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Objectives To clarify the indication of neck dissection (ND) for patient with submandibular gland (SMG) cancer. Methods A total of 43 patients with SMG cancer were retrospectively analyzed. Forty-one patients underwent ND: Levels I–V in 19 patients, Levels I–III in 18 patients, and Level Ib in 4 patients. The other two patients did not undergo ND, since preoperative diagnoses were benign. Postoperative radiotherapy was performed in 19 patients with positive surgical margin, high grade cancer or stage IV disease. Results LN metastases were pathologically confirmed in all patients with cN + and 6 out of 31 patients with cN–. No patients developed regional recurrence during follow-up periods. Ultimately, LN metastases were pathologically confirmed in 17 of 27 high grade, one out of 9 intermediate grade, but not in 7 low grade. Conclusions Prophylactic neck dissection should be considered in T3/4 and high grade SMG cancers.

Objective The blowing time ratio, which is the ratio of the blowing time when the nostrils are open and closed, is significantly correlated with velopharyngeal pressure, not only during speech but also during swallowing. This study aimed to further evaluate the usefulness of the blowing time ratio as a screening tool to evaluate the swallowing pressure of patients treated for oral and oropharyngeal cancers using high-resolution manometery (HRM). Methods Ten patients treated for oral or oropharyngeal cancer were recruited for this study. Swallowing pressures at the velopharynx, oropharynx , and upper esophageal sphincter (UES) were measured using HRM. Their correlations with the blowing time ratio were analyzed. Results The blowing time ratio was significantly correlated with the swallowing pressures of the oropharynx (CC = 0.815, p = 0.004) and the velopharynx (CC = 0.657, p = 0.039), but not of the UES. Conclusions The present results further support our previous finding that the blowing time ratio is a useful screening tool to evaluate velopharyngeal and oropharyngeal swallowing pressures in patients treated for oral and oropharyngeal cancer.

The tonsillar crypt is thought to be a hiding site for early cancer detected after tonsillectomy for primary lesion search in cancer of unknown primary site. In rare cases, a small lesion can be detected unexpectedly during surgical treatment for chronic tonsillitis and tonsillar focal diseases. We report the case of a 47-year-old woman undergoing tonsillectomy for palmoplantar pustulosis (PPP), resulting in the diagnosis of p16-positive oropharyngeal cancer (OPC) in the left tonsil. Postoperative radiation therapy was performed due to the presence of an adhesive lesion during surgery. Radiotherapeutic adverse effects were mild and improved 3 months after the radiotherapy. The symptoms of PPP completely resolved 3 months after the tonsillectomy and no recurrence has been observed so far. With an increase in the cases of HPV-related OPCs, routine pathological examination after tonsillectomy for benign-appearing tonsils in adults is necessary to detect incidental OPC regardless of its low cost-effectiveness.

Vertical partial laryngectomy is a well-established surgical procedure for early glottic cancers with acceptable functional and oncological outcomes. However, on a long-term basis, aspiration might be a serious problem with aging. Here we presented two cases of refractory aspiration pneumonia after vertical laryngectomy. Case 1: A 76-year old gentleman with a past history of malignant lymphoma treated by chemotherapy and radiotherapy had glottic cancer, which was treated by repeated vertical partial laryngectomies. Although glottic caner had been well controlled, he started to suffer from refractory aspiration pneumonia. Since his cervical skin was very thin and hard and his general condition was poor, we employed modified Kano's method for glottic closure. Case 2: A 87-year old Japanese male had a past history of glottic cancer treated by radiotherapy and vertical partial laryngectomy. He was repeatedly hospitalized for severe aspiration pneumonia. At the age of 87, he had second primary oropharyngeal cancer. Kano's method was simultaneously performed at the time of resection of oropharyngeal cancer. Postoperative courses were uneventful without sign of leakage in both cases. The patients started oral intake 2 weeks after the surgery. They have been alive without aspiration pneumonia and takes normal diet.

