Publications by authors named "Ryuji Yasumatsu"

90 Publications

Outcomes of long-term nivolumab and subsequent chemotherapy in Japanese patients with head and neck cancer: 2-year follow-up from a multicenter real-world study.

Int J Clin Oncol 2021 Nov 13. Epub 2021 Nov 13.

Department of Otolaryngology, Head and Neck Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Kita15 Nishi7, Kita-Ku, Sapporo, Hokkaido, 060-8638, Japan.

Background: We have previously reported the effectiveness and safety of nivolumab in patients with head and neck cancer (HNC) in real-world clinical practice in Japan. Here, we report long-term outcomes from this study in the overall population and subgroups stratified by subsequent chemotherapy.

Methods: In this multicenter, retrospective observational study, Japanese patients with recurrent or metastatic (R/M) HNC receiving nivolumab were followed up for 2 years. Effectiveness endpoints included overall survival (OS), OS rate, progression-free survival (PFS), and PFS rate. Safety endpoints included the incidence of immune-related adverse events (irAEs).

Results: Overall, 256 patients received a median of 6.0 doses (range: 1-52) of nivolumab over a median duration of 72.5 days (range: 1-736). Median OS was 9.5 months [95% confidence interval (CI) 8.2-12.0] and median PFS was 2.1 months (95% CI 1.8-2.7). A significant difference between 2-year survivors (n = 62) and non-2-year survivors was observed by median age (P = 0.0227) and ECOG PS (P = 0.0001). Of 95 patients who received subsequent chemotherapy, 54.7% received paclitaxel ± cetuximab. The median OS and PFS from the start of paclitaxel ± cetuximab were 6.9 months (95% CI 5.9-11.9) and 3.5 months (95% CI 2.3-5.5), respectively. IrAEs were reported in 17.2% of patients. Endocrine (7.0%) and lung (4.3%) disorders were the most common irAEs; kidney disorder (n = 1) was newly identified in this follow-up analysis.

Conclusions: Results demonstrated the long-term effectiveness of nivolumab and potential effectiveness of subsequent chemotherapy in patients with R/M HNC in the real-world setting. Safety was consistent with that over the 1-year follow-up.
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http://dx.doi.org/10.1007/s10147-021-02047-yDOI Listing
November 2021

Carcinoma showing thymus-like differentiation (CASTLE) of the salivary gland: Report of 2 cases of a hitherto under-recognized extrathyroid counterpart.

Pathol Res Pract 2021 Nov 8;227:153646. Epub 2021 Oct 8.

Department of Anatomic Pathology, Kyushu University, Graduate School of Medical Sciences, Fukuoka, Japan.

Carcinoma showing thymus-like differentiation (CASTLE) outside the thyroid gland is extremely rare. Here we report two cases of CASTLE of the major salivary gland. The tumors occurred in the parotid gland of a 31-year-old female (Case 1) and in the submandibular gland of a 40-year-old female (Case 2). Both tumors showed a lobulated growth pattern, and were histologically composed of a nested or sheet-like proliferation of carcinoma cells with round- to oval-shaped nuclei, distinct nucleoli and pale eosinophilic cytoplasm, accompanied by various degrees of lymphocytic infiltration. Immunohistochemical staining revealed that the tumors were positive for pan-cytokeratin, p40, CD5, CD117 and bcl-2. In addition, PD-L1 expression was seen in 10-90% of tumor cells. After the initial surgery, Case 1 remained tumor-free for 20 months, while Case 2 suffered lymph node recurrence at 4 months, followed by lung metastasis, which was treated with chemoradiotherapy and anti-PD-1 immune checkpoint inhibitor, resulting in a partial response. The present findings indicate that an extrathyroid counterpart of CASTLE can occur as a primary salivary gland neoplasm. Salivary CASTLEs seem to show a wide range of biological behavior, and long-term follow-up may be needed. Immune checkpoint inhibitor targeting PD-1 might become a promising treatment option in patients with CASTLE; however, further study with a larger number of cases is necessary to establish the optimal therapeutic strategy and prognostic factors for this rare cancer.
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http://dx.doi.org/10.1016/j.prp.2021.153646DOI Listing
November 2021

Evaluation of MR imaging findings differentiating parotid basal cell adenomas from other parotid tumors.

Eur J Radiol 2021 Nov 27;144:109980. Epub 2021 Sep 27.

Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.

Purpose: To evaluate the usefulness of magnetic resonance imaging (MRI) to differentiate basal cell adenomas (BCAs) from other parotid tumors.

Method: A total of 136 patients with histologically proven parotid gland tumors (13 BCAs, 66 pleomorphic adenomas [PAs], 30 Warthin tumors [WTs], and 27 parotid cancers [PCs]) who underwent a cervical MRI study between December 2011 and March 2019 were retrospectively enrolled. The MRI findings of the tumors were evaluated by two board-certified radiologists.

Results: All 13 of the BCAs showed smooth margins, while 19 of the 27 PCs showed irregular margins (p < 0.0001). Eleven BCAs had some cystic components, and five were cyst-dominant. The BCAs had significantly more cystic components than the PAs (p = 0.0077). The mean apparent diffusion coefficient (ADC) value of the BCAs was 1.21 ± 0.20 × 10 mm/sec, which was equivalent to that of the PCs (1.12 ± 0.25 × 10 mm/sec, p = 0.76), significantly lower than that of the PAs (1.61 ± 0.32 × 10 mm/sec, p < 0.0001), and significantly higher than that of the WTs (0.81 ± 0.19 × 10 mm/sec, p = 0.0004). The plateau time-intensity curve (TIC) was the most common type for both BCAs and PCs, seen in 8 of 12 BCAs and 21 of 26 PCs, with no significant difference between these groups (p = 0.34).

Conclusions: BCA should be considered a possibility when a parotid lesion has smooth margins with an entire capsule and includes a cystic component, even if the TIC and diffusion-weighted MR images suggest a malignant pattern.
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http://dx.doi.org/10.1016/j.ejrad.2021.109980DOI Listing
November 2021

Contribution of pre-existing neoantigen-specific T cells to a durable complete response after tumor-pulsed dendritic cell vaccine plus nivolumab therapy in a patient with metastatic salivary duct carcinoma.

Immunol Invest 2021 Sep 5:1-17. Epub 2021 Sep 5.

Department of Cancer Immunotherapy, Fukuoka General Cancer Clinic, Fukuoka, Japan.

