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1.
Nutr Cancer ; 76(2): 149-159, 2024.
Article in English | MEDLINE | ID: mdl-38066722

ABSTRACT

The sarcopenia index (SI), calculated as [(serum creatinine/serum cystatin C) × 100], maybe a simpler alternative for measuring muscle mass than computed tomography (CT) and bioelectrical impedance analysis (BIA). We enrolled 112 patients with head and neck cancers (HNC). The correlation of the SI with muscle surface area measured by CT (CTMSA, n = 82) and muscle mass by BIA (BIA-MM, n = 41) was tested. Cutoff values were set for SI, CTMSA, and BIA-MM. Overall survival (OS) was compared between the high- and low-SI/CTMSA/BIA-MM groups. The SI was correlated with CTMSA (r = 0.43) and BIA-MM (r = 0.52). The optimal cutoff values of SI, CTMSA, and BIA-MM were 76.1 (area under the curve [AUC] = 0.67), 129.2 (AUC = 0.59), and 46.1 (AUC = 0.62), respectively. OS was significantly lower in the low-SI group (78% at 1 year and 69% at 2 years) than in the high-SI group (94% at 1 year and 86% at 2 years; p = 0.006). There was no significant difference in OS between the low-and high-CTMSA and -BIA-MM groups. The SI, which only requires a blood sample, is a useful marker of muscle mass that correlates with short-term prognosis in patients with HNC.


Subject(s)
Head and Neck Neoplasms , Sarcopenia , Humans , Sarcopenia/diagnosis , Sarcopenia/etiology , Squamous Cell Carcinoma of Head and Neck , Prognosis , Electric Impedance , Muscle, Skeletal/diagnostic imaging , Body Composition/physiology
2.
Int J Clin Oncol ; 29(8): 1133-1141, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38727853

ABSTRACT

BACKGROUND: As a substantial waiting time is usually required for radical surgery, safe and effective preoperative neoadjuvant chemotherapy (NAC) is desired for the treatment of locally advanced head and neck squamous cell carcinoma (HNSCC). However, the significance of NAC in advanced HNSCC is still unclear. This study aimed to assess the safety and efficacy of NAC using the paclitaxel, carboplatin, and cetuximab (PCE) regimen. METHODS: We retrospectively evaluated the background characteristics, incidence of adverse events, overall response rate (ORR), pathological response, recurrence-free survival (RFS), and overall survival (OS) in 26 patients. Patients receiving the PCE regimen were further divided into two groups based on the number of chemotherapy cycles (one cycle or more) and eligibility for cisplatin. Patients aged ≥ 75 years and those with an estimated glomerular filtration rate (eGFR) < 60 mL/min were classified as ineligible for cisplatin. RESULTS: The median age was 70 (27-81) years. The median eGFR at treatment initiation was 63.2 (41.1-89.7) mL/min. Fourteen (53.8%) patients were ineligible for cisplatin. Grade 3 or higher neutropenia was observed in 11 of 25 (42.3%) patients. No delay in or withdrawal from surgery was observed. The ORR was 65.4%. The 2-year RFS and OS were 61.5% and 76.7%, respectively. No significant differences in safety and efficacy between the number of chemotherapy cycles and cisplatin eligibility were observed. CONCLUSION: NAC using the PCE regimen for patients with locally advanced HNSCC, including cisplatin-ineligible patients, has acceptable toxicity and favorable efficacy.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Carboplatin , Cetuximab , Head and Neck Neoplasms , Neoadjuvant Therapy , Paclitaxel , Squamous Cell Carcinoma of Head and Neck , Humans , Cetuximab/administration & dosage , Cetuximab/adverse effects , Cetuximab/therapeutic use , Aged , Male , Female , Carboplatin/administration & dosage , Carboplatin/therapeutic use , Carboplatin/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Retrospective Studies , Paclitaxel/administration & dosage , Paclitaxel/therapeutic use , Paclitaxel/adverse effects , Middle Aged , Squamous Cell Carcinoma of Head and Neck/drug therapy , Squamous Cell Carcinoma of Head and Neck/pathology , Squamous Cell Carcinoma of Head and Neck/mortality , Aged, 80 and over , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/pathology , Adult
3.
Int J Clin Oncol ; 29(1): 20-26, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37843751

