External auditory canal squamous cell carcinoma (EACSCC) is an extremely rare and aggressive malignancy. Due to its rarity, the molecular and genetic characteristics of EACSCC have not yet been ...elucidated. To reveal the genetic alterations of EACSCC, we performed whole exome sequencing (WES) on 11 primary tumors, 1 relapsed tumor and 10 noncancerous tissues from 10 patients with EACSCC, including 1 with a rare case of synchronous bilateral EACSCC of both ears. WES of the primary tumor samples showed that the most frequently mutated gene is TP53 (63.6%). In addition, recurrent mutations in CDKN2A, NOTCH1, NOTCH2, FAT1 and FAT3 were detected in multiple samples. The mutational signature analysis of primary tumors indicated that the mutational processes associated with the activation of apolipoprotein B mRNA‐editing enzyme catalytic polypeptide‐like (APOBEC) deaminases are the most common in EACSCC, suggesting its similarity to SCC from other primary sites. Analysis of arm‐level copy number alterations detected notable amplification of chromosomes 3q, 5p and 8q as well as deletion of 3p across multiple samples. Focal chromosomal aberrations included amplifications of 5p15.33 (ZDHHC11B) and 7p14.1 (TARP) as well as deletion of 9p21.3 (CDKN2A/B). The protein expression levels of ZDHHC11B and TARP in EACSCC tissues were validated by immunohistochemistry. Moreover, WES of the primary and relapsed tumors from a case of synchronous bilateral EACSCC showed the intrapatient genetic heterogeneity of EACSCC. In summary, this study provides the first evidence for genetic alterations of EACSCC. Our findings suggest that EACSCC mostly resembles other SCC.
As the genetic characteristics of external auditory canal squamous cell carcinoma (EACSCC) are not yet elucidated due to its rarity, we performed whole exome sequencing and copy number analysis in EACSCC samples. The genetic alterations of EACSCC mostly resemble other SCC, although the novel amplified loci that harbor oncogenes were found.
Although nivolumab treatment is effective in extending the overall survival (OS) in patients with recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC), only a few patients ...benefit from this treatment. Recent studies have reported that chemotherapy and cetuximab might be effective for R/M HNSCC after nivolumab treatment. In the present study, we aimed to elucidate the effectiveness of chemotherapy after nivolumab treatment in patients with R/M HNSCC.
This retrospective study included 10 patients with R/M HNSCC who were mainly treated with paclitaxel plus cetuximab (7/10, 70%) or S-1 (3/10, 30%) following nivolumab treatment. Chemotherapy was administered as a second-line or higher palliative treatment. The performance status of all patients ranged from 0 to 2. The progression-free survival (PFS) was analyzed using the Kaplan–Meier method.
The response rate (RR), clinical benefit rate, and median PFS were 60%, 90%, and 5.4 months, respectively. Regarding adverse effects, Grade 3 neutropenia and hypomagnesemia due to salvage chemotherapy administered after immunotherapy were observed in one patient. The treatment significantly increased the RR compared to that achieved with other palliative chemotherapies reported so far.
A higher RR and clinical benefit rate were observed for our strategy than for any first-line regimen, suggesting that our strategy might improve the PFS. Palliative chemotherapy with/without cetuximab after nivolumab treatment might be useful in patients with R/M HNSCC. Although the results of this retrospective study are limited, this strategy can be a good treatment option for patients with R/M HNSCC because of its strong clinical benefits and acceptable toxicity.
Currently, only lateral temporal bone resection (LTBR) and subtotal temporal bone resection (STBR) are widely utilized for the surgical treatment of advanced squamous cell carcinoma of the external ...auditory canal (EAC-SCC). However, there are few descriptions of variations on these surgical approaches. This study aimed to elucidate the variations of en bloc resection for advanced EAC-SCC. We dissected the four sides of cadaveric heads to reveal the anatomical structures related to temporal bone resection. From the viewpoint of surgical anatomy, surgical patterns of temporal bone cutting can be divided into four categories: conventional LTBR, extended LTBR, conventional STBR, and modified STBR. Extended LTBR is divided into four types: superior, inferior, anterior, and posterior extensions. Several extension procedures can be combined based on the extension of the tumor. Furthermore, en bloc resection with the temporomandibular joint or glenoid fossa increases the technical difficulty of a surgical procedure because the exposure and manipulation of the petrous segment of the internal carotid artery are limited from the middle cranial fossa. Surgical approaches for advanced SCC of the temporal bone are diverse. They require accurate preoperative evaluation of the tumor extension and preoperative consideration of the exact line of resection to achieve marginal negative resection.
