Efficacy of an enhanced recovery after surgery pathway to manage pain, nausea and vomiting after head and neck surgeries with free tissue transfer reconstruction.

BACKGROUND: Pain and post-operative nausea and vomiting are the main factors that impair the quality of recovery after surgery. Very few reports have analyzed patient-reported outcomes to investigate the efficacy of an enhanced recovery after surgery protocol to alleviate these symptoms after head and neck surgeries with free tissue transfer reconstruction. METHODS: We investigated post-operative pain and post-operative nausea and vomiting in 47 patients who underwent head and neck surgeries with free tissue transfer reconstruction with enhanced recovery after surgery support between February 2021 and August 2022. Patient-reported outcomes were assessed using the visual analog scale and Japanese version of the Quality of Recovery-40. RESULTS: Significant increases in the mean visual analog scale scores for pain and post-operative nausea and vomiting were observed only on post-operative Day 1 compared with preoperative values (pain: 3.19 ± 2.78 vs. 1.96 ± 2.42, P = 0.0408; post-operative nausea and vomiting: 1.52 ± 2.09 vs. 0.54 ± 1.37, P = 0.0194). From post-operative Day 2, there were no significant differences between the pre- and post-operative visual analog scale scores, and no significant increases in the incidences of moderate or severe pain and post-operative nausea and vomiting compared with preoperatively. The Japanese version of the Quality of Recovery-40 score for post-operative pain showed no significant deterioration compared with preoperatively, while the Japanese version of the Quality of Recovery-40 score for post-operative nausea and vomiting showed significant deterioration compared with the preoperative value on post-operative Days 2, 4 and 7. CONCLUSIONS: The visual analog scale and Japanese version of the Quality of Recovery-40 scores for post-operative pain and visual analog scale score for post-operative nausea and vomiting suggested that the enhanced recovery after surgery strategy favorably controlled pain and post-operative nausea and vomiting after head and neck surgeries with free tissue transfer reconstruction. However, as the post-operative Japanese version of the Quality of Recovery-40 score for post-operative nausea and vomiting was lower than the preoperative value, there is still a need for further improvement of the enhanced recovery after surgery pathway.

The geriatric-8 screening tool for predicting complications in older adults after surgery for locally advanced head and neck cancer with free flap reconstruction.

PURPOSE: Radical surgery with free flap reconstruction for locally advanced head and neck cancer (HNC) is quite challenging for older adults. This retrospective study aimed to elucidate the usefulness of the geriatric-8 (G8) screening tool for predicting postoperative complications in older adults with HNC. METHODS: A retrospective review of 37 older adults with HNC who underwent radical surgery with free flap reconstruction and were assessed by the G8 screening tool was performed. Postoperative complications during hospitalization were classified according to the Clavien-Dindo classification, and possible contributing factors, including the G8 score, for major and minor complications were subjected to univariate and multivariate analyses. RESULTS: The appropriate G8 cut-off value for both major and minor complications was 12 (area under the curve 0.56 and 0.55, respectively). Multivariate logistic regression analysis showed that both smoking and lower G8 score (≤ 12) were independently associated with the severity of complications (p = 0.043, p = 0.034, respectively). CONCLUSIONS: The G8 was a possible predictor of major and minor complications in older adults with HNC who underwent radical surgery with free flap reconstruction.

Simple laryngeal suspension procedure by suturing the digastric muscle to the periosteum of the mandible in neck dissection for tongue cancer.

PURPOSE: In this article, a simple, new laryngeal suspension procedure is described. The effect of hyoid bone suspension by suturing the digastric muscle to the periosteum of the mandible is analyzed. MATERIALS AND METHODS: To elucidate the effect of hyoid bone suspension, CT scans of 26 patients who underwent ipsilateral neck dissection with primary resection of tongue cancer were retrospectively reviewed, and the distance between the hyoid bone and the mandible was measured on the operated and unoperated sides of the neck. A total of 14 patients who underwent suturing of the digastric muscle to the mandible (digastric muscle-sutured group) and the 12 patients who did not (control group) were compared. RESULTS: In the digastric muscle-sutured group, the average distance between the hyoid bone and the mandible was significantly smaller on the operated side (17.8 ±â€¯0.57 mm) than on the unoperated side (19.8 ±â€¯0.93 mm; p < 0.05). In the control group, there was no significant difference between the operated side (21.0 ±â€¯1.42 mm) and the unoperated side (19.7 ±â€¯1.39 mm). The difference in the distance between the operated and unoperated sides was significantly larger in the digastric muscle-sutured group (1.97 ±â€¯0.79 mm) than in the control group (-1.32 ±â€¯0.61; p < 0.05). CONCLUSIONS: It was shown for the first time that suturing of the digastric muscle to the periosteum of the mandible in neck dissection with primary resection of tongue cancer resulted in hyoid bone suspension. This simple procedure can be useful for laryngeal suspension.

