Allergic Fungal Rhinosinusitis and Contralateral Chronic Granulomatous Invasive Fungal Sinusitis: A Case Report.

This case report describes rare concomitant allergic fungal rhinosinusitis (AFRS) and chronic granulomatous invasive fungal sinusitis (CGIFS) in a 34-year-old woman with acute lymphoblastic leukemia and graft-versus-host disease (GVHD) post bone marrow transplantation. Initially presenting with rhinorrhea and nasal obstruction, the patient was diagnosed with AFRS in the right maxillary sinus, followed by a postoperative course of CGIFS in the left nasal cavity, showcasing the unique occurrence. She was not immunocompromised during diagnosis. CGIFS may have occurred because of surgery; however, voriconazole led to significant improvement. This case highlights noninvasive and invasive fungal infections in patients with chronic rhinosinusitis and a history of GVHD and underscores the complexity of diagnosing and managing such cases.

Swallowing Function and Quality of Life in Patients Treated With Transoral Videolaryngoscopic Surgery for Pharyngolaryngeal Cancer.

BACKGROUND: It is controversial whether transoral resection for early pharyngolaryngeal cancer preserves swallowing function and quality of life. We investigated swallowing function and quality of life before and after transoral videolaryngoscopic surgery (TOVS). METHODS: Seventy-three patients with pharyngolaryngeal cancer who underwent TOVS between July 2012 and July 2022 were enrolled in this prospective analysis. The Hyodo score and European Organization for Research and Treatment of Cancer Quality of Life Questionnaires were recorded preoperatively and at three, six, and 12 months postoperatively, in addition to the postoperative functional outcome swallowing scale (FOSS) at six months postoperatively. RESULTS: Although most patients could consume food orally without restrictions with a preferable FOSS score, 23 patients showed impaired Hyodo scores. Age ≥65 years significantly predicted impaired swallowing. Sub-scores of the impaired patient group showed worsening for the glottal closure reflex when the endoscope touched the epiglottis or arytenoid, as well as a reduction in the extent of pharyngeal clearance following the ingestion of blue-dyed water. CONCLUSION: After TOVS, swallowing function is generally well preserved. Elderly patients, especially those with laryngeal hypoesthesia and poor clearance, are at risk of swallowing dysfunction.

Abscopal effect in maxillary sinus cancer: Insights from two case reports and a literature review.

BACKGROUND: The abscopal effect is a rare phenomenon in which localized radiation therapy triggers tumor reduction in nontargeted areas. Although this phenomenon has been observed in various cancer types, it remains infrequent and not fully understood. CASE: Two patients with maxillary sinus cancer with distant metastases were treated with radiotherapy after immune checkpoint inhibitor (ICI) therapy. The patients demonstrated abscopal effects following ICI therapy and radiotherapy, showing shrinkage in metastatic areas not directly targeted by radiation. CONCLUSION: This report was reviewed to examine the synergistic effects of ICI and radiotherapy and to identify optimal strategies to enhance the abscopal effect in clinical practice. It has also touched on various ongoing debates and clinical trials aimed at understanding and exploiting this effect to improve cancer treatment. The exact mechanisms and optimal treatment protocols remain areas for future research.

Two cases of parathyroid carcinoma associated with multiple brown tumours.

We present two rare cases of parathyroid carcinomas associated with multiple brown tumours. Plain radiographs, computed tomography, and neck ultrasonography revealed the presence of bone and parathyroid tumours. Despite the use of 99m Tc-methoxy isobutyl isonitrile (99mTc-MIBI) or 18F-fluorodeoxyglucose-positron emission tomography (18F-FDG PET)/CT, it was difficult to differentiate bone metastases from brown tumours. Parathyroid carcinoma was confirmed by histopathological examination following parathyroidectomy, resulting in spontaneous bone lesion improvement. In patients with parathyroid carcinoma presenting with bone lesions suggestive of metastasis, understanding the potential for brown tumour accumulation through 99mTc-MIBI or 18F-FDG PET/CT is pivotal. With this understanding, it is possible to diagnose brown tumours with parathyroidectomy and follow up for improvement of bone lesion and avoid invasive biopsy or surgery.

