The objective of this study was to compare the prognostic impact of sarcopenia in patients with head and neck cancer (HNC) treated with surgery or radiation.
We systematically searched electronic ...databases to identify articles reporting the impact of sarcopenia on the prognosis of patients with HNC. Hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS) were extracted and pooled. HR according to treatment modality were estimated using random-effects models. Statistical analyses were carried out using the Comprehensive Meta-Analysis software.
In total, 18 studies enrolling 3,233 patients were included. Sarcopenia was associated with poor OS in both surgery and radiotherapy groups (hazard ratio HR 2.50, 95% confidence interval CI 1.95-3.21; HR 1.63, 95% CI 1.40-1.90, respectively). The HR was significantly higher in the surgery group than in the radiotherapy group (p = 0.004), with similar results obtained for DFS (HR 2.59, 95% CI 1.56-4.31; HR 1.56, 95% CI 1.24-1.97 for the surgery and radiotherapy groups, respectively) and DSS (HR 2.96, 95% CI 0.73-11.95; HR 2.67, 95% CI 1.51-4.73 for the surgery and RT groups, respectively).
Sarcopenia was a poor prognostic factor for HNC, regardless of the treatment modality. However, the adverse effects of sarcopenia on survival were more prominent in the surgery group than in the radiotherapy group. Sarcopenia assessment is required for appropriate treatment decision-making.
Sarcopenia, which is characterized by a decrease in muscle quantity or quality, is commonly observed in patients with cancer. Recent research has reported contradictory results on the association ...between sarcopenia and the efficacy of immune checkpoint inhibitors (ICIs). We conducted a systematic review and meta‐analysis to investigate this discrepancy. We systematically searched three electronic databases to identify articles reporting on the association between sarcopenia and treatment outcomes in patients with solid cancers who received ICIs. The outcomes assessed were hazard ratios (HRs) for overall survival (OS) and progression‐free survival (PFS), and odds ratios (ORs) for objective response rate (ORR), disease control rate (DCR), and toxicity. Pooled estimates and their 95% confidence intervals (CIs) were calculated. A total of 2501 patients from 26 studies were analysed. Sarcopenia was observed in 44.7% (95% CI: 38.2–51.3) of the patients and was significantly associated with poor survival (HR = 1.55, 95% CI = 1.32–1.82 for OS and HR = 1.61, 95% CI = 1.35 to 1.93 for PFS). The HRs (95% CIs) for OS according to the diagnostic measures used were 1.97 (0.88–4.41) for psoas muscle index (PMI), 1.41 (0.87–2.28) for skeletal muscle density (SMD), and 1.43 (1.23–1.67) for skeletal mass index (SMI). The HRs (95% CIs) for PFS were 1.86 (1.08–3.21) for PMI, 1.27 (0.94–1.71) for SMD, and 1.38 (1.11–1.71) for SMI. Poor radiological response to ICI therapy was observed in patients with sarcopenia (OR = 0.52, 95% CI = 0.34–0.80 for ORR and OR = 0.45, 95% CI = 0.30–0.67 for DCR). The ORs for ORR (95% CIs) were 0.56 (0.15–2.05) for PMI and 0.78 (0.56–1.09) for SMI. The oncologic outcomes associated with melanoma and non‐small cell lung cancer (NSCLC) were comparable with those observed overall (HR for OS = 2.02, 95% CI = 1.26–3.24 for melanoma and HR for OS = 1.61, 95% CI = 1.19–2.18 for NSCLC). In contrast, the occurrence of severe toxicity was not associated with sarcopenia (OR = 1.13, 95% CI = 0.51–2.52). Poor survival and poor response in patients with sarcopenia indicate a negative association between sarcopenia and efficacy of ICIs. Sarcopenia's predictive ability is consistent across various tumour types. For the selection of patients who may respond to ICIs pre‐therapeutically, the presence of sarcopenia should be assessed in clinical practice.
