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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/methodsABSTRACT
PURPOSE: The retrolabyrinthine approach is a surgical method designed to preserve hearing after surgery. When paired with intraoperative monitoring and an endoscope, this approach has demonstrated high rates of postoperative hearing preservation. However, the long-term prognosis of hearing preservation after utilizing this approach for vestibular schwannomas remains unexplored. This study aimed to examine the long-term outcomes of preserved hearing, providing insights into the suitability of the retrolabyrinthine approach for hearing preservation surgery. METHODS: This study included 34 patients with preserved hearing after vestibular schwannoma surgery using the retrolabyrinthine approach at a single center. Long-term hearing prognosis and requirement for additional interventions were retrospectively examined. RESULTS: Immediate after post-operative hearing preservation rate was 71.7%. Among the 34 patients with preserved hearing post-vestibular schwannoma surgery, four (11.8%) required additional interventions. Other patients experienced a gradual deterioration in their hearing status, with an approximate 10 dB decline during the 5-year follow-up; however, a serviceable hearing level persisted long after the surgery in these individuals. CONCLUSIONS: This study indicated the rationale for the retrolabyrinthine approach as a hearing preservation surgery for vestibular schwannomas, emphasizing its long-term hearing prognosis.
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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.
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Olfactory neuroblastomas rarely secrete adrenocorticotropic hormone, leading to ectopic adrenocorticotropic hormone syndrome. However, the prevalence, timing, and triggers of ectopic adrenocorticotropic hormone syndrome in patients with olfactory neuroblastomas remain unclear. This study aimed to investigate these factors and conduct a literature review. Fifteen patients with olfactory neuroblastomas who underwent surgery at our institution were included. The prevalence of ectopic adrenocorticotropic hormone syndrome development was assessed by evaluating adrenocorticotropic hormone expression using immunohistochemistry. Furthermore, 26 patients with olfactory neuroblastomas who developed ectopic adrenocorticotropic hormone syndrome from previous reports were reviewed. Among the 15 patients, three (20%) showed adrenocorticotropic hormone-positive tumor cells at the time of initial surgery, and two (13%) developed ectopic adrenocorticotropic hormone syndrome. The timing of developing ectopic adrenocorticotropic hormone syndrome was 2.5 and 10 years following the initial treatment of olfactory neuroblastoma. Based on the literature review, nine patients with recurrent and metastatic olfactory neuroblastoma developed ectopic adrenocorticotropic hormone syndrome after the initial surgery, of whom, three had confirmed disease after developing ectopic adrenocorticotropic hormone syndrome, three developed during disease progression, two developed after receiving chemotherapy, and one developed after undergoing a biopsy. The timing of ectopic adrenocorticotropic hormone syndrome was 2.5-15 years after initial treatment. Our study revealed that acknowledging olfactory neuroblastomas can manifest as ectopic adrenocorticotropic hormone syndrome with a certain low prevalence is crucial. Moreover, our study speculated that tumor stimulation, such as biopsy or chemotherapy, as well as disease progression, could trigger ectopic adrenocorticotropic hormone syndrome onset. Thus, olfactory neuroblastomas can develop into ectopic adrenocorticotropic hormone syndrome, even long after the initial treatment.
