Mucosal melanoma of the head and neck: a retrospective analysis of 34 cases in Japan.

PURPOSE: Mucosal melanoma of the head and neck (MMHN) is a rare condition. This study aimed to investigate oncological outcomes of surgical intervention in patients with MMHN. MATERIALS AND METHODS: The study included 34 patients with MMHN who underwent surgical resection as initial treatment at 10 institutions in Japan between July 2005 and June 2015. Results: The 5-year overall survival (OS), local control rate (LCR), disease-free survival (DFS), and disease-specific survival (DSS) rates were 48.7%, 53.4%, 32.4%, and 55.1%, respectively. Based on multivariate analysis, no independent prognostic factors for the 5-year OS and DSS were found. Based on univariate analysis, the 5-year LCR was worse in patients with lesions in the nasal cavity and paranasal sinuses than in the oral cavity and pharynx. However, no differences in oncological outcomes were identified in relation to primary sites, and postoperative radiotherapy (PORT) and adjuvant systemic therapy did not contribute to improvements in the 5-year OS. CONCLUSIONS: No independent prognostic factors for the 5-year OS or DSS were identified. Regional or distant recurrences are often identified, regardless of local control with surgical resection. Difficult control of MMHN with conventional therapeutic strategies, such as surgical intervention, PORT, and systemic therapy, has been suggested.

Characteristics of oral squamous cell carcinoma focusing on cases unaffected by smoking and drinking: A multicenter retrospective study.

BACKGROUND: Some oral squamous cell carcinoma (OSCC) cases are unaffected by smoking or drinking. This study aimed to clarify distinctive groups among OSCC patients and examine the characteristics of multiple primary carcinomas (MPCs). METHODS: We analyzed data from 970 patients. The patients were divided into three groups: all individuals <45 years (<45 y), smokers/drinkers ≥45 years (SD ≥45 y), and non-smokers/non-drinkers ≥45 years (NSND ≥45 y). RESULTS: Tongue cancers were more common in the <45 y group than in the other groups (p < 0.001). The NSND ≥45 y group was significantly older and more likely to be female than the SD ≥45 y group (p < 0.001). MPCs in the upper aerodigestive tract were more common in men and smokers/drinkers, whereas women were at risk for multiple primary OSCCs (p = 0.022). CONCLUSIONS: The "young tongue" and "elderly female" subgroups and characteristics of MPCs suggest carcinogenic factors of OSCC other than smoking and drinking.

A multi-institutional retrospective study of 340 cases of sinonasal malignant tumor.

OBJECTIVE: Sinonasal malignant tumors (SNMT) are relatively rare among head and neck malignant tumors. Most are squamous cell carcinomas, and malignant melanomas, olfactory neuroblastomas, adenoid cystic carcinomas, sarcomas, and others also occur. The most common primary site of nasal sinus squamous cell carcinoma is the maxillary sinus. In recent years, a decrease in incidence of maxillary sinus squamous cell carcinoma (MSSCC) has been reported along with a decrease in the incidence of sinusitis. MSSCC is treated with a combination of surgery, radiation, and chemotherapy. Treatment decisions are made according to the progression of the disease, the patient's general condition, and the patient's own wishes. There are variations in treatment policies among facilities due to the specialty of staff and cooperation with other departments at each facility. We conducted a multi-institutional retrospective study to compare outcomes by treatment strategy. METHODS: In this study, 340 patients with SNMT who were treated at 13 Hospitals (Head and Neck Oncology Group (Kyoto-HNOG) ) during the 12-year period from January 2006 to December 2017 were included. There were 220 patients with squamous cell carcinoma, 32 with malignant melanoma, 21 with olfactory neuroblastoma, and 67 with other malignancies. Of the squamous cell carcinomas, 164 were of maxillary sinus origin. One hundred and forty cases of MSSCC that were treated radically were included in the detailed statistical analysis. RESULTS: There were 5 cases of cStage I, 9 cases of cStage II, 36 cases of cStage III, 74 cases of cStage IVa, and 16 cases of cStage IVb. There were 92 cases without clinical lymph node metastasis (cN(-)) and 48 cases with clinical lymph node metastasis(cN(+)). Primary tumors were treated mainly by surgery in 85 cases (Surg) and by radical radiation therapy (with or without chemotherapy) of 6-70 Gy in 55 cases(non-Surg). The 5-year overall/disease-free survival rate (OS/DFS) for MSSCC was 65.1%/51.6%. Old age, renal dysfunction, and clinical T progression were independent risk factors for OS, and renal dysfunction was an independent risk factor for DFS. In cN(-) patients, OS and DFS were significantly better in Surg group than in non-Surg group. In cN(+) patients, there was no significant difference in OS and DFS between Surg and non-Surg groups. CONCLUSION: For patients with MSSCC without lymph node metastasis, aggressive surgery on the primary tumor contributes to improved prognosis.