Background The advantage of up-front neck dissection (UFND) followed by chemoradiotherapy (CRT) for hypopharyngeal cancer (HPC) with advanced neck involvement remains controversial. We aimed to determine the indications. Methods The data of 41 and 14 patients with stage IVA/B (T1-T3 and ≥N2a) HPC who underwent UFND followed by CRT and received CRT, respectively, were retrospectively analyzed and compared. Results The 5-year overall survival (OS) and disease-specific survival rates for the UFND and CRT groups were 61% and 52% (p = 0.1019), and 89% and 74% (p = 0.2333), respectively. Moreover, patients aged ≥70 years or those with a pulmonary disease history had a significantly poorer prognosis due to aspiration pneumonia in the UFND group. The 5-year regional control (RC) for the UFND and CRT groups were 92% and 57%, respectively (p = 0.0001). Conclusions UFND followed by CRT was feasible with satisfactory RC. To further improve OS, aspiration pneumonia prevention is essential.

Objective This study aimed to investigate risk factors predictive of local recurrence and/or lymph node metastasis after transoral resection of early hypopharyngeal cancer. Methods Forty‐nine consecutive patients who underwent transoral videolaryngoscopic surgery (TOVS) as an initial treatment for hypopharyngeal cancer were evaluated. On univariate and multivariate analysis, local recurrence rates were assessed respectively using log‐rank test and cox regression analysis according to the following parameters: subsite, pT, mucosal margin, lymphatic invasion, vessel invasion, tumor thickness (> 4 mm vs ≤4 mm), history of esophageal cancer, and multiple Lugol‐voiding lesions (LVLs) in the esophagus. Categorical variables were evaluated for their associations with lymph node metastasis using chi‐squared test or Fisher's exact test. Result The subsites of primary lesions were piriform sinus in 24 patients, posterior wall in 15 patients, and postcricoid in 10 patients. Thirty patients had esophageal cancer. Local recurrence occurred in 14 patients. Three patients had lymph node metastasis at the time of diagnosis and four patients developed lymph node metastasis after the initial treatment, resulting a total of seven patients having lymph node metastasis. While mucosal margin and LVLs showed significant associations with local recurrence on univariate analysis, only LVLs remained as a significant risk factor on multivariate analysis (P = .0395; hazard ratio = 8.897; 95% confidence interval, 1.113‐71.15). Most cases of local recurrence were satisfactorily controlled by repeated TOVS. While multivariate analysis could not be performed due to the small number of the patients with lymph node metastases, venous invasion (P = .0166) and tumor thickness (P = .0092) were significantly associated with lymph node metastasis on univariate analysis. Conclusions Local recurrence was more frequent in patients with LVLs, but most of them were salvaged by repeated TOVS. Patients with venous invasion and/or tumor thickness greater than 4 mm should be followed up with special attention to lymph node metastasis. Level of Evidence: 3.

Three pathological grading systems advocated by Perzin/Szanto, Spiro, and van Weert are currently used for adenoid cystic carcinoma (AdCC). In these systems, the amount or presence of the solid tumor component in AdCC specimens is an important index. However, the “solid tumor component” has not been well defined. Salivary AdCC cases (N = 195) were collected after a central pathology review. We introduced a novel criterion for solid tumor component, minAmax (minor axis maximum). The largest solid tumor nest in each AdCC case was histologically screened, the maximum oval fitting the solid nest was estimated, and the length of the minor axis of the oval (minAmax) was measured. The prognostic cutoff for the minAmax was determined using training and validation cohorts. All cases were evaluated for the four grading systems, and their prognostic impact and interobserver variability were examined. The cutoff value for the minAmax was set at 0.20 mm. Multivariate prognostic analyses showed the minAmax and van Weert systems to be independent prognostic tools for overall, disease‐free, and distant metastasis‐free survival while the Perzin/Szanto and Spiro systems were selected for overall survival but not for disease‐free or distant metastasis‐free survival. The highest hazard ratio for overall survival (11.9) was obtained with the minAmax system. The reproducibility of the minAmax system (kappa coefficient of 0.81) was scored as very good while those of the other three systems were scored as moderate. In conclusion, the minAmax is a simple, objective, and highly reproducible grading system useful for prognostic stratification for salivary AdCC., The amount or presence of the solid tumor component is an important index for histopathological grading of adenoid cystic carcinoma. However, the “solid tumor component” has not been well defined. We introduced a novel objective criterion for solid tumor component, minAmax (minor axis maximum), and showed that the minAmax is a simple, objective, and highly reproducible grading system useful for prognostic stratification for salivary adenoid cystic carcinoma.

