Publications by authors named "Kenji Okami"

74 Publications

Sites of invasion of cancer of the external auditory canal predicting oncologic outcomes.

Head Neck 2021 Jul 9. Epub 2021 Jul 9.

Department of Head and Neck Surgery, National Cancer Center Hospital East, Kashiwa, Japan.

Background: This study aimed to reveal the influence of the invasion site of external auditory canal (EAC) cancer by analyzing the outcome of patients with advanced tumor.

Methods: A total of 111 patients with T4 EAC cancer were enrolled in this study. Of these patients, 79 underwent chemoradiotherapy and 32 underwent surgery under curative intent. Univariate and multivariate analyses and the Kaplan-Meier method were used to focus on the tumor invasion sites and overall survival of the patients.

Results: The 3-year overall survival rate of all patients was 55.0%. In multivariate analysis, the only significant invasion site for overall survival was the facial nerve, with the dura mater being the next most influential site. When Kaplan-Meier survival curve was calculated, facial nerve and dura mater were the significant factors resulting in poor patient outcomes.

Conclusion: The facial nerve and dura mater are crucial sites of EAC cancer for patient outcomes.
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http://dx.doi.org/10.1002/hed.26800DOI Listing
July 2021

Unusual Complication of Nasal Irrigation: Three Case Reports of Nasal Septal Perforation.

Tokai J Exp Clin Med 2021 Jul 20;46(2):105-109. Epub 2021 Jul 20.

Department of Otolaryngology, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan.

The usefulness of nasal irrigation for chronic rhinosinusitis is recognized, and it is widely used as a topical treatment after endoscopic sinus surgery (ESS). Generally, there are few complications due to nasal irrigation, and it is recognized as a highly safe treatment. There are no reports of nasal septal perforation due to nasal irrigation. The objective of this study was to describe three cases of nasal septal perforation occurring during self-nasal irrigation after ESS. Case patient 1 was a 38-year-old woman who was admitted to our hospital with a complaint of nasal obstruction. Based on a diagnosis of chronic rhinosinusitis and allergic rhinitis, we performed bilateral ESS and bilateral inferior turbinectomy. At discharge, we instructed the patient in how to perform self-nasal irrigation twice a day at home. At the time of the third visit after discharge, a black crust had adhered to the bilateral anterior nasal septum. Crust formation continued at the same site, and nasal septal perforation was seen two and a half months after the operation. The other two cases showed similar courses. Postoperative nasal irrigation can cause nasal septal perforation. We need to educate patients on proper nasal irrigation and regularly check the nasal septum.
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July 2021

A p16 Positive M1 Oral Tongue Cancer Completely Responsive to the EXTREME Regimen: A Case Report.

Tokai J Exp Clin Med 2021 Jul 20;46(2):97-100. Epub 2021 Jul 20.

Department of Otolaryngology-Head and Neck Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, 259-1193, Japan.

Methods: A 42-year-old woman presented to our clinic with tongue pain and dysarthria. She had a smoking history of 22 pack-years and no history of alcohol consumption. A deep ulcer at the left side of the tongue and induration across the whole tongue were observed. The bilateral cervical lymph nodes were palpable. A biopsy from the ulcer revealed squamous cell carcinoma. PET/CT showed sternal bone metastasis resulting in the final diagnosis of left-sided oral tongue cancer (cT4aN2cM1). Systemic chemotherapy treatment involving 6 courses of the EXTREME regimen followed by weekly cetuximab administration was indicated.

Results: After the first two courses, diminished tongue pain and improved dysarthria were observed; complete response was obtained after 6 courses. Re-examination of the biopsy specimen showed that the tumor was p16 positive. The p16 protein is a surrogate marker for HPV, but in this case HPV in-situ hybridization was negative. Locoregional or distant failure were not observed during the 5-year follow-up period.

Conclusions: The treatment regimen unexpectedly proved successful. It may be beneficial to examine p16 expression in oral tongue cancer to identify patients that are more likely to benefit from the EXTREME treatment regimen.
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July 2021

Immunohistochemical Marker Expression in Temporal Bone Squamous Cell Carcinoma.

Tokai J Exp Clin Med 2021 Jul 20;46(2):89-93. Epub 2021 Jul 20.

Department of Otolaryngology-Head and Neck Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan.

Background: The correlation between genomic mutations (or the overexpression of abnormal proteins) and prognosis in temporal bone squamous cell carcinoma (TBSCC) is not clear. We investigated the overexpression of EGFR and p53 as a pathological biomarker for predicting the clinical course of patients with TBSCC.

Methods: We performed a retrospective review of 22 TBSCC cases treated in Tokai University Hospital between January 2005 and October 2016. We assessed the overexpression of EGFR and p53 in TBSCC patients through immunohistochemical staining. We also evaluated the association between the overexpression of these proteins and clinicopathological variables, including survival outcomes.

Results: The primary lesion in all patients was the external auditory canal. Nine (40.9%) patients were EGFR positive, and 9 (40.9%) were p53 positive. The 5-year overall survival rate for EGFR-positive patients (55.6%) was significantly lower (p = 0.043) than that of the EGFR-negative patients (92.3%).

Conclusion: EGFR overexpression in TBSCC patients may be a prognostic biomarker.
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July 2021

Gardner syndrome with odontogenic sinusitis: A case report.