Intraoperative computed tomography imaging for laryngoplasty.

OBJECTIVES: Intraoperative cone beam computed tomography (CBCT) imaging has the potential to facilitate the surgical procedure. The current preliminary retrospective chart review investigated the benefits of intraoperative CBCT during laryngoplasty. METHOD: This study examined 26 cases that underwent intraoperative CBCT imaging during laryngoplasty, with one patient who counted twice due to first and revision surgery. The visual quality of structures of interest (glottal shape, thyroid cartilage, arytenoid cartilage, and implants) was determined using intraoperative CBCT during laryngoplasty. Each patient also underwent an aerodynamic assessment. RESULTS: CBCT provided unique information, such as surgical landmarks in severe scarring, the subglottal shape, and the rotation angle of the arytenoid cartilage during arytenoid adduction. Nonetheless, 26.9% (7 of 26) of cases were affected by motion artifact, due to the long acquisition time. When motion artifact-negative cases were evaluated, 100% of glottal shape and more than 89% of thyroid cartilage were well visualized. All arytenoids were well-visualized in patients ≥ 50 years of age and without motion artifact, while CBCT failed to visualize the arytenoids in 2 of 4 patients who were < 50 years, due to the lack of calcifications. After medialization surgery, the yields of improved maximal phonation times (MPTs) in the motion artifact-negative and -positive groups were 8.7 sec and 3.4 sec, respectively (p = 0.032; Welch's t test). This comparison indicates intraoperative CBCT would contribute in MPT improvement, if CBCT is taken in measurable quality. CONCLUSION: The potential benefits of intraoperative CBCT during laryngoplasty were demonstrated. A corollary, prospective study is warranted to further confirmation.

Disinfection of otorhinolaryngological endoscopes with electrolyzed acid water: A cross-sectional and multicenter study.

Glutaraldehyde, a germicide for reprocessing endoscopes that is important for hygiene in the clinic, might be hazardous to humans. Electrolyzed acid water (EAW) has a broad anti-microbial spectrum and safety profile and might be a glutaraldehyde alternative. We sought to assess EAW disinfection of flexible endoscopes in clinical otorhinolaryngological settings and its in vitro inactivation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and bacteria commonly isolated in otorhinolaryngology. Ninety endoscopes were tested for bacterial contamination before and after endoscope disinfection with EAW. The species and strains of bacteria were studied. The in vitro inactivation of bacteria and SARS-CoV-2 by EAW was investigated to determine the efficacy of endoscope disinfection. More than 20 colony-forming units of bacteria at one or more sampling sites were detected in 75/90 microbiological cultures of samples from clinically used endoscopes (83.3%). The most common genus detected was Staphylococcus followed by Cutibacterium and Corynebacterium at all sites including the ears, noses, and throats. In the in vitro study, more than 107 CFU/mL of all bacterial species examined were reduced to below the detection limit (<10 CFU/mL) within 30 s after contact with EAW. When SARS-CoV-2 was treated with a 99-fold volume of EAW, the initial viral titer (> 105 PFU) was decreased to less than 5 PFU. Effective inactivation of SARS-CoV-2 was also observed with a 19:1 ratio of EAW to the virus. EAW effectively reprocessed flexible endoscopes contributing to infection control in medical institutions in the era of the coronavirus disease 2019 pandemic.

Validation of Cepstral Acoustic Analysis for Normal and Pathological Voice in the Japanese Language.

