Published papers

Traumatic optic neuropathy often occurs as a complication of head and mid facial injury, and can cause permanent impairment of the visual acuity. From previous studies, optic nerve decompression surgery has been recommended for cases of traumatic optic neuropathy with optic nerve canal fracture. However, the indications for this surgery still remain controversial. Moreover, optic nerve canal fracture cannot be detected even by computed tomography (CT) in some cases. Patients diagnosed as having traumatic optic neuropathy with optic nerve canal fracture are treated by endoscopic optic nerve decompression surgery and steroid administration, by otorhinolaryngologist in collaboration with neurosurgeons and ophthalmologists at Keio University Hospital. Six patients were treated between May 2015 and May 2017. They ranged in age from 17 to 78 years old, and the intervals from injury to surgery ranged from 19 hours to 6 days. Five patients had injury of the outer half of the eyebrows. Preoperative CT revealed optic canal fracture in only 3 cases, whereas intraoperatively, all 6 cases were detected to have fracture. Preoperative visual acuity was hand motion or better in 4 patients, and no light perception in 2 patients. The visual acuity improved postoperatively in 5 patients. No improvement was observed in the patient who underwent surgery 6 days after the injury. Blunt injury on the outer half of the eyebrow was a useful clue for the diagnosis of optic nerve canal fracture, especially in cases where it could not be detected by CT. In cases of traumatic optic neuropathy with optic nerve canal fracture, early decompression of the optic canal and steroid administration play a key role in the recovery of the visual acuity.

Surgical removal of pterygopalatine fossa (PPF) tumors with endoscopic endonasal approach is still challenging. The present study aimed to evaluate our endoscopic endonasal management of PPF tumors based on the tumor pathology and purpose of the surgery. This comprised both a single nostril approach for biopsy and a binostril approach for complete resection of benign and noninfiltrating tumors. Based on this strategy, 12 patients underwent endoscopic endonasal surgery for PPF tumors between 2013 and 2018. The patients' data were analyzed retrospectively to demonstrate the significance of our treatment scheme. The surgery was terminated only after taking a biopsy specimen in 6 patients. Other 6 patients underwent gross total resection or bulk tumor reduction. Final pathological diagnosis was malignant in 6 cases and benign in the remaining 6. Post-operative treatment was needed in 7 patients. Four operations for the 6 patients who underwent either debulking or radical surgery were performed by the binostril approach; while 5 surgeries for the 6 biopsy patients were performed by the single nostril approach. Postoperative complications were tolerable. Endoscopic resection should be adopted preferentially for benign tumors that can be removed in a piecemeal fashion. However, as most malignant tumors were impossible to resect with a negative margin, priority should be given to tumor biopsy using an endoscopic approach, which is less invasive than an open approach, and an appropriate treatment customized to the pathological diagnosis should be administered.

Background: Ossifying fibroma arising in the sinonasal tract is rare. Its treatment includes complete resection; however, this can be challenging to perform due to the well-vascularized nature of the fibroma. Some surgical techniques can control intraoperative hemorrhage; however, to date, no reports have assessed the use of preoperative embolization. Methods: We report a case of a child with ossifying fibroma arising from the ethmoid sinus, which was resected by endoscopic surgery using preoperative transarterial embolization. Conclusions: Embolization was effective in decreasing intraoperative hemorrhage. No complications related to the procedure or operation were encountered. Preoperative embolization should be considered for better control of the bleeding that occurs in ossifying fibromas, similar to that in other well-vascularized tumors.

When treating advanced thyroid cancer cases with Lenvatinib, most of these patients are old and we sometimes hesitate to administer the drug to elderly cases. We have experienced administering low-dose Lenvatinib to aging patients who were over 80 years old. The first case was a 92-year-old man. He was administered 10mg of Lenvatinib at the outpatient clinic, could continue the treatment without serious side effects, and maintained PR for one year. The second case was an 86-year-old female. She had an obstructed airway due to tumor invasion. Due to her poor general condition, we decided to start with 4 mg of Lenvatinib. The trachea-invading tumor shrank, and she was able to stay at home, but eventually died when the tumor progressed. Low-dose Lenvatinib administration was shown to be tolerated and to reduce side effects even in the elderly. This treatment, however, may have insufficient antitumor effects. The organ function, social status, and living environment of older adults are varied, so we should decide the administration dose and method according to the condition of each case.