Approximately 20% of patients with differentiated thyroid cancer (DTC) have direct tumor extension with invasion of the surrounding tissues such as the larynx, trachea, esophagus, or recurrent ...laryngeal nerve. Recent progress of molecular-targeted therapy, such as the use of tyrosine kinase inhibitors, improves survival outcome in patients with advanced DTC. However, induction of tyrosine kinase inhibitors for locally-advanced DTC has presented novel fatal adverse events including fistula in patients with infiltration toward to the trachea, pharynx and esophagus, and fatal bleeding in patients with great vessel invasion. Surgery therefore still has an important role in DTC management, particularly in local control. The surgical strategy for laryngeal/tracheal invasion, which commonly occurs by DTC, is decided according to the extension (depths and area) of the tumor. The “shave procedure” is performed when the tumor has superficially invaded the larynx/trachea. However, intra-luminal extension requires resection and reconstruction of the larynx/trachea wall. Large veins, such as the internal jugular vein and the subclavian vein, are also frequently directly invaded by DTC. Three types of jugular vein reconstruction have been advocated to avoid fatal complications according to bilateral jugular vein ligation. The majority of carotid artery invasion by DTC can be managed with tumor resection of the sub-adventitial layer without reconstruction surgery using an artificial vessel. In this review article, we examine surgery for advanced DTC, showing the surgical strategy toward DTC that has invaded the laryngotracheal, recurrent laryngeal nerve, esophagus/hypopharynx, or great vessels.
Benign paroxysmal positional vertigo (BPPV) is characterized by positional vertigo (brief attacks of rotatory vertigo triggered by head position changes in the direction of gravity) and is the most ...common peripheral cause of vertigo. There are two types of BPPV pathophysiology: canalolithiasis and cupulolithiasis. In canalolithiasis, otoconial debris is detached from the otolithic membrane and floats freely within the endolymph of the canal. In cupulolithiasis, the otoconial debris released from the otolithic membrane settles on the cupula of the semicircular canal and the specific gravity of the cupula is increased. Consensus has been reached regarding three subtypes of BPPV: posterior-canal-type BPPV (canalolithiasis), lateral-canal-type BPPV (canalolithiasis) and lateral-canal-type BPPV (cupulolithiasis). In the interview-based medical examination of BPPV, questions regarding the characteristics of vertigo, triggered movement of vertigo, duration of vertigo and cochlear symptoms during vertigo attacks are important for the diagnosis of BPPV. The Dix–Hallpike test is a positioning nystagmus test used for diagnosis of posterior-canal-type BPPV. The head roll test is a positional nystagmus test used for diagnosis of lateral-canal-type BPPV. When the Dix–Hallpike test is repeated, positional nystagmus and the feeling of vertigo typically become weaker. This phenomenon is called BPPV fatigue. The effect of BPPV fatigue typically disappears within 30 min, at which point the Dix–Hallpike test again induces clear positional nystagmus even though BPPV fatigue had previously caused the positional nystagmus to disappear. For the treatment of BPPV, sequential head movements of patients can cause the otoconial debris in the semicircular canal to move to the utricle. This series of head movements is called the canalith repositioning procedure (CRP). The appropriate type of CRP depends on the semicircular canal in which the otoconial debris is located. The CRP for posterior-canal-type BPPV is called the Epley maneuver, and the CRP for lateral-canal-type BPPV is called the Gufoni maneuver. Including a time interval between each head position in the Epley maneuver reduces the immediate effect of the maneuver. This finding can inform the development of methods for reducing the effort exerted by doctors and the discomfort experienced by patients with posterior-canal-type BPPV during the Epley maneuver.