Clin Case Rep 2021 Jun 23;9(6):e04256. Epub 2021 Jun 23.

Department of Otolaryngology-Head and Neck Surgery Tokai University School of Medicine Kanagawa Japan.

Gardner syndrome with odontogenic sinusitis is rare but should be suspected in patients with multiple osteomas of the skull and facial bones, excess teeth, impacted teeth, and odontomas. Early diagnosis and treatment of GS may improve prognosis.
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http://dx.doi.org/10.1002/ccr3.4256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222643PMC
June 2021

Transoral surgery for superficial head and neck cancer: National Multi-Center Survey in Japan.

Cancer Med 2021 Jun 15;10(12):3848-3861. Epub 2021 May 15.

Department of Gastroenterology, Kobe City Medical Center General Hospital, Kobe, Japan.

Head and neck cancers, especially in hypopharynx and oropharynx, are often detected at advanced stage with poor prognosis. Narrow band imaging enables detection of superficial cancers and transoral surgery is performed with curative intent. However, pathological evaluation and real-world safety and clinical outcomes have not been clearly understood. The aim of this nationwide multicenter study was to investigate the safety and efficacy of transoral surgery for superficial head and neck cancer. We collected the patients with superficial head and neck squamous cell carcinoma who were treated by transoral surgery from 27 hospitals in Japan. Central pathology review was undertaken on all of the resected specimens. The primary objective was effectiveness of transoral surgery, and the secondary objective was safety including incidence and severity of adverse events. Among the 568 patients, a total of 662 lesions were primarily treated by 575 sessions of transoral surgery. The median tumor diameter was 12 mm (range 1-75) endoscopically. Among the lesions, 57.4% were diagnosed as squamous cell carcinoma in situ. The median procedure time was 48 minutes (range 2-357). Adverse events occurred in 12.7%. Life-threatening complications occurred in 0.5%, but there were no treatment-related deaths. During a median follow-up period of 46.1 months (range 1-113), the 3-year overall survival rate, relapse-free survival rate, cause-specific survival rate, and larynx-preservation survival rate were 88.1%, 84.4%, 99.6%, and 87.5%, respectively. Transoral surgery for superficial head and neck cancer offers effective minimally invasive treatment. Clinical trials registry number: UMIN000008276.
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http://dx.doi.org/10.1002/cam4.3927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209601PMC
June 2021

Localized Maxillary Sinus Papilloma: Management of Incidental Lesion.

Tokai J Exp Clin Med 2021 Apr 20;46(1):17-21. Epub 2021 Apr 20.

Department of Otolaryngology, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan.

Most maxillary sinus papillomas are confirmed when they have extended beyond the nasal cavity and are rarely found while localized in the maxillary sinus. We experienced two cases of localized papilloma in the maxillary sinus. Case 1 was a 69-year-old man with a localized left maxillary sinus lesion detected during a routine imaging examination. As the lesion was likely to be papilloma, we recommended that the patient undergo diagnostic surgery, which he refused. He experienced bloody rhinorrhea 1 year and 9 months after the first visit, and computed tomography (CT) showed increased lesions and bone destruction. Histological examinations revealed squamous cell carcinoma ex inverted papilloma. He died 5 years after the first visit. Case 2 was a 46-year-old woman in whom positron emission tomography/CT showed a localized right maxillary sinus lesion. Tissue biopsy results indicated oncocytic papilloma. Endoscopic resection was performed later. On an imaging examination, sinonasal papilloma was determined accidentally to be a localized lesion of the maxillary sinus. A detailed interpretation of the CT scan was useful in estimating sinonasal papilloma. Tissue biopsy or diagnostic surgery should be performed when sinonasal papilloma is suspected during appropriate image evaluation.
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April 2021

Peripheral Nerve Regeneration Using a Cytokine Cocktail Secreted by Skeletal Muscle-Derived Stem Cells in a Mouse Model.

J Clin Med 2021 Feb 17;10(4). Epub 2021 Feb 17.

Department of Otolaryngology, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan.

Severe peripheral nerve injury, which does not promise natural healing, inevitably requires clinical treatment. Here, we demonstrated the facilitation effect of peripheral nerve regeneration using a cytokine cocktail secreted by skeletal muscle-derived stem cells (Sk-MSCs). Mouse sciatic nerve was transected with a 6 mm gap and bridged collagen tube, and the culture supernatant of Sk-MSCs with 20% adult mouse serum (AMS)/Iscove's modified Dulbecco's medium (IMDM) was administered into the tube immediately after the operation, followed by an injection once a week for six weeks through the skin to the surrounding tube of the cytokine (CT) group. Similarly, 20% AMS/IMDM without cytokines was administered to the non-cytokine control (NT) group. Tension recovery in the plantar flexor muscles via electrical stimulation at the upper portion of the damaged nerve site, as well as the numerical recovery of axons and myelinated fibers at the damaged site, were evaluated as an index of nerve regeneration. Specific cytokines secreted by Sk-MSCs were compared with damaged sciatic nerve-derived cytokines. Six weeks after operation, significantly higher tension output and numerical recovery of the axon and myelinated fibers were consistently observed in the CT group, showing that the present cytokine cocktail may be a useful nerve regeneration acceleration agent. We also determined 17 candidate factors, which are likely included in the cocktail.
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http://dx.doi.org/10.3390/jcm10040824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922934PMC
February 2021

Fish Tank Granuloma Presenting as a Nasal Cavity Mass.