Subject(s)
ACTH Syndrome, Ectopic , Esthesioneuroblastoma, Olfactory , Nose Neoplasms , Humans , Esthesioneuroblastoma, Olfactory/metabolism , Esthesioneuroblastoma, Olfactory/pathology , Male , Female , Adult , Nose Neoplasms/metabolism , Nose Neoplasms/pathology , Middle Aged , Nasal Cavity/pathology , Nasal Cavity/metabolism , Aged , Young Adult , Adrenocorticotropic Hormone/metabolism , Adolescent , Retrospective StudiesABSTRACT
Do adults who stutter have abnormally high social anxiety? Is it related to maladaptive cognition? As these are persistent, unresolved questions in stuttering research, it behooves clinicians to at least assess and attempt to identify social anxiety in patients who stutter and its basis before decisions are made about stuttering treatment. The Unhelpful Thoughts and Beliefs About Stuttering (UTBAS) scale is a self-administered questionnaire that measures the degree of non-adaptive cognition in people who stutter (PWS) due to social anxiety. The 66-item UTBAS is time-consuming to complete, prompting the development of a shorter 6-item version, the UTBAS-6, which is in English. Here, we aimed to assess some psychometric properties of the Japanese version of the UTBAS-6, the UTBAS-6-J, which has not been done to date. In 56 adult patients (mean 32.6 ± 11.1 years) who stutter, we quantified the reliability, the internal consistency, and the concurrent validity of the UTBAS-6-J. Along with the UTBAS-6-J, patients also were administered the Overall Assessment of the Speaker's Experience of Stuttering - Japanese version (OASES-A-J), the Modified Erickson Communication Attitude Scale - Japanese version (S-24-J), and the Liebowitz Social Anxiety Scale - Japanese version (LSAS-J). Cronbach's alpha for UTBAS-6-J total scores was 0.974, indicating excellent internal consistency. UTBAS-6-J scores were significantly correlated with scores on the OASES-A-J, the S-24-J, and the LSAS-J (all p < 0.005). Concurrent validity of the UTBAS-6-J with these three questionnaires was confirmed. The UTBAS-6-J has good internal consistency and concurrent validity, which will aid clinical decision-making about stuttering treatments.
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A vestibular schwannoma is a benign tumor; however, the schwannoma itself and interventions can cause sensorineural hearing loss. Most vestibular schwannomas are unilateral tumors that affect hearing only on one side. Attention has focused on improving the quality of life for patients with unilateral hearing loss and therapeutic interventions to address this issue have been emphasized. Herein, we encountered a patient who was a candidate for hearing preservation surgery based on preoperative findings and had nonserviceable hearing after the surgery, according to the Gardner-Robertson classification. Postoperatively, the patient had decreased listening comprehension and ability to localize sound sources. He was fitted with bilateral hearing aids, and his ability to localize sound sources improved. Although the patient had postoperative nonserviceable hearing on the affected side and age-related hearing loss on the unaffected side, hearing aids in both ears were useful for his daily life. Therefore, the patient was able to maintain a binaural hearing effect and the ability to localize the sound source improved. This report emphasizes the importance of hearing preservation with vestibular schwannomas, and the demand for hearing loss rehabilitation as a postoperative complication can increase, even if hearing loss is nonserviceable.
Subject(s)
Hearing Aids , Neuroma, Acoustic , Humans , Neuroma, Acoustic/surgery , Male , Middle Aged , Hearing Loss, Sensorineural/surgery , Hearing Loss, Sensorineural/rehabilitation , Hearing Loss, Sensorineural/etiology , Quality of Life , Hearing Loss/etiology , Hearing Loss/surgery , Hearing Loss/rehabilitation , Postoperative Complications/etiologyABSTRACT
Many marine species are distributed across incredibly wide geographical ranges spanning thousands of kilometers often due to movement along prevailing ocean currents. However, data are lacking on genetic connectivity among populations of such widespread species within or among ecoregions, possibly due to the lack of appropriate datasets. In this study, we investigated the genetic structure of populations of the mangrove whelk, Terebralia palustris, using mitochondrial cytochrome oxidase subunit I (COI) sequences. Sequences generated for this study from Okinawa, Japan, were compared to samples from the coast of East Africa analyzed in a previous study. Interestingly, despite considerable distance separating them, the African and Japanese populations share major haplotypes and do not show clear genetic differentiation. At lower latitudes, core African populations exhibited higher genetic diversity than either the more southerly African and Japanese populations. Genetic ß-diversity revealed that the northern edge population in Japan has a greater proportion of ßSNE (the nestedness-resultant component), indicating contemporary migration, whereas the southern edge population in Africa is characterized by a predominant ßSIM (the turnover component), suggesting historical demography. A potential cause of this dissimilarity could be due to the strong Kuroshio Current along the Ryukyu Islands, which may promote larval dispersal. These differing patterns suggest that there may be divergent responses to future climate change at the population level at the periphery of the range of T. palustris.
