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Objective: This study aimed to investigate the distribution of human papillomavirus 16 (HPV16) variants that contribute to the development of HPV-related oropharyngeal carcinoma (HPV-OPC) in the Japanese population and to evaluate genetic variations in the sequence encoding the L1 antigen region of the viral outer shell that is targeted by existing vaccines and is relevant for designing a prevention strategy to combat the exponential increase in HPV-OPC cases in Japan.Methods: Seventy Japanese HPV-OPC patients treated at Tohoku University Hospital were included in the study. DNA was extracted from formalin-fixed, paraffin-embedded tissue samples. Polymerase chain reaction and direct nucleotide sequencing were performed to determine the nucleotide polymorphisms necessary for the classification of HPV16 variants and to assess genetic diversity in the HPV16 L1 antigen region, including the BC, DE, EF, FG, and HI loops.Results: The most common variant of HPV16 was the A4 sublineage (88.6%), conventionally called the Asian type, followed by the A1/2/3 (10.0%) sublineage, classified as the European type. The only nonsynonymous substitution detected in the L1 antigen loop region was p.N181T in the EF loop, which was found in 28/70 (40%) cases. In contrast, no nonsynonymous substitutions were observed in the DE, FG, and HI loops, which are particularly important regions in the antigen loop targeted by existing HPV vaccines.Conclusion: The most common HPV16 variant in Japanese HPV-OPC patients was the A4 subtype. The L1 antigen region is highly conserved, suggesting sufficient efficacy of existing HPV vaccines. These findings provide important information that will aid in the design of an HPV16 infection control strategy using existing HPV vaccines to prevent the spread of HPV-OPC in Japan. [ABSTRACT FROM AUTHOR]

The aim of this prospective, observational study was to evaluate the effectiveness of a simple endoscopic method for scoring swallowing function after treatment of advanced head and neck cancer patients. A prospective, observational study was conducted involving 60 patients who had undergone surgery or chemoradiation for advanced head and neck cancer. Endoscopic score of swallowing function, penetration aspiration scale (PAS) score measured by videofluorography, and functional oral intake scale (FOIS) score were recorded, and their correlations were examined. There was a positive correlation between endoscopic and PAS scores. Patients with endoscopic scores of 4 points or more had significantly higher PAS scores and lower FOIS scores than those with scores of 3 points or less. These positive correlations were found only in patients who underwent surgery, and not those who received chemoradiation. This study showed the effectiveness of the simple endoscopic method for scoring swallowing function in patients after surgery for advanced head and neck cancers. [ABSTRACT FROM AUTHOR]

Here we present a patient with a parotid secretory carcinoma (SC) with high-grade transformation. A 65-year-old female was referred to our hospital due to a gradually growing right parotid tumor discovered initially about 4 years earlier. MRI imaging detected a right parotid tumor 50 mm in the longer axis. Fine needle aspiration cytology indicated a class III tumor. Nine months after her initial visit, she revisited our department because of pain, trismus and facial paralysis. MRI detected a tumor 69 mm in the longer axis and 64 mm in the shorter axis and a biopsy specimen revealed parotid cancer. Furthermore, positron emission tomography revealed a synchronous small cell lung cancer (SCLC). Chemoradiotherapy for the SCLC was performed followed by an extended total parotidectomy for the parotid SC. Histological findings and ETV6-FISH analysis confirmed a parotid SC with high-grade transformation. Two months after the surgery, CT revealed a loco-regional recurrence and proton beam therapy (70.2 GyE/26 Fr) was performed. Three months after the proton beam therapy, CT indicated pleural effusion and lung metastasis, and fine needle aspiration cytology revealed the metastatic SC. Eight months after the surgery, the patient died due to the lung metastasis of SC. [ABSTRACT FROM AUTHOR]

Background: Adenoid cystic carcinoma is a rare malignant tumor arising from exocrine glands such as the major and minor salivary glands of the paranasal sinuses or the external auditory canal. Although multiple retrospective clinical studies of ACC have been reported to date, clinical questions, such as 1) long-term prognosis beyond 20 years, 2) usefulness and suitability for treatment of therapeutic interventions, 3) therapeutic goal to aim for, and 4) prognosis by recurrence sites, are still unclear. Methods: To improve understanding and management of adenoid cystic carcinoma of the head and neck (ACC), a retrospective study with 58 new ACC cases between 1991 and 2016 was performed. The median observation period was 66.8 months (range 3–316 months). The overall clinical stages were as follows: I, 6.9%; II, 25.9%; III, 19.0%; and IV, 48.2%. Histology was cribriform/tubular type (C-T type) in 62.0% and solid type in 27.5%. The main treatment strategy was definitive surgery, which was performed in 75.2% of cases. Results: Overall 10-year, 20-year, and 25-year survivals were 63.7, 27.3, and 20.0%, respectively. Similarly, disease-specific survival (DSSs) was 65.7, 51.2, and 38.4%, respectively, and disease-free survival was 25.2, 9.4, and 9.4%, respectively. Conducting surgery (HR: 0.19, 95% CI: 0.06–0.61, p = 0.005) and C-T type (HR: 0.32, 95% CI: 0.11–0.93, p = 0.036) were independent prognostic predictors of DSS. DSS was significantly prolonged after salvage surgery for both locoregional recurrence (p = 0.004) and lung metastatic recurrence (p = 0.012, vs best supportive care). Conclusions: In ACC cases, both initial surgical treatment and repetitive surgical resection of resectable recurrent lesions, including both locoregional and lung metastases, resulted in longer survival. The major goal of treatment for ACC may be long-term survival including cancer-bearing survival, resulting in either natural death or intercurrent-disease death, since judging cure of ACC is almost impossible. Trial registration: Retrospectively registered. [ABSTRACT FROM AUTHOR]

Background: Induction chemotherapy (IC) in locally advanced squamous cell carcinoma of the head and neck (LA‐SCCHN) often compromises compliance with subsequent chemoradiotherapy (CRT), which negatively affects outcomes. Here, we assessed the combination of paclitaxel (PTX), carboplatin (CBDCA), and cetuximab (Cmab) as IC for unresectable LA‐SCCHN. Methods: Induction chemotherapy consisted of weekly CBDCA area under the plasma concentration‐time curve = 1.5, PTX 80 mg/m2 and Cmab with an initial dose of 400 mg/m2 followed by 250 mg/m2 for 8 weeks. Following IC, CDDP (20 mg/m2, 4 days × 3 cycles) and concurrent radiotherapy (70 Gy/35 fr) were started. Primary endpoint was the proportion of CRT completion (%CRT completion). PCE was planned to be deemed effective if the Bayesian posterior probability (PP), defined as the probability that %CRT completion was larger than the threshold value of 65%, exceeded 84%. Results: Thirty‐five patients were enrolled. Cases were hypopharynx/oropharynx/larynx in 17/17/1 patients, all at Stage IV. Of 35 patients, 34 (97%) completed IC and 32 received CRT and met the criteria of full analysis set (FAS). In FAS, the %CRT completion was 96.9%, and PP was 99.9%, exceeding the prespecified boundary of 84%. Mean cumulative dose and relative to dose intensity of CDDP in CRT was 232.5 mg/m2 and 100%, respectively. Response rate was 88.6% by IC and 93.8% in the CRT phase. Three year overall survival was 83.5%. Main grade 3 toxicities included neutropenia (11.4%) and skin rash (5.7%) during IC; and oral mucositis (31.3%) and neutropenia (12.5%) during CRT. No grade 4 toxicity or treatment‐related death was seen. Conclusions: PCE as IC was feasible, with promising efficacy and no effect on compliance with subsequent CRT in unresectable LA‐SCCHN. [ABSTRACT FROM AUTHOR]