OBJECTIVES: Cepstral analysis does not require the detection of pitch within waveforms, which makes it suitable for acoustic evaluation of connected speech contexts and severely disordered voice. Although the utility of cepstral measurements, including cepstral peak prominence (CPP) and cepstral spectral index of dysphonia (CSID), has been reported for several languages, it has yet to be demonstrated in the Japanese language. The current study aimed to investigate the utility of cepstral acoustic analysis for the Japanese language as an indicator of dysphonia and the degree of dysphonia severity. METHODS: Ninety-five patients with dysphonia and thirty volunteers without voice complaint uttered the sustained vowel /a/ and read four Japanese sentences designed to elicit different laryngeal behaviors. The recorded voice samples were evaluated perceptually by three raters according to the GRBAS scale (grade) and overall severity (OS) on a visual analog scale. Participants were then divided into four groups based on grade and OS: non-, mildly, moderately, and severely dysphonic groups. For the acoustic analysis, CPP and CSID were computed using the Analysis of Dysphonia in Speech and Voice, while jitter percentage (Jitt), shimmer percentage (Shim), and noise to harmonic ratio were computed using the Multi-Dimensional Voice Program. RESULTS: Statistical analysis revealed that both CPP and CSID differed significantly between all groups, except for grade between the non-dysphonic and mildly dysphonic groups. Pearson correlation analysis between the acoustic measurements and the perceptual ratings revealed that the absolute correlation coefficients for CPP, CSID, and Jitt were greater than 0.7. Specifically, those for CPP and CSID were greater than 0.8 for OS. Receiver operating characteristic curve analysis showed that the AUC for CPP, CSID, Jitt, and Shim was greater than 0.8 for both grade and OS. The cut-off values for CPP and CSID, as determined by the Youden Index, were 6.74-7.18 and 12.16-20.39, respectively. CONCLUSION: The current study demonstrated the validity of CPP and CSID as indicators of dysphonia and indices of dysphonia severity in the Japanese language.

Relapsing polychondritis after treatment with PD-1 blockade.

Nivolumab, a programmed death 1 blockade drug, is used in various types of cancers and can cause a unique immune-related adverse event (irAE). Relapsing polychondritis (RP) is a rare autoimmune disease that mainly involves inflammation of the auricle, nose and airway cartilage. A 72-year-old man with mandibular cancer received nivolumab after surgery for the primary lesion and radiation therapy for lung metastases. He then developed radiation pneumonitis, and prednisolone (PSL) was started. During the tapering of PSL, he developed exertional dyspnea and cough. The condition of mandibular cancer and radiation pneumonitis had not deteriorated. Fluorodeoxyglucose (FDG)-PET/CT showed a thickening of and abnormal FDG uptake in the tracheobronchial and nasal septum cartilage. These characteristic findings were not observed before nivolumab was initiated; thus, we clinically diagnosed the patient as having RP induced by nivolumab. Since the symptoms were mild, the patient's condition was carefully managed with inhaled corticosteroids, and the RP has not progressed thus far. Physicians should be aware that RP can occur as an irAE because RP may progress to serious respiratory symptoms.

Clinicopathological Characteristics and Survival Outcomes of Patients with Buccal Squamous Cell Carcinoma: Results of a Multi-Institutional Study.

Background and Objectives: To investigate clinicopathological characteristics and survival outcomes of patients with buccal cancer in Japan. Materials and Methods: This study was conducted using a database of 1055 patients with oral cancers treated between 2010 and 2017 at 12 institutions in Japan. Ninety-two patients (8.7%) with primary buccal cancer were extracted and clinicopathological characteristics and survival outcomes were compared between patients with buccal cancers and patients with other oral cancers. Results: Ages were significantly higher in the patients with buccal cancer (73 years old vs. 69 years old). Buccal cancer had less advanced cT stage and cN stage than other oral cancers. Overall 5-year survival (OS) was 80.6%, and recurrence-free 5-year survival (RFS) of buccal cancers was 67.8%, and there were no significant differences in survival compared with other oral cancers in terms OS or RFS (5y-OS: 82.5%, 5y-RFS: 74.4%). However, patients with stage IV buccal cancer showed poorer prognosis in terms of OS and RFS compared with the same stage patients with other oral cancer. Advanced T stage was the only factor independently associated with both OS and RFS of patients with buccal cancer in this study. Conclusions: Postoperative radiotherapy or chemoradiotherapy should be considered to improve survival outcome of buccal cancer patients, especially for the patients with advanced primary site disease or a higher cancer stage.

The RNA Methylation Modification 5-Methylcytosine Impacts Immunity Characteristics, Prognosis and Progression of Oral Squamous Cell Carcinoma by Bioinformatics Analysis.