Clinical utility of dynamic-enhanced MRI in salivary gland tumors: retrospective study and literature review.

PURPOSE: To improve the diagnoses of the salivary gland tumors, a dynamic-enhanced MRI (dMRI) was investigated. METHODS: We conducted a retrospective chart review of 93 cases of salivary gland tumors. The histological diagnoses were obtained from all patients using a surgical specimen and/or an open biopsy specimen. The dMRI as well as fine-needle aspiration cytology (FNAC) and intraoperative frozen section (IFS) were analyzed. This study focused on the time-intensity curve (TIC) after injection, peak time (Tpeak), washout ratio (WR) as well as the gradient of enhancement and washout profile. RESULTS: The histological diagnoses included pleomorphic adenoma (PMA) in 53 cases, the Warthin tumors (WT) in 14 cases and malignant tumors (MT) in 26 cases. Incorrect diagnosis rate of FNAC and IFS were 5.2 and 8.3%, respectively. The TIC revealed differences among the three types of tumors. Tpeak as well as WR also revealed significant differences (p < 0.001). Tpeak were lower in order of WT, MT, PMA, respectively. WR of TICs at 30, 45 and 105 s after Tpeak were higher in order of WT, MT, PMA, respectively (p < 0.001). The gradient of increment and washout in the TIC curve was also an important parameter to distinguish the three types of tumors. In MT, the rapid enhancement pattern was found in high or intermediate histological grade tumors, whereas the slow enhancement pattern was exhibited in low grade tumors. CONCLUSIONS: Our findings indicate that using Tpeak and WR, it is possible to distinguish between WT, PMA and MT. Additionally, a rapid enhancement pattern may be a potential marker for these tumors.

Poor oral intake causes enteral nutrition dependency after concomitant chemoradiotherapy for pharyngeal cancers.

PURPOSE: To identify precipitating factors responsible for enteral nutrition (EN) dependency after concomitant chemoradiotherapy (CCRT) of head and neck cancers and to examine their statistical correlations. METHODS: Factors related to feeding condition, nutritional status, disease, and treatment of 26 oropharyngeal and hypopharyngeal cancer patients who received definitive CCRT were retrospectively investigated by examining their medical records. The days of no oral intake (NOI) during hospitalization and the months using enteral nutrition after CCRT were counted as representing the feeding condition, and the changes in body weight (BW) were examined as reflecting nutritional status. The factors related to EN dependency after CCRT were analyzed. RESULTS: Long duration of total NOI (≥ 30 days) and maximum NOI ≥ 14 days were significant predictors of EN dependency. Decreased BW (≥ 7.5 kg) was the next predictor identified, but it was not significant. Multivariate analysis showed that the total duration of NOI was more correlated with EN dependency than changes in BW. CONCLUSIONS: A long duration of NOI was more strongly related to EN dependency than nutritional factors.

Neck dissection for treatment of supraglottic carcinoma associated with deep-seated intermuscular lipoma in the neck: A case report.

Lipomas are superficial tumors that occur primarily in the subcutaneous region and very rarely occur deeply within or between the muscle layers. No reports to date have described cervical lipomas in patients with head and neck cancer who underwent neck dissection. We herein report a case involving a 72-year-old woman with supraglottic carcinoma complicated by a cervical lipoma who underwent simultaneous neck dissection and lipoma removal. The lipoma was a deep-seated intermuscular lipoma arising in the longus cervicis muscle. We initially considered that the lipoma would be removed en bloc with neck dissection, but the imaging findings clearly indicated that the tumor was located more deeply than the prevertebral layer of the deep cervical fascia and outside the range of neck dissection. The lipoma was removed by incision of the prevertebral fascial layer following neck dissection, and no complications occurred.