Subject(s)
Genetic Variation , Animals , Japan , Electron Transport Complex IV/genetics , Genetics, Population , Africa, Eastern , HaplotypesABSTRACT
PURPOSE: The humanized antivascular endothelial growth factor (VEGF) antibody bevacizumab (Bev) is efficacious for the treatment of NF2-related schwannomatosis (NF2), previously known as neurofibromatosis type 2. This study evaluated the safety and efficacy of a VEGF receptor (VEGFR) vaccine containing VEGFR1 and VEGFR2 peptides in patients with NF2 with progressive schwannomas (jRCTs031180184). MATERIALS AND METHODS: VEGFR1 and VEGFR2 peptides were injected subcutaneously into infra-axillary and inguinal regions, once a week for 4 weeks and then once a month for 4 months. The primary end point was safety. Secondary end points included tolerability, hearing response, imaging response, and immunologic response. RESULTS: Sixteen patients with NF2 with progressive schwannomas completed treatment and were assessed. No severe vaccine-related adverse events occurred. Among the 13 patients with assessable hearing, word recognition score improved in five patients at 6 months and two at 12 months. Progression of average hearing level of pure tone was 0.168 dB/mo during the year of treatment period, whereas long-term progression was 0.364 dB/mo. Among all 16 patients, a partial response was observed in more than one schwannoma in four (including one in which Bev had not been effective), minor response in 5, and stable disease in 4. Both VEGFR1-specific and VEGFR2-specific cytotoxic T lymphocytes (CTLs) were induced in 11 patients. Two years after vaccination, a radiologic response was achieved in nine of 20 assessable schwannomas. CONCLUSION: This study demonstrated the safety and preliminary efficacy of VEGFR peptide vaccination in patients with NF2. Memory-induced CTLs after VEGFR vaccination may persistently suppress tumor progression.
Subject(s)
Cancer Vaccines , Neurilemmoma , Vascular Endothelial Growth Factor Receptor-1 , Vascular Endothelial Growth Factor Receptor-2 , Humans , Male , Female , Adult , Middle Aged , Vascular Endothelial Growth Factor Receptor-2/immunology , Cancer Vaccines/therapeutic use , Cancer Vaccines/adverse effects , Cancer Vaccines/administration & dosage , Neurilemmoma/immunology , Vascular Endothelial Growth Factor Receptor-1/immunology , Skin Neoplasms/immunology , Skin Neoplasms/drug therapy , Skin Neoplasms/pathology , Neurofibromatosis 2 , Young Adult , Aged , NeurofibromatosesABSTRACT
Background and study aims Superficial pharyngeal cancers can be cured with transoral surgery (TOS), which preserves organ function and quality of life. Pharyngeal endoscopic submucosal dissection (ESD) is challenging to perform because of limited maneuverability and complex anatomical features. The water pressure method (WPM) is useful for natural traction techniques during ESD and is potentially useful for pharyngeal ESD. This study aimed to investigate the short-term outcomes of WPM-ESD for pharyngeal lesions. Patients and methods Therapeutic outcomes of patients who underwent WPM-ESD for pharyngeal lesions at Keio University between May 2019 and February 2022 were retrospectively analyzed. Results Twenty-one pharyngeal lesions treated with WPM-ESD were analyzed. Three lesions were located in the oropharynx and 18 in the hypopharynx. All ESD procedures were performed under general anesthesia. The endoscopic en bloc resection rate was 100%. The median procedure time was 15 minutes (range 4-45 minutes). All patients were successfully extubated on the day of ESD. No serious adverse events (AEs) related to WPM-ESDs were observed. None of the patients required nasogastric intubation, percutaneous endoscopic gastrostomy, or tracheotomy. The median fasting time and hospital stay were 2 days (range 2-5 days) and 6 days (range 6-10 days), respectively. All the histological results indicated squamous cell carcinoma. The complete histologic resection rate was 76.2%. Conclusions WPM-ESD achieved a high en bloc resection rate and short procedure time without serious AEs. Thus, it may be a useful treatment for pharyngeal lesions.