Although immune checkpoint inhibitors (ICIs) have emerged as new therapeutic options for refractory cancer, they are only effective in select patients. Tumor antigen-pulsed dendritic cell (DC) vaccine therapy activates tumor-specific cytotoxic T lymphocytes, making it an important immunotherapeutic strategy. Salivary ductal carcinoma (SDC) carries a poor prognosis, including poor long-term survival after metastasis or recurrence. In this study, we reported a case of refractory metastatic SDC that was treated with a tumor lysate-pulsed DC vaccine followed by a single injection of low-dose nivolumab, and a durable complete response was achieved. We retrospectively analyzed the immunological factors that contributed to these long-lasting clinical effects. First, we performed neoantigen analysis using resected metastatic tumor specimens obtained before treatment. We found that the tumor had 256 non-synonymous mutations and 669 class I high-affinity binding neoantigen peptides. Using synthetic neoantigen peptides and ELISpot analysis, we found that peripheral blood mononuclear leukocytes cryopreserved before treatment contained pre-existing neoantigen-specific T cells, and the cells obtained after treatment exhibited greater reactivity to neoantigens than those obtained before treatment. Our results collectively suggest that the rapid and long-lasting effect of this combination therapy in our patient may have resulted from the presence of pre-existing neoantigen-specific T cells and stimulation and expansion of those cells following tumor lysate-pulsed DC vaccine and ICI therapy.
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http://dx.doi.org/10.1080/08820139.2021.1973491DOI Listing
September 2021

Cancer of the External Auditory Canal with Extensive Osteoradionecrosis of the Skull Base after Re-Irradiation with Particle Beams: A Case Report.

Case Rep Oncol 2021 May-Aug;14(2):1097-1102. Epub 2021 Jul 13.

Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Re-irradiation with X-rays and particle beams can be used to treat localized recurrence of unresectable head and neck cancer after initial irradiation therapy. However, re-irradiation therapy increases the risk of severe and late sequelae by 4-to 8-fold. It can also result in fatal outcomes, such as rupture of the carotid artery and cerebral necrosis or abscess. A 41-year-old woman was diagnosed with squamous cell carcinoma of the external auditory canal. The patient was initially treated with X-ray irradiation. However, the patient underwent re-irradiation with heavy particle beams and neutron rays for a recurrent tumor. The patient developed necrosis of the skull base involving the facial skin and temporal bone 2 months after the last session of re-irradiation therapy. The tissue in the parapharyngeal and masticatory regions also became completely necrotic, resulting in extensive exposure of the brain parenchyma. Although the patient underwent conservative and surgical treatment, necrosis of the tissue progressed, and a large part of the brain was exposed. Approximately 2.5 years later, although the brain is still exposed, the patient is alive without disease. Although the tumor had subsided and long-term survival was achieved, our patient developed serious osteoradionecrosis of the skull base with extensive brain exposure. For patients who are not candidates for surgery, re-irradiation alone is an option, albeit with poor prospects. This approach should be discussed with the patient while balancing the potential survival gain against the burden of treatment and the risk of complications.
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http://dx.doi.org/10.1159/000516801DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299411PMC
July 2021

PD-L1 expression, tumor-infiltrating lymphocytes, mismatch repair deficiency, EGFR alteration and HPV infection in sinonasal squamous cell carcinoma.

Mod Pathol 2021 Nov 3;34(11):1966-1978. Epub 2021 Jul 3.

Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

The antitumor efficacies of immune checkpoint inhibitors (ICIs) and the usefulness of potential predictive markers such as programmed death-ligand 1 (PD-L1) expression, density of tumor-infiltrating lymphocytes (TILs) and microsatellite instability (MSI) in sinonasal squamous cell carcinoma (SNSCC) have not been fully elucidated. We retrospectively analyzed 131 SNSCCs with immunohistochemistry for PD-L1 expression, TIL subpopulations and loss of mismatch repair (MMR) proteins as a surrogate for MSI-high. We also comprehensively evaluated the mutual relationships among these immuno-markers, high-risk human papillomavirus (HPV) infection, epidermal growth factor receptor (EGFR) gene status, and KRAS mutation. PD-L1 expression (tumor proportion score ≥ 1%) was detected in 60 (45.8%) SNSCC cases and was significantly associated with worse overall survival (OS) (p = 0.0240). High density of cluster of differentiation 8 (CD8)-positive TILs was significantly associated with better progression-free survival (PFS) (p = 0.0368), and high density of forkhead box protein P3-positive TILs was significantly associated with better PFS and OS (p = 0.0007 and 0.0143, respectively). With respect to the combination of CD8 + TIL and PD-L1 expression, the high-CD8/PD-L1-negative group showed the most favorable prognosis, whereas the low-CD8/PD-L1-positive group showed the worst prognosis. MMR loss was detected in 3 (2.3%) of the 131 cases. HPV infection (6.1%), EGFR mutation (14.5%), EGFR copy number gain (26%), and MMR loss were essentially mutually exclusive; patients in these molecular groups showed significant differences in prognosis but not in the degree of PD-L1 expression or TILs. Among the nine ICI-treated patients, three (33.3%) were responders, and the EGFR-wild type cases (n = 7) showed better clinical responses to an ICI compared to the EGFR-mutant cases (n = 2). Among the patients with residual/recurrent EGFR-wild type tumors (n = 43), ICI treatment significantly improved OS (p = 0.0281). The results suggest that the evaluation of immuno-markers and molecular subclassification may be helpful for prognostic prediction and selecting an individualized therapeutic strategy for patients with SNSCC.
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http://dx.doi.org/10.1038/s41379-021-00868-wDOI Listing
November 2021

Feasibility of hepatic resection for liver metastasis of head-and-neck carcinoma or esophageal carcinoma: a multi-center experience.

Surg Today 2021 Dec 25;51(12):1932-1937. Epub 2021 May 25.

Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.

Purpose: Patients with liver metastasis of head-and-neck carcinoma and esophageal carcinoma are generally not treated with hepatic resection, but there are no established standard treatment methods. We report 11 cases of hepatic resection for liver metastasis of head-and-neck carcinoma or esophageal carcinoma performed at 5 Japanese institutions.

Methods: The subjects of this retrospective analysis were 11 patients who underwent hepatic resection for metastatic liver tumors, originating from head-and-neck carcinoma in 5 and from esophageal cancer in 6, between January, 2010 and March, 2020 RESULTS: There were nine men and two women (median age, 64 years; range 40-72 years). The primary disease was esophageal carcinoma in six patients and pharyngeal carcinoma in five patients. All cancers were squamous cell carcinoma. The time from the initial treatment to the diagnosis of liver metastasis was 15.3 months and the 1-year and 3-year overall survival rates after hepatic resection were 72% and 32%, respectively. The overall and disease-free survival rates after hepatic resection were significantly higher for patients who underwent hepatic resection more than 12 months after the initial treatment than for those who underwent hepatic resection within 12 months after the initial treatment (p = 0.0172 and p = 0.0120, respectively).

Conclusions: Liver resection may prolong the survival of patients with liver metastases controlled for more than 12 months after the initial treatment of head and neck or esophageal carcinoma.
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http://dx.doi.org/10.1007/s00595-021-02305-6DOI Listing
December 2021

Clinical Management of Early-Stage Hypopharyngeal Squamous Cell Carcinoma: A Single-Institution Clinical Analysis.