Purpose: Swallowing dysfunction and the risk of aspiration pneumonia are frequent clinical problems in the treatment of head and neck squamous cell carcinomas (HNSCCs). Breathing–swallowing coordination is an important factor in evaluating the risk of aspiration pneumonia. To investigate breathing–swallowing discoordination after chemoradiotherapy (CRT), we monitored respiration and swallowing activity before and after CRT in patients with HNSCCs. Methods: Non-invasive swallowing monitoring was prospectively performed in 25 patients with HNSCCs treated with CRT and grade 1 or lower radiation-induced dermatitis. Videoendoscopy, videofluoroscopy, Food Intake LEVEL Scale, and patient-reported swallowing difficulties were assessed. Results: Of the 25 patients selected for this study, four dropped out due to radiation-induced dermatitis. The remaining 21 patients were analyzed using a monitoring system before and after CRT. For each of the 21 patients, 405 swallows were analyzed. Swallowing latency and pause duration after the CRT were significantly extended compared to those before the CRT. In the analysis of each swallowing pattern, swallowing immediately followed by inspiration (SW-I pattern), reflecting breathing–swallowing discoordination, was observed more frequently after CRT (p = 0.0001). In 11 patients, the SW-I pattern was observed more frequently compared to that before the CRT (p = 0.00139). One patient developed aspiration pneumonia at 12 and 23 months after the CRT. Conclusion: The results of this preliminary study indicate that breathing–swallowing discoordination tends to increase after CRT and could be involved in aspiration pneumonia. This non-invasive method may be useful for screening swallowing dysfunction and its potential risks. [ABSTRACT FROM AUTHOR]

Purpose: To improve the diagnoses of the salivary gland tumors, a dynamic-enhanced MRI (dMRI) was investigated.Methods: We conducted a retrospective chart review of 93 cases of salivary gland tumors. The histological diagnoses were obtained from all patients using a surgical specimen and/or an open biopsy specimen. The dMRI as well as fine-needle aspiration cytology (FNAC) and intraoperative frozen section (IFS) were analyzed. This study focused on the time-intensity curve (TIC) after injection, peak time (Tpeak), washout ratio (WR) as well as the gradient of enhancement and washout profile.Results: The histological diagnoses included pleomorphic adenoma (PMA) in 53 cases, the Warthin tumors (WT) in 14 cases and malignant tumors (MT) in 26 cases. Incorrect diagnosis rate of FNAC and IFS were 5.2 and 8.3%, respectively. The TIC revealed differences among the three types of tumors. Tpeak as well as WR also revealed significant differences (p < 0.001). Tpeak were lower in order of WT, MT, PMA, respectively. WR of TICs at 30, 45 and 105 s after Tpeak were higher in order of WT, MT, PMA, respectively (p < 0.001). The gradient of increment and washout in the TIC curve was also an important parameter to distinguish the three types of tumors. In MT, the rapid enhancement pattern was found in high or intermediate histological grade tumors, whereas the slow enhancement pattern was exhibited in low grade tumors.Conclusions: Our findings indicate that using Tpeak and WR, it is possible to distinguish between WT, PMA and MT. Additionally, a rapid enhancement pattern may be a potential marker for these tumors. [ABSTRACT FROM AUTHOR]

Here we present an extremely rare case of giant infantile hemangiopericytoma (HPC) of the tongue diagnosed prenatally by fetal ultrasonography and MR imaging. Due to airway stenosis, the patient was delivered by the ex utero intrapartum treatment (EXIT) procedure at 36 weeks of pregnancy. Initial diagnosis was infantile hemangioma based on physical examination, diagnostic imaging and the high incidence of hemangioma. The tumor was resistant to conservative treatments. Due to severe tumor hemorrhage, the nutrient vessel was embolized by endovascular treatment on the 73th day after birth. Two days after embolization, a hemiglossectomy was performed. Histological analysis after surgery diagnosed infantile HPC with microscopically positive stumps. After receiving adjuvant chemotherapy, the patient has had no recurrence after 53 months with normal speech and swallowing function resulting in normal growth. Our findings support that infantile HPC is one of the differential diagnosis of infantile hemangioma. The EXIT procedure could be effective for infants with upper respiratory stenosis by head and neck tumor diagnosed prenatally. Though complete resection is required for infantile HPC, our report suggests that a conservative surgical approach followed by adjuvant chemotherapy should be used for giant head and neck infantile HPC. [ABSTRACT FROM AUTHOR]

Melanotic neuroectodermal tumor of infancy (MNTI) is an extremely rare, pigmented neoplastic entity of neural crest origin. Histological and immunohistochemical profiles indicate the presence of two components, small rounded neuroblast-like cellular areas and areas with large melanin-containing cells which consist of combination of neural, melanocytic, and epithelial cell types. Here we present two interesting cases of infants with MNTI which have different clinicopathological features. The first case is a 3-month-old female with rapidly growing MNTI involving the lacrimal sac and inferior wall of the orbital cavity, treated with total maxillectomy without orbital exenteration followed by chemotherapy. The second case is a 7-month-old male with slow-growing maxillary MNTI treated with complete surgical excision. In the female patient, histological findings revealed a predominance of neuroblast-like cellular areas and a high Ki67 index indicating rapid cellular proliferation. In the male patient however, large melanin-containing cells were dominant in this slow-growing tumor. These findings support the presence of two different types of MNTI, rapid-growing and slow-growing types, determined by the component of neuroblast-like cellular areas. [ABSTRACT FROM AUTHOR]

Summary: Objectives: For patients with tobacco-related head and neck squamous cell carcinoma (HNSCC), the occurrence of a second primary tumor (SPT) is an ominous development that is attributed to a field cancerization effect and portends a poor clinical outcome. The goal of this study was to determine whether patients with human papillomavirus (HPV)-related index tonsillar carcinomas can also develop SPTs in the contralateral tonsil, and to discern the molecular etiology of HPV-related tumor multifocality. Materials and methods: The surgical pathology archives of The Johns Hopkins Hospital were searched for all patients with primary HPV-related tonsillar squamous cell carcinoma who developed a synchronous or metachronous carcinoma in the contralateral tonsil. The HPV-16 E6 exon was sequenced from each independent cancer site to determine whether the tumor pairs harbored the same or a different HPV-16 variant. Results: Four patients with bilateral HPV-related tonsillar carcinomas were identified. In every case, the HPV DNA sequences derived from the index tumor and corresponding SPT were 100% concordant, indicating that the index and SPTs were caused by the same HPV-16 variant. Conclusion: For the small subset of patients with tonsillar carcinomas who develop SPTs in the contralateral tonsil, the index case and the SPT consistently harbored the same HPV variant. This finding suggests that HPV-related tumor multi-focality can be attributed either to independent inoculation events by the same virus, or by migration of HPV-infected cells from a single inoculation site to other regions of Waldeyer’s ring. [ABSTRACT FROM AUTHOR]