Spontaneous cerebrospinal fluid (sCSF) leaks are rare, and their diagnosis and treatment often present significant challenges. This paper discusses and reports cases experienced at our facility. We ...retrospectively reviewed three of five cases of sCSF leaks experienced at the Department of Otolaryngology and Head and Neck Surgery, Kyushu University, from December 2020 to December 2022, excluding CSF otorrhea. All three patients were female; their mean age was 56 years (44-71 years). Two of the three patients were obese (first degree), and one was average weight (according to the criteria of the Japan Society for the Study of Obesity). Two patients had hypertension, and one had sleep apnea syndrome as an underlying disease. In all cases, leakage sites, which were all the cribriform plate, can be endoscopically identified, and all could be closed by an endoscopic intranasal approach. We reviewed cases of sCSF leaks. Although some patients had difficulty identifying the leakage site in a narrow and complex nasal cavity, an endoscopic survey was useful in identifying the leakage site. All cases were closed and there were no signs of recurrence. Identifying the site of leakage and selecting the appropriate closure method depending on the extent of the leakage is essential in treating such cases.
Objectives/Hypothesis
The extreme rarity of temporal bone squamous cell carcinoma (TB‐SCC) has delayed the accumulation of high‐quality clinical evidence. For the purposes of retrospective ...meta‐analysis in the future, a large dataset with information from various institutions would be ideal. Our objective here was to retrospectively review cases of TB‐SCC encountered at a single tertiary referral center and explore survival outcomes and prognostic factors.
Study Design
Retrospective chart review.
Methods
The medical records of all TB‐SCC cases were retrospectively reviewed. The resulting dataset contained 71 cases of primary cancer eligible for initial definitive (curative) treatment.
Results
T4 status was associated with lower disease‐specific 5‐year survival than T1 to T3 staging (T1: 100%, T2: 92%, T3: 86%, T4: 51%). Survival was significantly higher in operable than in inoperable cases, even when restricted to advanced (T3/T4) cancers. The tumor extension to the middle ear cavity was observed in 13/17 of T3 cases, but it was not associated with poor survival. In addition, among operable cases, negative surgical margins were associated with significantly higher survival than positive margins.
Conclusions
Definitive treatments can offer disease‐specific 5‐year survival of over 85% in T1 to T3 cases of TB‐SCC. The tumor extension to the middle ear cavity is not associated with poor survival. T4 status, inoperability, nodal invasion, and positive surgical margin are identified as a predictor of poor prognosis. Still, the matter of how to deal with unresectable tumors remains an outstanding issue in the treatment of TB‐SCC.
Level of Evidence
4 Laryngoscope, 131:E583–E589, 2021
The benefit of sequential therapy after immune checkpoint inhibitor (ICI) treatment for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) has been recently reported. ...Furthermore, there is a growing interest in the impact of cetuximab (Cmab)-containing salvage chemotherapy (SCT) and the therapeutic efficacy and adverse events (AEs) of Cmab administration prior to ICI administration.
We retrospectively reviewed the medical records of 52 patients with R/M HNSCC treated with SCT (weekly paclitaxel PTX, n = 7, or weekly PTX and Cmab PC, n = 45).
The objective response rate (ORR) and a disease control rate (DCR) was 53.3% and 91.1% in the PC group and 42.9% and 57.1% in the PTX group, respectively. There was a significant difference in the DCR between the PC and PTX groups (p = 0.0143). The overall survival (OS) and progression-free survival were significantly better in the PC group than in the PTX group. On the other hand, the incidence of drug-induced interstitial pneumonia (DI-IP) in R/M HNSCC patients who received SCT was 21.2%. Patients in the PC group were divided according to whether they received Cmab (Group A) or did not receive Cmab (Group B) as palliative therapy prior to ICIs. Group B had a significantly better OS than Group A. Furthermore, our findings suggest that the incidence rate of DI-IP during SCT might be higher in Group B.