Ear Nose Throat J 2021 Apr 28:1455613211013084. Epub 2021 Apr 28.

Department of Otorhinolaryngology, Graduate School of Medical sciences, 12923Kyushu University, Fukuoka, Japan.

Objective: Early detection of hypopharyngeal squamous cell carcinoma (SCC) is important for both an improved prognosis and less-invasive treatment. We retrospectively analyzed the detection rates of early hypopharyngeal SCCs according to the evaluation methods and the clinical management of early hypopharyngeal SCCs.

Methods: Sixty-eight patients with early hypopharyngeal SCC who were diagnosed were reviewed.

Results: The number of early hypopharyngeal cancer patients with asymptomatic or synchronous or metachronous esophageal cancer examined by upper gastrointestinal endoscopy with narrow-band imaging (NBI) was significantly higher than those examined by laryngopharyngeal endoscopy with NBI. The 3-year disease-specific survival rates according to T classification were as follows: Tis, 100%; T1, 100%; T2, 79.8%; and overall, 91.2%, respectively.

Conclusions: Early-stage hypopharyngeal SCC can be cured by minimally invasive transoral surgery or radiotherapy. Observation of the pharynx using NBI in patients with a history of head and neck cancer, esophageal cancer, gastric cancer, or pharyngeal discomfort is very important, and routinely examining the pharynx with NBI, even in patients undergoing endoscopy for screening purposes, is recommended.
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http://dx.doi.org/10.1177/01455613211013084DOI Listing
April 2021

Effectiveness of nivolumab affected by prior cetuximab use and neck dissection in Japanese patients with recurrent or metastatic head and neck cancer: results from a retrospective observational study in a real-world setting.

Int J Clin Oncol 2021 Jun 8;26(6):1049-1056. Epub 2021 Apr 8.

Department of Otolaryngology, Head and Neck Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Kita15 Nishi7, Kita-Ku, Sapporo, Hokkaido, 060-8638, Japan.

Background: To examine the effect of prior use of cetuximab and neck dissection on the effectiveness of nivolumab, we conducted a large-scale subgroup analysis in Japanese patients with recurrent/metastatic head and neck cancer.

Methods: Data on the effectiveness of nivolumab were extracted from patient medical records. All patients were analyzed for effectiveness by prior cetuximab use. In the analyses for prior neck dissection, only patients with locally advanced disease were included.

Results: Of 256 patients analyzed, 155 had received prior cetuximab. Nineteen of 50 patients with local recurrence underwent neck dissection. The objective response rate was 14.7 vs 17.2% (p = 0.6116), median progression-free survival was 2.0 vs 3.1 months (p = 0.0261), and median overall survival was 8.4 vs 12 months (p = 0.0548) with vs without prior cetuximab use, respectively. The objective response rate was 23.1 vs 25.9% (p = 0.8455), median progression-free survival was 1.8 vs 3.0 months (p = 0.6650), and median overall survival was 9.1 vs 9.9 months (p = 0.5289) with vs without neck dissection, respectively.

Conclusions: These findings support the use of nivolumab for patients with recurrent/metastatic head and neck cancer regardless of prior cetuximab use or neck dissection history.

Trial Registration Number: UMIN-CTR (UMIN000032600), Clinicaltrials.gov (NCT03569436).
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http://dx.doi.org/10.1007/s10147-021-01900-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8134300PMC
June 2021

Treatment outcomes of transoral robotic and non-robotic surgeries to treat oropharyngeal, hypopharyngeal, and supraglottic squamous cell carcinoma: A multi-center retrospective observational study in Japan.

Auris Nasus Larynx 2021 Jun 22;48(3):502-510. Epub 2021 Feb 22.

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

Objectives: The aim of this multicenter retrospective cohort study was to compare efficacy and subsequent postoperative treatment between transoral robotic surgery (TORS) and any non-robotic transoral surgery in Japanese patients with early oropharyngeal squamous cell carcinoma (OPSCC), hypopharyngeal SCC (HPSCC), or supraglottic SCC (SGSCC).

Materials And Methods: Clinical information and surgical outcomes were compared between patients with early-stage OPSCC, HPSCC, and SGSCC who underwent TORS (TORS cohort) and those who underwent non-robotic transoral surgery, including transoral videolaryngoscopic surgery (TOVS), endoscopic laryngopharyngeal surgery (ELPS), and transoral laser microsurgery (TLM) (non-robotic cohort). The data of the Head and Neck Cancer Registry of Japan (registry cohort) were used to validate the comparison. The main outcomes were the presence of positive margins under pathology and the requirement for postoperative therapy, including radiotherapy or chemoradiotherapy.

Results: Sixty-eight patients in the TORS cohort, 236 patients in the non-robotic cohort, and 1,228 patients in the registry cohort were eligible for this study. Patients in the TORS cohort were more likely to have oropharyngeal tumor disease and T2/3 disease than those in the other cohorts (P<0.001 and P=0.052, respectively). The TORS cohort had significantly fewer patients with positive surgical margins than the non-robotic cohort (P=0.018), as well as fewer patients who underwent postoperative treatment, although the difference was not significant (P=0.069). In the subgroup analysis of patients with OPSCC, a total of 57 patients in the TORS cohort, 73 in the non-robotic cohort, and 171 in the registry cohort were eligible for the present study. Patients with OPSCC who underwent TORS were more likely to have lateral wall lesions than those in the other cohorts (P=0.003). The TORS cohort also had significantly fewer patients with positive surgical margins than the non-robotic cohort (P=0.026), and no patients in the TORS cohort underwent any postoperative treatment for OPSCC, although the difference was not significant (P=0.177).

Conclusions: Our results suggest that TORS leads to fewer positive surgical margins than non-robotic transoral surgeries. The clinical significance of TORS may be further validated through the results of all-case surveillance for patients who underwent TORS running in Japan in the future.
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http://dx.doi.org/10.1016/j.anl.2021.01.024DOI Listing
June 2021

Prognostic Significance of Systemic Inflammatory Response in Cases of Temporal Bone Squamous Cell Carcinoma.

Laryngoscope 2021 08 4;131(8):1782-1789. Epub 2021 Feb 4.

Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Objective/hypothesis: Squamous cell carcinoma (SCC) of the temporal bone is an extremely rare condition. This rarity has led to a delay in the establishment of a standard treatment protocol and adequate staging system. Identification of prognostic markers of this disease from a variety of fields is desirable in the establishment of treatment guidelines for temporal bone SCC. The aim of this study is to assess the prognostic role of inflammation-based prognostic scores in cases of temporal bone SCC.

Study Design: Case reries with chart review.