Recently, an inverse relationship between resistance to platinum-based chemotherapeutic agents and taxanes has been implicated in breast and ovarian cancers, and a possible pivotal role for BRCA1 has also been suggested. Because cisdiamminedichloroplatinum (CDDP) and taxanes are the most active antitumor agents against head and neck squamous cell carcinoma (HNSCC), we analyzed the sensitivity of nine HNSCC cell lines and their previously established derived CDDP-resistant cell lines to two representative taxanes: docetaxel and paclitaxel. None of the nine original cell lines showed any cross resistance between CDDP and taxanes, but one of the CDDP-resistant cell lines, RPMI2650CR, demonstrated hypersensitivity to both taxanes when compared to the parental cell line, RPMI2650. Furthermore, RPMI2650CR exhibited increased expression of BRCA1. These data suggest that (i) taxanes are a good candidate for a second-line therapeutic drug for HNSCC patients with acquired CDDP resistance and (ii) BRCA1 can be a candidate marker for predicting an inverse CDDP/taxane sensitivity phenotype in HNSCC. [ABSTRACT FROM AUTHOR]

Ten head and neck squamous cell carcinoma (HNSCC) cell lines that had acquired cis-diamminedichloroplatinum (CDDP) resistance were successfully established by means of in vitro culture with CDDP. Flow cytometry analysis showed the significantly decreased induction of apoptosis after the CDDP treatment in the acquired CDDP-resistant sublines. Among these, RPMI2650CR showed a 9.38-fold increased IC50 in comparison with the parental cell line, RPMI2650. The identification of the resistance-related gene clusters was conducted between RPMI2650CR and RPMI2650 using two distinct microarray platforms. The expressional profiles were quite similar, suggesting that a limited number of genes regulate the acquisition of CDDP resistance. IGF2 was found to be one of the candidates for acquired CDDP-resistance. The introduction of IGF2 into RPMI2650 caused CDDP resistance along with suppression of CDDP-dependent apoptosis. On the other hand, siRNA-mediated knockdown of IGF2 caused reduction of acquired CDDP-resistance in RPMI2650CR. These results demonstrate that expression of IGF2 plays an important and critical role in CDDP resistance in a HNSCC cell line RPMI2650. These findings suggest the possibility for developing a new strategy for treating patients with HNSCC, particularly those with acquired CDDP resistance, by combining CDDP with inhibition of the IGF2 pathway. [ABSTRACT FROM AUTHOR]

Abstract: We herein report a new patient with hypopharyngeal squamous cell carcinoma (SCC) who presented with recurrent metastasis in the mesenteric lymph nodes of a transplanted jejunum with resections of the anastomotic artery by means of definitive surgery. Our findings indicate that a path of collateral blood circulation had formed, at least in the mesentery, and although it is usually not predominant, the blood flow predominantly followed the path of collateral blood circulation due to the ligation of the nutrient vessels. The clinical presentation and clinical course are described with a review of the literature. [Copyright &y& Elsevier]

We have found a novel alternative splicing product of the apoptotic protease activating factor 1 (APAF-1), termed APAF-1-ALT, in the LNCaP human prostate cancer cell line. APAF-1-ALT harbors the caspase recruitment domain and an incomplete CED-4 like/ATPase domain, but lacks the WD-40 repeat units. The LNCaP cell expressed the full-length APAF-1 weakly and APAF-1-ALT rather abundantly, especially after mycoplasma infection. LNCaP underwent a retarded DNA damage-induced apoptosis, which was independent of caspase 9 activity. APAF-1-ALT functioned less effectively in inducing apoptosis than did APAF-1-XL, the full-length APAF-1, in transient transfection. Moreover, APAF-1-ALT interfered with APAF-1-XL’s ability to induce apoptosis in transient double transfection experiment. These results indicate that APAF-1-ALT is a molecule that is deficient and impeded for mediating apoptosis and that it may contribute to the resistance to DNA damage-induced treatment observed in LNCaP. [Copyright &y& Elsevier]

Purpose: The present study aimed to investigate CT imaging features, pathological findings, and prognosis in patients with thyroid hemiatrophy (THA) associated with papillary thyroid carcinoma (PTC). Methods: This retrospective study included 225 patients with histopathologically proven PTC treated by surgical resection who underwent preoperative CT scanning. On CT images, THA was defined as thyroid parenchymal hemiatrophy on the ipsilateral side of PTC. CT findings, overall survival, and disease-free survival were compared between patients with and without THA. Pathological findings were also assessed in PTCs with and without THA. Results: THA was observed in 35 of 225 (16%) patients with PTC. Atrophic thyroid parenchyma was observed in the right lobe of 20 patients (57%) and in the left lobe of the remaining 15 patients (43%). With respect to the solid components within PTCs, contrast-enhanced CT attenuation (114.2 ± 18.2 vs. 126.7 ± 31.3 HU; p < 0.05) and CT attenuation change for contrast-enhanced CT minus unenhanced CT (60.2 ± 18.1 vs. 72.3 ± 31.0 HU; p < 0.05) were significantly lower in PTCs with THA than in those without THA. Histopathologically, almost all PTCs with THA (97%) had keloid-like collagen, which is broad bundles of hypocellular collagen with bright eosinophilic hyalinization, typically observed in keloid. However, no significant differences were observed in the prognosis between the two groups. Conclusion: THA was occasionally observed in patients with PTC. Weak contrast-enhancement was distinct characteristic of PTC patients with THA, which is probably caused by keloid-like collagen. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to compare the radiological tumor (T)-category using multiparametric MRI with the pathological T category in patients with oral tongue squamous cell carcinoma (OTSCC) and to examine which is a better predictor of prognosis. Methods: This retrospective study included 110 consecutive patients with surgically resected primary OTSCC who underwent preoperative contrast-enhanced MRI. T categories determined by maximum diameter and depth of invasion were retrospectively assessed based on the pathological specimen and multiparametric MRI. The MRI assessment included the axial and coronal T1-weighted image (T1WI), axial T2-weighted image (T2WI), coronal fat-suppressed T2WI, and axial and coronal fat-suppressed contrast-enhanced T1WI (CET1WI). Axial and coronal CET1WI measurements were divided into two groups: measurements excluding peritumoral enhancement (MEP) and measurements including peritumoral enhancement. The prognostic values for recurrence and disease-specific survival after radiological and pathological T categorization of cases into T1/T2 and T3/T4 groups were compared. Results: The T category of MEP on coronal CET1WI was the most relevant prognostic factor for recurrence [hazard ratio (HR) = 3.30, p = 0.001] and the HR was higher than the HR for pathological assessment (HR = 2.26, p = 0.026). The T category determined by MEP on coronal CET1WI was also the most relevant prognostic factor for disease-specific survival (HR = 3.12, p = 0.03), and the HR was higher than the HR for pathological assessment (HR = 2.02, p = 0.20). Conclusion: The T category determined by MEP on the coronal CET1WI was the best prognostic factor among all radiological and pathological T category measurements. [ABSTRACT FROM AUTHOR]

Ultrasound (US) imaging effectively provides real-time anatomical information for clinical examinations. In otolaryngology, US imaging can visualize laryngeal muscles as well as cervical muscles. Here we present the case where US imaging was used while injecting botulinum toxin (BT) for the treatment of abductor spasmodic dysphonia, which provided definite results. We could visualize not only the injection pathway but also the infiltration of the BT solution into the posterior cricoarytenoid muscles. Therefore, our laryngeal US imaging is useful for both improving the success rate and avoiding injection complications of BT. [ABSTRACT FROM AUTHOR]