Background and purpose Boron neutron capture therapy (BNCT) can be performed without reactors due to development of cyclotron-based epithermal neutron source (C-BENS), which is optimized for treatment for deeper-seated tumors. The purpose of this study was to evaluate efficacy and safety of cyclotron-based BNCT with borofalan (10B) for recurrent or locally advanced head and neck cancer. Materials and methods In this open-label, phase II JHN002 trial of BNCT using C-BENS with borofalan (10B), patients with recurrent squamous cell carcinoma (R-SCC) or with recurrent/locally advanced non-squamous cell carcinoma (R/LA-nSCC) of the head and neck were intravenously administered 400 mg/kg borofalan (10B), followed by neutron irradiation. The tumor dose was determined passively as the mucosal maximum dose of 12 Gy-Eq. The primary endpoint was the objective response rate (ORR). Post-trial observational JHN002 Look Up study was planned for evaluating locoregional progression-free survival (LRPFS). Results Eight R-SCC and 13 R/LA-nSCC patients were enrolled. All R-SCC patients had prior radiotherapy with a median dose of 65.5 Gy (range, 59.4–76.0 Gy). The ORR for all patients was 71%, and complete response/partial response were 50%/25% in R-SCC and 8%/62% in R/LA-nSCC. The 2-year overall survival for R-SCC and R/LA-nSCC were 58% and 100%, respectively. The median LRPFS was 11.5 months for R-SCC. Frequently observed adverse events included alopecia (95%), hyperamylasemia (86%), and nausea (81%). Conclusion These data suggest that BNCT using C-BENS with borofalan (10B) is a promising treatment option for patients with R-SCC or R/LA-nSCC of the head and neck.

Immunotherapy has been shown to prolong survival in recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) in front-line use; however, subsequent systemic therapy has not been optimized. This study aimed to evaluate the safety and efficacy of cetuximab-containing chemotherapy after immunotherapy. We retrospectively analyzed patients with recurrent or metastatic SCCHN who underwent cetuximab-containing regimens after progression on immunotherapy. Of the 22 patients who met the inclusion criteria, 21 received paclitaxel and cetuximab, and 1 carboplatin and fluorouracil and cetuximab after immunotherapy. Nine patients achieved a partial response, 10 patients had stable disease as their best response on cetuximab-containing chemotherapy, yielding an overall response rate and disease control rate of 40.9 and 86.4%, respectively. The median progression-free survival was 5.2 months, and the median overall survival was 14.5 months. Ten patients developed grade 3-4 adverse events, including neutropenia (31.8%), acneiform rash (9.1%), anemia (4.5%), hypertransaminasemia (4.5%) and stomatitis (4.5%). The most frequent cetuximab-related toxicities across all grades were skin reactions (77.3%), hypomagnesemia (40.9%), stomatitis (27.3%), paronychia (13.6%) and keratitis (4.5%). There was no treatment-related death. Taken together, cetuximab-containing chemotherapy was effective and feasible even after immunotherapy.

Background Nivolumab improves overall survival (OS) in patients with platinum-refractory recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC). In one study, however, Kaplan–Meier OS and progression-free survival (PFS) curves for the nivolumab and cytotoxic agent arms crossed at 3–6 months, suggesting that patients with initial resistance to immunotherapy might have better outcomes with cytotoxic treatment. Here, we explored the conditions and candidates which are predictive of nivolumab outcomes in R/M HNSCC. Methods We retrospectively reviewed the clinical records of 27 consecutive R/M HNSCC patients treated with nivolumab from 2014 to 2018. Tumor size was evaluated by RECIST ver.1.1. Tumor growth rate (Gr) was defined as 3log(D-0/D-pre)/t, where D(0) and D(pre) are the sum of the diameters of the target lesions (SumTLs) at baseline and pre-baseline, and t is time, with 1t defined as 4 weeks. Results Twenty-five patients were enrolled. Survival was significantly worse in patients with disease progression within 3 months. Outcomes appeared poorer in patients with higher pre-treatment Gr and bigger SumTLs at baseline. We therefore explored the association between prognosis, Gr and SumTLs. Recursive partitioning analysis showed that the characteristics of patients with disease progression after 3 months were Gr