Safety and outcome of three-dimensional transoral videolaryngoscopic surgery.

BACKGROUND: Transoral videolaryngoscopic surgery (TOVS) is widely used in Japan, and conventional two-dimensional (2D) endoscopic methods have been established. Three-dimensional (3D) endoscopic surgery offers superior distance perception because it provides stereoscopic views. Recently, we have developed 3D endoscopy for TOVS (3D TOVS). METHODS: This study included 46 patients with pharyngeal cancer who underwent 3D TOVS. The perioperative complications and survival curves were retrospectively analyzed. RESULTS: One patient with oropharyngeal cancer who underwent neck dissection and transoral resection simultaneously experienced postoperative hemorrhage of the neck. Another patient with oropharyngeal cancer underwent hemostasis for postoperative pharyngeal hemorrhage. There was one case of aspiration pneumonia. One patient developed cervical lymph node recurrence; however, there was no local recurrence or primary mortality. The 2-year overall survival, disease-specific survival, local control rates, locoregional control rate, and invasive disease-free survival were 90.9%, 100%, 100%, 97.4%, and 79.9%, respectively. CONCLUSIONS: Three-dimensional endoscopy can be safely applied to TOVS.

Recurrent Inferior Laryngeal Nerve Preservation During Thyroid Surgery in a Patient with Right Aortic Arch: A Case Report.

Patients with aortic arch malformations may present with recurrent inferior laryngeal nerve abnormalities that require special attention. Herein, we reported a case of thyroid surgery in a patient with a right aortic arch. The left inferior laryngeal nerve was presumed to be the right inferior laryngeal nerve by confirming the location of the aortic arch and subclavian artery, and the presence of the ductus arteriosus on preoperative computed tomography. Continuous intraoperative nerve monitoring is useful for safe surgery in patients with possible inferior laryngeal nerve abnormalities. Laryngoscope, 134:1986-1988, 2024.

Defining the relationship of salivary gland malignancies to novel cell subpopulations in human salivary glands using single nucleus RNA-sequencing.

Salivary glands have essential roles in maintaining oral health, mastication, taste and speech, by secreting saliva. Salivary glands are composed of several types of cells, and each cell type is predicted to be involved in the carcinogenesis of different types of cancers including adenoid cystic carcinoma (ACC), acinic cell carcinoma (AciCC), salivary duct carcinoma (SDC), myoepithelial carcinoma (MECA) and other histology. In our study, we performed single nucleus RNA-seq on three human salivary gland samples to clarify the gene expression profile of each complex cellular component of the salivary glands and related these expression patterns to expression found in salivary gland cancers (SGC) to infer cell of origin. By single nucleus RNA-seq, salivary gland cells were stratified into four clusters: acinar cells, ductal cells 1, ductal cells 2 and myoepithelial cells/stromal cells. The localization of each cell group was verified by IHC of each cluster marker gene, and one group of ductal cells was found to represent intercalated ductal cells labeled with HES1. Furthermore, in comparison with SGC RNA-seq data, acinar cell markers were upregulated in AciCC, but downregulated in ACC and ductal cell markers were upregulated in SDC but downregulated in MECA, suggesting that markers of origin are highly expressed in some SGC. Cell type expressions in specific SGC histology are similar to those found in normal salivary gland populations, indicating a potential etiologic relationship.

Metachronous immune-related adverse events involving type 1 diabetes and isolated adrenocorticotropic hormone deficiency associated with pembrolizumab monotherapy for metastatic head and neck cancer: a case report.

BACKGROUND: Immune checkpoint inhibitors might cause immune-related adverse events that are still largely unknown. CASE PRESENTATION: An 80-year-old Asian female was diagnosed with cervical lymph node metastasis from lip cancer (cT1N0M0) and underwent right cervical neck dissection. Subsequently, she developed right cervical lymph node relapse and lung metastasis. The patient was deemed eligible for pembrolizumab owing to unresectable neck recurrence and pulmonary metastasis. The Combined Positive Score of the submandibular lymph nodes was 100. Pembrolizumab monotherapy was initiated, and complete remission was achieved. She developed diabetic ketoacidosis in the eighth month and was diagnosed with fulminant type 1 diabetes mellitus. Insulin induction was performed. The patient developed adrenal insufficiency after 10 months. These were immune-related adverse events, caused by pembrolizumab. The patient has remained in complete remission, and pembrolizumab therapy was continued. CONCLUSIONS: The study presents the first reported case of type 1 diabetes in a patient with head and neck squamous cell carcinoma treated with pembrolizumab monotherapy, in Japan. Efficient interdepartmental collaboration will promote the management of severe immune-related adverse events and improve the quality of life of patients.