Methods: A total of 71 cases of primary malignancy eligible for curative treatment at a single tertiary medical institute were retrospectively analyzed. Univariate and multivariate regression analyzes were used to investigate the association between the inflammation-based scores and 5-year overall survival.

Results: Univariate Cox regression analyzes showed that a high neutrophil-to-lymphocyte ratio, high platelet-to-lymphocyte ratio, low lymphocyte-to-monocyte ratio, a Glasgow prognostic score of 2, and the systemic inflammation score of 2 were significantly associated with a poor prognosis, as well as a classification of T4 stage, presence of cervical lymph node metastasis, high white blood cell counts, and high C-reactive protein levels. The multivariate analysis showed that a clinical stage of T4 and a systemic inflammation score of 2 were independent prognostic markers.

Conclusions: Inflammation-based prognostic markers are associated with the survival of patients with temporal bone SCC, as well as other head and neck SCCs.

Level Of Evidence: 4 Laryngoscope, 131:1782-1789, 2021.
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http://dx.doi.org/10.1002/lary.29421DOI Listing
August 2021

Volumetric changes of transferred free anterolateral thigh flaps in head and neck lesions.

Auris Nasus Larynx 2021 Aug 16;48(4):751-757. Epub 2021 Jan 16.

Department of Plastic and Reconstructive Surgery, Kyushu University Hospital, 1-1, 3-chome, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.

Objective: The purpose of this study was to clarify sequential volumetric changes of anterolateral thigh (ALT) flaps transferred to head and neck lesions.

Patients And Methods: We retrospectively analyzed volumetric changes in fat and muscle of 22 ALT flaps. We assessed "true" flap volume using the water-displacement method intraoperatively. Postoperative flap volume was assessed using three-dimensional volume-calculating software.

Results: The average duration until the entire flap volume decreased to its minimal size was 8.7 months. After 8.7 months, entire flap volume decreased to 47.4% of its initial intraoperative volume. The fat volume decreased to 62.5%, and the muscle volume decreased to 30.2%. The rate of muscle volume decrease was significantly larger than that of fat volume decrease (p<0.005). The only significant factor which affected entire flap volume decrease was the recipient site where the ALT flap was transferred (oral and pharyngeal lesions) (p=0.001), and the factor that affected fat volume decrease was postoperative body-weight loss (p=0.046).

Conclusion: To minimize the influence of postoperative ALT flap volume decrease, an ALT flap should mainly comprise fatty tissue, and its size should be 1.6-times larger (100/62.5) than the ideal volume intraoperatively. Maintaining the body weight is crucial to avoid ALT flap volume decrease.
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http://dx.doi.org/10.1016/j.anl.2020.12.006DOI Listing
August 2021

p16 overexpression and Rb loss correlate with high-risk HPV infection in oropharyngeal squamous cell carcinoma.

Histopathology 2021 Sep 6;79(3):358-369. Epub 2021 May 6.

Department of Anatomic Pathology, Kyushu University, Graduate School of Medical Sciences, Fukuoka, Japan.

Aims: p16 is a sensitive surrogate marker for transcriptionally active high-risk human papillomavirus (HR-HPV) infection in oropharyngeal squamous cell carcinoma (OPSCC), but it is not sufficient in all clinical settings.

Methods And Results: We examined the p16 and Rb expression status in 177 OPSCC cases by immunohistochemistry and the presence of transcriptionally active HR-HPV infection by mRNA in-situ hybridisation. The 177 cases were divided into p16 /HPV (n = 105, 59.3%), p16 /HPV (n = 8, 4.5%) and p16 /HPV (n = 64, 36.2%) groups. The p16 /HPV and p16 /HPV groups had a trend towards worse overall survival (OS) or significantly worse OS than the p16 /HPV group (n = 105) (P = 0.0610, P = 0.0004, respectively). We divided the Rb status into preserved expression (> 90%, n = 68), partial loss (PL) (10-90%, n = 97) and complete loss (CL) (< 10%, n = 12). Among the HPV-positive cases (n = 105), the Rb pattern was typically PL (n = 97, 92.4%) and rarely CL (n = 8, 7.6%), but never preserved expression (0%). In contrast, among the HPV-negative cases (n = 72), the Rb pattern was typically preserved expression (n = 68, 94.4%) and rarely CL (n = 4, 5.6%), but never PL (0%). Compared to p16 alone, the combination of p16 overexpression and Rb-PL/CL showed equally excellent sensitivity (each 100%) and improved specificity (97.2 versus 88.9%) and positive predictive values (98.1 versus 92.9%).

Conclusions: These results suggest that the combined use of p16 and Rb immunohistochemistry could be a reliable, cost-effective method to predict HR-HPV infection in OPSCCs; however, HPV specific testing is necessary on inconclusive cases. We propose a diagnostic algorithm for practical use of these markers.
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http://dx.doi.org/10.1111/his.14337DOI Listing
September 2021

Genomic Sequencing of Cancer-related Genes in Sinonasal Squamous Cell Carcinoma and Coexisting Inverted Papilloma.

Anticancer Res 2021 Jan;41(1):71-79

Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Background: The genetic basis of sinonasal inverted papilloma (SNIP)-derived squamous cell carcinoma (SCC) has not yet been well characterized.

Aim: To characterize the genetic abnormalities of SNIP and SNIP-derived SCC and to uncover their differences.

Materials And Methods: Mutations of 409 genes were analyzed using amplicon targeted sequencing in a total of six papilloma/carcinoma samples from four patients with SNIP-derived SCC.

Results: The genes that were mutated in multiple cases were epidermal growth factor receptor (EGFR) (3/6), cyclin-dependent kinase inhibitor 2A (CDKN2A) (3/6), lysine methyltransferase 2D (KMT2D) (3/6), tumor protein p53 (TP53) (3/6), neurofibromin 1 (NF1) (3/6), phosphodiesterase 4D interacting protein (PDE4DIP) (3/6), cytochrome P450 family 2 subfamily D member 6 (CYP2D6) (2/6), fms-related receptor tyrosine kinase 4 (FLT4) (2/6) and myosin heavy chain 9 (MYH9) (2/6). Of the two cases analyzed in the papilloma-oncology carcinoma pair, one did not have any common mutations; the other showed a staged functional deletion of TP53 during the process of malignant transformation from SNIP to SCC.

Conclusion: CDKN2A, KMT2D, NF1, PDE4DIP, CYP2D6, FLT4, and MYH9 were identified as candidate novel SNIP-derived SCC-related genes.
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http://dx.doi.org/10.21873/anticanres.14752DOI Listing
January 2021

Drug-induced interstitial lung disease in recurrent and/or metastatic head and neck cancer patients treated with cetuximab and/or nivolumab.

Oral Oncol 2021 02 22;113:105129. Epub 2020 Dec 22.

Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.