Disorders pertaining to 5-methylcytosine (m5C) modifications are involved in the pathological process of many diseases. However, the effect of m5C on the tumorigenesis and progression of oral squamous cell carcinoma (OSCC) remains unclear. In this study, we integrated the genomic and clinical data of 558 OSCC samples to comprehensively evaluate m5C modification patterns. Based on 16 m5C methylation regulators, two m5C modification clusters were identified with distinct tumor immune microenvironment (TIME) characteristics and prognosis in OSCC. We then performed weighted gene co-expression network analysis (WGCNA) to identify m5C modification cluster-related modules. Genes in the selected module were chosen to construct the m5Cscore scoring system for evaluating m5C modification pattern in individual OSCC patients. Patients with a high m5Cscore had higher immune, stromal, and ESTIMATE scores; lower tumor purity score; lower immune activity; and higher tumor mutational burden. The overall survival rate and progression-free survival rate were markedly worse and the tumor recurrence rate was higher in OSCC patients with a high m5Cscore. Furthermore, patients with oral leukoplakia who also had a high m5Cscore had a higher risk of deterioration to OSCC. This study demonstrated that m5C modification patterns might affect the TIME in OSCC. m5Cscore may provide a new approach for predicting the prognosis and progression of OSCC.

Development and Validation of the Japanese Version of the Consensus Auditory-Perceptual Evaluation of Voice.

PURPOSE: Auditory-perceptual evaluation is essential for the assessment of voice quality. The Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) provides a standardized protocol and assessment form for clinicians to analyze the voice quality and has been adapted into several different languages. The aims of this study were to develop the Japanese version of the CAPE-V and to investigate its reliability and validity. METHOD: The Japanese CAPE-V consisted of the same three speech contexts (vowels, sentences, and conversation) as developed in the original English version. The sentences were designed according to the concepts of the original version and reviewed by Japanese phoneticians. To validate the usefulness of the Japanese CAPE-V, voices of 173 Japanese-speaking subjects (76 subjects with dysphonia and 97 without voice complaints) were evaluated by five experienced judges, according to the Japanese CAPE-V as well as the GRBAS (Grade, Roughness, Breathiness, Asthenia, Strain) scale. RESULTS: The Japanese CAPE-V provided a high interrater reliability (intraclass correlation coefficients [ICCs] > .85 for all the parameters) as well as a high intrarater reliability (ICCs > .85 for all the parameters). In addition, overall severity, roughness, and breathiness in the Japanese CAPE-V were highly correlated with the corresponding dimensions in the GRBAS scale, having Spearman correlation coefficients greater than .8. CONCLUSION: This study demonstrated the reliability and validity of the newly developed Japanese CAPE-V as an auditory-perceptual evaluation instrument.

The Impact of m1A Methylation Modification Patterns on Tumor Immune Microenvironment and Prognosis in Oral Squamous Cell Carcinoma.

N1-methyladenosine (m1A) modification widely participates in the occurrence and progression of numerous diseases. Nevertheless, the potential roles of m1A in the tumor immune microenvironment (TIME) are still not fully understood. Based on 10 m1A methylation regulators, we comprehensively explored the m1A modification patterns in 502 patients with oral squamous cell carcinoma (OSCC). The m1A modification patterns were correlated with TIME characteristics and the m1A score was established to evaluate the effect of the m1A modification patterns on individual OSCC patients. The TIME characteristics and survival outcomes under the three m1A modification patterns were significantly distinct. OSCC patients in the high m1A score group were characterized by poorer prognosis, lower immune infiltration, lower ssGSEA score, lower expression levels of immune checkpoint molecules, and higher tumor mutation loads. The present study revealed that m1A modification might be associated with the TIME in OSCC, and has potential predictive ability for the prognosis of OSCC.

Lingual Lymph Node Metastases as a Prognostic Factor in Oral Squamous Cell Carcinoma-A Retrospective Multicenter Study.