Case Reports Immunol 2021 12;2021:8820720. Epub 2021 Jan 12.

Department of Otolaryngology, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan.

is a free-living nontuberculous mycobacterium that is widely distributed in freshwater and seawater around the world. Granulomatous skin infection from in people who are exposed to fish or aquatic environments is a rare condition known as fish tank granuloma. The granuloma mainly occurs on the skin of the upper limb, in a few cases on the face, and rarely in the nasal cavity. We describe a case of infection that presented as a nasal cavity mass. A 57-year-old woman who was receiving infliximab for psoriatic arthritis visited our hospital with a complaint of right nasal obstruction. A granulomatous mass with an irregular surface was found in the anterior part of the right nasal cavity. Tissue biopsy revealed granulation tissue. Since the application of steroid ointment did not reduce the size of the mass, the tumor was resected under local anesthesia, and the base was cauterized. The pathological finding was an inflammatory granuloma with negative Ziehl-Neelsen staining. The granuloma recurred 3 months after resection. The interferon-gamma release assay (IGRA) test was positive, and therefore, a mycobacterial tissue culture test was performed because of suspected nasal tuberculosis, which identified . The nasal cavity mass disappeared 2 months after the administration of minocycline, followed by clarithromycin, and subsequent discontinuation of infliximab. infection can cause an intranasal mass. IGRA and the mycobacterial tissue culture test are useful for diagnosis. As in this case, the nasal lesion may be excised as an inflammatory nasal granuloma, and therefore, there may be many more "hidden" cases of infection. If nasal granulation is present, the possibility of infection should be considered.
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http://dx.doi.org/10.1155/2021/8820720DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815405PMC
January 2021

Computed Tomography to Diagnose Paranasal Sinus Chemical Burns and Tissue Damage: A Case Report.

Laryngoscope 2021 Jan 18. Epub 2021 Jan 18.

Department of Otolaryngology Head and Neck Surgery, Tokai University School of Medicine, Isehara, Japan.

Chemical burns of the paranasal sinus are rare; therefore, assessment methods for treatment of and prognoses for the exposure site are unknown. We experienced a case in which a hydrochloric acid burn of the paranasal sinuses caused irreversible tissue damage. Computed tomography is useful for identifying the exposure site and assessing tissue damage over time. Identification of the exposure site and proactive washing are recommended for patients with chemical burns of the paranasal sinuses. Laryngoscope, 2021.
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http://dx.doi.org/10.1002/lary.29408DOI Listing
January 2021

Pathological evaluation of tumor grade for salivary adenoid cystic carcinoma: A proposal of an objective grading system.

Cancer Sci 2021 Mar 2;112(3):1184-1195. Epub 2021 Feb 2.

Department of Pathology and Molecular Diagnostics, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan.

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.
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http://dx.doi.org/10.1111/cas.14790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935776PMC
March 2021

The significance of tyrosine kinase receptor B and brain-derived neurotrophic factor expression in salivary duct carcinoma.

Ann Diagn Pathol 2021 Feb 23;50:151673. Epub 2020 Nov 23.

Department of Pathology, Tokai University School of Medicine, Isehara, Kanagawa 259-1193, Japan.

Salivary duct carcinoma (SDC) is a high-grade salivary gland neoplasm. It may occur de novo or secondarily from pleomorphic adenoma (ex-PA), with secondary development accounting for more than 50% of the cases. In recent years, the expression of tyrosine kinase receptor B (TrkB), which is in the same family as HER2, has been confirmed in various types of carcinomas. However, there are a few studies on SDC. In order to examine the expression and role of TrkB in SDC, we investigated it. Immunohistochemistry was used to detect the expression of TrkB and its ligands, brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4) in 20 patients with SDC. The mRNA levels of TrkB, BDNF, and NT-4 were analyzed using quantitative polymerase chain reaction. TrkB was negative in 10 cases and positive in 10 cases, BDNF was negative in 11 cases and positive in 9 cases, and NT-4 was positive in all cases. There was a high number of TrkB-positive cases in the pT4 group and The H-score of TrkB was also significantly higher in the stage III and IV groups. There was a high number of BDNF-positive cases in the ex-PA group and Histo-score of BDNF had a trend of high expression in ex-PA. There were no significant differences or correlations in mRNA expression. Our results suggest that TrkB may be involved in SDC tumor growth.
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http://dx.doi.org/10.1016/j.anndiagpath.2020.151673DOI Listing
February 2021

Multi-institutional Survey of Squamous Cell Carcinoma of the External Auditory Canal in Japan.

Laryngoscope 2021 03 30;131(3):E870-E874. Epub 2020 Jul 30.

Department of Head and Neck Surgery, National Cancer Center Hospital East, Kashiwa, Japan.

Objectives: This study aimed to evaluate the efficacy of chemoradiotherapy (CRT) for patients with advanced cancer of the external auditory canal (EAC) by analyzing the outcome of the patients.

Methods: This is a multi-institutional retrospective survey, and we reviewed the medical records of the subjects. A total of 181 patients with tumor (T)3 or T4 tumor in 17 institutions were enrolled. Further analysis was performed for 74 patients who underwent CRT under curative intent.