Breathing-Swallowing discoordination after definitive chemoradiotherapy for head and neck cancers is associated with aspiration pneumonia.

PURPOSE: Swallowing dysfunction and the risk of aspiration pneumonia are frequent clinical problems in the treatment of head and neck squamous cell carcinomas (HNSCCs). Breathing-swallowing coordination is an important factor in evaluating the risk of aspiration pneumonia. To investigate breathing-swallowing discoordination after chemoradiotherapy (CRT), we monitored respiration and swallowing activity before and after CRT in patients with HNSCCs. METHODS: Non-invasive swallowing monitoring was prospectively performed in 25 patients with HNSCCs treated with CRT and grade 1 or lower radiation-induced dermatitis. Videoendoscopy, videofluoroscopy, Food Intake LEVEL Scale, and patient-reported swallowing difficulties were assessed. RESULTS: Of the 25 patients selected for this study, four dropped out due to radiation-induced dermatitis. The remaining 21 patients were analyzed using a monitoring system before and after CRT. For each of the 21 patients, 405 swallows were analyzed. Swallowing latency and pause duration after the CRT were significantly extended compared to those before the CRT. In the analysis of each swallowing pattern, swallowing immediately followed by inspiration (SW-I pattern), reflecting breathing-swallowing discoordination, was observed more frequently after CRT (p = 0.0001). In 11 patients, the SW-I pattern was observed more frequently compared to that before the CRT (p = 0.00139). One patient developed aspiration pneumonia at 12 and 23 months after the CRT. CONCLUSION: The results of this preliminary study indicate that breathing-swallowing discoordination tends to increase after CRT and could be involved in aspiration pneumonia. This non-invasive method may be useful for screening swallowing dysfunction and its potential risks.

Trismus after partial maxillectomy and radiotherapy: Free flap reconstruction versus prosthetic obturation.

OBJECTIVE: Partial maxillectomy and postoperative radiotherapy are both risk factors associated with trismus. This retrospective study aimed to evaluate the incidence and severity of trismus in patients following partial maxillectomy with or without postoperative radiotherapy and to compare free flap reconstruction and prosthetic obturation. METHODS: A retrospective review of 40 oral cancer patients who underwent partial maxillectomy with or without postoperative radiotherapy was performed. Maximum interincisal distance recorded at least 6 months after surgery was classified according to a revised subjective-objective management-analytical (SOMA) scale and compared between the free flap reconstruction group (n = 12) and the prosthetic obturation group (n = 28). RESULTS: Trismus was observed in 16/40 (40%) patients, and severe trismus was observed in 4/40 (10%) patients. Although no significant difference in trismus grade was observed between the free flap reconstruction and prosthetic obturation groups, both severe trismus and radiation-induced osteonecrosis were only seen in the prosthetic obturation group with postoperative radiotherapy. CONCLUSION: Free flap reconstruction was preferable to prosthetic obturation to avoid severe trismus and radiation-induced osteonecrosis in patients who underwent both partial maxillectomy and postoperative radiotherapy.

Salivary gland cancer organoids are valid for preclinical genotype-oriented medical precision trials.

Salivary gland cancers (SGCs) are heterogeneous tumors, and precision oncology represents a promising therapeutic approach; however, its impact on SGCs remains obscure. This study aimed to establish a translational model for testing molecular-targeted therapies by combining patient-derived organoids and genomic analyses of SGCs. We enrolled 29 patients, including 24 with SGCs and 5 with benign tumors. Resected tumors were subjected to organoid and monolayer cultures, as well as whole-exome sequencing. Organoid and monolayer cultures of SGCs were successfully established in 70.8% and 62.5% of cases, respectively. Organoids retained most histopathological and genetic profiles of their original tumors. In contrast, 40% of the monolayer-cultured cells did not harbor somatic mutations of their original tumors. The efficacy of molecular-targeted drugs tested on organoids depended on their oncogenic features. Organoids recapitulated the primary tumors and were useful for testing genotype-oriented molecular targeted therapy, which is valuable for precision medicine in patients with SGCs.