ABSTRACT

BACKGROUND: The optimal chemotherapy regimen in concurrent chemoradiotherapy (CCRT) for cisplatin-ineligible head and neck squamous cell carcinoma (HNSCC) has not been established. We aimed to evaluate the feasibility, efficacy, and safety of CCRT with weekly low-dose carboplatin for the treatment of advanced HNSCC in patients who are cisplatin-ineligible. METHODS: This prospective phase II study enrolled adult patients (age ≥ 20 years) with HNSCC receiving whole-neck irradiation including bilateral levels II-IV and who were aged (≥ 75-year-old patients with 40 mL/min estimated glomerular filtration rate [eGFR] or better) or had renal dysfunction (< 75-year-old patients with 30-60 mL/min eGFR). Carboplatin was administered weekly (area under the plasma concentration-time curve = 2.0) for up to seven cycles during concurrent radiotherapy (70 Gy/35 Fr). The primary endpoint was the completion rate of CCRT. Secondary endpoints included overall response rate and incidence of adverse events. RESULTS: Among the 30 patients enrolled, 28 were men. The median age was 73.5 years. Seventeen patients were < 75 years whereas 13 were ≥ 75 years old. The completion rate of CCRT was 90%. The overall response rate was 90%. Grade 3 adverse events that occurred in 10% or more patients were oral/pharyngeal mucositis (47%), leukocytopenia (20%), and neutropenia (10%). Grade 4 adverse events occurred in one patient (elevation of alanine aminotransferase level). No treatment-related deaths occurred. CONCLUSION: CCRT with weekly low-dose carboplatin is a promising treatment option, with favorable feasibility, efficacy, and acceptable toxicity, for patients who are cisplatin-ineligible with advanced HNSCC. CLINICAL TRIAL REGISTRATION NUMBER: jRCTs031190028.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Adult , Male , Humans , Aged , Female , Cisplatin , Squamous Cell Carcinoma of Head and Neck/drug therapy , Carboplatin , Prospective Studies , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/radiotherapy , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/radiotherapy , Chemoradiotherapy , Antineoplastic Combined Chemotherapy Protocols/adverse effects
4.
Eur Arch Otorhinolaryngol ; 281(4): 2037-2040, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38308762

ABSTRACT

INTRODUCTION: Immune-related adverse events (irAEs) due to immune checkpoint inhibitors may lead to discontinuation and treatment-related death. Acute aortitis is a rare but severe irAE. CASE PRESENTATION: A 67-year-old man with recurrent lower gingival carcinoma received nivolumab therapy. Twenty-three months later, he experienced chest compression, which resulted in syncope. Following a whole-body computed tomography (CT) scanning, which revealed diffuse thickening of the aorta, and systemic assessments of the causes of aortitis, he was diagnosed with acute aortitis due to irAE. Nivolumab discontinuation and oral steroids improved CT findings. However, 11 months after nivolumab discontinuation, he developed an aortic aneurysmal rupture. Endovascular aortic repair rescued him. A durable anti-cancer response was still observed 4 months after the aortic rupture. CONCLUSION: Although severe irAE, such as acute aortitis, occurred, the patient may still achieve a durable response. A broad examination and prompt treatment of irAE can help improve the patient's survival.


Subject(s)
Aortic Rupture , Aortitis , Carcinoma , Humans , Male , Aged , Nivolumab/adverse effects , Aortitis/chemically induced , Aortitis/diagnostic imaging , Aortic Rupture/chemically induced , Aortic Rupture/diagnostic imaging , Aortic Rupture/surgery , Tomography, X-Ray Computed
5.
Eur Arch Otorhinolaryngol ; 278(6): 2001-2009, 2021 Jun.
Article in English | MEDLINE | ID: mdl-32772234

ABSTRACT

PURPOSE: Sarcopenia, defined as a decrease in the skeletal muscle mass and its function, is associated with a poor clinical outcome in several malignancies. We aimed to examine whether sarcopenia can be a predictor of incompletion of concurrent chemoradiotherapy (CCRT) and survival for head and neck cancer (HNC) patients. METHODS: Forty-one male HNC patients who received CCRT were enrolled in the study. Cross-sectional muscle areas at the third lumbar vertebral level were normalized by the squared height of the patients and were termed the lumbar skeletal muscle index (LSMI, cm2/m2), a marker of sarcopenia. Patients were divided into high (30/41, 73%) and low (11/41, 27%) LSMI groups. The LSMI cut-off value was set at 39.7 cm2/m2 based on a receiver operating characteristic curve for incompletion of CCRT. The groups were compared for survival rate by the Kaplan-Meier method. Factors predicting incompletion of CCRT were investigated among several variables. RESULTS: Multivariate analysis showed that a pre-treatment low LSMI (P = 0.033) and age over 70 years (P = 0.023) were the only significant predictors for incompletion of CCRT. The 2-year disease-specific survival (DSS) rate was significantly lower in the low LSMI group (61%) than in the high LSMI group (97%, P = 0.012), whereas there were no differences in the DSS rate between the low and high body mass index groups. CONCLUSION: The prevalence of sarcopenia in HNC patients receiving CCRT was 27%. Its presence before treatment was a significant predictor of incomplete CCRT and poor DSS rate in HNC patients.


