Published papers

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, 2021.

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.

Purpose: Carotid artery invasion by metastatic lymph nodes in head and neck squamous cell carcinoma (HNSCC) is one of the diagnostic criteria for unresectable tumors. However, to date, the diagnostic criteria for carotid artery invasion have not been well documented. This study investigated the utility of computed tomography (CT) findings as a predictor of carotid artery invasion by metastatic lymph nodes in HNSCC. Methods: Twenty-eight patients who had metastatic lymph nodes of HNSCC attached to the carotid artery as seen on CT images before neck dissection from January 2011 to November 2017 were included. Five imaging parameters (angle of contact [AC], length of contact [LC], haziness of the carotid artery wall [HW], size of the lymph node, and involvement of the bifurcation of the carotid artery [IB]) were assessed using CT to predict carotid artery invasion. Furthermore, the utility of the combination of these five parameters was evaluated. Results: There were significant differences in AC, LC, and IB between patients with and without carotid artery invasion. There were significant differences in all combinations of the two image findings between patients with and without carotid artery invasion. In particular, the combinations of LC and HW, and LC and IB could clearly predict carotid artery invasion. Conclusion: AC, LC, and IB were useful predictors of carotid artery invasion of metastatic lymph nodes in HNSCC. This study is the first to report that IB is a useful predictor of carotid artery invasion in HNSCC.

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.

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.

Carotid body tumor (CBT) is classified as a paraganglioma (PGL). Here, we report the genetic background, protein expression pattern, and clinical findings of 30 Japanese CBT cases. Germline pathogenic or likely pathogenic (P/LP) variants of genes encoding succinate dehydrogenase subunits (SDHs) were detected in 15 of 30 cases (50%). The SDHB variants were the most frequently detected, followed by SDHA and SDHD variants. One case with SDHAF2 variant was bilateral CBT, and other two multiple PGL cases were not detected P/LP variants. The three cases with germline variants that could be tested did not have somatic P/LP variants of the same genes. Immunohistochemical analysis showed negative SDHB signals in CBT tissues in five cases with germline P/LP variants of SDHB, SDHD, or SDHA. In addition, SDHB signals in CBT tissues were negative in four of nine cases without germline P/LP variants of SDHs. These findings suggest the involvement of unidentified molecular mechanisms affecting SDHs.

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.

Purpose: Lenvatinib achieves favorable therapeutic outcomes for patients with radioactive iodine therapy refractory differentiated thyroid cancer (DTC); however, its use is associated with a high incidence of adverse events. To avoid severe adverse events, planned drug holidays (PDH) have been proposed. This study aimed to evaluate treatment effects, identify prognostic factors, and investigate the usefulness of PDH in patients with unresectable DTC who received lenvatinib across the multi-institutions. Methods: Fifty-one patients with unresectable DTC treated with lenvatinib were evaluated retrospectively. Overall survival (OS) and progression-free survival (PFS) were calculated, and prognostic factors were assessed. OS, PFS, and time to treatment failure (TTF) were compared between patients with and without PDH. Lenvatinib administration schedule was evaluated in PDH. Results: The 3-year OS and PFS rate were 53.5% and 42.1%, respectively. Multivariate analysis revealed that presence of maximum size of lung metastasis ≥10 mm was independent prognostic factor for poorer OS and PFS, and histology other than papillary thyroid carcinoma was the independent prognostic factor for poorer PFS. Twenty-five patients (49%) treated with PDH. There were significant differences in OS, PFS, and TTF between patients with and without PDH. Various schedules were used in PDH. Eight (32%) patients required switch to the different administration schedule. Conclusion: Our results suggest that PDHs may extend OS, PFS, and TTF. In patients with PDH, various schedules used for lenvatinib administration highlight the difficulty in determining a uniform administration schedule. Therefore, it is crucial to consider the optimal lenvatinib administration schedule on a case-by-case basis.

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.