Verrucous carcinoma (VC) is a rare variant of squamous cell carcinoma. Although VC is considered radioresistant, concrete evidence for this is absent. We obtained data on VC treated with surgery or ...radiation from the Surveillance, Epidemiology, and End Results database. Treatment selection bias was reduced by propensity score matching. Overall survival (OS) and disease-specific survival (DSS) rates were estimated using the Kaplan-Meier method. Hazard ratios (HRs) were estimated using Cox proportional hazards models. Five-year OS rates in the radiation and surgery groups were 72.7% and 72.0%, respectively (P = 0.111); five-year DSS rates in the same were 86.7% and 88.4%, respectively (P = 0.234). HRs of radiation compared with surgery were 1.68 (95% confidence interval (CI), 0.96-2.95) for OS and 1.95 (95% CI, 0.69-5.53) for DSS. Similar prognoses were observed in patients with VC treated with radiation and surgery. VC can be treated using radiation.
Positron emission tomography and computed tomography (PET‐CT) is widely used to assess the response to radiotherapy. However, the ability of PET‐CT to predict treatment failure in human ...papillomavirus (HPV)‐related squamous cell carcinoma of the head and neck (HNSCC) is unsatisfactory. We quantified circulating tumor HPV type16 DNA (ctHPV16DNA) using optimized droplet digital PCR in 35 patients with HPV16‐related HNSCC, who received radiotherapy with or without chemotherapy, and prospectively correlated ctHPV16DNA and metabolic response with treatment failure. After a median follow‐up of 21 months, ctHPV16DNA and PET‐CT had similar negative predictive values (89.7% vs 84.0%), whereas the positive predictive value was much higher in ctHPV16DNA than in PET‐CT (100% vs 50.0%). Notably, six patients who had detectable posttreatment ctHPV16DNA all had treatment failure irrespective of metabolic response, whereas none of five patients who had partial metabolic response without detectable posttreatment ctHPV16DNA had treatment failure. The risk of treatment failure was high in patients who had incomplete metabolic response with detectable posttreatment ctHPV16DNA (hazard ratio HR, 138.8; 95% confidence interval CI, 15.5‐3366.4; P < .0001) and intermediate in patients who had discordant results between metabolic response and posttreatment ctHPV16DNA (HR, 4.7; 95% CI, 0.8‐36.2, P = .09) as compared with patients who had complete metabolic response without detectable posttreatment ctHPV16DNA. One‐year event‐free survival rates of each risk group were 0%, 88% (95% CI, 46‐98) and 95% (95% CI, 72‐99), respectively (P < .0001). In conclusion, posttreatment ctHPV16DNA complements PET‐CT and helps guide decisions managing patients with HPV16‐related HNSCC after radiotherapy.
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Decisions regarding salvage surgery following radiotherapy for head and neck squamous cell carcinoma (HNSCC) are fraught with uncertainty. Post‐radiotherapy disease surveillance currently is managed with positron emission tomography and computed tomography (PET‐CT), though predictive value is exceedingly low for human papillomavirus (HPV)‐related HNSCC. This study shows that circulating tumor HPV DNA (ctHPVDNA), quantified by droplet digital PCR, complements PET‐CT in predicting post‐radiotherapy treatment failure in HPV‐related HNSCC. In particular, incomplete metabolic response with detectable post‐treatment ctHPVDNA was associated with high risk of treatment failure. Detection of ctHPVDNA after radiotherapy in HPV‐related HNSCC could help identify patients who require close follow‐up.
We previously reported that L-glutamine reduces the severity of mucositis caused by chemoradiotherapy in patients with head and neck cancer. However, the impact of glutamine on the anti-tumor effect ...of chemoradiotherapy remains controversial. This study, which included 40 patients, investigated whether L-glutamine influences survival. Radiation therapy (total: 66 or 70 Gy), cisplatin, and docetaxel were co-administered for a period of 6 weeks. Patients were randomly assigned to receive either glutamine (glutamine group, n = 20) or placebo (placebo group, n = 20) during the entire course of chemoradiotherapy. We compared the overall survival and progression-free survival rates between the two groups. At 5-year follow-up, 16 (80%) and 13 (72%) patients in the glutamine and placebo groups, respectively, survived (with no significant difference in overall survival glutamine group: 55.2 ± 12.7 months vs. placebo group: 48.3 ± 21.3 months). A total of 14 (70%) and 12 (67%) patients in the glutamine and placebo groups, respectively, did not experience disease progression (with no significant difference in progression-free survival glutamine group: 46.7 ± 19.5 months vs. placebo group: 43.6 ± 25.2 months). These findings indicate that L-glutamine does not influence the survival of patients with locally advanced head and neck cancer receiving chemoradiotherapy.