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DNA analysis of large herbivore feces samples collected from seagrass beds at two distant sites (Irabu Island in Miyako Islands and Kushi in Okinawa Island) in the Ryukyu Islands proved that some of these feces were from dugongs, which had been treated in recent studies as extinct in this region since the last stranding of a deceased individual in 2019. In addition, local knowledge of sightings of animals thought to be dugongs and confirmed cases of dugong feeding trails since 2010 were compiled to estimate its recent distribution. This is the first scientific report on the presence of this mammal in the Ryukyu Islands within the last four years, and particularly in the Miyako Islands within the last half-century. As the Ryukyu Islands are known to be the northern limit of the dugong's fragmented distribution in East Asia, conservation efforts are therefore needed.
Subject(s)
Dugong , Animals , DNA , Asia, Eastern , Feces , Islands , JapanABSTRACT
OBJECTIVE: Pemphigus Vulgaris (PV) is a rare autoimmune disease that could cause laryngeal lesions; however, only a few studies have described the localization of the laryngeal lesions associated with this disease owing to its rarity. Therefore, this study aimed to determine the localization of laryngeal lesions in patients with PV. METHODS: Fourteen patients with PV accompanied by laryngeal or pharyngeal lesions, who underwent flexible laryngeal endoscopy performed by laryngologists, were examined retrospectively. RESULTS: The arytenoid area was the most frequently affected site in the larynx, followed by the epiglottis and aryepiglottic folds. Vocal folds and ventricular bands were the least affected. CONCLUSION: Lesions in the arytenoid area were observed more frequently in this study than in previous studies. This result suggests that a more careful inspection of arytenoid lesions in patients with PV is required under laryngeal fiber observation. Moreover, we proposed a novel classification system for laryngeal findings in patients with PV and a systematic observation method. This novel classification and method would be useful not only for determining the lesions but also for careful inspection in this field. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:3719-3725, 2024.
Subject(s)
Laryngeal Diseases , Laryngoscopy , Pemphigus , Humans , Pemphigus/pathology , Pemphigus/diagnosis , Male , Female , Retrospective Studies , Middle Aged , Laryngeal Diseases/pathology , Laryngeal Diseases/diagnosis , Laryngoscopy/methods , Adult , Aged , Arytenoid Cartilage/pathology , Larynx/pathologyABSTRACT
OBJECTIVES: To determine the natural history of hearing loss and tumor volume in patients with untreated neurofibromatosis type 2 (NF2)-related schwannomatosis. Moreover, we statistically examined the factors affecting hearing prognosis. METHODS: This retrospective cohort study was conducted on 37 ears of 24 patients with NF2-related vestibular schwannomatosis followed up without treatment for more than 1 year. We obtained detailed chronological changes in the PTA and tumor volume in each case over time, and the rate of change per year was obtained. Multivariate analysis was also conducted to investigate factors associated with changes in hearing. RESULTS: The average follow-up period was approximately 9 years, and hearing deteriorated at an average rate of approximately 4 dB/year. The rate of maintaining effective hearing decreased from 30 ears (81%) at the first visit to 19 ears (51%) at the final follow-up. The average rate of change in tumor growth for volume was approximately 686.0 mm3/year. This study revealed that most patients with NF2 experienced deterioration in hearing acuity and tumor growth during the natural course. A correlation was observed between an increase in tumor volume and hearing loss (r = 0.686; p < 0.001). CONCLUSIONS: Although the hearing preservation rate in NF2 cases is poor with the current treatment methods, many cases exist in which hearing acuity deteriorates, even during the natural course. Patients with an increased tumor volume during the follow-up period were more likely to experience hearing deterioration. Trial registration number 20140242 (date of registration: 27 October 2014).