An 18-year-old man had a painless, elastic, firm mass in his left parotid area that gradually increased in size over a period of 6 months. At the time of examination, the parotid mass was poorly mobile and 46 mm in size. Although fine needle aspiration cytology revealed no malignant findings, we suspected a malignancy because the movement of his left mouth angle was slightly impaired; facial nerve paralysis as a result of tumor invasion was suspected. A superficial parotidectomy was performed. The tumor had a strong adhesion to the subcutaneous tissue and facial nerve. Histologically, multiple, randomly distributed cystic structures containing keratinized lamellae were present. The cystic spaces were lined with stratified squamous epithelium lacking a granular layer, and no skin appendage was observed. We diagnosed this case as a keratocystoma. Keratocystoma of the parotid gland is a rare benign tumor with only 6 cases reported worldwide. This case is the first to describe facial nerve palsy in association with a keratocystoma.

To clarify the patterns of the recurrence and to assess the oncological and functional outcomes after salvage surgery for the patients with structural local recurrence of papillary thyroid cancer (PTC), twenty-five patients who underwent salvage surgery for structural local recurrence of PTC were retrospectively reviewed. Structural recurrences were observed in the tracheal lumen in 5 patients, intraluminal or intramuscular esophagus in 5 patients, trachea, and cricoid cartilage in 9 patients, cricoid and thyroid cartilage in 2 patients, intra-lumen of the larynx in 1 patient and soft tissue around thyroid in 3 patients, respectively. Although all local disease was resected with macroscopically negative margin, 10 patients diagnosed as microscopically positive margin. Major surgical complications occurred in 6 patients, including common carotid artery injury (n = 1), unintentional pharyngeal or esophageal injury (n = 2), recurrent laryngeal nerve paralysis (n = 2), and pharyngeal fistula resulting in common carotid artery rupture (n = 1), and were successfully managed. During the follow-up periods, 6 patients were alive without disease, 15 patients survived with distant metastases and/or locoregional recurrence, and 4 patients died of the disease. While tracheocutaneous fistula remained in 7 patients, the vocal function was preserved in all patients but one who underwent total laryngectomy. Normal oral intake was retained in all patients. In conclusion, although salvage surgery for structural recurrence of PTC has a high risk of complications, it may be worthwhile when macroscopic curative resection is available. The decision should be made considering various factors including curability, risk of surgical procedure, functional outcome, and life expectancy.

Background No clear consensus has been reached on the indication of supraomohyoid neck dissection (SOHND) for clinically positive lymph-node metastasis. Patients Consecutive 100 patients with previously untreated oral cancer treated at Kobe University Hospital were included in this study. All patients were clinically staged as anyTN1M0 and underwent radical dissection of the primary site and level I–V neck dissection as the initial treatment. Results None of the 100 patients had pathological lymph-node metastasis (pLN) to level V. pLN to level IV was observed in two patients with tongue cancer in whom clinical lymph-node metastasis was preoperatively observed at level II. Conclusions Level V may be excluded in the neck dissection for patients with N1 oral cancers. Level IV dissection should be considered in the patient with tongue cancer and clinical lymph-node metastasis at level II.

Objectives Hematoma in the retropharyngeal space (RPS) is a life-threatening condition that leads to rapid airway obstruction. However, the indication for airway management remains unclear. Additionally, the requirement for surgical hematoma evacuation remains undetermined. Therefore, we attempt to suggest some criteria for the management of hematoma in such cases. Methods We report three cases of hematoma in the RPS wherein one patient was treated without surgery and the other two underwent tracheotomy followed by hematoma evacuation. Results We found that airway management should be based on whether the glottis could be visible on laryngoscopy and dyspnea severity. The degree of hematoma, swelling, subcutaneous bleeding in the anterior neck, and emotional stability should also be considered. Proper management during the acute phase may allow for conservative treatments. Hematomas extending below the tracheal bifurcation may help ease upper airway obstruction due to pressure distribution, allowing for conservative treatment. When hematomas are surgically evacuated, tracheotomy should be performed simultaneously. Our report suggests that mediastinal hematoma evacuation could be avoided. Conclusion We should determine a therapeutic strategy for hematoma in RPS based on glottis visualization, patient’s condition, and extent of hematoma growth under careful observation.