Subject(s)
Head and Neck Neoplasms , Sarcopenia , Aged , Chemoradiotherapy/adverse effects , Cross-Sectional Studies , Head and Neck Neoplasms/therapy , Humans , Male , Prognosis , Sarcopenia/etiology , Sarcopenia/therapy , Squamous Cell Carcinoma of Head and Neck , Treatment Outcome
6.
Eur Arch Otorhinolaryngol ; 277(8): 2341-2347, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32239313

ABSTRACT

PURPOSE: The importance of nivolumab for recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) is rapidly increasing. However, prognostic factors have not been determined for predicting treatment outcome. We aimed to investigate the prognostic factors in R/M HNSCC patients treated with nivolumab. METHODS: This retrospective study included 42 patients with R/M HNSCC who received nivolumab therapy. Correlations of overall survival (OS) with various patient characteristics including age, recurrent/metastatic site, performance status (PS), programmed death-ligand 1 positivity, body mass index, neutrophil-to-lymphocyte ratio, modified Glasgow prognostic score (mGPS), previous cetuximab administration, and immune-related adverse events were investigated. RESULTS: The overall response rate and disease control rate were 16.7% and 45.2%, respectively. Estimated 1-year OS and progression-free survival (PFS) were 56.4% and 24.5%, respectively. Multivariate analysis revealed that PS = 2 (hazard ratio 0.147; 95% CI 0.041-0.527; p = 0.003) and mGPS = 2 (hazard ratio 0.188; 95% CI, 0.057-0.620; p = 0.006) were independent predictors of poor OS. Given that the PS and mGPS were independent prognostic factors, we classified patients into three groups according to PS and mGPS: Group 1, both PS and mGPS were 0 or 1 (n = 30); Group 2, either PS or mGPS was 2 (n = 9); Group 3, both PS and mGPS were 2 (n = 3). The OS curves were significantly stratified among the three groups. CONCLUSION: The combination of PS and mGPS accurately predicted OS after nivolumab therapy. Preventive intervention to maintain general condition without simultaneously exceeding level 2 of PS and mGPS might be important for improving treatment outcomes of nivolumab.


Subject(s)
Head and Neck Neoplasms , Nivolumab , Head and Neck Neoplasms/drug therapy , Humans , Prognosis , Retrospective Studies , Squamous Cell Carcinoma of Head and Neck/drug therapy , Treatment Outcome
7.
Histopathology ; 73(6): 943-952, 2018 Dec.
Article in English | MEDLINE | ID: mdl-29993139

ABSTRACT

AIMS: Salivary duct carcinoma (SDC) is an uncommon, aggressive tumour that, histologically, resembles high-grade mammary ductal carcinoma, and is characterised by the expression of androgen receptor (AR). The androgen signalling pathway, a potential therapeutic target, can be regulated by FOXA1. This study aimed to evaluate the clinicopathological implications of FOXA1 in SDC. METHODS AND RESULTS: We examined the relationship between the immunoexpression of FOXA1 and FOXA1 mutations and clinicopathological factors, including the biomarker status and clinical outcome, in 142 SDCs. FOXA1 was expressed in 128 SDCs (90.1%); the immunoexpression was heterogeneous. SDCs with a higher FOXA1 labelling index (LI) (≥20%) more frequently showed less advanced tumors on T classification (P = 0.002). FOXA1 LI was correlated positively with the AR expression value (r = 0.430, P < 0.001). PI3K and p-mTOR positivity, and intact-PTEN, were associated with a higher FOXA1 LI. Twenty-two of 121 SDCs (18.2%) harboured FOXA1 gene mutations at the flanking regions in and around the forkhead DNA binding domain; however, the given gene mutation and the expression of FOXA1 were not significantly correlated. A multivariate analysis revealed that SDCs with a higher FOXA1 LI were associated with longer overall survival and progression-free survival (P = 0.029 and 0.016, respectively). CONCLUSIONS: In SDC, FOXA1, which may biologically interact with the AR and PI3K signalling pathways, is a putative biomarker that may be associated with a favourable prognosis. Further studies are needed to apply the findings to the development of targeted personalised therapy for patients with SDC.