Subject(s)
Neurofibromatoses , Neurofibromatosis 2 , Neuroma, Acoustic , Skin Neoplasms , Humans , Male , Retrospective Studies , Female , Neurofibromatosis 2/complications , Neurofibromatosis 2/pathology , Middle Aged , Adult , Neuroma, Acoustic/pathology , Neuroma, Acoustic/complications , Neuroma, Acoustic/physiopathology , Neurofibromatoses/complications , Skin Neoplasms/pathology , Skin Neoplasms/complications , Neurilemmoma/complications , Neurilemmoma/pathology , Neurilemmoma/surgery , Follow-Up Studies , Aged , Tumor Burden , Hearing Loss/etiology , Young Adult , Disease Progression , Adolescent , Audiometry, Pure-Tone , PrognosisABSTRACT
Carotid body tumors (CBTs) are neoplasms that occur at the bifurcation of the carotid artery and are pathologically classified as paragangliomas. In the 4th edition of the WHO classification, paragangliomas are categorized as neoplasms with malignant potential. Clinically, about 5% of CBTs present with malignant features such as metastasis. Currently, it is challenging to distinguish between tumors with benign courses and those that present malignantly. Recent advances in genetic testing have elucidated the genetic characteristics of paragangliomas, including carotid body tumors. Over 20 genes have been identified as being involved in tumor development. Particularly in head and neck paragangliomas, abnormalities in genes related to succinate dehydrogenase are frequently observed. Research is ongoing to understand the mechanisms by which these genes contribute to tumor development. The definitive treatment for CBTs is surgical resection. These tumors are prone to bleeding and often adhere firmly to the carotid artery, making intraoperative bleeding control challenging. The risk of lower cranial nerve paralysis is relatively high, and there is a risk of stroke because of manipulation of the carotid artery. Preoperative evaluation with angiography is essential, and a multi-disciplinary surgical team approach is necessary. In cases where the tumor is difficult to resect or has metastasized, radiation therapy or chemotherapy are employed. Clinical trials involving targeted molecular therapies and radiopharmaceuticals have recently been conducted, with some applied clinically. The development of various new treatments is anticipated, providing hope for therapeutic options in refractory cases.
Subject(s)
Carotid Body Tumor , Carotid Body Tumor/therapy , Carotid Body Tumor/genetics , Carotid Body Tumor/surgery , Humans , Succinate Dehydrogenase/geneticsABSTRACT
BACKGROUND: Salivary duct carcinoma (SDC) is a high-grade adenocarcinoma with a 5-year survival rate of 40%. Although drug therapy has improved patients' prognosis, the impact of brain metastasis (BM) remains poorly understood. We aimed to retrospectively examine the incidence of BM in patients with SDC (n = 464) and develop a tool to estimate their prognoses. METHODS: We retrospectively examined 464 patients with SDC enrolled in a multicenter study. We investigated the incidence of BM, overall survival (OS) rates, and factors affecting prognosis in patients with BM. We also developed an SDC-graded prognostic assessment (GPA) score for disease prognostication. RESULTS: Sixty-five (14%) patients had BM. The median OS (mOS) was 13.1 months. On univariate and multivariate analyses, factors such as Eastern Cooperative Oncology Group Performance Status >1, human epidermal growth factor receptor 2-negative status, and locoregional uncontrolled disease were associated with poor OS. SDC-GPA scores according to the prognostic factors were 0, 1, 2, and 3 points, and mOS estimates were 50.5, 16.1, 3.9, and 1.2 months, respectively (p < 0.001). CONCLUSION: The SDC-GPA score emerged as a useful prognostication tool for patients with BM.