Objective: Tumor cells can acquire a large amount of energy and structural components by reprogramming energy metabolism; moreover, metabolic profiles slightly differ according to cancer type. This study compared and assessed the metabolic profile of head and neck squamous cell carcinoma (HNSCC) and normal tissues, which were collected from patients without cancer. Subjects and Methods: Overall, 23 patients with HNSCC and 6 patients without cancer were included in the analysis. Metabolomic profiles were analyzed using capillary electrophoresis‐mass spectrometry. Gene expression was evaluated using real‐time reverse transcription‐polymerase chain reaction. Results: Glycolysis, the pentose phosphate pathway, tricarboxylic acid cycle, and glutamine metabolism were upregulated in HNSCC tissues based on gene expression analysis. HNSCC could then have enhanced energy production and structural component. The levels of lactate, succinate, glutathione, 2‐hydroxyglutarate, and S‐adenosylmethionine, considered as oncometabolites, increased and these had accumulated in HNSCC tissues. Conclusions: The level of metabolites and the expression of enzymes differ between HNSCC and normal tissues. Reprogramming metabolism in HNSCC provides an energy source as well as structural components, creating a system that offers rapid proliferation, progression, and is less likely to be eliminated. [ABSTRACT FROM AUTHOR]

The aim of the "Japanese Clinical Practice Guidelines for Head and Neck Cancer - 2022 Update" is to review the latest evidence regarding head and neck cancer and to present the current standard approaches for diagnosis and treatment. These evidence-based recommendations were created with the consensus of the Guideline Committee, which is composed of otorhinolaryngologists and head and neck surgeons, together with radiologists, radiation oncologists, medical oncologists, plastic surgeons, dentists, palliative care physicians, and rehabilitation physicians. These guidelines were created by the Clinical Practice Guideline Committee of the Japan Society for Head and Neck Cancer based on the "Head and Neck Cancer Treatment Guidelines 2018 Edition," and the revised draft was compiled after evaluation by the Assessment Committee and public comments. The 'Clinical questions and recommendations' section consists of 13 categories, and 59 clinical questions are described in total. Here we describe 6 clinical questions specific to other sets of guidelines with recommendations and comments. [ABSTRACT FROM AUTHOR]

Head and neck cancer (HNC) is a tumor occurring in various primary sites with limited chemotherapy options for its treatment. Recently, comprehensive genomic profiling (CGP) testing has become clinically widespread. In this study, we examined the utility of CGP in diagnosing and treating HNC. This study included 29 patients with HNC who underwent CGP testing at the Gifu University Hospital between December 2019 and April 2022. We analyzed the types of gene mutations and tumor mutational burden (TMB) based on the CGP results. Squamous cell carcinoma accounted for 55.2%, and other cancers accounted for 44.8%. And we investigated the correlation of prognosis with gene mutations and TMB. Gene mutations were detected in TP53(48.3%), CDKN2A (27.6%), CDKN2B (17.2%), NOTCH1 (17.2%), PIK3CA (17.2%), ARID1A (13.8%), and NF1 (13.8%). TP53, CDKN2A and CDKN2B mutations significantly decreased survival rate in HNC. Five cases (17.2%) were TMB-high and 82.8% were TMB-low. In SCC cases treated with immune checkpoint inhibitors, TMB-high had better Overall survival than TMB-low. And all patients with TMB-high were oropharyngeal cancer. Although there were no cases in which effective treatment was actually performed based on the results of CGP, many gene mutations have been detected and several gene mutations correlated with prognosis. Furthermore, TMB can be used as a biomarker to predict the therapeutic effects of immune checkpoint inhibitors in cases of SCC. [ABSTRACT FROM AUTHOR]

We herein report a rare case of a patient with hypopharyngeal squamous cell carcinoma (SCC) who presented with recurrent metastasis in the mesenteric lymph node of a transplanted jejunum. Removal of the metastatic lymph node required resection of the nutrient vessels which risked the current state of the transplanted jejunum. Importantly, although the nutrient vessels were resected, the jejunum did not become necrotic. This case and another similar case indicate that it may be possible to predict the viability of a transplanted jejunum where jejunal nutrient vessels must subsequently be resected. Key indicators for jejunal survival include determining jejunal blood flow by intraoperative indocyanine green fluorescence imaging, confirming good jejunal color and observation of peristaltic movement by intraoperative blood flow blockage of nutrient vessels. In conclusion, if intraoperative indocyanine green fluorescence imaging in the entire jejunum can be confirmed, there is a high possibility that the jejunum can be well preserved. The clinical presentation and clinical course are described with a proposed new schema of the resectable site of the transplanted jejunal mesentery. [ABSTRACT FROM AUTHOR]

Long-term voice-abuse or sudden vocal fold microvascular disruption can lead to injury and subsequent repair/remodeling of the vocal fold mucosa. Periostin is known to be involved in airway remodeling and in various otolaryngological diseases. In ischemic heart disease, increased CD31 expression has been observed around cardiomyocytes during remodeling, and endothelial proliferation has been reported to occur at these sites. We investigated the expression and the roles of CD31, CD34, and periostin in the formation of vocal fold polyps. Fifty-seven samples of vocal fold polyps were investigate histopathologically and immunohistochemically. Expression of CD31 and CD34 was detected in 41 (71.9%) and 53 (93.0%) samples, respectively, obtained from patients with vocal fold polyp. Expression of periostin was detected in 41 (71.9%) samples obtained from patients with vocal polyps. The vocal polyp samples could be classified into three histological subtypes. Three patterns of CD31 and CD34 expression were observed in the vocal polyp. Four patterns of periostin expression were observed in vocal polyps. An association was observed between the CD31 expression pattern and the histological subtype of vocal fold polyps. In vocal fold polyps, evaluation of vascular endothelial markers may be useful for staging. [ABSTRACT FROM AUTHOR]

Purpose: To identify precipitating factors responsible for enteral nutrition (EN) dependency after concomitant chemoradiotherapy (CCRT) of head and neck cancers and to examine their statistical correlations.Methods: Factors related to feeding condition, nutritional status, disease, and treatment of 26 oropharyngeal and hypopharyngeal cancer patients who received definitive CCRT were retrospectively investigated by examining their medical records. The days of no oral intake (NOI) during hospitalization and the months using enteral nutrition after CCRT were counted as representing the feeding condition, and the changes in body weight (BW) were examined as reflecting nutritional status. The factors related to EN dependency after CCRT were analyzed.Results: Long duration of total NOI (≥ 30 days) and maximum NOI ≥ 14 days were significant predictors of EN dependency. Decreased BW (≥ 7.5 kg) was the next predictor identified, but it was not significant. Multivariate analysis showed that the total duration of NOI was more correlated with EN dependency than changes in BW.Conclusions: A long duration of NOI was more strongly related to EN dependency than nutritional factors. [ABSTRACT FROM AUTHOR]

Recently, diffusion-weighted imaging (DWI) is an essential magnetic resonance imaging (MRI) protocol for head and neck imaging in clinical practice as it plays an important role in lesion detection, tumor extension evaluation, differential diagnosis, therapeutic effect prediction, therapy evaluation, and recurrence diagnosis. Especially in the parotid gland, several studies have already attempted to achieve accurate differentiation between benign and malignant tumors using DWI. A conventional single-shot echo-planar-based DWI is widely used for head and neck imaging, whereas advanced DWI sequences, such as intravoxel incoherent motion, diffusion kurtosis imaging, periodically rotated overlapping parallel lines with enhanced reconstruction, and readout-segmented echo-planar imaging (readout segmentation of long variable echo-trains), have been used to characterize parotid tumors. The mean apparent diffusion coefficient values are easily measured and useful for assessing cellularity and histological characteristics, whereas advanced image analyses, such as histogram analysis, texture analysis, and machine and deep learning, have been rapidly developed. Furthermore, a combination of DWI and other MRI protocols has reportedly improved the diagnostic accuracy of parotid tumors. This review article summarizes the current state of DWI in differentiating parotid tumors. [ABSTRACT FROM AUTHOR]