Results: Overall 5-year survival rates of the patients who underwent CRT (n = 74) were 54.6%. Those of the patients who underwent CRT with modified TPF (docetaxel, cisplatin [CDDP], and 5-fluorouracil) regimen (n = 50) and CRT with CDDP regimens (n = 24) were 64.4% and 36.7%, respectively. Significant differences were observed between these two groups.

Conclusion: Given the tendency that head and neck surgeons prefer CRT for advanced larger cancer of the EAC, CRT for advanced EAC cancer using the modified TPF regimen showed good clinical outcomes.

Level Of Evidence: 4 Laryngoscope, 131:E870-E874, 2021.
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http://dx.doi.org/10.1002/lary.28936DOI Listing
March 2021

Jervell and Lange-Nielsen syndrome with novel KCNQ1 and additional gene mutations.

Hum Genome Var 2020 15;7:34. Epub 2020 Oct 15.

Department of Pediatrics, Tokai University School of Medicine, Isehara, Japan.

We encountered a boy with Jervell and Lange-Nielsen syndrome (JLNS) with compound heterozygous mutations, maternal Trp248Phe and a novel paternal mutation, Leu347Arg. His father showed long QT (LQT) and arrhythmia. His mother was asymptomatic with no ECG abnormalities. The proband and his father had an additional mutation ( Thr372Met), which is reportedly related to SIDS. These results suggest that multiple gene mutations influence the phenotype of mutation-related arrhythmia.
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http://dx.doi.org/10.1038/s41439-020-00121-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7562699PMC
October 2020

Association between swallowing function and muscle strength in elderly individuals with dysphagia.

Auris Nasus Larynx 2021 Apr 23;48(2):261-264. Epub 2020 Sep 23.

Nishiyama ENT Clinic, Japan.

Objective: This study aimed to investigate the association among swallowing function, hand grip strength, and peak expiratory flow in elderly patients with dysphagia.

Methods: A total of 35 patients (26 men and 9 women, 80.7 ± 8.1 years) were included in the final analysis. They underwent videoendoscopy (VE) for the assessment of swallowing function, hand grip strength test, and peak expiratory flow test. We used the Hyodo score, the objective scale of VE developed by Hyodo et al. (2010), which consists of the following 4 parameters: salivary pooling degree at the vallecula and pyriform sinuses, glottal closure reflex induced by touching of the endoscope to the epiglottis or arytenoid, swallowing reflex initiation assessed by "white-out" timing, and pharyngeal clearance after blue-dyed water is swallowed.

Results: The Hyodo score significantly correlated to hand grip strength and peak expiratory flow, and hand grip strength was significantly correlated to peak expiratory flow. Although a significant correlation was noted between the Hyodo score and hand grip strength after adjustment for peak expiratory flow, no significant correlation was found between the Hyodo score and peak expiratory flow after adjustment for hand grip strength.

Conclusions: This study indicated that unlike peak expiratory flow, hand grip strength is associated with swallowing function, which was evaluated by an objective scale, and can be used as an indicator for whole body muscle strength. This result may contribute to the investigation of the effect of muscle training on dysphagia.
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http://dx.doi.org/10.1016/j.anl.2020.09.007DOI Listing
April 2021

Prognostic impact of CRTC1/3-MAML2 fusions in salivary gland mucoepidermoid carcinoma: A multiinstitutional retrospective study.

Cancer Sci 2020 Nov 14;111(11):4195-4204. Epub 2020 Sep 14.

Department of Pathology and Molecular Diagnostics, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan.

Mucoepidermoid carcinoma (MEC) is rare, but the most common primary malignancy of the salivary gland and not infrequent in young individuals. CRTC1/3-MAML2 fusions are frequently detected in MEC and are useful as a diagnostic biomarker. However, there has been debate as to whether the fusions have prognostic significance. In this study, we retrospectively collected 153 salivary gland MEC cases from 11 tertiary hospitals in Japan. As inclusion criteria, the MEC patients in this study had curative surgery as the initial treatment, received no preoperative treatment, and had no distant metastasis at the time of the initial surgery. The MEC diagnosis was validated by a central pathology review by five expert salivary gland pathologists. The CRTC1/3-MAML2 fusions were detected using FISH and RT-PCR. In 153 MEC cases, 90 (58.8%) were positive for CRTC1/3-MAML2 fusions. During the follow-up period, 28 (18.3%) patients showed tumor recurrence and 12 (7.8%) patients died. The presence of the fusions was associated with favorable tumor features. Of note, none of the fusion-positive patients died during the follow-up period. Statistical analysis showed that the presence of the fusions was a prognostic indicator of a better overall survival in the total and advanced-stage MEC cohorts, but not in the early-stage MEC cohort. In conclusion, CRTC1/3-MAML2 fusions are an excellent biomarker for favorable overall survival of patients with salivary gland MEC.
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http://dx.doi.org/10.1111/cas.14632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648036PMC
November 2020

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

Cancer 2020 09 10;126(18):4177-4187. Epub 2020 Jul 10.

University Hospital Medical Information Network, Tokyo, Japan.

Background: Although the American Joint Committee on Cancer TNM classification has been amended to include human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) as an independent entity, to the authors' knowledge the optimized de-escalating treatment modality has not been established to date.

Methods: The authors conducted a retrospective, nationwide, observational study in patients with HPV-related OPSCC who were treated from 2011 to 2014 in Japan to determine the best treatment modality.