The clinical utility of systemic therapy and genomic profiling in non-squamous-cell head and neck cancer (NSCHNC) has not been fully elucidated. This phase II trial evaluated the efficacy and safety of docetaxel and cisplatin combination in the first-line setting. Eligibility criteria were recurrent and/or metastatic NSCHNC; progressive disease within the last 6 months; no prior systemic therapy; and ECOG performance status of 0–1. Patients received docetaxel (75 mg/m2 on day 1) and cisplatin (75 mg/m2 on day 1), repeated every 21 days for 6 cycles. The primary endpoint was confirmed objective response rate (ORR). The secondary endpoints included progression-free survival (PFS), overall survival (OS), and adverse events. Next-generation sequencing (NGS) was performed using the Ion AmpliSeq Cancer Hotspot Panel v2. Twenty-three patients were enrolled from November 2012 to October 2016, of whom 8 were male. Median age was 57 years. Ninety-six percent of cases were metastatic. Among 22 evaluable patients, confirmed ORR was 45% (95% confidential interval 24–68%). With a median follow-up period of 18.8 months, median PFS and OS were 6.7 and 20.1 months, respectively. Grade 3/4 adverse events included febrile neutropenia (39%) and anemia (22%). No treatment-related deaths were observed. NGS analysis revealed potential treatment targets, including ERBB2, KIT, and ALK. The docetaxel and cisplatin combination regimen can be considered a new treatment option in recurrent and/or metastatic NSCHNC, although primary prophylaxis for febrile neutropenia should be considered. Diverse genomic alterations may lead novel treatment options. This trial was registered with the UMIN Clinical Trials Registry as UMIN000008333 on [September 1st, 2012].

Background The purpose of this study was to investigate the effectiveness of dental intervention before and after radiation therapy (RT) for head and neck malignancy on prevention of osteoradionecrosis (ORN) of the jaws. Methods This is a single-arm prospective study according to intervention protocol of prophylactic dental extraction before RT and routine follow-up after RT. The primary endpoint was the occurrence of jawbone exposure during the first 2 years after RT. Results Sixty-seven patients were assessed. Before RT, 144 teeth among 39 patients (58%) were prophylactically extracted. The occurrence of transient jawbone exposure during the first 2 years after RT was 7%. Because those jawbone exposures healed with intervention after RT, no jawbone exposure was found at 2 years after RT. Conclusions Dental intervention both before and after RT seemed to be important to prevent ORN development. Further studies in larger cohorts are necessary.

Papillary thyroid carcinoma frequently metastasizes to central and lateral neck lymph nodes, but metastasis to retropharyngeal lymph nodes (RPLN) is rare. We retrospectively reviewed 16 patients with RPLN metastasis of PTC who underwent therapeutic dissection of RPLN metastases. Among 16 patients, 7 patients underwent RPLN dissection with initial surgery and remaining 9 patients as salvage surgery. RPLN metastasis arose unilaterally in 15 patients and bilaterally in 1 patient. Eleven patients showed temporal dysphagia and four patients showed temporal vocal cord paralysis, but both symptoms eventually recovered in all cases. Two patients with salvage RPLN dissection died of distant metastasis and six patients survived with distant metastasis and/or persistent loco-regional disease. Other eight patients have been alive without disease. Although transcervical approach for RPLN metastases of PTC provided acceptable functional and oncological outcomes, half of the patients with RPLN metastasis have had distant metastasis and/or persistent locoregional disease. Indications of surgery for patients with RPLN metastasis need to be performed carefully in consideration of patients' prognosis and quality of life.

Prostate cancer is one of the most common cancers in men. The overactivation of IL-6/JAK/STAT3 signaling and silencing of SOCS3 are frequently observed in prostate cancer. In the present study we undertook to develop Ad-SOCS3 gene therapy for the treatment of prostate cancer and also investigated whether Ad-SOCS3 increased sensitivity to NK cells. We demonstrated that Ad-SOCS3 could significantly inhibit growth of castration-resistant prostate cancer (CRPC) cell lines expressing pSTAT3, DU-145 (at 10, 20, and 40 MOI), and TRAMP-C2 (at 40 MOI), but not the PC-3 CRPC cell line with the STAT3 gene deleted. Ad-SOCS3 (40 MOI) could suppress IL-6 production in DU-145 cells and PD-L1 expression induced by IFN-γ in TRAMP-C2 cells, and increased the NK cell sensitivity of both TRAMP-C2 and DU-145 cells. In the DU-145 mouse xenograft tumor model, intratumoral injections (twice/week for 3 weeks) of 1 × 108 pfu of Ad-SOCS3 significantly inhibited tumor growth and combining the Ad-SOCS3 treatment with intratumoral injections (once/week for 2 weeks) of 1 × 107 human NK cells showed the highest tumor growth inhibitory effect. These results suggested that a combination of Ad-SOCS3 gene therapy and NK cell immunotherapy could be a powerful treatment option for advanced CRPC overexpressing pSTAT3.