Simple Summary: Long non-coding RNAs (lncRNAs) have emerged as a significant player in various cancers, including pancreatic cancer. However, how lncRNAs are aberrantly expressed in cancers is largely unknown. We hypothesized that lncRNAs would be regulated by signaling pathways and contribute to malignant phenotypes of cancer. In this study, to understand the significance of mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) for the expression of lncRNAs in pancreatic cancer, we performed comparative transcriptome analyses between pancreatic cancer cell lines with or without activation of MAPK. We identified 45 lncRNAs presumably associated with MAPK in pancreatic cancer cells; among these, LINC00941 was consistently upregulated by MAPK. The promoter of LINC00941 was determined and found to be preferentially associated with MAPK activity via ETS-1 binding site. TCGA data analysis indicated that high expression of LINC00941 was associated with poor prognosis of pancreatic cancer patients. Downstream targets of LINC00941 were involved in 44 biological processes, including the glycoprotein biosynthetic process, beta-catenin-TCF complex assembly, and histone modification. These results indicate that MAPK mediates the aberrant expression of lncRNAs, and LINC00941 is the most consistently promoted lncRNA by MAPK in pancreatic cancer. Therefore, MAPK-associated lncRNAs might represent both potentially valid therapeutic targets and diagnostic biomarkers. Long non-coding RNAs (lncRNAs) have emerged as a significant player in various cancers, including pancreatic cancer. However, how lncRNAs are aberrantly expressed in cancers is largely unknown. We hypothesized that lncRNAs would be regulated by signaling pathways and contribute to malignant phenotypes of cancer. In this study, to understand the significance of mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK), which is a major aberrant signaling pathway in pancreatic cancer, for the expression of lncRNAs, we performed comparative transcriptome analyses between pancreatic cancer cell lines with or without activation of MAPK. We identified 45 lncRNAs presumably associated with MAPK in pancreatic cancer cells; among these, LINC00941 was consistently upregulated by MAPK. The immediate genomic upstream region flanking LINC00941 was identified as a promoter region, the activity of which was found to be preferentially associated with MAPK activity via ETS-1 binding site. LINC00941 promoted cell proliferation in vitro. Moreover, TCGA data analysis indicated that high expression of LINC00941 was associated with poor prognosis of patients with pancreatic cancer. Transcriptomes comparing transcriptions between cells with and without LINC00941 knockdown revealed 3229 differentially expressed genes involved in 44 biological processes, including the glycoprotein biosynthetic process, beta-catenin-TCF complex assembly, and histone modification. These results indicate that MAPK mediates the aberrant expression of lncRNAs. LINC00941 is the lncRNA by MAPK most consistently promoted, and is implicated in the dismal prognosis of pancreatic cancer. MAPK-associated lncRNAs may play pivotal roles in malignant phenotypes of pancreatic cancer, and as such might represent both potentially valid therapeutic targets and diagnostic biomarkers. [ABSTRACT FROM AUTHOR]

Ototoxicity is a dose-limiting adverse event for concurrent chemoradiotherapy (CCRT) with high-dose cisplatin for locally advanced head and neck squamous cell carcinoma (HNSCC). Both irradiation to the Eustachian tube (ET) and weight loss are risk factors for patulous ET. The aim of this prospective, observational study was to elucidate the incidences of patulous ET conditions before and after CCRT in HNSCC patients by means of ET function tests. This prospective, observational study was conducted in 27 HNSCC patients who received CCRT with high-dose cisplatin, and ET function tests (sonotubometry and tubo-tympano-aerodynamic graphy) were performed before and 3 months after CCRT. Factors potentially affecting the incidence of patulous ET conditions after CCRT were evaluated. Of the 54 ears from 27 patients investigated, patulous ET conditions were observed in 12 ears (22.2%) from 9 patients (33.3%) before CCRT and 15 ears (27.8%) from 11 patients (40.7%) at 3 months after CCRT. Only patulous ET conditions before CCRT in each ear were significantly associated with patulous ET conditions after CCRT (p = 0.010). This is the first report to describe the incidences of patulous ET conditions before and after CCRT in HNSCC patients. HNSCC patients are potentially at higher risk of patulous ET. [ABSTRACT FROM AUTHOR]

Simple Summary: Among elderly adults, there is an increasing rate of those receiving chemoradiotherapy to preserve function and maintain quality of life. Many currently used guidelines on therapies for head and neck squamous cell carcinoma (HNSCC) exclude elderly adults, although the number of elderly patients with HNSCC is drastically increasing worldwide. In this review, we present the current status and potential new treatment strategies for elderly patients with HNSCC. Poor tolerance to chemoradiotherapy-related toxicity is a bigger concern in older patients than in younger individuals. Then, we describe toxicities particularly severe in elderly patients and provide an overview of countermeasures in chemotherapy and radiotherapy, particularly with a focus on cisplatin-based chemotherapy (the main treatment for HNSCC). In addition, we describe the molecular target drug therapy and immunotherapy for older patients with HNSCC. Consistent with the increasing rate of head and neck cancers among elderly adults, there has been an increase in the rate of those receiving nonsurgical treatments to maintain their function and quality of life. However, various problems, such as poor tolerance to chemoradiotherapy-related toxicity, are of greater concern in elderly adults than in younger individuals. In this review, we describe adverse events that should be particularly noted in elderly patients and provide an overview of countermeasures in nonsurgical treatments. We mainly focus on cisplatin-based chemoradiotherapy—the primary treatment for head and neck squamous cell carcinoma (HNSCC). Furthermore, we review the molecular targeted drugs and immune checkpoint inhibitors for elderly patients with HNSCC. Although the number of older patients is increasing worldwide, clinical trials aimed at determining the standard of care typically enroll younger or well-conditioned elderly patients. There is still very little evidence for treating elderly HNSCC older patients, and the question of optimal treatment needs to be explored. [ABSTRACT FROM AUTHOR]

Radiation-induced oral mucositis is one of the most common adverse events in radiation therapy for head and neck cancers, but treatments for oral mucositis are limited to palliative and supportive care. New approaches are required to prevent radiation-induced mucositis and to improve treatments. The Keap1-Nrf2 system regulates cytoprotection against oxidative and electrophilic stresses. Nrf2 also regulates keratin layer thickness in mouse tongues. Therefore, we hypothesized that Nrf2 may protect the tongue epithelium against radiation-induced mucositis via elimination of reactive oxygen species and induction of keratin layer thickening. To test this hypothesis, we prepared a system for γ-ray exposure of restricted areas and irradiated the tongues of model mice with Nrf2 and Keap1 loss-of-function. We discovered that loss of Nrf2 expression indeed sensitized the tongue epithelium to radiation-induced ulcer formation with inflammation. Constitutive Nrf2 activation by genetic Keap1 knockdown alleviated radiation-induced DNA damage by increasing antioxidation. In agreement with the genetic Nrf2 activation model, the Nrf2 inducer CDDO-Im prevented irradiation damage to the tongue epithelium. These results demonstrate that Nrf2 activation has the potential to prevent the development of radiation-induced mucositis and that Nrf2 inducers are an important therapeutic drug for protection of the upper aerodigestive tract from radiation-induced mucositis. [Display omitted] • Nrf2 protects against radiation-induced mucositis. • Constitutive Nrf2 activation mitigates DNA damage via antioxidation. • A thickened keratin layer in Nrf2-activated mouse tongues prevents the occurrence of radiation-induced ulcers. • Pharmacological Nrf2 activation prevents radiation-induced mucositis. [ABSTRACT FROM AUTHOR]