Results: A total of 688 patients who were newly diagnosed with HPV-related OPSCC who were treated with curative intent at 35 institutions and had coherent clinical information and follow-up data available were included in the current study. In patients with T1-T2N0 disease (79 patients), both the 3-year recurrence-free survival and overall survival (OS) rates were 100% in the group treated with radiotherapy (RT) as well as the group receiving concurrent chemoradiotherapy (CCRT). The 3-year OS rates were 94.4% (for patients with T1N0 disease) and 92.9% (for patients with T2N0 disease) among the patients treated with upfront surgery. In patients with stage I to stage II HPV-related OPSCC, the 5-year recurrence-free survival and OS rates were 91.4% and 92%, respectively, in the patients treated with CCRT with relatively high-dose cisplatin (≥160 mg/m ; 114 patients) and 74.3% and 69.5%, respectively, in the patients treated with low-dose cisplatin (<160 mg/m ; 17 patients).

Conclusions: Despite it being a retrospective observational trial with a lack of information regarding toxicity and morbidity, the results of the current study demonstrated that patients with T1-T2N0 HPV-related OPSCC could be treated with RT alone because of the equivalent outcomes of RT and CCRT, and patients with stage I to stage II HPV-related OPSCC other than those with T1-T2N0 disease could be treated with CCRT with cisplatin at a dose of ≥160 mg/m .
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http://dx.doi.org/10.1002/cncr.33062DOI Listing
September 2020

The impact of clinicopathological factors on clinical outcomes in patients with salivary gland adenoid cystic carcinoma: a multi-institutional analysis in Japan.

Int J Clin Oncol 2020 Oct 1;25(10):1774-1785. Epub 2020 Jul 1.

Department of Pathology and Molecular Diagnostics, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-ku, Nagoya, 467-8601, Japan.

Background: Owing to the low incidence of adenoid cystic carcinoma (AdCC), reliable survival estimates and prognostic factors remained unclarified.

Methods: In this multi-institutional retrospective analysis, we collected 192 AdCC cases, and investigated the impact of clinicopathological factors on clinical outcomes of the patients. All AdCC cases were of salivary gland origin and were surgically treated with curative intent. Diagnoses of AdCC were validated by a central pathology review by expert pathologists.

Results: The 5-year overall survival (OS) and disease-free survival (DFS) rates were 92.5 and 50.0%, respectively. Treatment failure occurred in 89 patients (46%) with the distant failures in 65 (34%). Multivariate analysis indicated that pN2 and a pathologically positive surgical margin were independent prognostic factors for both OS and DFS. Histological grade III was an independent prognostic factor for OS. A primary site in the submandibular gland, pT3/4, pN1, and histological grade II were independent prognostic factors for DFS. Postoperative radiation therapy (PORT) improved the locoregional control (LRC) rate. Prophylactic neck dissection was not associated with a better OS or better LRC among patients with cN0. Facial nerve dissection did not improve clinical outcomes in parotid AdCC cases without facial nerve palsy.

Conclusions: A higher TN classification, a pathologically positive surgical margin, and a higher histological grade were associated with a lower OS. PORT improved LRC rates but neck dissection failed to improve clinical outcomes in patients with cN0. As the distant metastasis was frequent, effective systemic therapy is imperative to improve the survival of AdCC patients.
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http://dx.doi.org/10.1007/s10147-020-01731-9DOI Listing
October 2020

The clinicopathological significance of the adipophilin and fatty acid synthase expression in salivary duct carcinoma.

Virchows Arch 2020 Aug 26;477(2):291-299. Epub 2020 Feb 26.

Department of Otorhinolaryngology/Head & Neck Surgery, Chiba University Graduate School of Medicine, Chiba, Japan.

Salivary duct carcinoma (SDC) is an aggressive, uncommon tumor histologically comparable to high-grade mammary ductal carcinoma. SDCs are usually androgen receptor (AR)-positive and often HER2-positive. Recently, therapies targeting these molecules for SDC have attracted attention. Lipid metabolism changes have been described in association with biological behavior in various cancers, although no such relationship has yet been reported for SDC. We therefore analyzed the clinicopathological relevance of the immunohistochemical expression of adipophilin (ADP) and fatty acid synthase (FASN), representative lipid metabolism-related proteins, in 147 SDCs. ADP and FASN were variably immunoreactive in most SDCs (both 99.3%), and the ADP and FASN expression was negatively correlated (P = 0.014). ADP-positive (≥ 5%) SDCs more frequently exhibited a prominent nuclear pleomorphism and high-Ki-67 labeling index than those ADP-negative (P = 0.013 and 0.011, respectively). In contrast, a high FASN score, calculated by the staining proportion and intensity, (≥ 120) was correlated with the high expression of AR and FOXA1 (P < 0.001 and = 0.003, respectively). The ADP and FASN expression differed significantly among the subtypes based on biomarker immunoprofiling, as assessed by the AR, HER2, and Ki-67 status (P = 0.017 and 0.003, respectively). A multivariate analysis showed that ADP-positive expression was associated with a shorter overall and progression-free survival (P = 0.018 and 0.003, respectively). ADP was associated with an aggressive histopathology and unfavorable prognosis, and FASN may biologically interact with the AR signaling pathway in SDC. ADP may, therefore, be a new prognostic indicator and therapeutic target in SDC.
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http://dx.doi.org/10.1007/s00428-020-02777-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7371671PMC
August 2020

Central pathology review of salivary gland adenoid cystic carcinoma.