Background: Drug-induced interstitial lung disease (DI-IP) is one of the most serious adverse reactions associated with the use of anticancer drugs. DI-IP prevalence among molecular-targeting drugs and immune checkpoint inhibitors (ICIs) is relatively high in Japanese patients. To assess the risk of cetuximab and/or nivolumab-related IP is important.

Patients And Methods: The medical records of 138 patients with recurrent and/or metastatic head and neck squamous cell carcinoma treated with cetuximab-containing chemotherapy and/or nivolumab monotherapy were retrospectively reviewed.

Results: The incidence of DI-IP with R/M HNSCC was 7.2%. DI-IP occurred more frequently in patients treated with cetuximab-containing chemotherapy following nivolumab monotherapy than in patients with other regimens. However, tumor suppression was detected in all patients treated with cetuximab-containing chemotherapy following nivolumab monotherapy, and two achieved a complete response.

Conclusions: Although patients treated with cetuximab-containing chemotherapy following nivolumab showed dramatic efficacy, careful monitoring should be recommended.
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http://dx.doi.org/10.1016/j.oraloncology.2020.105129DOI Listing
February 2021

Effectiveness and safety of nivolumab in patients with head and neck cancer in Japanese real-world clinical practice: a multicenter retrospective clinical study.

Int J Clin Oncol 2021 Mar 21;26(3):494-506. Epub 2020 Nov 21.

Department of Otolaryngology, Head and Neck Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Kita15 Nishi7, Kita-Ku, Sapporo, Hokkaido, 060-8638, Japan.

Background: To fill the data gap between clinical trials and real-world settings, this study assessed the overall effectiveness and safety of nivolumab in patients with head and neck cancer (HNC) during Japanese real-world clinical practice.

Methods: This was a multicenter, retrospective study in Japanese patients with recurrent or metastatic HNC who received nivolumab for the first time between July and December 2017. Data on the clinical use, effectiveness, and safety of nivolumab were extracted from patient medical records.

Results: Overall, 256 patients were enrolled in this study. The median duration of nivolumab treatment was 72.5 days, with patients receiving a median of 6.0 (range 1-27) doses. Median overall survival (OS) was 9.5 (95% confidence interval [CI] 8.2-12.0) months and the estimated 12-month OS rate was 43.2%. The objective response rate (ORR) was 15.7% overall and 21.1%, 7.1%, and 13.6% in patients with primary nasopharynx, maxillary sinus, and salivary gland tumors, respectively, who had been excluded from CheckMate 141. Grade ≥ 3 immune-related adverse events occurred in 5.9% of patients. No new safety signals were identified compared with adverse events noted in CheckMate 141.

Conclusions: The effectiveness and safety of nivolumab in real-world clinical practice are consistent with data from the CheckMate 141 clinical trial. Therapeutic response was also observed in the groups of patients excluded from CheckMate 141.

Trial Registration Number: UMIN-CTR (UMIN000032600), Clinicaltrials.gov (NCT03569436).
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http://dx.doi.org/10.1007/s10147-020-01829-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7895797PMC
March 2021

Thoracoscopic esophagectomy in total pharyngolaryngoesophagectomy for esophageal cancer; A case series.

Ann Med Surg (Lond) 2020 Dec 12;60:9-13. Epub 2020 Oct 12.

Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Japan.

Background: Total pharyngolaryngoesophagectomy (TPLE) is associated with major complications and is extremely invasive. In 2011, our institution introduced thoracoscopic esophagectomy in the left hemi-prone position and laparoscopic reconstruction with a gastric tube in patients undergoing TPLE. Herein, we describe the use of this operative method in 26 patients, focusing on the technical aspects of the surgery.

Materials And Methods: From January 2011 to December 2018, 26 patients underwent minimally invasive TPLE with gastric tube reconstruction in our institute. The thoracoscopic procedure was performed with the patient in the semi-prone position. The patient was then moved to the supine position, and the laparoscopic procedure and pharyngolaryngectomy were started simultaneously. After pharyngolaryngectomy, microvascular anastomoses or free jejunal flap interposition were performed at the site of the gastric tube reconstruction. The data from these 26 patients were retrospectively analyzed.

Results: The median age was 66 years, and 3.8% of the patients were female. The Union for International Cancer Control stages of esophageal cancer were 0 ( = 2), I ( = 4), II ( = 7), III ( = 8), and IV ( = 5). Eight patients had concomitant esophageal cancer and head and neck cancer. Reconstruction with only a narrow gastric tube was used in 16 patients, while free jejunal flap interposition was used in 10 patients. The surgical procedures resulted in minimal complications. Postoperative complications of Clavien-Dindo grade ≥1 included anastomotic leakage in two patients and pneumonia in one.

Conclusion: Thoracoscopic esophagectomy in the left hemi-prone position and laparoscopic reconstruction with a gastric tube in patients undergoing TPLE was safe and effective. The complications were improved via the development of various procedures. Further improvement is necessary before this thoracoscopic approach is established as a standard procedure for TPLE.
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http://dx.doi.org/10.1016/j.amsu.2020.10.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567906PMC
December 2020

Clinicopathological features and immunohistochemical utility of NTRK-, ALK-, and ROS1-rearranged papillary thyroid carcinomas and anaplastic thyroid carcinomas.

Hum Pathol 2020 12 25;106:82-92. Epub 2020 Sep 25.

Department of Otorhinolaryngology, Kyushu University, Graduate School of Medical Sciences, Fukuoka, 812-8582, Japan. Electronic address:

NTRK1/3, ALK, and ROS1 translocations have been reported in a minor subset of papillary thyroid carcinomas (PTCs). We aimed to elucidate the prevalence and clinicopathological characteristics of these gene rearrangements and the utility of immunohistochemistry (IHC) in PTC and anaplastic thyroid carcinoma (ATC). We screened nonradiation-exposed cases of 307 PTCs and 16 ATCs by IHC for pan-Trk, ALK, and ROS1, followed by fluorescence in situ hybridization (FISH). In the PTC group, IHC for pan-Trk, ALK, and ROS1 was positive in 18 cases (5.9%), 1 case (0.3%), and 12 cases (3.9%), respectively. Among the pan-Trk IHC-positive cases (n = 18), 2 cases (11.1%; 0.7% of all PTCs) had NTRK1 or NTRK3 gene rearrangement with conventional PTC histology. The ALK IHC-positive case (n = 1) was the follicular variant of PTC with consistent ALK gene rearrangement. ROS1 gene rearrangement was not detectable in the ROS1 IHC-positive PTCs (0/12) by FISH. Most (approximately 70%) of the pan-Trk or ROS1 IHC-positive/FISH-negative cases had BRAF gene mutation with conventional PTC morphology. In the ATC group, neither ALK nor ROS1 IHC was positive, whereas pan-Trk IHC was positive in 1 case (6.3%) in which NTRK1 gene rearrangement was confirmed by FISH. These results suggest that NTRK, ALK, and ROS1 rearrangements are rare molecular events in nonradiation-exposed Japanese patients with PTC and ATC. Although IHC is not an entirely specific surrogate for these abnormalities and does not serve as a stand-alone companion diagnosis, the combined use of IHC and molecular testing may be helpful for determining promising therapeutic strategies with tyrosine kinase inhibitors.
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http://dx.doi.org/10.1016/j.humpath.2020.09.004DOI Listing
December 2020

Clinicopathologic Significance of EGFR Mutation and HPV Infection in Sinonasal Squamous Cell Carcinoma.