Purpose: Radical surgery with free flap reconstruction for locally advanced head and neck cancer (HNC) is quite challenging for older adults. This retrospective study aimed to elucidate the usefulness of the geriatric-8 (G8) screening tool for predicting postoperative complications in older adults with HNC. Methods: A retrospective review of 37 older adults with HNC who underwent radical surgery with free flap reconstruction and were assessed by the G8 screening tool was performed. Postoperative complications during hospitalization were classified according to the Clavien–Dindo classification, and possible contributing factors, including the G8 score, for major and minor complications were subjected to univariate and multivariate analyses. Results: The appropriate G8 cut-off value for both major and minor complications was 12 (area under the curve 0.56 and 0.55, respectively). Multivariate logistic regression analysis showed that both smoking and lower G8 score (≤ 12) were independently associated with the severity of complications (p = 0.043, p = 0.034, respectively). Conclusions: The G8 was a possible predictor of major and minor complications in older adults with HNC who underwent radical surgery with free flap reconstruction. [ABSTRACT FROM AUTHOR]

Background: The progression of hearing impairment and the bilateral involvement of Meniere's disease (MD) may depend on the disease duration and aging. Recent studies reported that MD might involve dysfunction of the microvascular circulation damaged due to inflammatory changes. Objectives: The aim of this study was to determine that the progress of the MD's hearing impairment and bilateral disability may be associated with the pathogenesis of several pro-inflammatory processes. Patients and Methods: We recruited 30 unilateral MD patients (56.8 ± 14.7 years old), 7 bilateral MD patients (65.3 ± 13.9 years old), and 17 age-matched control subjects (53.5 ± 14.4 years old, p > 0.05). We measured the plasma vascular endothelial growth factor (VEGF), plasma interleukin-6 (IL-6), plasma tumor-necrosis factor α (TNFα), and plasma monocyte chemotactic protein-1 (MCP-1). Results: The bilateral MD group and the unilateral MD group had higher plasma MCP-1 (204.7 ± 41.0 pg/mL and 169.5 ± 32.0 pg/mL) than the control group (149.2 ± 30.7 pg/mL) (p < 0.05). There was no significant difference in plasma TNFα, IL-6, and VEGF among 3 groups (p > 0.05). There was a strong correlation between the plasma MCP-1 and age in MD patients (r = 0.58, p < 0.01); however, no significant correlation between the plasma MCP-1 and age was found in control subjects (p > 0.05). The plasma MCP-1 significantly correlated with the average hearing level of 500, 1,000, 2,000, and 4,000 Hz, and the maximum slow phase eye velocity in caloric test in the better side (p < 0.05). Also, the plasma MCP-1 showed significant positive correlations with the plasma IL-6 (r = 0.49, p < 0.01) and plasma TNFα (r = 0.32, p < 0.05) in MD group. Conclusions: Our results suggest that the increased plasma MCP-1 accompanying pro-inflammatory processes are associated with the progression of the hearing impairment and the bilateral disability of MD. [ABSTRACT FROM AUTHOR]

Abstract: For the fast and accurate cognition of external information, the human brain seems to integrate information from multi-sensory modalities. We used positron emission tomography (PET) to identify the brain areas related to auditory–visual speech perception. We measured the regional cerebral blood flow (rCBF) of young, normal volunteers during the presentation of dynamic facial movement at vocalization and during a visual control condition (visual noise), both under the two different auditory conditions of normal and degraded speech sounds. The subjects were instructed to listen carefully to the presented speech sound while keeping their eyes open and to say what they heard. The PET data showed that elevation of rCBF in the right fusiform gyrus (known as the “face area”) was not significant when the subjects listened to normal speech sound accompanied by a dynamic image of the speaker''s face, but was significant when degraded speech sound (filtered with a 500Hz low-pass filter) was presented with the facial image. The results of the present study confirm the possible involvement of the fusiform face area (FFA) in auditory–visual speech perception, especially when auditory information is degraded, and suggest that visual information is interactively recruited to make up for insufficient auditory information. [Copyright &y& Elsevier]

Purpose: Radiation dermatitis is one of the most common acute toxicities induced by chemoradiation therapy (CRT) for head and neck cancer (HNC). The benefit of topical steroids in the management of radiation dermatitis is still unclear. This phase 3, multi-institutional, randomized, double-blind, placebo-controlled trial evaluated the efficacy and safety of topical steroids for radiation dermatitis in patients with locally advanced HNC receiving CRT.Methods and Materials: Eligible patients were scheduled to receive bilateral neck irradiation (≥66 Gy) with concurrent cisplatin (≥200 mg/m2) as definitive or postoperative CRT. Patients were randomly assigned to receive either topical steroid or placebo when grade 1radiation dermatitis was observed or the total radiation dose reached 30 Gy. Basic skin care including gentle washing and moistening in the head and neck region was performed in both groups. The primary endpoint was the frequency of grade ≥2 radiation dermatitis, in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. Grading of radiation dermatitis was performed by independent central review using photographs taken weekly.Results: A total of 211 patients were enrolled (intention to treat: steroid 101 and placebo 102). The frequency of grade ≥2 radiation dermatitis was not significantly reduced with the steroid (73.3%; 95% confidence interval, 64.6%-81.9%) compared with the placebo (80.4%; 95% confidence interval, 72.7%-88.1%; P = .23), whereas the steroid significantly reduced the frequency of grade ≥3 radiation dermatitis (13.9% vs 25.5%; P = .034). No significant differences in adverse events, including local infection or compliance with CRT, were observed between the groups.Conclusions: Topical steroid may reduce the severity of radiation dermatitis in patients with HNC and thus may become an important therapeutic tool in the management of radiation dermatitis. [ABSTRACT FROM AUTHOR]

Objective: Computer-aided design and computer-aided manufacturing (CAD/CAM) techniques are increasingly applied to mandibular reconstruction, but the superiority of this method in oral food intake has not been well established. Considering the extent of mandibular defects, this retrospective study was aimed to clarify the impact of CAD/CAM mandibular reconstruction on chewing and swallowing function after surgery for locally advanced oral cancer.Materials and Methods: We performed a retrospective review of 50 patients who had undergone segmental mandibulectomy with free flap reconstruction for locally advanced oral cancer. The patients' Functional Oral Intake Scale scores were measured at 3 months after surgery, and possible contributing factors including CAD/CAM mandibular reconstruction and the extent of mandibular defects for oral food intake were subjected to univariate analysis and multivariate logistic regression analysis.Results: Multivariate logistic regression analysis showed that CAD/CAM mandibular reconstruction was independently associated with good oral intake, whereas both anterior or extensive mandibular resection and glossectomy were also independently associated with poor oral intake after surgery.Conclusion: The present study showed the positive impact of CAD/CAM mandibular reconstruction on chewing and swallowing function after surgery for locally advanced oral cancer for the first time. [ABSTRACT FROM AUTHOR]