Subject(s)
Brain Neoplasms , Carcinoma, Ductal , Salivary Gland Neoplasms , Humans , Retrospective Studies , Salivary Ducts/pathology , Prognosis , Salivary Gland Neoplasms/pathology , Carcinoma, Ductal/pathology , Brain Neoplasms/pathologyABSTRACT
Objectives: Evaluation of sarcopenia accompanied by systemic inflammation status is a more beneficial prognostic marker than sarcopenia alone in various cancers. However, few studies have focused on this combination in patients with head and neck squamous cell cancer (HNSCC). In this study, we investigated how the combination of sarcopenia and systemic inflammation could affect survival in patients with HNSCC. Moreover, we explored which systemic inflammation markers could be better prognostic indicators when accompanied by sarcopenia. Materials and methods: We retrospectively reviewed the medical records of patients with HNSCC treated between 2012 and 2016. Sarcopenia was defined by the skeletal muscle area measured on a computed tomography image slice at the level of the third cervical vertebra. The neutrophil/lymphocyte, platelet/lymphocyte, and lymphocyte/monocyte ratios (NLR, PLR, and LMR, respectively) were used as systemic inflammation markers that were combined with sarcopenia to evaluate prognosis. Results: A total of 100 patients were enrolled, and 71 patients were considered sarcopenia. Patients with sarcopenia had significantly lower LMR and higher NLR and PLR. They also showed worse overall survival (OS) and progression-free survival (PFS). The comparative assessment of multiple combination patterns of sarcopenia and systemic inflammation indices proved that sarcopenia plus LMR considered as most reliable indicator for prognosis in HNSCC patients. Sarcopenia plus low LMR was a significantly poor prognostic factor both for OS and PFS with greater HR values than sarcopenia alone. Conclusions: The combination of sarcopenia and LMR was considered the most sensitive prognostic factor in patients with HNSCC, suggesting it might be beneficial for identifying poor outcome risks.
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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.
Subject(s)
Antineoplastic Agents , Phenylurea Compounds , Quinolines , Thyroid Neoplasms , Humans , Thyroid Neoplasms/drug therapy , Thyroid Neoplasms/pathology , Male , Quinolines/therapeutic use , Quinolines/administration & dosage , Quinolines/adverse effects , Female , Middle Aged , Phenylurea Compounds/therapeutic use , Phenylurea Compounds/adverse effects , Phenylurea Compounds/administration & dosage , Retrospective Studies , Adult , Aged , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/administration & dosage , Treatment Outcome , Prognosis , Drug Administration ScheduleABSTRACT
Recurrent respiratory papilloma (RRP) often presents multiple lesions in the respiratory tract and sometimes becomes fatal because of severe airway obstruction. We report the case of a 69-year-old woman who had juvenile-onset RRP in the trachea that was refractory to surgical treatment, and complete remission was achieved by low-dose cisplatin combined with de-escalated radiotherapy without any side effects. This case report is the first to illustrate the data on low-dose cisplatin for refractory benign RRP, and our experience reinforces the opinion that low-dose cisplatin combined with de-escalated radiotherapy can be an effective and safe treatment alternative for uncontrollable and lethal RRP. Laryngoscope, 134:2335-2337, 2024.