Subject(s)
Carcinoma/metabolism , Hepatocyte Nuclear Factor 3-alpha/metabolism , Salivary Ducts/metabolism , Salivary Gland Neoplasms/metabolism , Aged , Biomarkers, Tumor , Carcinoma/genetics , Carcinoma/mortality , Carcinoma/pathology , Female , Hepatocyte Nuclear Factor 3-alpha/genetics , Humans , Immunohistochemistry , Male , Middle Aged , Mutation , Phosphatidylinositol 3-Kinases/metabolism , Phosphorylation , Prognosis , Receptors, Androgen/metabolism , Salivary Ducts/pathology , Salivary Gland Neoplasms/genetics , Salivary Gland Neoplasms/mortality , Salivary Gland Neoplasms/pathology , Signal Transduction/physiology , Survival Rate
8.
Ann Surg Oncol ; 23(6): 2038-45, 2016 06.
Article in English | MEDLINE | ID: mdl-26790669

ABSTRACT

BACKGROUND: Among salivary gland malignancies, the prognosis of salivary duct carcinoma (SDC) is assumed to be the poorest. However, because of its low incidence, reliable survival estimates and prognostic factors based on a large number of patients remain to be elucidated, thereby making it impossible to standardize the optimal treatment for SDC. METHODS: We performed this multi-institutional, retrospective analysis by collecting the clinical information of 141 patients with SDC without distant metastasis who underwent curative surgery as the initial treatment to elucidate overall survival (OS) and disease-free survival (DFS) along with their prognostic factors. RESULTS: The 3-year OS and DFS rates were 70.5 and 38.2 %, respectively. Multivariate analysis revealed that age ≥65 years (p < 0.001) and N1 and N2 (p = 0.047 and <0.001, respectively) were independent prognostic factors for OS, whereas the primary site of the minor salivary and sublingual gland (p < 0.001) and N2 (p < 0.001) were those for DFS. The most common treatment failure was distant metastasis (55 patients, 39.0 %). For early parotid SDC, neither total parotidectomy in the patients with early T stage nor nerve resection in the patients without facial nerve palsy showed survival benefits. CONCLUSIONS: Advanced N stage independently affects both OS and DFS. Partial parotidectomy with facial nerve preservation could be a less invasive standard surgical procedure for parotid gland SDC in the early T stage without facial nerve palsy. Effective systemic therapy is imperative to improve DFS of SDC.


Subject(s)
Carcinoma, Ductal/pathology , Salivary Gland Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Carcinoma, Ductal/surgery , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Salivary Gland Neoplasms/surgery , Survival Rate
9.
Nihon Jibiinkoka Gakkai Kaiho ; 118(1): 40-5, 2015 Jan.
Article in Japanese | MEDLINE | ID: mdl-26333271

ABSTRACT

Typical osteomyelitis is reportedly caused by Pseudomonous aeruginosa in elderly diabetic patients after malignant external otitis. Recently, complications have arisen due to the emergence of atypical osteomyelitis. We have experiensed 5 cases of skull base osteomyelitis at our hospital. All patients were male with a mean age of 75.2 years. Four patients had diabetes. Regarding the clinical and radiographic findings, patients 1, 2, and 3 had typical osteomyelitis after malignant external otitis, whereas patients 4 and 5 had atypical osteomyelitis without temporal bone findings. Sample culturing revealed Pseudomonas aeruginosa in 4 cases and Aspergillus in one. Intravenous antibiotics were administered to all patients. Two patients responded positively and survived, while 3 died. Typical osteomyelitis is reportedly caused by P. aeruginosa in elderly diabetic patients after malignant external otitis. Recently, complications have arisen due to the emergence of atypical osteomyelitis. The prognosis of skull base osteomyelitis is still poor in Japan. Early diagnosis and long-term antibiotic administration is required to improve outcome.


Subject(s)
Osteomyelitis/pathology , Skull Base/pathology , Aged , Aged, 80 and over , Anti-Bacterial Agents/therapeutic use , Aspergillus , Humans , Male , Middle Aged , Osteomyelitis/microbiology , Osteomyelitis/therapy , Pseudomonas , Tomography, X-Ray Computed , Treatment Outcome
10.
Nihon Jibiinkoka Gakkai Kaiho ; 118(9): 1150-4, 2015 Sep.
Article in Japanese | MEDLINE | ID: mdl-26615666

ABSTRACT

A 62-year-old woman, who had dysesthesia in the throat, and polyposia the previous year, was admitted in a coma because of respiratory failure. Computed tomography scans demonstrated dilatation of the esophagus and stenosis of the trachea. After emergency intubation, extubation was not possible due to a collapsed trachea, so we performed a tracheostomy. The tracheoscopy from the stoma showed an esophagus-like trachea due to disappearance of the tracheal cartilage and the straight pattern on the membranous portion, and the lumen deformed with coughing. With the continuous dyspnea episode, the patient was diagnosed as having tracheomalacia. Anti-type II collagen antibody and pathological findings of the trachea led us to the diagnosis of Relapsing Polychondritis.