Objective: The objective is to conduct a questionnaire survey regarding pharyngolaryngeal sensation evaluation in dysphagia to understand the current situation in Japan.Method: The questionnaire was sent to the councilor of the Society of Swallowing and Dysphagia of Japan and the Japanese Society of Dysphagia Rehabilitation-Certified Clinician. The prospective questionnaire survey included the questions listed below: Q1: What do you think of the importance of pharyngolaryngeal sensory evaluation? Q2: Select one of the essential swallowing sensations. Q3: Select one of the following regarding the frequency of sensory examination of the larynx. Q4: Select the proportion of cases the sensory test results affect. Q5: As a pharyngolaryngeal sensory evaluation method in swallowing function evaluation, please fill in the table below for the frequency, difficulty, and effectiveness of the following tests, such as gag reflex, touching the larynx by endoscopy, touching the larynx by the probe with endoscopy, cough reflex test, swallowing provocation test.Results: The essential swallowing sensations of mechanical stimulation, chemical stimulation, thermal stimulation were 84.9%, 5.4%, and 9.7%, respectively. The frequency of touching the larynx by endoscopy in the otolaryngology group and cough reflex test in dentistry was significantly higher than the other groups (p < 0.05). The correlation between the frequency and difficulty or effectiveness of the sensory tests indicated that the frequency and difficulty are significantly correlated between each item.Conclusion: Our results aid in increasing understanding and selection of pharyngolaryngeal sensation evaluation for dysphagia patients. [ABSTRACT FROM AUTHOR]

Purpose: To clarify the correlations among symptoms, swallowing functions, and ingestion status and to validate a method of swallowing evaluation during chemoradiotherapy (CRT) for head and neck cancer.Methods: Oropharyngeal and hypopharyngeal cancer patients who were to receive definitive CRT as initial treatment were included in this prospective, single-center, observational study. The Functional Oral Intake Scale (FOIS) for ingestion status and grades of symptoms (dryness, dysgeusia, mucositis, and the analgesic ladder); the Yale Pharyngeal Residue Severity Rating Scale on fiberoptic endoscopic evaluation of swallowing (FEES) and the Penetration-Aspiration Scale (PAS) on videofluoroscopic (VF) evaluation for swallowing functions; and the 10-item Eating Assessment Tool (EAT-10) questionnaire were assessed at 5 time points unless the participant refused. The FEES and VF evaluation findings at each point were also compared.Results: There were 38 participants. Dysgeusia, mucositis, and pain grade, as well as the FOIS score, were the worst at 70 Gy and then improved after treatment. The improvements of pharyngeal residue and the PAS after treatment were limited. The EAT-10 and the pain ladder were highly correlated with the FOIS changes at many time points. The VF evaluation rate dropped after 40 Gy, whereas the FEES rate remained high. There were good correlations between pharyngeal residue and the PAS at 0 Gy, 70 Gy, and 3 months.Conclusion: The EAT-10 and pain reflected the FOIS score changes well, while two swallowing evaluations did not. To avoid aspiration, VF evaluation may not be necessary during CRT because of high correlations with pharyngeal residue on FEES. [ABSTRACT FROM AUTHOR]

Therapeutic cancer vaccines have met limited clinical success. In the setting of cancer, the immune system is either tolerized and/or has a limited tumor-specific T cell repertoire. In this study, we explore whether intratumoral (IT) vaccination with an HPV vaccine can elicit quantitative and qualitative differences in immune response as compared to intramuscular (IM) vaccination to overcome immune resistance in established tumors. We report that IT administration of an HPV-16 E7 peptide vaccine formulated with polyinosinic–polycytidylic acid [poly(I:C)] generated an enhanced antitumor effect relative to IM delivery. The elicited anti-tumor effect with IT vaccination was consistent among the vaccinated groups and across various C57BL/6 substrains. IT vaccination resulted in an increased frequency of PD-1hi TILs, which represented both vaccine-targeted and non-vaccine-targeted tumor-specific CD8+ T cells. Overall, the CD8+/Treg ratio was increased within the tumor microenvironment using IT vaccination. We also assessed transcriptional changes in several immune-related genes in the tumor microenvironment of the various treated groups, and our data suggest that IT vaccination leads to upregulation of a broad complement of immunomodulatory genes, including upregulation of interferon gamma (IFNγ) and antigen presentation and processing machine (APM) components. IT vaccine delivery is superior to traditional IM vaccination routes with the potential to improve tumor immunogenicity, which has potential clinical application in the setting of accessible lesions such as head and neck squamous cell carcinomas (HNSCCs). [ABSTRACT FROM AUTHOR]

Parapharyngeal neuroglial heterotopia is a rare entity, and the specific radiographical findings are unclear. We present a case of parapharyngeal neuroglial heterotopia examined with proton magnetic resonance spectroscopy (1H-MRS) and 18F-fluorodesoxyglucose positron emission tomography (18F-FDG PET). Our neonate patient presented with neck mass and polyhydramnios during gestation. Computed tomography and magnetic resonance imaging demonstrated the morphological characteristics, but failed to establish the diagnosis. 1H-MRS showed a non-malignant pattern, but 18F-FDG PET demonstrated high glucose metabolism. Complete resection was achieved and the histopathological diagnosis was neuroglial heterotopia. Assessment of biological activity may be useful for both preoperative diagnosis and postoperative evaluation of residual lesions. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to compare the therapeutic outcomes of total pharyngolaryngectomy with those of concomitant chemoradiotherapy in advanced hypopharyngeal cancer. Methods: This is a retrospective multi-institutional study. The medical records of 979 patients with hypopharyngeal cancer, who were initially treated between 2006 and 2008, were reviewed. In this study, we matched a group of total pharyngolaryngectomy patients with a second group of chemoradiotherapy patients, according to age, gender, subsite, arytenoid fixation, cartilage invasion, and N classification, and analyzed overall survival, disease-specific survival, and locoregional control rates. Results: The matched-pair analysis included 254 patients. The 5-year overall survival, disease-specific survival, and locoregional control rates were 58.5% and 53.5% ( P = 0.30), 68.9% and 68.0% ( P = 0.80), and 82.2% and 63.6% ( P < 0.01), respectively, for patients in the total pharyngolaryngectomy and chemoradiotherapy groups. For T4a patients with cartilage invasion, the matched-pair analysis included 46 patients. The 5-year overall survival, disease-specific, and locoregional control rates were 56.5% and 26.0% ( P = 0.092), 56.5% and 41.3% ( P = 0.629), and 43.0% and 42.5% ( P = 0.779), respectively, for patients in the total pharyngolaryngectomy and chemoradiotherapy groups. Conclusions: The data from this large-scale multi-institutional joint research program of hypopharyngeal cancer in Japan suggest that chemoradiotherapy may provide adequate survival benefit for hypopharyngeal cancer patients with the distinct advantage of larynx preservation. Our data also suggest that chemoradiotherapy is as beneficial as total pharyngolaryngectomy for the local control of locally advanced hypopharyngeal cancer. [ABSTRACT FROM AUTHOR]