Head Neck 2020 08 23;42(8):1721-1727. Epub 2020 Jan 23.

Department of Pathology and Molecular Diagnostics, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan.

Background: To assess the role of a central pathology review in the diagnosis of salivary gland adenoid cystic carcinoma (AdCC).

Methods: Surgically resected salivary gland tumors diagnosed as AdCC (n = 219) in 15 reference hospitals in Japan were subjected to a retrospective pathological re-evaluation.

Results: After the review, the AdCC diagnosis was revised in 21/219 cases (9.6%). The six benign tumors (2.7%) comprised five basal cell adenomas and one pleomorphic adenoma, and among these six patients, three received postoperative radiotherapy. The remaining 15 malignant tumors (6.8%) comprised nine basal cell adenocarcinomas and six other carcinomas. All revised basal cell adenoma/adenocarcinoma cases were of rare cribriform variants.

Conclusions: A significant proportion of AdCC pathology reports were revised after the central pathology review. It should be emphasized that the greatest attention should be paid in differentiating AdCC from cribriform variant basal cell adenoma/adenocarcinoma, which is very rare in salivary gland tumors.
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http://dx.doi.org/10.1002/hed.26081DOI Listing
August 2020

A multicenter phase II trial of paclitaxel, carboplatin, and cetuximab followed by chemoradiotherapy in patients with unresectable locally advanced squamous cell carcinoma of the head and neck.

Cancer Med 2020 03 13;9(5):1671-1682. Epub 2020 Jan 13.

Department of Head and Neck Medical Oncology, National Cancer Center Hospital East, Chiba, Japan.

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/m and Cmab with an initial dose of 400 mg/m followed by 250 mg/m for 8 weeks. Following IC, CDDP (20 mg/m , 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/m 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.
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http://dx.doi.org/10.1002/cam4.2852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7050099PMC
March 2020

Prognostic Implication of Histopathologic Indicators in Salivary Duct Carcinoma: Proposal of a Novel Histologic Risk Stratification Model.

Am J Surg Pathol 2020 04;44(4):526-535

Departments of Anatomic Pathology.

Salivary duct carcinoma (SDC) is a rare, aggressive malignancy that histologically resembles high-grade mammary duct carcinoma. Because of the rarity of this entity, data verifying the association between histologic features and patient survival are limited. We conducted a comprehensive histologic review of 151 SDC cases and performed an analysis of the association between various histomorphologic parameters and the clinical outcome with the aim of developing a histologic risk stratification model that predicts the prognosis of SDC patients. A multivariate analysis revealed that prominent nuclear pleomorphism (overall survival [OS]: P=0.013; progression-free survival [PFS]: P=0.019), ≥30 mitoses/10 HPF (PFS: P=0.013), high tumor budding (OS: P=0.011; PFS: P<0.001), and high poorly differentiated clusters (OS: P<0.001; PFS: P<0.001) were independent prognostic factors. Patients with vascular invasion demonstrated a marginally significant association with shorter PFS (P=0.064) in a multivariate analysis. We proposed a 3-tier histologic risk stratification model based on the total number of positive factors among 4 prognostically relevant parameters (prominent nuclear pleomorphism, ≥30 mitoses/10 HPF, vascular invasion, and high poorly differentiated clusters). The OS and PFS of patients with low-risk (0 to 1 point) (23% of cases), intermediate-risk (2 to 3 points) (54% of cases), and high-risk (4 points) (23% of cases) tumors progressively deteriorated in this order (hazard ratio, 2.13 and 2.28, and 4.99 and 4.50, respectively; Ptrend<0.001). Our histologic risk stratification model could effectively predict patient survival and may be a useful aid to guide clinical decision-making in relation to the management of patients with SDC.
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http://dx.doi.org/10.1097/PAS.0000000000001413DOI Listing
April 2020

Addition of S-1 to radiotherapy for treatment of T2N0 glottic cancer: Results of the multiple-center retrospective cohort study in Japan with a propensity score analysis.

Oral Oncol 2019 12 30;99:104454. Epub 2019 Oct 30.

Department of Otorhinolaryngology, Head and Neck Surgery, Yokohama City University, School of Medicine, Yokohama, Kanagawa, Japan.

Objectives: This multicenter retrospective cohort study aimed to evaluate the significance of adding S-1 to radiotherapy (RT) for the treatment of T2N0 glottic cancer using a propensity score matched analysis in Japan.

Materials And Methods: This study was conducted on 287 patients with T2N0 glottic cancer who were treated with definitive RT or chemoradiotherapy with S-1 (S-1 RT) between April 2007 and March 2017. Propensity score matched analysis was performed to ensure the well-balanced characteristics of the groups of patients who received RT alone and S-1 RT. Overall, progression-free and laryngectomy-free survivals and local control and laryngeal preservation rates were compared.