Although PC following ICIs shows dramatic efficacy, careful monitoring of AEs, including DI-IP, is recommended.
Abstract Objective The use of the retrosigmoid approach has recently been expanded by several modifications including the suprameatal, transmeatal, suprajugular, and inframeatal extensions. ...Intradural temporal bone drilling without damaging vital structures inside or beside the bone, such as the internal carotid artery and jugular bulb, is a key step for these extensions. This study aimed to examine the microsurgical and endoscopic anatomy of the extensions of the retrosigmoid approach, and to evaluate the clinical feasibility of an electromagnetic navigation system during intradural temporal bone drilling. Methods Five temporal bones and 8 cadaveric cerebellopontine angles were examined to clarify the anatomy of retrosigmoid intradural temporal bone drilling. Twenty additional cerebellopontine angles were dissected in a clinical setting with an electromagnetic navigation system while measuring the target registration errors (TREs) at 8 surgical landmarks on and inside the temporal bone. Results Retrosigmoid intradural temporal bone drilling expanded the surgical exposure to allow access to the petroclival and parasellar regions (suprameatal), internal acoustic meatus (transmeatal), upper jugular foramen (suprajugular), and petrous apex (inframeatal). The electromagnetic navigation continuously guided the drilling without “line of sight” limitation, and its small devices were easily manipulated in the deep and narrow surgical field in the posterior fossa. Mean TRE was less than 0.50 mm during these procedures. Conclusions The combination of endoscopic and microsurgical techniques aids in achieving optimal exposure for retrosigmoid intradural temporal bone drilling. The electromagnetic navigation system had clear advantages with acceptable accuracy including the usability of small devices without “line of sight” limitation.
Background: Positive-margin resection of external auditory canal squamous cell carcinoma (EAC-SCC) is still a major cause of recurrence. The aim of this study is to examine the clinical impact of ...positive-margin resection of EAC-SCCs. Methods: We retrospectively reviewed 40 surgical cases with en bloc temporal bone resection of EAC-SCC at a tertiary referral center from October 2016 to March 2022. Results: Two-year disease-specific, overall, and disease-free survival rates for all 40 cases reviewed were 85.2%, 88.85%, and 76.96%, respectively. En bloc resection with a negative margin significantly improved patient prognosis (p < 0.001). Positive-margin resection was observed in 9/40 cases (22.5%). Insufficient assessment of preoperative images was the cause in two of these cases. Postoperative lymph node metastasis and distant metastasis were observed in cases in which vascular, lymphatic duct or perineural invasion was found on postoperative pathological examination. In addition, three cases in which no vascular, lymphatic duct, or perineural invasion was found exhibited local recurrence during the follow-up period. Of the nine positive-margin resection cases, only two showed no postoperative recurrence. Conclusions: Once positive-margin resections are confirmed, cases might have a high risk of tumor recurrence, even with the addition of postoperative adjuvant chemoradiotherapy.
Squamous cell carcinoma of the external auditory canal (EACSCC) is an extraordinarily rare and aggressive malignant disease. Establishment of EACSCC cell line with robust molecular characteristics is ...essential for the basic and translational research of EACSCC. Here, we show the newly established EACSCC cell line SCEACono2, derived from a patient with well-to-moderately differentiated EACSCC. We analyzed histologic and genetic features of SCEACono2 hiring multiple experiments, including next-generation sequencing (NGS). Immunocytochemical staining of SCEACono2 showed positivity of p53 and SCC1/2. Furthermore, SCEACono2 exhibited a unique characteristic that cytokeratin, vimentin as well as cancer stem cell markers (CD44, CD133, ALP and Oct3/4) were positive. SCEACono2 had an ability to form tumors at the temporal lesion xenograft nude mice model. NGS revealed that SCEACono2 harbored the somatic mutations of TP53 (p.G245S) and NOTCH1 (p.A465T). RNA-seq and downstream bioinformatics analysis revealed significant enrichment of genes involved in inflammation and cell adhesion in SCEACono2 compared to SCC-9 and HSC-4. STR profiling indicated no evidence of cross-contamination. In conclusion, SCEACono2 could serves as a promising and robust research resource of EACSCC in vitro and in vivo.
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