Subject(s)
Polychondritis, Relapsing/diagnosis , Tracheal Diseases/diagnosis , Female , Humans , Middle Aged
11.
Laryngoscope ; 134(1): 496-500, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37140028

ABSTRACT

Ectopic parathyroid lesions can be difficult to detect. In the present study, we used near-infrared autofluorescence imaging (NIFI) in three cases of ectopic parathyroid lesions. Our results suggest that NIFI may be a confirmation tool for parathyroid pathology and an intraoperative navigation tool in vivo and ex vivo. Laryngoscope, 134:496-500, 2024.


Subject(s)
Parathyroidectomy , Thyroidectomy , Humans , Parathyroidectomy/methods , Thyroidectomy/methods , Optical Imaging/methods , Parathyroid Glands/surgery
12.
Laryngoscope ; 134(4): 1679-1686, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37698411

ABSTRACT

OBJECTIVE: Recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) treatment has changed dramatically with the introduction of immune checkpoint inhibitors (ICIs). However, there are few reports of treatment outcomes on HNSCC with distant metastasis (M1) at initial diagnosis, and its treatment strategy has not been standardized. We aimed to analyze the treatment outcome and prognostic factors of patients with HNSCC with initial M1 disease. METHODS: In this multi-institutional retrospective study, 98 patients with HNSCC were initially diagnosed with M1 disease between 2007 and 2021. The patients were divided into the non-palliative (received any systemic chemotherapy, n = 60) and palliative (did not receive systemic chemotherapy, n = 38) groups. Overall survival (OS) was compared between the groups. In the non-palliative group, predictors of OS were explored based on patient characteristics and treatment details. RESULTS: The median OS in the non-palliative group was 15 months (95% confidence interval [CI], 10-20), which was significantly longer than that in the palliative group (3 months, 95% CI, 2-5) (p < 0.001). Multivariate analysis revealed that administration of locoregional radiation therapy (RT) (hazard ratio [HR] 0.407 [95% CI 0.197-0.844]; p = 0.016), ICIs (HR 0.216 [95% CI 0.088-0.532]; p < 0.001) and RT/surgery for distant metastasis (HR 0.373 [95% CI 0.150-0.932]; p = 0.034) were the independent prognostic factors of OS. CONCLUSION: An intensive treatment strategy combining systemic therapy using ICIs with RT/surgery for locoregional or distant metastasis may yield a survival benefit for patients with HNSCC with M1 disease. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:1679-1686, 2024.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Humans , Head and Neck Neoplasms/therapy , Neoplasm Recurrence, Local/pathology , Retrospective Studies , Squamous Cell Carcinoma of Head and Neck/therapy , Treatment Outcome
13.
Sci Rep ; 14(1): 19794, 2024 08 27.
Article in English | MEDLINE | ID: mdl-39187586

ABSTRACT

Although immune checkpoint inhibitors (ICIs) are effective in some patients with salivary gland carcinoma (SGC), biomarkers which predict the efficacy and prognosis of SGC patients treated with pembrolizumab have not been identified. We conducted a multi-institutional retrospective cohort study to evaluate the efficacy and safety of pembrolizumab monotherapy in patients with recurrent and/or metastatic SGC and to determine optimal cut-off values of the combined positive score (CPS) and tumor proportion score (TPS) as numerical expression levels of programmed death-ligand 1 (PD-L1), which predict the efficacy of pembrolizumab. Furthermore, we investigated the association of patient characteristics and hematological markers with clinical outcomes, including overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). From 2016 to 2021, 27 patients were included in the analysis. ORR of SGC was 25.9%. Optimal cut-off values of CPS and TPS were 15 and 25%, respectively. ORRs of CPS-high and TPS-high were 55.6 and 75.0%, respectively, and significantly higher than those of CPS-low and TPS-low. Furthermore, patients with a low platelet-lymphocyte ratio (PLR) had a significantly longer PFS. No grade 4 or greater adverse events were observed. This study demonstrated the efficacy and safety of pembrolizumab monotherapy and identified optimal cut-off values of CPS and TPS.


Subject(s)
Antibodies, Monoclonal, Humanized , B7-H1 Antigen , Biomarkers, Tumor , Salivary Gland Neoplasms , Humans , Antibodies, Monoclonal, Humanized/therapeutic use , Salivary Gland Neoplasms/drug therapy , Salivary Gland Neoplasms/pathology , Salivary Gland Neoplasms/metabolism , Salivary Gland Neoplasms/mortality , Male , Female , Middle Aged , Aged , B7-H1 Antigen/metabolism , Biomarkers, Tumor/metabolism , Retrospective Studies , Adult , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/pathology , Prognosis , Neoplasm Metastasis , Antineoplastic Agents, Immunological/therapeutic use , Aged, 80 and over , Treatment Outcome , Progression-Free Survival
14.
Virchows Arch ; 485(3): 439-452, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39042207