In spite of significant technical advances, genesis and progression of non-small cell lung cancer (NSCLC) remain poorly understood. We undertook an integrated genetic approach to discover novel microRNAs that were deregulated in NSCLCs. A total 119 primary NSCLCs with matched normal were analyzed for genome-wide copy number changes. We also tested a subset of matched samples by microRNA expression array, and integrated them to identify microRNAs positioned in allelic imbalance area. Our findings support that most of the identified deregulated microRNAs (miR-21, miR-23b, miR-31, miR-126, miR-150, and miR-205) were positioned in allelic imbalance areas. Among microRNAs tested in independent 114 NSCLCs, overexpression of miR-23b was revealed to be a significantly poor prognostic factor of recurrence free survival (HR = 2.40, P = 0.005, 95%CI: 1.32-4.29) and overall survival (HR = 2.35, P = 0.005, 95%CI: 1.30-4.19) in multivariable analysis. In addition, overexpression of miR-23b in H1838 cell line significantly increased cell proliferation, while inhibition of miR-23b in H1437 and H1944 cell lines significantly decreased cell doubling time. In summary, integration of genomic analysis and microRNA expression profiling could identify novel cancer-related microRNAs, and miR-23b could be a potential prognostic marker for early stage NSCLCs. Further biological studies of miR-23b are warranted for the potential development of targeted therapy. [ABSTRACT FROM AUTHOR]

Conclusion: Lymph node swelling in the neck is one of the initial symptoms of malignant lymphoma (ML). The present study showed that clinical factors including higher age, higher level of maximum standardized uptake value (SUV-max) of positron-emission tomography, elevated serum lactate dehydrogenase (LDH), and elevated serum soluble interleukin-2 receptor (sIL-2R) were all useful indicators to suggest the diagnosis of ML, so may be helpful in the selection of patients for lymph node dissection. Objective: Lymph node dissection is essential for the diagnosis of ML. The factors important for the diagnosis of ML were investigated, to establish surgical indicators. Methods: Preoperative data including age, number and side of lymph nodes, SUV-max, serum LDH, serum sIL-2R, and size of lymph nodes were obtained from medical records. The cut-off level for each factor was calculated using the Youden Index for logistic regression analysis. Results: Multivariate logistic regression analysis showed that the following factors were associated with ML: higher age (≥ 53 years), higher level of SUV-max (≥ 9.0), elevated serum LDH (≥ 203 U/L), elevated serum sIL-2R (≥ 2590 U/ml), with odds ratios of 3.7, 4.9, 3.7, and 11.9, respectively. [ABSTRACT FROM AUTHOR]

Background and Aim Dysphagia caused by pharyngo-upper esophageal stricture is a complication of treatment for head and neck cancer. Endoscopic balloon dilation ( EBD) is in widespread use as an effective and safe treatment for stricture in many areas of the gastrointestinal tract. In the present study, we investigated the efficacy and safety of EBD for pharyngo-upper esophageal strictures that developed after treatment for head and neck cancer. Methods From January 2010 to December 2013, the medical records and endoscopic findings of 19 consecutive patients with pharyngo-upper esophageal strictures occurring after surgery and/or chemoradiotherapy for head and neck cancer were retrospectively examined. Results Mean number of EBD sessions per patient was 6.6 (1-30), and mean maximum diameter of dilation was 15.8 (11-20) mm. Technical success was achieved in 16 of 19 (84.2%) patients, and only two major complications (bleeding and pha ryngeal edema) occurred in a total of 125 dilatation sessions (1.6%). Regarding the influence of chemoradiotherapy on the outcome of EBD, patients who had undergone chemoradiotherapy plus surgery experienced significantly more restenosis during the follow-up period compared to those who had undergone surgery alone (50% vs 0%, P < 0.05). Conclusions This retrospective analysis demonstrated the efficacy and safety of exclusive EBD for pharyngo-upper esophageal strictures occurring after treatment for head and neck cancer, indicating that the therapeutic application of EBD could be extended to such strictures. Patients who underwent chemoradiotherapy and surgery experienced more restenosis; hence, such patients should be carefully followed up after EBD treatment. [ABSTRACT FROM AUTHOR]

Summary: Objective: A standardized assay to determine the HPV status of head and neck squamous cell carcinoma (HNSCC) specimens has not yet been established, particularly for cytologic samples. The goal of this study was to determine whether the hybrid capture-2 (HC-2) assay, already widely used for the detection of high risk HPV in cervical brushings, is applicable to cytologic specimens obtained from patients with suspected HNSCCs. Materials and methods: Fine needle aspirates (FNA) of cervical lymph nodes were pre-operatively obtained from patients with suspected HNSCCs and evaluated for the presence of HPV using the HC-2 assay. HPV analysis was performed on the corresponding resected tissue specimens using p16 immunohistochemistry (IHC) and HR-HPV in situ hybridization (ISH). A cost analysis was performed using the Center for Medicare & Medicaid Services. Results: HPV status of the cervical lymph node metastases was correctly classified using the HC-2 assay in 84% (21/25) of cases. Accuracy was improved to 100% when cytologic evaluation confirmed the presence of cancer cells in the test samples. The estimated cost savings to CMS using the HC-2 assay ranged from $113.74 to $364.63 per patient. Conclusions: HC-2 is a reliable method for determining the HPV status of HNSCCs. Its application to HNSCCs may reduce costs by helping to localize the primary site during the diagnostic work-up as well as decrease the interval time of determining the HPV status which would be relevant for providing prognostic information to the patient as well as determining eligibility for clinical trials targeting this unique patient population. [Copyright &y& Elsevier]

Background: Salivary gland adenoid cystic carcinoma (ACC) is a rare cancer, accounting for only 1% of all head and neck malignancies. ACC is well known for perineural invasion and distant metastasis, but its underlying molecular mechanisms of carcinogenesis are still unclear. Principal Findings: Here, we show that a novel oncogenic candidate, suprabasin (SBSN), plays important roles in maintaining the anchorage-independent and anchorage-dependent cell proliferation in ACC by using SBSN shRNA stably transfected ACC cell line clones. SBSN is also important in maintaining the invasive/metastatic capability in ACC by Matrigel invasion assay. More interestingly, SBSN transcription is significantly upregulated by DNA demethylation induced by 5-aza- 29-deoxycytidine plus trichostatin A treatment and the DNA methylation levels of the SBSN CpG island located in the second intron were validated to be significantly hypomethylated in primary ACC samples versus normal salivary gland tissues. Conclusions/Significance: Taken together, these results support SBSN as novel oncogene candidate in ACC, and the methylation changes could be a promising biomarker for ACC. [ABSTRACT FROM AUTHOR]

Objective: Concurrent chemoradiotherapy (CCRT) with three-weekly high-dose cisplatin (100 mg/m2) is a standard treatment for locally advanced head and neck squamous cell carcinoma (HNSCC), but compliance with cisplatin is often poor due to various adverse events. The aim of this prospective, observational study was to determine the predictors of achievement of full-dose cisplatin.Methods: A prospective, observational study was conducted involving 60 patients who received CCRT with three-weekly high-dose cisplatin (100 mg/m2) for locally advanced HNSCC. Possible predictors affecting compliance with cisplatin were subjected to univariate and multivariate logistic regression analyses. Age, sex, primary site, clinical stage, treatment intent, history of hypertension, diabetes mellitus, smoking and drinking habits, body mass index, creatinine clearance, serum albumin, controlling nutrition status, trace elements (Fe, Zn, Cu, Se), acute kidney injury, white blood cell count decrease, neutrophilia, and weight loss were the variables evaluated.Results: Twenty-seven patients achieved full-dose cisplatin (300 mg/m2), and the other 33 patients did not. Multivariate logistic regression analysis showed that both mild renal dysfunction and selenium deficiency before treatment independently had negative impacts on achievement of full-dose cisplatin.Conclusions: As well as renal function, selenium deficiency is a potential therapeutic target for CCRT with high-dose cisplatin in HNSCC patients. [ABSTRACT FROM AUTHOR]