In the design of whole-genome sequencing (WGS) studies, sequencing depth is a crucial parameter to define variant calling accuracy and study cost, with no standard recommendations having been ...established. We empirically evaluated the variant calling accuracy of the WGS pipeline using ultra-deep WGS data (approximately 410×). We randomly sampled sequence reads and constructed a series of simulation WGS datasets with a variety of gradual depths (n = 54; from 0.05× to 410×). Next, we evaluated the genotype concordances of the WGS data with those in the SNP microarray data or the WGS data using all the sequence reads. In addition, we assessed the accuracy of HLA allele genotyping using the WGS data with multiple software tools (PHLAT, HLA-VBseq, HLA-HD, and SNP2HLA). The WGS data with higher depths showed higher concordance rates, and >13.7× depth achieved as high as >99% of concordance. Comparisons with the WGS data using all the sequence reads showed that SNVs achieved >95% of concordance at 17.6× depth, whereas indels showed only 60% concordance. For the accuracy of HLA allele genotyping using the WGS data, 13.7× depth showed sufficient accuracy while performance heterogeneity among the software tools was observed (the highest concordance of 96.9% was observed with HLA-HD). Improvement in HLA genotyping accuracy by further increasing the depths was limited. These results suggest a medium degree of the WGS depth setting (approximately 15×) to achieve both accurate SNV calling and cost-effectiveness, whereas relatively higher depths are required for accurate indel calling.
Chronic rhinosinusitis is classified into eosinophilic chronic rhinosinusitis (ECRS) and non-eosinophilic chronic rhinosinusitis (NECRS). ECRS is a refractory allergic disease involving a variety of ...immune and epithelial cells. S100A8 is a damage-associated molecular pattern that is closely related to allergic inflammation. However, the pathological implications of S100A8 in ECRS have not been clarified.
We evaluated the role of S100A8 in the pathogenesis of ECRS. Gene expression profiles of nasal polyps obtained from patients with ECRS or NECRS were evaluated using RNA sequencing.
S100A8 was identified as a significantly upregulated gene in nasal polyps associated with ECRS. Immunohistochemistry consistently revealed intense S100A8 staining in nasal polyps from patients with ECRS. Human nasal epithelial cells expressed the receptor for advanced glycation end products and Toll-like receptor 4. Recombinant S100A8 protein induced interleukin-1β secretion in human nasal epithelial cells.
Our data demonstrate that S100A8 results in production of interleukin-1β in the nasal epithelium, which may be involved in the pathogenesis of ECRS.
Ménière's disease (MD) is an inner ear disorder in which the main pathological feature is endolymphatic hydrops (EH). Positive pressure therapy (PPT) using a portable device is now a second-line ...therapy for intractable MD when initial medical treatment fails. However, it remains unknown whether PPT causes the morphological and functional changes of inner ear in patients with active MD in accordance with reduction of vertigo attacks. In this nonrandomized controlled trial of 52 patients with MD, the volume of EH significantly decreased with reduction of vertigo attacks during 8 months of PPT combined with medications while the volume of that significantly increased with medications alone. There was no difference between Control group (n = 26) and PPT group (n = 26) regarding the vertigo control, however, PPT group achieved a significant functional improvement of vertical semicircular canals. The effect of volume reduction by PPT has been firstly demonstrated and the functional changes of all semicircular canals during PPT have been firstly examined. Morphological and functional changes in the inner ear by administrating local positive pressure are quite different from those caused by medications alone.Clinical trial registration: UMIN-CTR UMIN000041164 (registered on July 20, 2020).
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