The prolonged presence of a fish bone in the neck.

Fish bones are one of the most frequently observed ingested foreign bodies in the pharynx-esophagus. Fish bones have a tendency to stick and penetrate the mucosa, which can occasionally lead to severe or lethal complications. The extraluminal migration of fish bones in the upper digestive tract is a rare event, and it is even more unlikely that the foreign body will remain in the neck for a prolonged period. We report the unique case of a 69-year-old woman who remained asymptomatic, while a fish bone was lodged in her neck for 9 months. Finally, after her anterior neck had become swollen, she underwent neck exploration, which revealed that the fish bone was embedded in the scar tissue running from within the thyroid gland to outside of the thyroid. Treatment proceeded without complications, and the foreign body was removed successfully. The length of the fish bone was 34 mm. Intraoperative ultrasonography was able to identify the fish bone in situ using real-time imaging; therefore, we recommend this technique for locating migrated foreign bodies in the neck.

Simple Endoscopic Method of Scoring Swallowing Function After Treatment in Advanced Head and Neck Cancer Patients.

The aim of this prospective, observational study was to evaluate the effectiveness of a simple endoscopic method for scoring swallowing function after treatment of advanced head and neck cancer patients. A prospective, observational study was conducted involving 60 patients who had undergone surgery or chemoradiation for advanced head and neck cancer. Endoscopic score of swallowing function, penetration aspiration scale (PAS) score measured by videofluorography, and functional oral intake scale (FOIS) score were recorded, and their correlations were examined. There was a positive correlation between endoscopic and PAS scores. Patients with endoscopic scores of 4 points or more had significantly higher PAS scores and lower FOIS scores than those with scores of 3 points or less. These positive correlations were found only in patients who underwent surgery, and not those who received chemoradiation. This study showed the effectiveness of the simple endoscopic method for scoring swallowing function in patients after surgery for advanced head and neck cancers.

Investigation of the diversity of human papillomavirus 16 variants and L1 antigenic regions relevant for the prevention of human papillomavirus-related oropharyngeal cancer in Japan.

OBJECTIVE: This study aimed to investigate the distribution of human papillomavirus 16 (HPV16) variants that contribute to the development of HPV-related oropharyngeal carcinoma (HPV-OPC) in the Japanese population and to evaluate genetic variations in the sequence encoding the L1 antigen region of the viral outer shell that is targeted by existing vaccines and is relevant for designing a prevention strategy to combat the exponential increase in HPV-OPC cases in Japan. METHODS: Seventy Japanese HPV-OPC patients treated at Tohoku University Hospital were included in the study. DNA was extracted from formalin-fixed, paraffin-embedded tissue samples. Polymerase chain reaction and direct nucleotide sequencing were performed to determine the nucleotide polymorphisms necessary for the classification of HPV16 variants and to assess genetic diversity in the HPV16 L1 antigen region, including the BC, DE, EF, FG, and HI loops. RESULTS: The most common variant of HPV16 was the A4 sublineage (88.6%), conventionally called the Asian type, followed by the A1/2/3 (10.0%) sublineage, classified as the European type. The only nonsynonymous substitution detected in the L1 antigen loop region was p.N181T in the EF loop, which was found in 28/70 (40%) cases. In contrast, no nonsynonymous substitutions were observed in the DE, FG, and HI loops, which are particularly important regions in the antigen loop targeted by existing HPV vaccines. CONCLUSION: The most common HPV16 variant in Japanese HPV-OPC patients was the A4 subtype. The L1 antigen region is highly conserved, suggesting sufficient efficacy of existing HPV vaccines. These findings provide important information that will aid in the design of an HPV16 infection control strategy using existing HPV vaccines to prevent the spread of HPV-OPC in Japan.

High diagnostic accuracy for lymph node metastasis of oral squamous cell carcinoma using PET/CT with a silicon photomultiplier.