Objective: The histological grade of parotid gland carcinoma (PGC) is an important prognostic factor; however, the diagnosis prior to treatment has been challenging to make. This study aimed to investigate whether the pretreatment clinical findings, including hematological inflammatory, nutritional, and immune markers, could predict the histological grade of PGC. Study Design: Retrospective study. Methods: We retrospectively enrolled 111 patients with PGC and evaluated the correlation between histological grade and pretreatment clinical findings such as age, sex, tumor staging, facial nerve paralysis, pain or tenderness, adhesion to the surrounding tissues or tumor immobility, and hematological markers. Results: Sixty patients (54%) were diagnosed with histological high-grade PGC. Univariate analysis revealed that age, T classification, N classification, TNM stage, facial nerve paralysis, adhesion/immobility, C-reactive protein (CRP), and CRP-to-albumin ratio (CAR) were significant predictors of PGC histological grade. On multivariate analysis, high T classification (T3, 4), high N classification (≥1), and elevated CRP (≥0.22 mg/dL) were independent predictors of high-grade PGC. Conclusions: Pretreatment T classification, N classification, and CRP are significant predictors of the histological grading of PGC. Our results are useful for treatment planning and obtaining appropriate informed consent from the patients before treatment. Level of Evidence: 4 Laryngoscope, 132:96–102, 2022.

Objective: Previous studies have evaluated various markers as prognostic predictors in patients with many types of cancers. However, the influence of such factors on the outcomes of patients with parotid gland carcinoma (PGC) is unknown. This study investigated the roles of alternative markers in the prognoses of patients with PGC. Methods: Overall, 101 patients who underwent curative treatment for PGC were retrospectively evaluated, and their 5-year overall and disease-free survival rates were calculated. The prognostic values of clinical and pathologic factors were determined. Results: The 5-year overall and disease-free survival rates were 73.1% and 62.8%, respectively. Multivariate analysis revealed that a low lymphocyte-to-monocyte ratio (LMR), high T classification, high N classification, and perineural invasion were independent predictors of poor prognosis. Conclusions: Thus, we identified LMR as an independent prognostic factor for patients with PGC. Patients with low LMRs who are amenable to treatment may require adjuvant treatment to improve their prognoses. Level of Evidence: 4 Laryngoscope, 131:E864–E869, 2021.

Background: One of the major complications in endoscopic endonasal skull base surgery (EESBS) is postoperative cerebrospinal fluid (CSF) leaks. Recently, EESBS has been applied to various skull base diseases as well as more complicated cases influenced by previous treatment with or without various comorbidities. Aims/objectives: This study aimed to assess the factors that influence the results of postoperative CSF leak after EESBS with mixed patient backgrounds. Materials and methods: We conducted a retrospective analysis of the clinical records of patients undergoing EESBS in our institution from 2012 to 2017. Results: Out of a total of 230 cases of EESBS, 11 (4.8%) suffered from postoperative CSF leakage. The rate of CSF leakage for pituitary adenoma, Rathke’s cleft cyst, chordoma, and meningioma was 3.5%, 0%, 3.6% and 8.0%, respectively. Multiple variate analysis revealed that repeated surgery (p =.008) and intraoperative CSF leak (p =.044) were significant risk factors for postoperative CSF leakage. Conclusions and significance: The rate of postoperative CSF leakage in this study was comparable to previous reports, and repeated surgery may increase postoperative CSF leakage. The surgical strategy for tumor removal as well as skull base reconstruction should be given careful consideration according to tumor pathology and the patient’s condition.