Results: Fifty-four pairs of patients were selected after performing propensity score matched analysis. Clinical characteristics were well-balanced between the two groups. The overall survival of patients in the S-1 RT group was significantly better than those in the RT alone group (P = 0.008). The progression-free and laryngectomy-free survivals of patients in the S-1 RT group were also better than those in the RT alone group; however, the differences were not significant. In contrast, patients in the S-1 RT group had slightly lower local control and laryngeal preservation rates compared with those in the RT alone group. The incidence of dermatitis in the S-1 RT group was significantly higher than that in the RT alone group in the matched population (P = 0.013).

Conclusions: The addition of S-1 to RT for the treatment of T2N0 glottic cancer was not associated with better local control and laryngeal preservation rates in this study.
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http://dx.doi.org/10.1016/j.oraloncology.2019.104454DOI Listing
December 2019

[II. Trend and Future of the Surgery for Head and Neck Cancer].

Authors:
Kenji Okami

Gan To Kagaku Ryoho 2018 Jul;45(7):1046-1051

Dept. of Otolaryngology, Tokai University.

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July 2018

The high expression of FOXA1 is correlated with a favourable prognosis in salivary duct carcinomas: a study of 142 cases.

Histopathology 2018 Dec 25;73(6):943-952. Epub 2018 Sep 25.

Department of Anatomic Pathology, Tokyo Medical University, Tokyo, Japan.

Aims: Salivary duct carcinoma (SDC) is an uncommon, aggressive tumour that, histologically, resembles high-grade mammary ductal carcinoma, and is characterised by the expression of androgen receptor (AR). The androgen signalling pathway, a potential therapeutic target, can be regulated by FOXA1. This study aimed to evaluate the clinicopathological implications of FOXA1 in SDC.

Methods And Results: We examined the relationship between the immunoexpression of FOXA1 and FOXA1 mutations and clinicopathological factors, including the biomarker status and clinical outcome, in 142 SDCs. FOXA1 was expressed in 128 SDCs (90.1%); the immunoexpression was heterogeneous. SDCs with a higher FOXA1 labelling index (LI) (≥20%) more frequently showed less advanced tumors on T classification (P = 0.002). FOXA1 LI was correlated positively with the AR expression value (r = 0.430, P < 0.001). PI3K and p-mTOR positivity, and intact-PTEN, were associated with a higher FOXA1 LI. Twenty-two of 121 SDCs (18.2%) harboured FOXA1 gene mutations at the flanking regions in and around the forkhead DNA binding domain; however, the given gene mutation and the expression of FOXA1 were not significantly correlated. A multivariate analysis revealed that SDCs with a higher FOXA1 LI were associated with longer overall survival and progression-free survival (P = 0.029 and 0.016, respectively).

Conclusions: In SDC, FOXA1, which may biologically interact with the AR and PI3K signalling pathways, is a putative biomarker that may be associated with a favourable prognosis. Further studies are needed to apply the findings to the development of targeted personalised therapy for patients with SDC.
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http://dx.doi.org/10.1111/his.13706DOI Listing
December 2018

Chronological Progression of an Enlarged Styloid Process: A Case Report of Eagle Syndrome.

Case Rep Otolaryngol 2018 15;2018:9207264. Epub 2018 Jan 15.

Department of Otolaryngology, Head and Neck Surgery, Tokai University, Kanagawa, Japan.

Eagle syndrome is characterized by an elongated styloid process. However, the time frame over which the styloid process becomes elongated and extends is unknown. How the condition worsens over time is also unclear. To date, there has been no report describing the chronologic change that occurs in the styloid process in Eagle syndrome. We describe a 53-year-old patient with Eagle syndrome in whom the styloid process enlarged progressively over time and the elongated styloid process fused with the hyoid bone. The styloid process was resected via a transcervical approach, and the patient's subjective symptoms improved. This is the first report showing how the styloid process can enlarge over a few years in a patient with Eagle syndrome. Surgical resection via a transcervical approach is an appropriate treatment for a patient in whom the styloid process has become excessively enlarged and elongated.
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http://dx.doi.org/10.1155/2018/9207264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5821999PMC
January 2018

Prognostic and histogenetic roles of gene alteration and the expression of key potentially actionable targets in salivary duct carcinomas.

Oncotarget 2018 Jan 4;9(2):1852-1867. Epub 2017 Dec 4.

Department of Otorhinolaryngology, Showa University School of Medicine, Tokyo, Japan.

The molecular characteristics of therapeutically-relevant targets and their clinicopathological implications in salivary duct carcinomas (SDCs) are poorly understood. We investigated the gene alterations and the immunoexpression of crucial oncogenic molecules in 151 SDCs. The mutation rates that were identified, in order of frequency, were as follows: , 68%; , 18%; , 16%; , 4%; and , 1.5%. mutations were more common in SDC than in SDC ex-pleomorphic adenoma. Furthermore, these mutations were mutually exclusive for HER2 overexpression/amplification. mutations were frequently detected in cases with the aberrant p53 expression, and missense and truncating mutations were associated with p53-extreme positivity and negativity, respectively. DISH analysis revealed no cases of amplification. The rates of PI3K, p-Akt, and p-mTOR positivity were 34%, 22%, and 66%, respectively; PTEN loss was observed in 47% of the cases. These expressions were correlated according to the signaling axis. Cases with PI3K negativity and PTEN loss appeared to show a lower expression of androgen receptor. In the multivariate analysis, patients with SDC harboring truncating mutations showed shorter progression-free survival. Conversely, p-Akt positivity was associated with a favorable outcome. This study might provide information that leads to advances in personized therapy for SDC.
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http://dx.doi.org/10.18632/oncotarget.22927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5788604PMC
January 2018

Synchronous HPV-Related Cancer of Bilateral Tonsils Detected Using Transoral Endoscopic Examination with Narrow-Band Imaging.

