carcinoma. Both the first and second FNAC specimen slides showed a large number of scattered or aggregated atypical cells consisting of large, pleomorphic nuclei with irregular membranes, chromatin clumps and prominent nucleoli. The morphology of the surgical specimen was similar to that of an anaplastic carcinoma and although it showed signs of transition from a normal follicular epithelium, there was no invasive growth or mitosis. This lesion was diagnosed as an atypical adenoma, and a papillary carcinoma was also present in the right lobe of the thyroid. Here we evaluate the molecular features of atypical adenomas in comparison with 9 ATC samples, and discuss whether or not atypical adenomas represent a form of premalignant lesion. Ki-67 expression was found to be very low in atypical adenomas whereas all ATC samples showed high levels of Ki-67 expression. Epithelial-mesenchymal transition (EMT) marker expression suggested that atypical adenomas maintain their epithelial phenotype to a higher degree than do ATCs. Differential diagnosis between ATC and atypical adenoma is difficult by cytological and histological methods alone, and Ki-67 and EMT marker expression may support the diagnosis.

Confirmation of the eighth edition of the AJCC/UICC TNM staging system for HPV-mediated oropharyngeal cancer in Japan.

BACKGROUND: Several studies have demonstrated that the seventh edition of the American Joint Committee on Cancer/American Joint Committee on Cancer (AJCC/UICC) TNM staging system does not consistently distinguish between prognostic subgroups for human papillomavirus (HPV)-mediated oropharyngeal squamous cell carcinoma (OPSCC). The eighth edition of the AJCC/UICC TNM staging system came into effect for use with HPV-mediated OPSCC on or after 1 January 2017. This study confirms that the eighth edition of the AJCC/UICC TNM staging system for HPV-mediated OPSCC accurately reflects disease outcomes. PATIENTS AND METHODS: We retrospectively analyzed 195 patients with OPSCC treated at Hokkaido University Hospital, Sapporo, Japan between 1998 and 2015. HPV status was evaluated by immunohistochemical analysis of p16. RESULTS: Of the 195 OPSCC patients evaluated, 111 (56.9%) were p16 positive and 84 (43.1%) were p16 negative. The 3-year overall survival rate (OS) was significantly lower in the p16-negative patients with stage III-IV in comparison with those with stage I-II (55.0 vs. 93.1%, respectively; p < 0.01). The 3-year OS did not differ significantly between stage I-II and stage III-IV in the p16-positive patients (86.7 vs 87.7%). According to the eighth edition of the AJCC/UICC TNM staging system, stage I-II and stage III can be differentiated on the basis of the 3-year OS in the p16-positive patients (90.9 vs 70.2%, respectively; p < 0.01). CONCLUSIONS: The seventh edition of the AJCC/UICC TNM staging system is suitable for use with p16-negative patients; however, it does not effectively discriminate between p16-positive patients. Therefore, the eighth edition of the AJCC/UICC TNM staging system is more suitable for HPV-mediated OPSCC in Japan.