ABSTRACT

Many researchers have focused on the role of the autonomic nervous system in the tumor microenvironment. Autonomic nerves include the sympathetic and parasympathetic nerves, which are known to induce cancer growth and metastasis. However, in salivary duct carcinoma (SDC), a rare and highly malignant tumor, the issue should be investigated from both biological and therapeutic perspectives. We explored the clinicopathological and prognostic implications of the autonomic nerves in 129 SDCs. Immunohistochemistry was performed to determine the nature of each nerve using antibodies against S100, tyrosine hydroxylase (TH) as a sympathetic marker, and vesicular acetylcholine transporter (VAChT) as a parasympathetic marker. The area of each marker-positive nerve was digitized and evaluated quantitatively. Double immunofluorescence for TH and VAChT was performed in selected cases. The expression of the secreted neurotrophins was also examined. S100-positive nerves were present in the cancer tissue in 94 of 129 cases (72.9%). Among them, TH-positive sympathetic nerves and/or VAChT-positive parasympathetic nerves were identified in 92 cases (97.9%), and 59 cases (62.8%) had TH/VAChT-co-expressing nerves. Double immunofluorescence revealed a mosaic pattern of sympathetic and parasympathetic fibers in co-expressing nerve bundles. The presence of autonomic nerves, regardless of their area, was significantly associated with aggressive histological features, advanced T/N classification, and a poor prognosis, with shorter disease-free and overall survival. There was an association between some tumor immune microenvironment-related markers and the autonomic nerve status, but not the latter and the secreted neurotrophin expression. This study suggests that autonomic nerves might play a role in the progression of SDC.


Subject(s)
Salivary Gland Neoplasms , Humans , Male , Female , Middle Aged , Aged , Adult , Prognosis , Salivary Gland Neoplasms/pathology , Salivary Gland Neoplasms/metabolism , Aged, 80 and over , Biomarkers, Tumor/analysis , Biomarkers, Tumor/metabolism , Salivary Ducts/pathology , Salivary Ducts/innervation , Vesicular Acetylcholine Transport Proteins/metabolism , Tyrosine 3-Monooxygenase/metabolism , Tyrosine 3-Monooxygenase/analysis , Immunohistochemistry , Autonomic Pathways/pathology , Autonomic Nervous System/pathology , Autonomic Nervous System/metabolism , Carcinoma, Ductal/pathology , S100 Proteins/metabolism , S100 Proteins/analysis , Tumor Microenvironment
15.
Front Immunol ; 15: 1390873, 2024.
Article in English | MEDLINE | ID: mdl-39136017

ABSTRACT

Background: In view of improving biomarkers predicting the efficacy of immunotherapy for head and neck squamous cell carcinoma (R/M HNSCC), this multicenter retrospective study aimed to identify clinical, tumor microenvironmental, and genomic factors that are related to therapeutic response to the anti- Programmed cell death protein 1 (PD-1) antibody, nivolumab, in patients with R/M HNSCC. Methods: The study compared 53 responders and 47 non-responders, analyzing formalin-fixed paraffin-embedded samples using 14-marker multiplex immunohistochemistry and targeted gene sequencing. Results: Of 100 patients included, responders had significantly lower smoking and alcohol index, higher incidence of immune related adverse events, and higher PD-1 ligand (PD-L1) expression in immune cells as well as PD-L1 combined positive score (CPS) than non-responders. The frequency of natural killer cells was associated with nivolumab response in patients with prior cetuximab use, but not in cetuximab-naïve status. Age-stratified analysis showed nivolumab response was linked to high CPS and lymphoid-inflamed profiles in patients aged ≥ 65. In contrast, lower NLR in peripheral blood counts was associated with response in patients aged < 65. Notably, TP53 mutation-positive group had lower CPS and T cell densities, suggesting an immune-excluded microenvironment. Patients with altered tumor suppressor gene pathways, including TP53, CDKN2A, and SMAD4 mutations, had lower CPS, higher smoking index, and were associated with poor responses. Conclusion: Nivolumab treatment efficacy in HNSCC is influenced by a combination of clinical factors, age, prior treatment, immune environmental characteristics, and gene mutation profiles.