Shoulder function after neck dissection with level IIb preservation: a prospective observational study.

BACKGROUND: Shoulder syndrome can be reduced by preserving the spinal accessory nerve (SAN). However, it is unclear whether performing level IIb preservation will decrease the risk of SAN injury and shoulder syndrome. AIMS/OBJECTIVES: We investigated whether neck dissection with level IIb preservation can reduce shoulder dysfunction and postoperative quality of life (QOL) in head and neck cancer patients. MATERIAL AND METHODS: This prospective observational study enrolled patients who underwent neck dissection from 2011 to 2014. Patients were divided into three groups (level IIb preservation group [group 1], IIb dissection group [group 2], and IIb and V dissection group [group 3]). Postoperative shoulder function and QOL were evaluated among the three groups. RESULTS: There were a total of 35 neck sides in three groups, with nine neck sides in group 1, 16 neck sides in group 2, and 10 neck sides in group 3. Although the results showed less shoulder dysfunction in group 1 at early postoperative period. The QOL in group 1 was preserved in the early postoperative period. CONCLUSIONS AND SIGNIFICANCE: Neck dissection with level IIb preservation may help reduce shoulder syndrome and maintain QOL in the early postoperative period.

Chemotherapy following immune checkpoint inhibitors in recurrent or metastatic head and neck squamous cell carcinoma: clinical effectiveness and influence of inflammatory and nutritional factors.

OBJECTIVE: This study aimed to evaluate the clinical effectiveness of chemotherapy following immune checkpoint inhibitors (ICI). The association between inflammatory and nutritional factors and prognosis has also been investigated. METHODS: We retrospectively reviewed the medical records of recurrent or metastatic head and neck squamous cell carcinoma (RMHNSCC) patients who received chemotherapy following ICI therapy. The response rate and survival after chemotherapy, and nutritional and inflammatory factors, were examined. RESULTS: The ICI before chemotherapy was nivolumab in 36 patients (70.6%) and pembrolizumab in 15 patients (29.4%). The chemotherapy regimens consisted of PTX in 32 patients (62.7%), PTX + Cmab in 9 (17.6%), and S1 in 10 (19.6%). The median overall survival (OS) was 20 months (95% CI 12-25), the estimated 12-month OS rate was 63.3%, the median progression-free survival (PFS) was 5 months (CI 4-6), and the 12-month PFS estimate was 8.9%. Univariate analysis significantly correlated Neutrophil-to-Lymphocyte Ratio (NLR), platelet-to-lymphocyte ratio (PLR), controlling nutritional status score (CONUT), and prognostic nutrition index (PNI) with OS and PFS. Additionally, these factors were significantly correlated with OS and PFS in the log-rank tests. CONCLUSIONS: Chemotherapy following ICI is highly effective. There were no significant differences in the chemotherapy regimens. Inflammatory and nutritional factors may associate with patient prognosis after chemotherapy.

Salvage transoral videolaryngoscopic surgery for post-irradiation recurrence of hypopharyngeal carcinoma.

Background: Transoral salvage surgery has the potential to preserve a patient's quality of life. Therefore, we investigated the outcomes, safety, and risk factors for postoperative complications of salvage transoral videolaryngoscopic surgery (TOVS) for recurrent hypopharyngeal carcinoma after radiotherapy (RT) or chemoradiotherapy (CRT). Methods: This retrospective analysis enrolled patients with hypopharyngeal cancer who had a history of RT or CRT and underwent TOVS from January 2008 to June 2021. The factors related to postoperative complications, postoperative swallowing functions and survival rates were analyzed. Results: Seven patients (36.8%) of the 19 patients developed complications. Severe dysphagia was the primary complication, and post-cricoid resection was a complication risk factor. The FOSS score was significantly lower in the salvage treatment group. The survival rates were: 3-year overall survival: 94.4%; disease-specific survival: 94.4%; 5-year overall survival: 62.3%; and disease-specific survival: 86.6%. Conclusions: Salvage TOVS for hypopharyngeal cancer was feasible, and oncologically and functionally reasonable. Level of Evidence: 2b.