Interdigitating dendritic cell sarcoma (IDCS) is an extremely rare neoplasm derived from antigen-presenting cells of the immune system. It mostly occurs in the lymph node of the neck or axilla. We report a case of IDCS occurring in an 82-year-old female who presented with multiple masses in her right parotid gland. The patient was successfully treated with conservative surgery preserving the facial nerve followed by radiotherapy for the macroscopic lesion remnants. Most localized diseases were treated by surgery with or without irradiation, while advanced diseases were treated with systematic chemotherapy, such as CHOP. Radiotherapy may be an effective alternative to complete resection in patients with localized IDCS that involves functional and/or vital structures. The present case demonstrated that conservative surgery preserving the facial nerve followed by radiotherapy is an effective alternative option for the treatment of IDCS.

Background In 2008, Kano developed a new laryngeal closure technique (Kano's method) for the treatment of severe aspiration. The aim of this study was to evaluate the safety and efficacy of this technique in patients with head and neck cancer. Methods Since June 2014 until March 2018, six patients underwent Kano's method for management of severe aspiration after the treatment of head and neck cancers. The anterior parts of the thyroid and the cricoid cartilages were excised widely. The glottis was closed by suturing bilateral vocal folds and reinforced by the sternohyoid muscle. A tracheostoma was created with skin flaps, subglottic mucosal flaps, and stumps of cricoid and trachea cartilages. Results No severe complications were observed after the surgery. Oral intake improved without developing aspiration. Conclusions Kano's method can provide satisfactory functional results with minimal invasion for treating severe aspiration after advanced surgery, chemotherapy, and/or chemoradiotherapy, in patients with head and neck cancer. Level of evidence 4.

Although acromegaly has been reported in patients with Neurofibromatosis type 1 (NF1), these cases have not been associated with growth hormone (GH)-producing somatotroph adenoma, but with optic pathway glioma. A 68 year-old Japanese woman, who had been clinically diagnosed with NF1, was referred to our hospital due to a thyroid tumor and hypercalcemia. Acromegaly was suspected due to her facial features, and subsequent examinations revealed the presence of GH excess with a pituitary tumor, leading to the diagnosis of acromegaly. Histological and immunohistochemical analysis demonstrated an eosinophilic pituitary adenoma with diffuse positivity for GH, indicating typical somatotroph adenoma. In addition, her thyroid tumor was diagnosed histologically as follicular thyroid carcinoma (FTC) with primary hyperparathyroidism (PHPT). To investigate the pathogenesis of this untypical multiple endocrine tumor case of NF1, genetic analysis was performed using peripheral leukocytes and tissue of resected tumors. A heterozygous novel germline nonsense mutation (p.Arg1534*) in exon 35 of the NF1 gene was detected from peripheral leukocytes, which results in a truncated protein lacking the critical domain for GTPase activity, strongly suggesting its causal role in NF1. The loss of heterozygosity (LOH) in exon 35 of the NF1 gene was not detected in the somatotroph adenoma, parathyroid adenoma, and FTC. Although any mutations of the following genes; MEN1, CDKN1B, and PAX8-PPARγ were not detected, a heterozygous GNAS R201C mutation was detected in the somatotroph adenoma. To our knowledge, this is the first rare MEN1-like case of genetically diagnosed NF1 complicated with acromegaly caused by a somatotroph adenoma.