Subject(s)
Head and Neck Neoplasms , Nivolumab , Squamous Cell Carcinoma of Head and Neck , Tumor Microenvironment , Humans , Tumor Microenvironment/immunology , Nivolumab/therapeutic use , Nivolumab/adverse effects , Male , Squamous Cell Carcinoma of Head and Neck/drug therapy , Squamous Cell Carcinoma of Head and Neck/immunology , Squamous Cell Carcinoma of Head and Neck/genetics , Female , Aged , Middle Aged , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/immunology , Head and Neck Neoplasms/genetics , Retrospective Studies , Biomarkers, Tumor/genetics , Antineoplastic Agents, Immunological/therapeutic use , Antineoplastic Agents, Immunological/adverse effects , Immune Checkpoint Inhibitors/therapeutic use , Immune Checkpoint Inhibitors/adverse effects , Treatment Outcome , Adult , B7-H1 Antigen/genetics , Aged, 80 and over , Mutation , Genomics/methods
16.
Ann Anat ; 250: 152118, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37302433

ABSTRACT

BACKGROUND: During oral and head and neck surgery, oral vestibular incisions may require a transverse incision on the upper lip mucosa, resulting in possible sensory disturbances in the area innervated by infraorbital nerve (ION) branches. Although sensory disturbances are attributed to nerve injuries, anatomy textbooks have not showed the precise distribution patterns of the ION branches in the upper lip. Furthermore, no detailed study has been available on this issue. This study aimed to reveal the precise distribution patterns of ION branches in the upper lip by dissecting the detached upper lip and cheek area using a stereomicroscope. METHODS: During a gross anatomy course at Niigata University (2021-2022), nine human cadavers were examined with special focus on the relationship between ION branches in the upper lip and the layered structure of facial muscles. RESULTS: The ION branched to the inferior palpebral (IP), external and internal nasal, and superior labial (lateral and medial) nerves. The ION branches in the upper lip did not run in a horizontal pattern from outside to inside but showed a predominantly vertical pattern. Considering their course, incising the upper lip mucosa transversely may cause paresthesia of the ION branches. The internal nasal (IN) and medial superior labial (SLm) branches tended to penetrate the orbicularis oris and descend between this muscle and labial glands, whereas the lateral superior labial (SLl) branches tended to innervate the skin. CONCLUSIONS: These findings suggest that a lateral mucosal incision is recommended for oral vestibular incisions of the upper lip and that deeper incisions to the labial glands should be avoided when incising the medial side to preserve the ION during surgery from an anatomical point of view.


Subject(s)
Facial Muscles , Nose , Humans , Facial Muscles/innervation , Lip , Coronary Vessels , Cadaver
17.
Cancer Med ; 12(22): 20810-20820, 2023 11.
Article in English | MEDLINE | ID: mdl-37902133

ABSTRACT

INTRODUCTION: Immune-related adverse events (irAEs) are prognostic factors for patients on nivolumab. However, predictors of irAEs have not yet been identified. We aimed to investigate the predictors of irAEs occurrence and nivolumab discontinuation due to irAEs. METHODS: Sixty-two patients with recurrent/metastatic head and neck squamous cell carcinoma received nivolumab therapy between June 2017 and December 2020. Treatment outcome was compared between the groups with or without irAEs. The irAE (+) group was further divided by nivolumab discontinuation. Progression-free survival (PFS) and overall survival (OS) were compared between the groups. Predictors of irAE occurrence were analyzed. RESULTS: Twenty-one patients (33.9%) developed irAEs, and six (28.6%) discontinued nivolumab due to severe irAEs. The irAE (+) group had significantly longer PFS and OS than the irAE (-) group (median PFS, 12.7 vs. 1.9 months; median OS, 33.1 vs. 12.8 months). The treatment outcomes in the discontinuation group were comparable to those in the non-discontinuation group. The maximum absolute eosinophil count (AEC) during nivolumab therapy was significantly higher in the irAE (+) group than in the irAE (-) group (548.8 vs. 182) and higher in the discontinuation group than in the non-discontinuation group (729.3 vs. 368.6). The receiver operating characteristic curve showed that the maximum AEC had a moderate-to-high accuracy for predicting irAE occurrence (area under the curve [AUC], 0.757) and nivolumab discontinuation (AUC, 0.893). DISCUSSION: Monitoring AEC during nivolumab therapy may be useful in predicting irAE occurrence, nivolumab discontinuation, and disease prognosis.


Subject(s)
Antineoplastic Agents, Immunological , Carcinoma, Non-Small-Cell Lung , Eosinophilia , Head and Neck Neoplasms , Lung Neoplasms , Humans , Nivolumab/adverse effects , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/pathology , Squamous Cell Carcinoma of Head and Neck/drug therapy , Squamous Cell Carcinoma of Head and Neck/chemically induced , Antineoplastic Agents, Immunological/adverse effects , Neoplasm Recurrence, Local/drug therapy , Head and Neck Neoplasms/drug therapy , Retrospective Studies
18.
Endocrine ; 78(1): 151-158, 2022 10.
Article in English | MEDLINE | ID: mdl-35913569