Cyclooxygenase-2 (Cox-2) has been shown to promote cancer initiation and progression through pleiotropic functions including induction of epithelial-to-mesenchymal transition (EMT) via its predominant product prostaglandin E2 that binds to the cognate receptor EP2. Hence, pharmacological inhibition at the level of EP2 is assumed to be a more selective alternative with less risk to Cox-2 inhibition. However, little is known regarding the anti-cancer effect of an EP2 antagonist on the malignant properties of cancers including hypopharyngeal squamous cell carcinoma (HPSCC). The present study found that both the Cox-2 inhibitor celecoxib and the EP2 antagonist PF-04418948 upregulated CDH-1 expression, restored membranous localization of E-cadherin, and reduced vimentin expression, by downregulating the transcriptional repressors of E-cadherin in BICR6 and FaDu cells. Such Cox-2 or EP2 inhibition-induced EMT reversal led to repressed migration ability in both cells. Immunohistochemical analysis of surgical HPSCC specimens demonstrated an inverse relationship in expression between Cox-2 and E-cadherin both in the context of statistics (P = 0.028) and of reciprocal immunolocalization in situ. Multivariate logistic regression revealed that overexpression of Cox-2 (P < 0.001) and downregulation of E-cadherin (P = 0.016) were both independently predictive of neck metastasis. These results suggest that suppression of cell migration ability via reversing EMT by inhibiting the Cox-2/EP2 signaling may contribute to preventing the development and progression of lymphatic metastasis. Collectively, targeting Cox-2/EP2, especially using EP2 antagonist, can be a promising therapeutic strategy by exerting an anti-metastatic effect via EMT reversal for improving the treatment outcomes of patients with various cancers including HPSCC.

This paper presents an extremely rare case of synovial sarcoma arising from the maxillary sinus, which resulted in a clinically complete response to chemotherapy. Synovial sarcoma is a rare soft tissue malignant tumor, most commonly affecting the extremities. While ∼10% occur in the head and neck region, synovial sarcoma of the sinonasal tract is extremely rare, with only 11 cases having been reported previously. As with other sarcomas, the standard treatment is complete resection while allowing for a safe margin, but this is often difficult in the head and neck area due to the complicated anatomy there. This makes the treat­ment of head and neck sarcoma challenging and leads to the need for a multimodal approach in advanced cases. However, the exact efficacy of chemotherapy is not well understood. In this report, we present a case of unresectable maxillary sinus synovial sarcoma that was success­fully treated by chemotherapy followed by radiation therapy. A 53-year-old Japanese man was referred to our hospital with a history of left nose obstruction over the previous couple of years. Computed tomography/magnetic resonance imaging revealed a tumor arising from the maxillary sinus that extended to adjacent tissues. A biopsy was performed, and the tumor was diagnosed as synovial sarcoma. Since the tumor was unresectable, neoadjuvant chemotherapy was administered. The response was excellent, and the tumor became undetectable under endoscopy and radiological imaging. This provided us with a clinical evaluation of “complete response”. The treatment was concluded with definitive radiotherapy and two more cycles of adjuvant chemotherapy. The patient remains free of disease 12 months after treatment. Synovial sarcoma of the head and neck is a rare entity; complete resection is the treatment of choice but (neo)adjuvant chemotherapy can be considered in unresectable cases, as we show here in the present case.

Background: Induction chemotherapy (IC) for head and neck cancer (HNC) often causes severe side-effects. However, it has still been challenging to predict the adverse events. The present study aimed to evaluate the role of hematological inflammatory markers in predicting severe side-effects caused by IC. Materials and Methods: A total of 54 HNC patients who underwent IC were enrolled. The association between severe side-effects and pre-treatment hematological inflammatory markers [the C-reactive protein (CRP) to albumin ratio (CAR), the modified Glasgow Prognostic Score (mGPS), the neutrophil-to-lymphocyte ratio (NLR), and the platelet-to-lymphocyte ratio (PLR)] were evaluated. Results: In the univariate analysis, the incidence of whole severe side-effects (grade 4), febrile neutropenia (above grade 3), and hyponatremia (above grade 3) were significantly higher in the high CAR and high GPS groups. Multivariate analysis revealed that high CAR and mGPS were independent predictors of these side-effects. Conclusion: CAR and mGPS were significant predictors of severe side-effects. These data can potentially offer patients an improved quality of life during cancer therapy.