Subject(s)
Papillomavirus Infections , Respiratory Tract Infections , Female , Humans , Aged , Cisplatin/therapeutic use , Papillomavirus Infections/pathology , Respiratory Tract Infections/pathology , Trachea/pathologyABSTRACT
OBJECTIVE: Asymmetric sensorineural hearing loss (ASHL) is the most common symptom of sporadic vestibular schwannoma (VS). However, there is still no universally accepted MRI protocol for diagnosing VS. This study identified the characteristics of pure tone audiogram (PTA) in patients with VS. METHODS: We conducted a retrospective chart review of patients diagnosed with sporadic unilateral VS. In the analysis, we focused on the shape and interaural differences of PTA, stratified by the mode of onset and patient age. RESULTS: In total, 390 patients met the inclusion criteria. The U-shaped audiogram showed the highest proportion in patients with the onset of sudden sensorineural hearing loss (SSNHL). In patients with SSNHL, U-shaped audiograms were younger than other audiograms, and 86.7 % of patients under 40 had U-shaped audiograms. Patients with VS were more likely to have interaural differences at higher frequencies than at lower frequencies. Patients with SSNHL had a significantly higher percentage of interaural differences at 500-4000 Hz than those with onset other than SSNHL (non-SSNHL patients). In addition, non-SSNHL patients had a significant trend toward a higher percentage of interaural differences at all frequencies with increasing age. CONCLUSION: MRI screening can be considered in patients with SSNHL with U-shaped audiograms under 40 years of age. In ASHL, not SSNHL, MRI screening can be considered for older patients with interaural differences at wider continuous frequencies. Patients with interaural differences at high frequencies had a higher priority than those with interaural differences at low frequencies as indications for MRI screening for VS.
Subject(s)
Hearing Loss, Sensorineural , Hearing Loss, Sudden , Neuroma, Acoustic , Humans , Neuroma, Acoustic/complications , Neuroma, Acoustic/diagnostic imaging , Retrospective Studies , Audiometry , Hearing Tests , Hearing Loss, Sensorineural/diagnosis , Caffeine , Audiometry, Pure-ToneABSTRACT
Relapsing polychondritis (RP) is a rare chronic inflammatory disease characterized by recurrent inflammation of cartilages throughout the body, with treatment-resistant dizziness and hearing loss in 40%-50% of patients with RP. Although rare, severe binaural hearing loss in RP is an indication for cochlear implantation (CI). Therefore, there are only a few reports on CI insertion in cases of RP. This report describes a 68-year-old woman who developed binaural hearing loss due to RP. She was treated with steroids and immunosuppressive drugs; however, her hearing did not improve significantly, and she relied on written communication for conversation. Subsequently, the patient underwent CI in the right ear. The patient showed improvement in speech perception; at 14 months postoperatively, she was able to speak with lipreading, and at 2 years postoperatively, she was able to speak without lipreading. Previous case reports on CI in patients with RP have shown varying degrees of postoperative hearing improvement. Our case demonstrates the effectiveness of CI in improving hearing and speech recognition in patients with RP having semicircular canal calcification. However, previous reports have shown that speech recognition declines 13 years after CI for RP. Therefore, continuous long-term follow-up is necessary.
ABSTRACT
RATIONALE: Hypertrophic pachymeningitis (HP) is a local or diffuse fibrous thickness of the dura mater of the brain or spinal cord, caused by infection or connective tissue disease. Headache is the most common clinical symptom, followed by various cranial nerve disorders such as visual impairment, diplopia, and hearing loss. HP can be classified into secondary and idiopathic. Here, we report a case of bilateral progressive profound sensorineural hearing loss diagnosed in a patient with idiopathic HP, where a cochlear implant was effectively used. PATIENT CONCERNS: The patient was a 77-year-old woman. Hearing loss gradually progressed bilaterally, and magnetic resonance imaging showed a space-occupying lesion with a continuous contrast enhancement in the bilateral internal auditory canals, and diffused dural thickening from the middle to the posterior cranial fossa. DIAGNOSES: A trans-labyrinthine biopsy was conducted, and a definite diagnosis of idiopathic HP was made. Thickening of the dura mater in the bilateral internal auditory canals was thought to cause profound hearing loss. INTERVENTIONS AND OUTCOMES: A cochlear implant was implemented 4 months after biopsy, and a favorable hearing response was obtained postoperatively. LESSONS: This is the first report of a cochlear implant in a patient with idiopathic HP. Cochlear implantation was considered a good treatment for profound hearing loss due to idiopathic HP, which provides a reference for patients to receive timely and correct treatment.