OBJECTIVE: The higher sensitivity of the new-generation positron emission tomography/computed tomography (PET/CT) with silicon photomultiplier (SiPM) may increase false-positive rates in detecting metastatic lymph nodes (LNs). This study aimed to clarify the usefulness of the SiPM PET scanner in diagnosing LN metastasis of oral squamous cell carcinoma (SCC). METHODS: We retrospectively reviewed consecutive F-18 fluorodeoxyglucose PET/CT images of 39 SCC patients using SiPM PET and 31 SCC patients using non-SiPM PET. We measured the maximum standardized uptake value (SUVmax) of the LNs on PET images and maximum short-axis diameter on transverse CT images. RESULTS: The sensitivity and specificity of SiPM PET were 86.2% and 95.6%, respectively (cut-off SUVmax, 4.6). The area under the curve (AUC) of SiPM PET (0.977; 95% confidence interval [CI], 0.958-0.995) was significantly higher than that of non-SiPM PET (0.825; 95% CI 0.717-0.934) (P < 0.01). In a size-limited analysis of diameter, the AUC of SiPM PET (≥ 0.96 for all diameters) was significantly higher than that of non-SiPM PET (tended to decrease as the LN diameter decreased) for the diagnosis of LN metastasis by SUVmax. CONCLUSION: SiPM PET had higher diagnostic accuracy for LN metastasis of oral SCC than non-SiPM PET, even for small LN metastasis without increasing false-positives.

Eustachian Tube Functions in Concurrent Chemoradiotherapy for Head and Neck Cancer Patients.

Ototoxicity is a dose-limiting adverse event for concurrent chemoradiotherapy (CCRT) with high-dose cisplatin for locally advanced head and neck squamous cell carcinoma (HNSCC). Both irradiation to the Eustachian tube (ET) and weight loss are risk factors for patulous ET. The aim of this prospective, observational study was to elucidate the incidences of patulous ET conditions before and after CCRT in HNSCC patients by means of ET function tests. This prospective, observational study was conducted in 27 HNSCC patients who received CCRT with high-dose cisplatin, and ET function tests (sonotubometry and tubo-tympano-aerodynamic graphy) were performed before and 3 months after CCRT. Factors potentially affecting the incidence of patulous ET conditions after CCRT were evaluated. Of the 54 ears from 27 patients investigated, patulous ET conditions were observed in 12 ears (22.2%) from 9 patients (33.3%) before CCRT and 15 ears (27.8%) from 11 patients (40.7%) at 3 months after CCRT. Only patulous ET conditions before CCRT in each ear were significantly associated with patulous ET conditions after CCRT (p = 0.010). This is the first report to describe the incidences of patulous ET conditions before and after CCRT in HNSCC patients. HNSCC patients are potentially at higher risk of patulous ET.

Bach1-dependent and -independent regulation of heme oxygenase-1 in keratinocytes.

Bach1 is a member of the basic leucine zipper transcription factor family, and the Bach1/small Maf heterodimer specifically represses transcriptional activity directed by the Maf recognition element (MARE). Because Bach1 is a repressor of the oxidative stress response, we examined the function(s) of Bach1 in keratinocytes subjected to oxidative stress. Oxidative stress induced by H(2)O(2) led to an increase in MARE activity and expression of heme oxygenase-1 (HO-1), an inducible antioxidant defense enzyme. Bach1 depletion by small interfering RNAs or by deletion of Bach1 enhanced HO-1 expression in the absence of H(2)O(2), indicating that Bach1 is a critical repressor of HO-1 in keratinocytes. Although Bach1-deficient or -reduced keratinocytes expressed higher levels of HO-1 than control cells in response to H(2)O(2), Bach1 down-regulation did not attenuate the production of reactive oxygen species by H(2)O(2). In contrast, Bach1 overexpression abolished HO-1 induction by H(2)O(2), which led to increased reactive oxygen species accumulation. HO-1 was induced during keratinocyte differentiation, but MARE activity did not change during differentiation. Furthermore, Bach1 overexpression did not inhibit differentiation-associated induction of HO-1 expression, suggesting that HO-1 induction in differentiation is independent of Bach1. Thus, in response to oxidative stress, Bach1 regulates the oxidation state through the negative control of HO-1 expression prior to terminal keratinocyte differentiation. However, Bach1-mediated repression is negated during keratinocyte differentiation.

Distinct features of second primary malignancies in head and neck cancer patients in Japan.