Teratocarcinosarcoma is a rare, highly malignant tumor, that occurs mainly in the nasal cavity and paranasal sinuses. The prognosis is poor because the tumor invades the surrounding tissues even from an early stage. We report a case of sinonasal teratocarcinosarcoma that was treated by transnasal endoscopic skull base surgery and radiotherapy. The patient was a 65-year-old man who presented with a 2-month history of recurrent left epistaxis. Examination revealed a mass in the left nasal cavity. Computed tomography (CT) revealed a tumor extending from the left ethmoid sinus to the sphenoid sinus, and bone destruction of the anterior skull base. Magnetic resonance imaging (MRI) revealed intracranial extension of the tumor, but no apparent invasion of the brain parenchyma. Biopsy findings led to the suspicion of olfactory neuroblastoma. Since an olfactory neuroblastoma was suspected by biopsy and the possibility of invasion of the brain parenchyma was low, we performed endoscopic endonasal skull base surgery. The tumor was resected with the bone of the skull base and the dura. The skull base was reconstructed with the skull periosteum, fascia lata, and a nasal septum flap. Postoperative histopathological examination revealed the diagnosis of teratocarcinosarcoma. Therefore, after the surgery, the patient received radiotherapy. One year and ten months after the radiotherapy, metastasis to the left cervical lymph nodes was found, and neck dissection was performed. A follow-up examination at 4 years after the radiotherapy showed no evidence of local recurrence or distant metastases to other organs. It was difficult to confirm the histological diagnosis before surgery, and the diagnosis could be confirmed only by histopathology of the resected tumor specimen. The main treatment modality for teratocarcinosarcoma is surgical excision. However, teratocarcinoma is a highly malignant tumor, and radiotherapy and chemotherapy may be useful in addition to surgery, to obtain a better prognosis.

Carcinoma of the external auditory canal is a rare tumor, accounting for about 1% of all head and neck cancers. Although no treatment method has been established yet, surgical treatment is the primary treatment method in cases where resection is possible. At our institution, we adopt surgical treatment, mainly lateral temporal bone resection （LTBR）, for cases with T1―T3 disease, and chemoradiation therapy（CCRT）for cases with T4 disease, as the treatment of first choice. We have adopted cartilage conduction hearing aids（CC―HAs）in some cases following LTBR. We examined the short―term outcomes, at two years, in the patients treated at our department. This study was a retrospective case review of 22 ears with carcinoma of the external auditory canal in 21 patients who underwent initial treatment at our institution between January 2012 and June 2018. The observation period was 2 to 81 months（median 26 months）. The tumors were analyzed using the modified Pittsburgh tumor staging system. The tumor T stage was T1 in four ears, T2 in nine ears, T3 in six ears, and T4 in three ears. CCRT was performed in three ears with T4 disease and one ear with T2 disease, heavy ion radiotherapy was performed in one ear with T2 disease, and surgery（LTBR in 16 ears and partial external auditory meatus resection in one ear）was performed for all the other cases. The surgical margin after LTBR was positive in three out of six cases with T3 disease and negative in all of the cases with T1 and T2 disease. The positive surgical margin was mainly found in the medial wall of the tympanic cavity or cartilaginous portion of the external acoustic meatus. The overall 2―year survival rate was 87.4%; the rate was 100% in the T1 cases, 87.5% in the T2 cases, 75.0% in the T3 cases, and 100% in the T4 cases. Four out of five patients who tried CC―HAs continued to use them after the LTBR. The indication for LTBR should be carefully judged in cases with T3 disease. The appropriate indication for LTBR in cases with T3 disease are: 1）a small amount of soft tissue shadow beyond the tympanum in the preoperative CT, and/ or 2）a clear boundary between the tumor and the soft tissue around the external acoustic meatus in the preoperative enhanced MRI. In cases with T3 disease not fulfilling these criteria, CCRT should be selected as the treatment of first choice. However, considering the side effects after CCRT, including sensorineural hearing loss and persistent otorrhea in some cases, LTBR with postoperative CC―HAs is one of the optimal treatment options that would allow the remaining hearing ability to be utilized.