Am J Surg Pathol 2021 01;45(1):108-118

Departments of Anatomic Pathology.

Sinonasal squamous cell carcinoma (SNSCC) is sometimes associated with high-risk human papillomavirus (HR-HPV) infection and inverted sinonasal papilloma or oncocytic sinonasal papilloma. Frequent mutations of EGFR and KRAS are reported in inverted sinonasal papilloma-related sinonasal squamous cell carcinoma (ISP-SCC) and oncocytic sinonasal papilloma-related SNSCC, respectively. Here, we attempted to determine the prevalence and the prognostic significances of these alterations in SNSCC. We retrospectively collected 146 SNSCCs, including 14 ISP-SCCs, and comprehensively analyzed the HR-HPV infection by human papillomavirus (HPV)-RNA in situ hybridization, EGFR gene copy number gain (CNG) by chromogenic in situ hybridization, and gene mutations in EGFR and KRAS by Sanger sequencing. HR-HPV was detected in 11 cases (7.5%), whereas all 14 ISP-SCCs were negative. EGFR mutations were present in 21 (14.7%) of 143 SNSCCs, including 13/14 (92.9%) ISP-SCCs and 8/129 (6.2%) non-ISP-SCCs (P<0.0001). The majority of EGFR mutations were exon 20 insertions, with the remainder composed of deletions and single-nucleotide substitutions in exons 19 and 20. All of 142 SNSCCs harbored no KRAS mutation. EGFR CNG was detected in 41 (28.1%) of 146 SNSCCs; all of them were HPV negative and 3 had EGFR mutations. Collectively, EGFR mutation, EGFR CNG, and HR-HPV were essentially mutually exclusive, and each subgroup had distinct clinicopathologic features. The HPV-negative/EGFR-mutant group, the HPV-negative/EGFR CNG-positive group, and the triple-negative group had significantly worse prognoses than the HPV-positive group (P=0.0265, 0.0264, and 0.0394, respectively). In conclusion, EGFR mutation may play a pathogenetically important role in some populations of SNSCCs, especially ISP-SCCs. The molecular subclassification of SNSCCs may contribute to prognostic prediction and molecular-targeted precision medicine.
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http://dx.doi.org/10.1097/PAS.0000000000001566DOI Listing
January 2021

Prognostic Biomarkers of Salvage Chemotherapy Following Nivolumab Treatment for Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma.

Cancers (Basel) 2020 Aug 15;12(8). Epub 2020 Aug 15.

Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.

Recent studies have suggested the benefit of salvage chemotherapy (SCT) after immune checkpoint inhibitor (ICI) treatment for recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC). We retrospectively examined the outcome of SCT and the usefulness of the serum C-reactive protein level (CRP) and neutrophil-to-lymphocyte ratio (NLR) as prognostic biomarkers. Thirty-nine patients with R/M HNSCC were enrolled in this study. Twenty-five patients (64.1%) received combination chemotherapy of weekly paclitaxel and cetuximab (PC) as SCT, and 14 patients (35.9%) received tegafur-gimestat-otastat potassium (S1), an oral fluoropyrimidine. In all patients, the response rate, disease control rate, median progression-free survival (PFS), and median overall survival (OS) were 45.2%, 85.7%, 6.5 months, and 13.5 months, respectively. No chemotherapy-related deaths were observed. These PC groups had low CRP (<1.2 mg/dL) or low NLR (<7.0) values at the time of SCT induction, which was significantly associated with an improved OS ( = 0.0440, = 0.0354). A multivariate analysis also showed that a lower CRP value was significantly associated with a better OS ( = 0.0078). We clarified the usefulness of the PC and S1 regimens as SCT. In addition, SCT with the PC regimen showed a better prognosis with a lower CRP or NLR at induction than a higher CRP or NLR. This is the first report on biomarkers of SCT in R/M HNSCC.
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http://dx.doi.org/10.3390/cancers12082299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463840PMC
August 2020

Clinical outcome in recurrent and/or metastatic head and neck cancer patients after discontinuation of nivolumab monotherapy due to immune-related adverse events.

Acta Otolaryngol 2020 Dec 18;140(12):1043-1048. Epub 2020 Aug 18.

Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Background: Significant immune-related adverse events (irAEs) requiring therapy discontinuation sometimes occur. The influence of discontinuation on disease control after an irAE is unclear.

Objectives: The aim of this study was to investigate whether or not patients continued to show a response or durable disease control even after stopping therapy following an irAE.

Material And Methods: The response after nivolumab monotherapy discontinuation was examined for 14 patients in whom therapy was stopped without progression.

Results: The best response was CR in 5 (36%) patients, PR in 8 (57%) patients and SD in 1 (7%) patient. The estimated 1-year overall and progression-free survival rates were 92.9% and 78.6%, respectively. The best response during nivolumab therapy in patients who developed PD was CR in 0 of 5 patients (0%), PR in 3 of 8 patients (38%) and SD in 1 patient (100%). Patients obtaining CR tended to have a lower risk of PD than those with PR or SD.

Conclusions And Significance: Patients with CR status may continue to show a response or durable disease control even after stopping therapy due to an irAE.
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http://dx.doi.org/10.1080/00016489.2020.1807601DOI Listing
December 2020

Characterization of parotid gland tumors: added value of permeability MR imaging to DWI and DCE-MRI.

Eur Radiol 2020 Dec 1;30(12):6402-6412. Epub 2020 Jul 1.

Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka, 812-8582, Japan.

Objectives: To determine added value of permeability MRI in parotid tumor characterization to T2-weighted imaging (T2WI), semi-quantitative analysis of time-intensity curve (TIC), and intra-voxel incoherent motion diffusion-weighted imaging (IVIM-DWI).

Methods: This retrospective study was approved by the institutional review board, and the informed consent was waived. Sixty-one parotid tumors in 61 patients were examined using T2WI, IVIM-DWI, and permeability MRI. TIC patterns were categorized as persistent, washout, or plateau. Signal intensity ratio of lesion-to-muscle on T2WI, apparent diffusion coefficients (ADCs), D and f values from IVIM-DWI, and K, k, V, and V values from permeability MRI were measured. Multiple comparisons were applied to determine whether any differences among 4 histopathologic types (pleomorphic adenomas, Warthin's tumors, other benign tumors, and malignant tumors) existed. Diagnostic accuracy was compared before and after modification diagnosis referring to permeability MRI. In a validation study, 60 parotid tumors in 60 patients were examined.