Backgrounds and Objectives: The epidemiology and prognostic role of lingual lymph node (LLN) metastasis in patients with oral squamous cell carcinoma (OSCC) remain unclear. Here, we aimed to analyze the clinicopathological features, risk factors, and prognostic role of LLN metastasis in patients with OSCC. Materials and Methods: In total, 945 patients with OSCC were retrospectively analyzed. Clinicopathological features were compared between patients with and without LLN metastasis. The risk factors of LLN metastasis and its effects on survival outcomes were evaluated using multi-variate analysis. Results: LLN metastasis was noted in 67 patients (7.1%). Habitual alcohol consumption and clinical neck node metastasis were independent risk factors for LLN metastasis. LLN metastasis was an independent prognostic factor for disease-free and overall survival, although LLN dissection did not improve survival outcomes. Conclusion: LLN metastasis is an independent adverse prognostic factor. Further prospective studies are needed to fully assess the extent of LLN dissection required in OSCC patients.

Is surgical resection without radioactive iodine treatment a safe alternative treatment for T1-2N1bM0 papillary thyroid carcinoma?

OBJECTIVE: Postoperative radioactive iodine (RAI) adjuvant therapy improves the prognosis in patients with advanced papillary thyroid carcinoma (PTC), although the role of RAI adjuvant therapy remains unclear in intermediate-risk patients, as defined by the American Thyroid Association. The ATA cautiously recommended RAI adjuvant therapy in patients with T1-3N1b, but the Japanese Society of Thyroid Surgery suggests lobectomy without RAI adjuvant therapy in these patients. This study assessed the role and efficacy of RAI adjuvant therapy in patients with T1-3N1b PTC. METHODS: A single-center retrospective observational study was performed. We included patients with T1-3N1bM0 PTC who underwent complete resection between January 2003 and December 2017. Patients with bilateral PTC were excluded. We compared recurrence rates after surgery with RAI adjuvant therapy and surgery alone. RESULTS: A total of 61 patients (male:female ratio, 18:43; mean age, 57.1 ± 16.7 years) were included, and the median follow-up period was 6.8 years. Of the included patients, 33 were treated with surgery with RAI adjuvant therapy and 28 were treated with surgery alone. The RAI treatment group that underwent surgery had larger tumors, more lymph node metastases, and were younger. There were no disease-specific deaths, and 10 patients experienced local recurrence. The recurrence rate was 24.2% in patients who underwent surgery with RAI adjuvant therapy and 7.1% in patients who underwent surgery alone. Compared to T1-2 stage patients, the T3 stage patients tended to have a higher recurrence rate (odds ratio, 2.38; 95% confidence interval, 0.51-10.7). CONCLUSIONS: The recurrence rate was higher in patients who underwent surgery with RAI adjuvant therapy than in patients who underwent surgery alone. Patients in the former group had larger tumors and more lymph node metastases, and this difference in baseline characteristics could explain their higher recurrence rate. The recurrence rate was lower in patients with small tumors, and RAI adjuvant therapy would likely not play a major role in T1-2N1bM0 patients.

Variation of treatment decision-making for laryngeal cancer in Japan a retrospective observational study using a claim- and electronic medical record-based database.

BACKGROUND: Primary curative treatment of resectable laryngeal cancer includes surgery and chemoradiotherapy. Other treatment options include radiotherapy, chemoradiotherapy, partial laryngectomy, and total laryngectomy. Larynx-preserving treatments (partial laryngectomy, radiotherapy, and chemoradiotherapy) are recommended in early stage cases, although total laryngectomy is needed in advanced cases. Here, we evaluated trends in treatment strategies and identified the factors that are important in decision making. METHODS: We performed a retrospective analysis of data acquired from electronic medical records in Japan. Hospitalized laryngeal cancer patients admitted between January 2014 and December 2018 were included in our analyses. The primary outcome was the initial treatment. RESULTS: A total of 363 patients (mean age 71.8 ± 9.5, male/female = 333/30) met the inclusion criteria. Of these, 10.1% of the patients were treated with total laryngectomy, while 17.9% underwent partial resection, 65.8% received radiotherapy (chemoradiotherapy), and 6.1% had no treatment. Larynx-preserving treatment was used in most T1-2 cases (96.9%), and 40% of the patients with T3 cancer underwent total laryngectomy (adjusted odds ratio 26.7 [95% CI, 9.29-91.6]). Of the T3 cancers that were treated, total laryngectomy was performed in only 26.7% of patients aged ≤65 years, but in more than 50% of those aged >65 years. CONCLUSIONS: This retrospective study showed that larynx-preserving treatments were used in most T1-2 cases, and suggested that T stage is the most important factor affecting decision making in the treatment of laryngeal cancer. Older patients with T3 disease tended to undergo total laryngectomy, and age is an important factor in the decision-making process for cases of T3 laryngeal cancer.