ABSTRACT

PURPOSE: Persistent hypoparathyroidism (hypoPT) is a major complication of total thyroidectomy. Nonetheless, previous reports may have underestimated the prevalence of hypoPT due to patient selection bias. We aimed to estimate the actual prevalence of persistent hypoPT after total thyroidectomy and to find predictive factors for postoperative hypoPT. METHODS: This study retrospectively reviewed data from a health insurance claims-based database provided by the Japan Medical Data Center Co., Ltd. From 2009 to 2019, 2388 patients who underwent total thyroidectomy were identified using the medical procedure codes. Persistent hypoPT was defined as the prescription of active vitamin D supplements for >1 year postoperatively and the assignment of hypoPT codes. The prevalence of persistent hypoPT was estimated at two different levels: minimum and maximum estimations with or without postoperative osteoporosis and/or renal failure codes. Correlates for persistent hypoPT were investigated among several demographic and clinical variables. RESULTS: Of the 2388 patients, 1752 (73.4%) were women with a mean age of 45 years. The types of diseases were: benign thyroid disease (n = 235), malignant thyroid tumors (n = 1570), Graves ' disease (n = 558), and malignancy combined with Graves' disease (n = 25). The minimum and the maximum estimation of the prevalence of persistent hypoPT were 15.0 and 20.3%, respectively. Multivariate logistic regression analysis showed that the malignant tumor (odds ratio, 1.8) independently correlated with persistent hypoPT. CONCLUSIONS: The prevalence of persistent hypoPT after total thyroidectomy estimated by the claims-based database was higher than previously recognized. Comprehensive attempts to preserve parathyroid function, especially in malignant diseases, are essential.


Subject(s)
Graves Disease , Hypoparathyroidism , Female , Graves Disease/complications , Humans , Hypoparathyroidism/complications , Hypoparathyroidism/etiology , Insurance, Health , Male , Middle Aged , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Prevalence , Retrospective Studies , Thyroidectomy/adverse effects
19.
Article in English | MEDLINE | ID: mdl-36028291

ABSTRACT

OBJECTIVE: The management for malodour of malignant fungating wounds (MFWs) in head and neck cancer (HNC) is unestablished. We evaluated the effects of a novel odour transferrer on malodour generated by MFWs in patients with HNC. METHODS: A spray-type odour transferrer approved by the Japanese government for safe use in humans produces a good scent by binding to bad odour. The odour of MFWs in 13 patients with HNC was scored by 37 medical staff and the patients' families using an odour scale ranging from 0 to 4 before and 1 week after application of the odour transferrer. RESULTS: The odour score marked by all investigators (n=37), nurses (n=21) and doctors (n=11) decreased significantly (p<0.01). The odour score decreased by more than 2 points for 73% of all investigators after odour transferrer application. CONCLUSION: This novel odour transferrer functions as an effective deodorant for MFWs in patients with HNC. It can be used by non-medical staff and may benefit patients with bad odours arising from MFWs as well as their families and medical staff.

20.
Auris Nasus Larynx ; 49(1): 152-156, 2022 Feb.
Article in English | MEDLINE | ID: mdl-32883576

ABSTRACT

Endoscopic submucosal dissection (ESD) has gained wide acceptance as a minimally invasive and curative surgery for superficial head and neck carcinoma. However, the safety of ESD for superficial pharyngeal carcinoma after radiotherapy has not been elucidated. Superficial hypopharyngeal carcinoma of the left pyriform sinus developed in a 76-year-old man who had undergone concurrent chemoradiotherapy for T2N2bM0 pyriform sinus carcinoma on the opposite side 12 months before. He underwent ESD without complications. Because tumor invasion into the muscular layer was a concern, the muscular layer was partially resected with the tumor. Twelve days after discharge, he presented with a sore throat and difficulty in swallowing. Endoscopy and computed tomography revealed necrosis due to wound infection with abscess formation around the left carotid artery. The common carotid artery subsequently ruptured. Although the surgical intervention was performed, he passed away 46 days after ESD due to carotid blowout. ESD is a minimally invasive treatment for superficial head and neck carcinoma, but carotid blowout can occur in cases after radiation. Prior radiotherapy and deeper dissection into the muscular layer may hamper wound epithelization, resulting in infection-induced necrosis and carotid blowout. Diligent monitoring of wound healing is essential in patients who have previously undergone irradiation.


Subject(s)
Carcinoma, Squamous Cell/surgery , Carotid Artery Diseases/etiology , Endoscopic Mucosal Resection/adverse effects , Head and Neck Neoplasms/surgery , Hypopharyngeal Neoplasms/surgery , Rupture, Spontaneous/etiology , Surgical Wound Infection/complications , Aged , Carcinoma, Squamous Cell/therapy , Chemoradiotherapy/adverse effects , Dissection/adverse effects , Dissection/methods , Fatal Outcome , Humans , Hypopharyngeal Neoplasms/therapy , Male , Wound Healing
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