Results: ADC and D values of malignant tumors were significantly lower than those of benign tumors other than Warthin's tumors, but higher than those of Warthin's tumors. k and V values of Warthin's tumors were significantly higher than those of malignant tumors. Multivariate analyses showed that TIC pattern, D, and k values were suitable parameters. McNemar's test showed a significant increase of sensitivity (11/12, 92%) and specificity (46/49, 94%) with adding k. The validation study yielded high sensitivity (14/16, 88%) and specificity (41/44, 93%).

Conclusion: Permeability MRI offers added value to IVIM-MRI and semi-quantitative TIC analysis of DCE-MRI in characterization of parotid tumors KEY POINTS: • Permeability MR imaging offers added value in the characterization of parotid gland tumors in combination with semi-quantitative TIC analysis and IVIM analyses with D parameter. • The combination of TIC pattern, D, and k might facilitate accurate characterization of parotid gland tumor, thereby avoiding unnecessary surgery for benign tumors or delayed treatment for malignant tumors. • A combination of permeability and diffusion MR imaging can be used to guide the selection of an appropriate biopsy site.
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http://dx.doi.org/10.1007/s00330-020-07004-3DOI Listing
December 2020

Amide proton transfer (APT) imaging of parotid tumors: Differentiation of malignant and benign tumors.

Eur J Radiol 2020 Aug 21;129:109047. Epub 2020 May 21.

Department of Health Sciences, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.

Purpose: To assess the usefulness of amide proton transfer (APT) imaging in differentiating parotid tumors.

Material And Methods: We retrospectively analyzed 43 histopathologically proven parotid solid tumors with diameters ≥2 cm. Twenty-one tumors were benign and 12 tumors were malignant. Two-dimensional APT imaging was performed using a saturation pulse with a duration of 2 s and a saturation power level of 2 μT. For acquiring Z-spectra, the imaging was repeated at 25 saturation frequency offsets from ω = -6 to +6 ppm with a step of 0.5 ppm as well as one scan acquired far off-resonance (-1560 ppm) for signal normalization. For the APT imaging, the asymmetry analysis at 3.5 ppm downfield from the water signal was calculated. The mean APT signal intensity (SI) was compared between the benign and malignant tumors.

Results: The mean APT SI was 2.23 ± 0.80 % in the benign tumors and significantly higher at 2.99 ± 0.99 % in the malignant tumors (P = 0.01). A receiver operating curve analysis revealed that the optimal APT SI threshold was 2.40 for distinguishing malignant tumors from benign tumors with an area under the curve of 0.74. The sensitivity, specificity, and accuracy were 83.3%, 61.3%, and 67.4%, respectively.

Conclusion: The mean APT SI of the malignant parotid tumors was significantly higher than that of the benign parotid tumors.
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http://dx.doi.org/10.1016/j.ejrad.2020.109047DOI Listing
August 2020

Therapeutic effect of Nivolumab for advanced / recurrent temporal bone squamous cell carcinoma.

Auris Nasus Larynx 2020 Oct 20;47(5):864-869. Epub 2020 May 20.

Department Otolaryngology Head and Neck Surgery, Kyushu University, 3-1-1 Maidashi, Fukuoka, Japan.

Objective: The immune checkpoint inhibitor Nivolumab was approved for the treatment of platinum-refractory head and neck squamous cell carcinoma (SCC), expanding the treatment options for recurrent or advanced head and neck SCC. However, since temporal bone squamous cell carcinoma (TB-SCC) is very rare cancer, the effectiveness of Nivolumab remains unclear. We investigated the effects of Nivolumab for TB-SCC.

Method: Chart information was collected for all patients who underwent the first administration of Nivolumab for recurrent or residual TB-SCC in our hospital between September 2017 and December 2019. Tumor staging followed the modified Pittsburgh classification. Changes in the tumor burden and survival outcome were examined.

Results: We examined 9 patients with recurrent or residual TB-SCC who started administration of Nivolumab. In these cases, recurrent or residual SCC was observed after chemotherapy and/or chemoradiotherapy including platinum. The duration of Nivolumab was 2-54 weeks (median 20.0 weeks). The evaluation of the therapeutic effect according to the RECIST method showed partial response in 1 case, stable disease in 2 cases, progressive disease in 4 cases, and size unevaluated in 2 case. Although the number of cases was small, comparing with 5 cases without Nivolumab, these cases showed longer overall survival (1-year OS 33.3% vs 20.0%).

Conclusion: We used Nivolumab as palliative chemotherapy in 9 patients with recurrent/residual TB-SCC, and we were able to obtain a certain therapeutic effect on TB-SCC as well as other head and neck SCC.
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http://dx.doi.org/10.1016/j.anl.2020.03.011DOI Listing
October 2020

A clinical analysis of sinonasal squamous cell carcinoma: a comparison of squamous cell carcinoma and squamous cell carcinoma arising from inverted papilloma.

Acta Otolaryngol 2020 Aug 13;140(8):706-711. Epub 2020 May 13.

Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Sinonasal squamous cell carcinoma (SCC) is a rare tumor arising either or in association with inverted papillomas (IPs). The aim of this study was to investigate and compare the oncological features and prognosis of patients with sinonasal SCCs based on their etiology. The medical records of 117 patients who had been diagnosed with SCC or those arising from IP (IP-SCC) were retrospectively reviewed. hybridization analyses to detect HPV 16/18DNA and p16 immunohistochemistry were also performed in 10 cases with IP-SCC. The three-year disease-specific survival (DSS) rate was higher in cases with T1, 2 and 3 than in cases with T4 in both tumor groups. T4 cases with SCC had a better DSS than those with IP-SCCs. HPV16/18 was not detected in any of the 10 IP-SCCs. T4 cases with SCC tended to have a better DSS than those with IP-SCC. Since some T4 patients with IP-SCC were found to have a highly aggressive disease, careful treatment planning should be performed. High-risk HPV may not play a vital role in the carcinomatous transformation of most IP-SCC cases.
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http://dx.doi.org/10.1080/00016489.2020.1758342DOI Listing
August 2020

Primary Advanced Squamous Cell Carcinoma of the Temporal Bone: A Single-Center Clinical Study.

Laryngoscope 2021 02 8;131(2):E583-E589. Epub 2020 Apr 8.

Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Objectives/hypothesis: The extreme rarity of temporal bone squamous cell carcinoma (TB-SCC) has delayed the accumulation of high-quality clinical evidence. For the purposes of retrospective meta-analysis in the future, a large dataset with information from various institutions would be ideal. Our objective here was to retrospectively review cases of TB-SCC encountered at a single tertiary referral center and explore survival outcomes and prognostic factors.