Endotracheal Metastasis Causing Airway Obstruction.

Endotracheal metastasis, a critical complication of primary lung cancer, is an extremely rare lesion. A 73-year-old woman who had previously received treatment for lung cancer presented to our emergency department with dyspnea. A chest computed tomography and nasopharyngolaryngoscopy showed an endotracheal mass below the epiglottis, obstructing the trachea almost completely. The patient had an emergency tracheostomy, and then the mass was removed via median laryngotomy. This lesion was proven to be a recurrent metastasis of lung cancer. Clinicians should recognize endotracheal metastasis as an important differential diagnosis in cancer patients presenting with respiratory symptoms.

A retrospective multicenter study of sublingual gland carcinoma in Japan.

OBJECTIVE: Salivary gland carcinoma is rare among head and neck cancers. Sublingual gland carcinoma, a type of salivary gland carcinoma, is even rarer; therefore, the number of cases at a single institute is too small for sufficient evaluation of tumor characteristics. We conducted a multicenter, retrospective analysis of sublingual gland carcinomas in patients who visited 12 institutions associated with the Kyoto Hospital and Affiliated Facilities Head and Neck Clinical Oncology Group. METHODS: Thirteen previously untreated patients who visited the institutions between 2006 and 2015 were enrolled. The overall survival (OS) and disease-free survival (DFS) rates for all patients and by disease stage were analyzed. Statistical analyses were performed for all patients with respect to disease stage. RESULTS: Eight of thirteen patients were diagnosed with adenoid cystic carcinoma on pathological study. A significant difference in OS rate was observed between patients with Stage I-III and Stage IV disease; however, the difference in DFS rate by disease stage was not significant. CONCLUSION: Stage IV disease was identified as a poor prognostic factor in patients with sublingual gland carcinoma. However, even patients with Stage I-III disease experienced relatively short DFS. Distant metastasis is a serious problem among patients with sublingual gland carcinoma.

Clinical features of nasal and sinonasal inverted papilloma associated with malignancy.

OBJECTIVE: Nasal and sinonasal inverted papilloma (IP) are rare benign tumors and have the potential to exhibit malignancy in approximately 10% of cases. This study aimed to analyze the clinical features of IP associated with malignancy. Furthermore, we reviewed our therapeutic strategy and the clinical course of malignant IP. METHODS: Overall, 70 patients with IP at our institution were retrospectively analyzed from April 2006 to December 2015; of these, six (9%) had associated malignancy. Data was collected on sex, age, presenting symptoms (nasal bleeding, rhinorrhea, facial or cheek pain, and nasal obstruction), bone destruction, and extent of disease on CT and MRI. Categorical data of patients with and without malignancy were compared using the chi-square test. A p value of <0.05 was considered statistically significant. Our therapeutic strategy for IP with malignancy, particularly the surgical procedure, i.e., the external incision or the endoscopic nasal approach, varied based on when the carcinoma was detected. In addition, we considered postoperative radiation therapy depending on histological examination. RESULTS: Nasal bleeding (p<0.001), pain (p=0.040), bone destruction (p<0.001), and extent of disease (p=0.026) on CT and MRI findings were significantly associated with malignancy. Carcinoma was diagnosed preoperatively in two (33%) and postoperatively in four patients (67%). We operated five patients (one case was not treated because of end-stage pancreatic cancer). Two patients underwent endoscopic sinus surgery (ESS) alone, two ESS plus Denker's method, and one ESS plus anterior craniotomy. Three patients underwent surgery only, and two patients received postoperative radiotherapy. The median follow-up period was 69.3 months. One patient died of the disease and the remaining patients are alive without recurrence. CONCLUSION: For IP patients exhibiting these clinical findings preoperatively, we should suspect complication with malignancy and plan a treatment. Even if postoperative histology does not confirm malignancy, we should ensure careful observation because of metachronous malignant transformation or the possibility to overlook small malignant lesions. Our result suggests that our strategy for malignant IP could be a reasonable option.

Survival in patients with submandibular gland carcinoma - Results of a multi-institutional retrospective study.