Background: Because the incidence of schwannoma arising from the parapharyngeal space (PPS) is very low, no studies have analyzed extirpation methods and postoperative neurological complications exclusively in PPS schwannomas. Methods: The preoperative diagnosis and clinical outcomes of surgical treatment in 21 patients with PPS schwannoma who underwent surgery were investigated. Results: Neurological deficit of the involved nerve developed in all patients regardless of the extirpation method used. However, the incidence of first bite syndrome in sympathetic chain schwannoma was significantly lower after intracapsular enucleation (40%) than after total resection (100%; P =.045). Furthermore, the incidence of postoperative complications unrelated to the involved nerve was lower after intracapsular enucleation (0%) than after total resection (42.9%; P =.055). Conclusion: Although postoperative neurological deficit of the involved nerve was unavoidable in PPS schwannoma, intracapsular enucleation could be beneficial by reducing its severity and the incidence of complications unrelated to the involved nerve.

Background: This study aimed to investigate p16 and COX2 expression in oropharyngeal squamous cell carcinoma (OPSCC), and evaluate the prognostic role of COX2 expression under the new TNM classification. Materials and Methods: Biopsy specimens obtained from 75 patients with OPSCC were stained for p16 and COX2 expression immunohistochemically. The results and clinical records were analyzed retrospectively. Results: Fifty-nine patients (79%) were positive for p16. COX2 expression was correlated with poor relapse-free survival in patients overall, and in p16-positive patients. Smoking was positively associated with COX2 expression. Moreover, both positive COX2 expression and anterior wall tumor subsite were independently correlated with lymph node metastasis, which was the only independent prognostic factor in p16-positive OPSCC. Conclusion: The p16-positive rate in this study was comparable with that in the USA and Europe, and higher than that in other Asian countries. COX2 expression might affect the prognosis of p16-positive OPSCC through promoting lymph node metastasis.

Cyclooxygenase‑2 (COX‑2) is one of the two isoforms of COX, an enzyme that catalyzes the conversion of arachidonic acid to prostaglandins. COX‑2 is associated with the progression in various types of cancer, and its expres‑ sion has been associated with a poor prognosis in head and neck squamous cell carcinoma (HNSCC). Furthermore, COX‑2 expression has been associated with resistance to anticancer drugs. However, the precise mechanism of COX‑2 for chemoresistance in HNSCC has not been fully elucidated. The present study aimed to investigate the effect of COX‑2 on cancer stem cell (CSC) property and to reveal its effect on chemoresistance using in vitro and clinicopathological assays in HNSCC cells and tissues. The current study analyzed the immunohistochemical expression levels of COX‑2 and clinicopathological factors using matched samples of pretreatment biopsy and surgical specimens from patients with hypopharyngeal carcinoma who underwent tumor resec‑ tion with preoperative chemotherapy, including docetaxel. Additionally, the chemoresistance to docetaxel with or without a COX‑2 inhibitor (celecoxib) was examined in HNSCC cell lines by MTS assays. To evaluate the association of COX‑2 expression with stemness property, the expression levels of CSC‑associated genes after exposure to celecoxib were assessed by reverse transcription‑quantitative PCR. A sphere formation assay was also performed using ultra‑low attachment dishes and microscopic imaging. The immunohistochemical analysis of biopsy specimens revealed a negative association between COX‑2 expression in biopsy specimens and the pathological effect of induction chemotherapy in surgical specimens. The cell survival rate under exposure to docetaxel was decreased by the addition of celecoxib. COX‑2 inhibition led to downregulation of CSC‑associated gene expression and sphere formation. The present findings suggested that COX‑2 expression may be associated with chemoresistance through the cancer stemness property, and inhibition of COX‑2 may enhance chemo‑sensitivity in HNSCC. Therefore, COX‑2 may be an attractive target for the treatment of HNSCC.