Study Design: Retrospective chart review.

Methods: The medical records of all TB-SCC cases were retrospectively reviewed. The resulting dataset contained 71 cases of primary cancer eligible for initial definitive (curative) treatment.

Results: T4 status was associated with lower disease-specific 5-year survival than T1 to T3 staging (T1: 100%, T2: 92%, T3: 86%, T4: 51%). Survival was significantly higher in operable than in inoperable cases, even when restricted to advanced (T3/T4) cancers. The tumor extension to the middle ear cavity was observed in 13/17 of T3 cases, but it was not associated with poor survival. In addition, among operable cases, negative surgical margins were associated with significantly higher survival than positive margins.

Conclusions: Definitive treatments can offer disease-specific 5-year survival of over 85% in T1 to T3 cases of TB-SCC. The tumor extension to the middle ear cavity is not associated with poor survival. T4 status, inoperability, nodal invasion, and positive surgical margin are identified as a predictor of poor prognosis. Still, the matter of how to deal with unresectable tumors remains an outstanding issue in the treatment of TB-SCC.

Level Of Evidence: 4 Laryngoscope, 131:E583-E589, 2021.
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http://dx.doi.org/10.1002/lary.28653DOI Listing
February 2021

Malignant perivascular epithelioid cell tumor mimicking jugular foramen schwannoma: A case report and literature review.

Heliyon 2020 Jan 17;6(1):e03200. Epub 2020 Jan 17.

Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Background: Perivascular epithelioid cell tumors (PEComas) of the skull base are extremely rare. Here we report the first description of a malignant PEComa mimicking jugular foramen schwannoma and presenting as Collet-Sicard syndrome, and we review the previous literature on PEComas of the head, neck and skull base.

Case Description: A 29-year-old woman presented with hoarseness, dysphagia, vomiting, and headache. She was first diagnosed with Collet-Sicard syndrome caused by thrombosis of the sigmoid and transverse sinuses. She was treated with anticoagulant therapy, and the hoarseness and paralysis of the accessory nerve improved. Later, at age 31, the hoarseness again worsened. At another hospital, enhanced computed tomography revealed a tumor in the jugular foramen extending to the neck and medially displacing the internal carotid artery. She was referred to our hospital for further examination and was diagnosed with jugular foramen schwannoma causing thrombosis of the sinuses. At the one-year follow-up, the tumor had grown rapidly and had started to surround the internal carotid artery. We therefore performed a tissue biopsy of the tumor in the jugular foramen and neck. Based on pathological analysis, we made a definitive diagnosis of malignant PEComa.

Conclusions: It may be extremely challenging to reach an accurate diagnosis of PEComa in the skull-base region, which can cause a delay in treatment initiation. When atypical clinical features for a skull-base tumor are found, we recommend preliminary biopsy to obtain a definitive diagnosis and initiate an appropriate treatment strategy as early as possible.
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http://dx.doi.org/10.1016/j.heliyon.2020.e03200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7002787PMC
January 2020

The effect of preventive oral care on postoperative infections after head and neck cancer surgery.

Auris Nasus Larynx 2020 Aug 7;47(4):643-649. Epub 2020 Feb 7.

Department of Otorhinolaryngology, Graduate School of Medical Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka City, Fukuoka, 812-8582, Japan.

Objective: This study aimed to investigate the incidence of postoperative pneumonia (PP) and surgical site infection (SSI) in head and neck cancer (HNC) patients and clarify the relationship between oral care and postoperative infection.

Methods: We conducted a retrospective observation survey based on the medical records of 209 HNC surgery patients managed at a University Hospital in 2016-2018. The incidence of PP and SSI were assessed in patients who underwent operations of the nose and paranasal sinuses to the larynx. Factors associated with PP and SSI in a univariate analysis were included in a multiple logistic regression analysis. A Cox proportional hazards model was used analyze the incidence of PP according to time after surgery. The present study was approved by the ethical review board of our Institute.

Results: The rates of PP and SSI in our study population were 20.5% and 23.0%. Operative time (P < 0.01), blood loss (P = 0.004), tracheostomy (P < 0.01), reconstruction (P < 0.01), and preoperative plaque control record (PCR) (P < 0.01) were significantly associated with PP. The PCR depicted the oral hygiene based on the percentage of plaque attached to the tooth neck. A multiple logistic regression analysis indicated that the incidence of PP was significantly higher in patients with PCR values of ≥50% after preoperative oral care (OR=10.174, 95% CI 2.14-48.32, P = 0.004). Tracheostomy (P < 0.01), reconstruction (P = 0.044), a lower preoperative albumin level (P = 0.019), and a lower preoperative hemoglobin level (P < 0.01) were significantly associated with SSI.

Conclusions: The incidence of PP among patients who received oral care was high in those patients with high PCR values, indicating the importance of increasing compliance to preoperative oral care.
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http://dx.doi.org/10.1016/j.anl.2020.01.001DOI Listing
August 2020

Larynx-preserving reconstruction after extended base of the tongue resection.

J Plast Reconstr Aesthet Surg 2020 Apr 28;73(4):740-748. Epub 2019 Nov 28.

Department of Otorhinolaryngology and Head and Neck Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Background: As the base of the tongue (BOT) plays essential roles in speech and swallowing, surgical resection of BOT cancer is typically avoided. Moreover, standard reconstructive procedures for larynx-preserving BOT defects have not yet been established. We performed immediate flap reconstruction after wide resection of BOT cancer with laryngeal preservation. Herein, the functional and oncological results of our strategy were analysed.

Methods: We retrospectively evaluated patients who underwent extended BOT resection (including the oral tongue, upper/lateral oropharyngeal wall, epiglottis and false vocal cord) with laryngeal preservation between April 2006 and April 2016. We classified defects involving the oral tongue or upper/lateral oropharyngeal wall as the lateral extension type and those involving the epiglottis or false vocal cord as the laryngeal extension type. Lateral extension-type defects were closed primarily and filled with a deepithelialised skin or muscle flap. Laryngeal extension-type defects were reconstructed using a bulky skin flap plus hyo-thyroid-pexy to create a neo-epiglottis. Postoperative functional and oncologic outcomes were assessed.

Results: We enrolled 18 patients with extended BOT defects. Of them, 11 had a history of irradiation. The tracheal cannula was removed in all cases, although laryngeal extension defects were associated with a longer duration to removal. All patients achieved complete oral intake and retained intelligible speech, with preservation of laryngeal function. There was no local recurrence, and the 5-year overall survival was 88.9%.

Conclusions: Following wide BOT resection, reconstruction with laryngeal preservation is feasible even in cases involving irradiated tumours with laryngeal extension.
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http://dx.doi.org/10.1016/j.bjps.2019.11.018DOI Listing
April 2020
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