OBJECTIVE: Clinical studies demonstrating the prognostic factors in submandibular gland carcinoma are limited because the tumor is relatively rare. The aim of this study was to identify clinical outcomes and prognostic factors in submandibular gland carcinoma. METHODS: The study included 65 patients with submandibular gland carcinoma who underwent initial surgical treatment at the Kyoto University and its affiliated hospitals. RESULTS: The 3-year overall survival (OS), disease specific survival, locoregional control (LRC), and no distant metastasis (NDM) rates were 74.2%, 74.2%, 90.0%, and 64.8%, respectively. In the current follow-up study, 16 patients died of the disease, 5 patients were alive with recurrence, 43 patients were alive without disease, and 1 patient died of unrelated disease without recurrence. All patients who died of the disease had developed distant metastasis. Based on univariate analysis, tumor grade (high grade) and lymph node metastases (≥N2) were significant prognostic factors for OS and LRC. It also revealed tumor grade (high grade), T classification (≥T3), and lymph node metastases (≥N2) were significant for distant metastasis. Multivariate analysis showed the following significant prognostic factors: lymph node metastases (≥N2) for OS, LRC, and NDM, and high tumor grade for NDM. CONCLUSION: Our study suggested death of submandibular gland carcinoma occurred mainly due to distant metastasis. The significant predictors of distant metastasis were lymph node metastases (≥N2) and tumor grade (high grade).

Unknown primary squamous cell carcinoma of the head and neck: retrospective analysis of 80 cases.

OBJECTIVES: The management of patients with cervical metastasis in head and neck cancer of unknown primary (HNCUP) remains controversial. This current multicenter retrospective study investigated the treatment outcomes of patients with HNCUP. METHODS: The study included patients who were treated curatively at 12 institutions in Japan from January 2006 to December 2015. RESULTS: Eighty patients with HNCUP were included. The median follow-up period was 34 months. The three-year overall survival (OS), disease-specific survival (DSS), regional relapse-free survival (RRFS), local progression-free survival (LPFS), and distant metastasis-free survival (DMFS) rates were 72.5%, 80.3%, 74.0%, 89.7%, and 86.9%, respectively. Nodal status was a significant factor for OS, DSS, RRFS, and DMFS; and extracapsular extension (ECE) was significant for OS and DSS. There was a distinct difference between the survival rates of patients with N1-2a and N2b-3 disease. RT was a significant positive factor for LPFS (3-year LPFS, RT 93.0% vs. no RT 83.0%, p = .043). CONCLUSIONS: For N2a as well as N1 disease without ECE, a single treatment modality, including ND or RT alone is acceptable. When ND alone is performed, thorough monitoring should be continued during follow-up to identify the emergence of the primary lesion.

A phase I/II exploratory clinical trial for intracordal injection of recombinant hepatocyte growth factor for vocal fold scar and sulcus.

Vocal fold scar and sulcus are intractable diseases with no effective established treatments. Hepatocyte growth factor (HGF) has preclinically proven to have potent antifibrotic and regenerative effects on vocal fold scar. The current Phase I/II clinical trial aims to examine the safety and effectiveness of intracordal injection of a recombinant human HGF drug for patients with vocal fold scar or sulcus. This is an open-label, dose-escalating, first-in-human clinical trial. Eighteen patients with bilateral vocal fold scar or sulcus were enrolled and divided into three groups: Step I received 1 µg of HGF per vocal fold; Step II received 3 µg of HGF; and Step III received 10 µg of HGF. Injections were administered once weekly for 4 weeks. The protocol treatment was performed starting with Step I and escalating to Step III. Patients were followed for 6 months post-treatment. Local and systemic safety aspects were examined as primary endpoints, and therapeutic effects were assessed as secondary endpoints using voice handicap index-10; maximum phonation time; vocal fold vibratory amplitude; grade, rough, breathy, asthenic, strained scale; and jitter. The results indicated no serious drug-related adverse events in either the systemic or local examinations. In whole-subject analysis, voice handicap index-10, vocal fold vibratory amplitude, and grade, rough, breathy, asthenic, strained scale were significantly improved at 6 months, whereas maximum phonation time and jitter varied. There were no significant differences in phonatory data between the step groups. In conclusion, intracordal injection of a recombinant human HGF drug was safe, feasible, and potentially effective for human patients with vocal fold scar or sulcus.