Prognostic Value of Inflammatory and Nutritional Biomarkers of Immune Checkpoint Inhibitor Treatment for Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck.

This study aimed to determine the prognostic value of inflammatory and nutritional biomarkers of immune checkpoint inhibitor (ICI) therapy for recurrent or metastatic squamous cell carcinoma of the head and neck (RMHNSCC) and to identify the most useful factor for prognosis assessment. We retrospectively reviewed the medical records of patients with RMHNSCC who received ICI therapy. The response rate for ICI therapy and the relationship between inflammatory and nutritional biomarkers and overall survival were examined. The included biomarkers did not correlate with an objective response rate but were associated with a disease control rate. Univariate analysis showed significant correlations between the serum albumin level, C-reactive protein level, platelet to lymphocyte ratio, neutrophil to lymphocyte ratio, lymphocyte to monocyte ratio (LMR), systemic immune-inflammation index, and controlling the nutritional status score and overall survival; multivariate analysis showed that LMR was significantly correlated with overall survival. LMR was the most important biomarker according to the machine learning model. This study suggests that LMR may be the most useful biomarker for predicting the prognosis of ICI treatment for RMHNSCC.

Malignant Lymphoma with the MRI Findings Mimicking Inflammatory Disease: A Case Report.

Magnetic resonance imaging (MRI) is a more useful diagnostic modality for detecting paranasal tumors compared with computed tomography (CT). We encountered a case of malignant lymphoma of the maxillary sinus. Although CT findings suggested malignancy, MRI findings indicated an inflammatory disease. The patient was a 51-year-old man with a chief complaint of right maxillary toothache. Edema in the right middle meatus and bloody rhinorrhea were observed. CT revealed r ight maxillary s inus shadow with partial bone loss, suggesting malignancy. However, MRI performed two weeks later showed an internal homogeneous lesion with neither contrast effect, nor invasion outside the maxillary sinus. The patient also had no fever, weight loss, or night sweats. Additionally, no palpable cervical lymphadenopathy was observed. Endoscopic sinus surgery was performed to confirm the diagnosis. Upon opening the maxillary sinus, highly viscous retention and a large amount of yellowish-white debris were observed. Allergic fungal rhinosinusitis was suspected. However, histopathological analysis of the debris established a diagnosis of malignant lymphoma. The debris exhibited pathological findings of necrosis. The patient remained in remission after undergoing radiochemotherapy. Malignant lymphomas of the paranasal sinuses, which have a minimal tendency for invasion but with considerable predominance of necrosis, may be diagnosed as an inflammatory disease, based on MRI findings. In cases in which a thorough physical examination could not rule out malignant lymphomas, an endoscopic biopsy should be immediately considered.

Identification of novel prognostic and predictive biomarkers in salivary duct carcinoma via comprehensive molecular profiling.

Molecular targets and predictive biomarkers for prognosis in salivary duct carcinoma (SDC) have not been fully identified. We conducted comprehensive molecular profiling to discover novel biomarkers for SDC. A total of 67 SDC samples were examined with DNA sequencing of 464 genes and transcriptome analysis in combination with the clinicopathological characteristics of the individuals. Prognostic biomarkers associated with response to combined androgen blockade (CAB) treatment were explored using mRNA expression data from 27 cases. Oncogenic mutations in receptor tyrosine kinase (RTK) genes or genes in the MAPK pathway were identified in 55 cases (82.1%). Alterations in the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway were identified in 38 cases (56.7%). Interestingly, patient prognosis could be predicted using mRNA expression profiles, but not genetic mutation profiles. The risk score generated from the expression data of a four-gene set that includes the ADAMTS1, DSC1, RNF39, and IGLL5 genes was a significant prognostic marker for overall survival in the cohort (HR = 5.99, 95% confidence interval (CI) = 2.73-13.1, p = 7.8 × 10-6). Another risk score constructed from the expression of CD3E and LDB3 was a strong prognostic marker for progression-free survival for CAB treatment (p = 0.03). Mutations in RTK genes, MAPK pathway genes, and PI3K/AKT pathway genes likely represent key mutations in SDC tumorigenesis. The gene expression profiles identified in this study may be useful for stratifying patients who are good candidates for CAB treatment and may benefit from additional systemic therapies.