Case Rep Otolaryngol 2017 12;2017:9647010. Epub 2017 Oct 12.

Department of Otolaryngology-Head and Neck Surgery, Tokai University, Isehara, Japan.

Background: The incidence of human papillomavirus- (HPV-) related oropharyngeal squamous cell carcinoma (OPSCC) has been rapidly increasing worldwide. HPV is reported in approximately 50% cases of OPSCC in Japan. However, there are few reports of synchronous bilateral HPV-positive tonsillar carcinoma, and, in almost all those cases, carcinoma was detected using positron emission tomography/computed tomography and/or bilateral tonsillectomy.

Methods And Results: We report the case of a 63-year-old male with bilateral tonsillar carcinoma detected using transoral endoscopic examination with narrow-band imaging (NBI). A biopsy of the bilateral tonsils revealed squamous cell carcinoma, which was demonstrated to be HPV-related using in situ hybridization and p16 immunohistochemistry. The patient was diagnosed as synchronous bilateral tonsillar carcinoma: T1 (2) N2b M0. He was treated with induction chemotherapy, bilateral radical tonsillectomy with neck dissection, and radiotherapy.

Conclusion: To our knowledge, this is the first report of a synchronous bilateral tonsillar carcinoma detected using transoral NBI in the outpatient setting. Early diagnosis without the inspection under general anesthesia is beneficial for the patients with lymph node metastasis from unknown primary lesion.
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http://dx.doi.org/10.1155/2017/9647010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5660802PMC
October 2017

Biomarker immunoprofile in salivary duct carcinomas: clinicopathological and prognostic implications with evaluation of the revised classification.

Oncotarget 2017 Aug 2;8(35):59023-59035. Epub 2017 Aug 2.

Department of Anatomic Pathology, Tokyo Medical University, Tokyo, Japan.

Salivary duct carcinoma (SDC) is an uncommon, aggressive malignant neoplasm histologically resembling high-grade mammary ductal carcinoma. SDC can arise or ex pleomorphic adenoma. To clarify the correlation of biomarker immunoprofile with clinicopathological findings and clinical outcome of SDC, we conducted immunohistochemistry for EGFR, HER2, HER3, AR, CK5/6, p53, and Ki-67, along with HER2 fluorescence hybridization in 151 SDCs. SDCs ex pleomorphic adenoma more commonly overexpressed EGFR, HER2, HER3, and Ki-67 than SDCs ( = 0.015, < 0.001, 0.045, and 0.02, respectively). In multivariate analysis, AR- and CK5/6+ were associated with shorter progression-free survival ( = 0.027 and 0.004, respectively). Moreover, patients with p53-extreme negative/positive demonstrated poorer overall survival ( = 0.007). On assessing the revised classification by the combination of biomarker expression, the percentages of each subtype were as follows: 'apocrine A' (AR+/HER2-/Ki-67-low) (24%), 'apocrine B' (AR+/HER2-/Ki-67-high) (18%), 'apocrine HER2' (AR+/HER2+) (35%), 'HER2-enriched' (AR-/HER2+) (12%), and 'double negative' (AR-/HER2-) (11%). 'Double negative' was further subclassified into 'basal-like' (EGFR and/or CK5/6+) (7%) and 'unclassified' (3%). Consequently, patients with 'apocrine A' showed a better progression-free survival than those with any other subtypes. Our revised immunoprofiling classification was valuable for predicting the survival and might be useful in personalized therapy for patients with SDC.
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http://dx.doi.org/10.18632/oncotarget.19812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5601711PMC
August 2017

Avoidance of postoperative irradiation for cervical lymph node metastases of human papillomavirus-related tonsillar cancer.

Laryngoscope Investig Otolaryngol 2017 04 10;2(2):63-68. Epub 2017 Mar 10.

Department of Otolaryngology-Head and Neck Surgery Tokai University Kanagawa Japan.

Background: everal reports have suggested that selected patients with human papillomavirus-related oropharyngeal cancer can be managed with surgery alone. We retrospectively reviewed tonsillar cancer cases to analyze treatment de-intensification after transoral resection.

Methods: Eighteen patients with tonsillar cancer who had undergone transoral resection were included. The patients' characteristics, p16 status, adverse features, clinical course, overall survival, and relapse-free survival according to p16 status were retrospectively examined.

Results: Four lesions showed positive surgical margins and one lesion showed close surgical margin; these patients were treated with postoperative irradiation. Seven p16-positive patients had multiple node metastases and two had extracapsular spread. No p16-positive patients agreed to postoperative irradiation, and recurrence within the surgical field was not observed. The five-year overall and relapse-free survival rates were 89% and 74%, respectively. The five-year relapse-free survival rates of p16-positive and p16-negative patients were 81% and 50%, respectively (p = .075).

Conclusions: Postoperative irradiation for cervical lymph node metastases might be avoidable in selected patients with human papillomavirus-related tonsillar cancer.

Level Of Evidence: 4.
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http://dx.doi.org/10.1002/lio2.70DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5527367PMC
April 2017
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