Ghost cell is one of several unique cellular morphologies associated with aberrant keratinization. We encountered a novel parotid tumor containing numerous ghost cells and herein describe its histological features and discuss diagnostic problems. The patient was a 90-year-old Japanese male, who complained of swelling of the left parotid area for four months. Positron emission tomography indicated no cervical lymph node metastasis or distant metastasis. The tumor was successfully resected with no signs of recurrence or metastasis for six months after surgery. Histologically, the tumor was mainly composed of squamous cells forming irregularly shaped nests with a mixture of pleomorphic giant or multinucleated cells and bland basaloid cell. Keratinized areas were occupied by a prominent ghost cell population. Immunohistochemically, CK5/6 and CK19 were widely positive as well as AE1/AE3, p40 and p63. Nuclear expression of β-catenin was also observed. The present case can be regarded as a particular form of squamous cell carcinoma and is believed to contain a large number of ghost cells resulting from an unclear mechanism. However, it seems difficult to consider such tumors as a clinicopathologically independent entity at present. Applying a term such as "salivary ghost cell carcinoma" would be premature.

BackgroundThe prognosis of patients with advanced squamous cell carcinoma of the external auditory canal and middle ear has been improved by advances in skull base surgery and multidrug chemoradiotherapy during the last two decades.MethodsNinety-five patients with squamous cell carcinoma of the external auditory canal and middle ear who were treated between 1998 and 2017 were enrolled. The number of patients with tumour stages T1, T2, T3 and T4 was 15, 22, 24 and 34, respectively. Oncological outcomes and prognostic factors were retrospectively investigated.ResultsAmong patients with T4 disease, invasion of the brain (p = 0.024), carotid artery (p = 0.049) and/or jugular vein (p = 0.040) were significant predictors of poor prognosis. The five-year overall survival rate of patients with at least one of these factors (T4b) was significantly lower than that of patients without these factors (T4a) (25.5 vs 65.5 per cent, p = 0.049).ConclusionIt is proposed that stage T4 be subclassified into T4a and T4b according to the prognostic factors.

BackgroundWe previously reported that a high tumor burden is a prognostic factor based on an analysis of 26 patients with radioactive iodine-refractory differentiated thyroid cancer (RR-DTC) who were treated with lenvatinib. However, the optimal tumor burden for starting lenvatinib still remains to be defined. The aim of this retrospective study was to further explore in the same patient cohort the optimal timing for the start of lenvatinib by focusing on the pre- and post-treatment tumor burden.MethodsThe 26 patients were treated with lenvatinib from 2012 to 2017. We explored the optimal timing for the start of lenvatinib by comparing the characteristics of long-term responders who were defined as patients with progression-free survival ≥ 30 months and non-long-term responders.ResultsLong-term responders had a smaller post-treatment tumor burden at maximum shrinkage than non-long-term responders. Further, post-treatment tumor burden had a strong linear correlation with baseline tumor burden. We created an estimation formula for baseline tumor burden related to prognosis, using these regression lines. Patients with a sum of diameters of target lesions < 60 mm or maximum tumor diameter < 34 mm at baseline were estimated to have significantly better survival outcomes.ConclusionsWe found a strong linear correlation between pre- and post-treatment tumor burden. Our results suggested a cut-off value for baseline tumor burden for long-term prognosis among patients treated with lenvatinib.

We hypothesized that, in discrimination between benign and malignant parotid gland tumors, high diagnostic accuracy could be obtained with a small amount of imbalanced data when anomaly detection (AD) was combined with deep leaning (DL) model and the L2-constrained softmax loss. The purpose of this study was to evaluate whether the proposed method was more accurate than other commonly used DL or AD methods. Magnetic resonance (MR) images of 245 parotid tumors (22.5% malignant) were retrospectively collected. We evaluated the diagnostic accuracy of the proposed method (VGG16-based DL and AD) and that of classification models using conventional DL and AD methods. A radiologist also evaluated the MR images. ROC and precision-recall (PR) analyses were performed, and the area under the curve (AUC) was calculated. In terms of diagnostic performance, the VGG16-based model with the L2-constrained softmax loss and AD (local outlier factor) outperformed conventional DL and AD methods and a radiologist (ROC-AUC = 0.86 and PR-ROC = 0.77). The proposed method could discriminate between benign and malignant parotid tumors in MR images even when only a small amount of data with imbalanced distribution is available.