A Study of Patients with Recurrent or Metastatic Head and Neck Cancer Treated with Pembrolizumab.

BACKGROUND/AIM: In December 2019, pembrolizumab was approved in Japan for the treatment of head and neck cancer with recurrence or distant metastasis, making it a new option for first-line treatment. However, there are still many unanswered questions about Overall survival (OS), Progression free survival (PFS), adverse events including immune-related adverse events (irAEs), and biomarkers. AIMS/OBJECTIVES: The aim of this study was to retrospectively review first-line treatment of head and neck cancer with recurrence or distant metastasis treated with pembrolizumab and to determine whether Combined positive score (CPS) is still useful as a biomarker in the clinical practice. MATERIAL AND METHODS: We retrospectively reviewed clinical records of 20 patients who received pembrolizumab as first-line treatment for head and neck cancer with recurrence or distant metastasis between December 2019 and March 2021. RESULTS: Age ranged from 45 to 83 years (median 66 years), 17 male patients and 3 female patients. The response rate was 40%, and the disease control rate was 60%. OS and PFS in patients with CPS < 1 were significantly worse than those with CPS ≤ 1 (CPS-positive patients). The OS and PFS of patients with CPS < 1 were s ignificantly worse than those of p atients with 1 < = CPS (CPS-positive p atients), and there was no significant difference between the group with CPS between 1 and 20 and the group with CPS over 20. And we experiences several CR cases with high CPS. CONCLUSION: CPS is a useful biomarker for pembrolizumab. SIGNIFICANCE: There are no reported cases of CR after two courses of pembrolizumab in head and neck cancer. There are no reports of pembrolizumab in patients with head and neck cancer in Japan.

Survival benefit of HER2-targeted or androgen deprivation therapy in salivary duct carcinoma.

Background: The efficacy and safety of human epidermal growth factor receptor 2 (HER2)-targeted therapy and androgen deprivation therapy (ADT) for locally advanced or recurrent or metastatic (LA/RM) salivary duct carcinoma (SDC) have been reported in prospective studies. However, the survival benefit of these therapies to conventional therapy remains controversial, and whether HER2-targeted therapy or ADT should be chosen in HER2- and androgen receptor (AR)-positive SDC patients remains unknown. Methods: Overall, 323 LA/RM SDC patients treated at seven institutions between August 1992 and June 2020 were retrospectively enrolled. The primary aim was to analyze the effect of HER2-targeted therapy and ADT on overall survival from the diagnosis of LA/RM disease to death from any cause (OS1). The secondary indicators included the overall response rate (ORR), clinical benefit rate (CBR), overall survival from therapy initiation for LA/RM disease (OS2), progression-free survival (PFS), time to second progression (PFS2), duration of response (DoR), and duration of clinical benefit (DoCB) of HER2-targeted therapy or ADT as first-line therapy for HER2-positive/AR-positive SDC. Results: Patients treated with HER2-targeted therapy or ADT had longer OS1 than those treated without these therapies (Median OS1: historical control, 21.6 months; HER2-targeted therapy, 50.6 months; ADT, 32.8 months; HER2-targeted therapy followed by ADT, 42.4 months; and ADT followed by HER2-targeted therapy, 45.2 months, p < 0.001). Among HER2-positive/AR-positive SDC patients, although HER2-targeted therapy had better ORR, CBR, and PFS than those of ADT as first-line therapy, we found no significant differences between HER2-targeted therapy and ADT regarding OS2, PFS2, DoR, and DoCB. Conclusion: Patients treated with HER2-targeted therapy and ADT showed longer survival in LA/RM SDC. HER2-targeted therapy can be recommended prior to ADT for HER2-positive/AR-positive SDC. It is warranted to establish a biomarker that could predict the efficacy of clinical benefit or better response in ADT.

Tumor detection with transoral use of flexible endoscopy for unknown primary head and neck cancer.

OBJECTIVES: With the advent of new optical technologies, early pharyngolaryngeal cancerous lesions can be better visualized. Although the conventional transnasal approach offers great views of the hypopharynx and larynx, the visualization of the oropharynx and palatine tonsils is limited. Through the transoral insertion of a flexible video-laryngoscope, direct views of the oropharynx and oral cavity can be obtained. Thus, transoral examination may contribute to primary detection of cancers of unknown primary (CUP). METHODS: Eighty-five CUP patients from Tokai University were included retrospectively in this study, from 2006 to 2017. Starting in 2010, we employed the transoral examination in addition to our conventional method. The primary detection rates were compared before and after 2010. Oropharyngeal primaries were further analyzed for tumor subsite and p16 status. RESULTS: The overall primary detection rate did not improve with the addition of transoral examination. However, greater numbers of oropharyngeal primaries were detected. The oropharyngeal lesions detected by transoral examination were mainly p16 positive, located on the palatine tonsil. CONCLUSION: Transoral examination is a noninvasive, easy method to adopt in an outpatient setting, and a promising technique to improve tumor detection in this era of human papillomavirus-associated head and neck cancers. LEVEL OF EVIDENCE: 3.

Immunohistochemical Marker Expression in Temporal Bone Squamous Cell Carcinoma.

BACKGROUND: The correlation between genomic mutations (or the overexpression of abnormal proteins) and prognosis in temporal bone squamous cell carcinoma (TBSCC) is not clear. We investigated the overexpression of EGFR and p53 as a pathological biomarker for predicting the clinical course of patients with TBSCC. METHODS: We performed a retrospective review of 22 TBSCC cases treated in Tokai University Hospital between January 2005 and October 2016. We assessed the overexpression of EGFR and p53 in TBSCC patients through immunohistochemical staining. We also evaluated the association between the overexpression of these proteins and clinicopathological variables, including survival outcomes. RESULTS: The primary lesion in all patients was the external auditory canal. Nine (40.9%) patients were EGFR positive, and 9 (40.9%) were p53 positive. The 5-year overall survival rate for EGFR-positive patients (55.6%) was significantly lower (p = 0.043) than that of the EGFR-negative patients (92.3%). CONCLUSION: EGFR overexpression in TBSCC patients may be a prognostic biomarker.

A p16 Positive M1 Oral Tongue Cancer Completely Responsive to the EXTREME Regimen: A Case Report.

METHODS: A 42-year-old woman presented to our clinic with tongue pain and dysarthria. She had a smoking history of 22 pack-years and no history of alcohol consumption. A deep ulcer at the left side of the tongue and induration across the whole tongue were observed. The bilateral cervical lymph nodes were palpable. A biopsy from the ulcer revealed squamous cell carcinoma. PET/CT showed sternal bone metastasis resulting in the final diagnosis of left-sided oral tongue cancer (cT4aN2cM1). Systemic chemotherapy treatment involving 6 courses of the EXTREME regimen followed by weekly cetuximab administration was indicated. RESULTS: After the first two courses, diminished tongue pain and improved dysarthria were observed; complete response was obtained after 6 courses. Re-examination of the biopsy specimen showed that the tumor was p16 positive. The p16 protein is a surrogate marker for HPV, but in this case HPV in-situ hybridization was negative. Locoregional or distant failure were not observed during the 5-year follow-up period. CONCLUSIONS: The treatment regimen unexpectedly proved successful. It may be beneficial to examine p16 expression in oral tongue cancer to identify patients that are more likely to benefit from the EXTREME treatment regimen.

Computed Tomography to Diagnose Paranasal Sinus Chemical Burns and Tissue Damage: A Case Report.

Chemical burns of the paranasal sinus are rare; therefore, assessment methods for treatment of and prognoses for the exposure site are unknown. We experienced a case in which a hydrochloric acid burn of the paranasal sinuses caused irreversible tissue damage. Computed tomography is useful for identifying the exposure site and assessing tissue damage over time. Identification of the exposure site and proactive washing are recommended for patients with chemical burns of the paranasal sinuses. Laryngoscope, 131:E2490-E2493, 2021.