Boron neutron capture therapy (BNCT) can be performed without reactors due to development of cyclotron-based epithermal neutron source (C-BENS), which is optimized for treatment for deeper-seated tumors. The purpose of this study was to evaluate efficacy and safety of cyclotron-based BNCT with borofalan (In this open-label, phase II JHN002 trial of BNCT using C-BENS with borofalan (Eight R-SCC and 13 R/LA-nSCC patients were enrolled. All R-SCC patients had prior radiotherapy with a median dose of 65.5 Gy (range, 59.4-76.0 Gy). The ORR for all patients was 71%, and complete response/partial response were 50%/25% in R-SCC and 8%/62% in R/LA-nSCC. The 2-year overall survival for R-SCC and R/LA-nSCC were 58% and 100%, respectively. The median LRPFS was 11.5 months for R-SCC. Frequently observed adverse events included alopecia (95%), hyperamylasemia (86%), and nausea (81%).These data suggest that BNCT using C-BENS with borofalan (

Background Epidermal growth factor receptor (EGFR) is overexpressed in head and neck squamous cell carcinomas (HNSCCs). Midkine expression is restricted in adult tissues but is increased in several malignant tumors, including HNSCCs. Aim Here, we evaluated the antitumor effect of Midkine promoter–based conditionally replicative adenovirus expressing siRNA against EGFR for targeting HNSCCs expressing Midkine. Methods and results A conditionally replicative adenovirus vector controlled by the Midkine promoter, Ad‐MK‐siEGFR, was generated by integrating gene‐expressing siRNA against EGFR. Antitumor effect of Ad‐MK‐siEGFR was tested in vitro using established HNSCC cell line, T891 with strong Midkine expression. Expression of EGFR in T891 infected with Ad‐MK‐siEGFR was significantly lower than that of T891 infected with control. Cytotoxicity assays showed significant growth suppression of Ad‐MK‐siEGFR in T891 cells. Conclusions This study demonstrated the possibility of oncolytic therapy using the Midkine promoter–based conditional replication‐selective adenovirus containing siRNA against EGFR in HNSCC cell line T891. Further validation of the findings in more cell lines and in vivo should be performed to clarify the potential clinical application.

Non-recurrent inferior laryngeal nerve (NRILN) is rare but one of the important anatomical variations in thyroid and parathyroid surgery. Almost all cases were observed on the right side with aberrant right subclavian artery and left NRILN have been reported in only five cases so far. Here, we reported a 38 year-old Japanese male with left NRILN accompanying adenomatous goiter. He was referred to our hospital for the surgical treatment of left thyroid goiter. Preoperative computed tomography revealed right-sided aortic arch and aberrant left subclavian artery with no signs of complete situs inversus viscerum, suggesting possible left NRLN. Left hemithyroidectomy was performed using nerve monitoring system. Intraoperatively, left recurrent laryngeal nerve was not identified along tracheoesophageal groove, but directly originated from vagal nerve and was running horizontally to larynx. Mobility of vocal cords were not impaired and postoperative course was uneventful. During thyroid surgery for the patients with right-sided aortic arch, meticulous care should be taken using nerve monitoring system to avoid nerve injury.

Sorafenib and lenvatinib showed efficacy for patients with radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC) in pivotal phase 3 clinical trials. Although the efficacy of lenvatinib in patients who received previous treatment with multi-target kinase inhibitors (m-TKIs), including sorafenib, was reported, the efficacy of sorafenib in patients who previously received lenvatinib remains unknown. A 75-year-old woman diagnosed as RAI-refractory poorly differentiated carcinoma with multiple lung metastases and started treatment with lenvatinib. She continued to receive lenvatinib but with repeated dose interruptions and reductions due to continuous proteinuria. Because of severe and persistent proteinuria as well as newly developed renal impairment, lenvatinib was suspended after two years of treatment. After the 7-month suspension, her proteinuria and renal impairment were partially improved, but her lung metastases progressed. Because she was unable to tolerate previous treatment with lenvatinib, sorafenib was started. At 7 months of treatment with sorafenib, her lung metastases shrank and she could continue sorafenib without exacerbation of proteinuria or renal impairment. This case may suggest that sorafenib does not exacerbate the proteinuria or renal impairment induced by lenvatinib, and may be an effective treatment option for RAI-refractory DTC patients who are unable to tolerate lenvatinib.