Second primary malignancies (SPMs) are one of the most critical problems in treating head and neck cancer patients. Our hospital had 742 patients with a diagnosis of malignant head and neck tumors during the five-year period from 2002 to 2006. In this study, we analyzed 360 of those patients who were assumed to have risk factors such as alcohol and tobacco use: 106 oral, 120 laryngeal, 50 oropharyngeal and 84 hypopharyngeal cancer patients. Synchronous SPMs are defined as second cancers diagnosed at the same time or within 6 months of the diagnosis of the index head and neck cancers. There were 4 (3.8%) and 11 (10.4%) oral cancer patients, 11 (8.3%) and 8 (5.8%) laryngeal cancer patients, 7 (14.0%) and 4 (8.0%) oropharyngeal cancer patients, and 30 (28.6%) and 7 (8.3%) hypopharyngeal cancer patients with synchronous and metachronous SPMs, respectively. The number of metachronous patients with synchronous SPMs tended to increase during this time period. The frequencies of SPMs in oropharyngeal and hypopharyngeal cancer patients are similar to those in oral and laryngeal cancer patients. Notably, the most frequent SPMs are upper gastrointestinal tract cancers in Japan, compared to lung cancers in Europe. The five-year overall survival rate of patients with synchronous SPMs was significantly poorer than that of patients without any other tumor except for the index cancer, according to the Kaplan-Meier analysis. In conclusion, searching for SPMs in the upper gastrointestinal tract is a critical issue in head and neck cancer patients in Japan.

Use of the Geriatric-8 screening tool to predict prognosis and complications in older adults with head and neck cancer: A prospective, observational study.

OBJECTIVES: To clarify the usefulness of geriatric assessment screening tools for predicting prognosis and complications in older adults with head and neck cancer (HNC). MATERIAL AND METHODS: The geriatric-8 (G8) screening tool was administered to 78 older adults with HNC at their first visit to the hospital before any treatments. The ability of the G8 to predict survival was evaluated by receiver operating characteristic (ROC) curve analysis and determining the cut-off value using Youden's Index. The G8 and other factors related to prognosis (age, performance status (PS), Charlson comorbidity index, number of oral medicines (polypharmacy), the controlling nutritional status (CONUT) score for biological nutrition status, and treatment intent (curative or palliative)) were validated by Cox proportional hazards regression analysis. The survival analysis was validated in a propensity score-weighting cohort to correct for confounding factors. Correlations between these factors and complications were examined using Fishers exact test. RESULTS: The G8 cut-off value for overall survival was 10.5 (area under the curve (AUC) 0.69; 95% confidence interval (CI) 0.56-0.82). In the propensity score-weighted cohort, on Cox proportional hazards regression analysis, the hazard ratio of an abnormal G8 (<11) was 3.70 [1.59-8.61 (p = 0.002)], and the hazard ratio of PS-abnormal (≥2) was 0.85 [0.09-7.60 (p = 0.88)]. Thirty-day mortality and all-complication rates were significantly higher in the G8-abnormal group. Neither major complications nor transfer to other institutions was correlated with an abnormal G8. CONCLUSION: The G8 was a strong prognostic factor and a possible predictor of complications in older adults with HNC.

Impact of CAD/CAM mandibular reconstruction on chewing and swallowing function after surgery for locally advanced oral cancer: A retrospective study of 50 cases.

OBJECTIVE: Computer-aided design and computer-aided manufacturing (CAD/CAM) techniques are increasingly applied to mandibular reconstruction, but the superiority of this method in oral food intake has not been well established. Considering the extent of mandibular defects, this retrospective study was aimed to clarify the impact of CAD/CAM mandibular reconstruction on chewing and swallowing function after surgery for locally advanced oral cancer. MATERIALS AND METHODS: We performed a retrospective review of 50 patients who had undergone segmental mandibulectomy with free flap reconstruction for locally advanced oral cancer. The patients' Functional Oral Intake Scale scores were measured at 3 months after surgery, and possible contributing factors including CAD/CAM mandibular reconstruction and the extent of mandibular defects for oral food intake were subjected to univariate analysis and multivariate logistic regression analysis. RESULTS: Multivariate logistic regression analysis showed that CAD/CAM mandibular reconstruction was independently associated with good oral intake, whereas both anterior or extensive mandibular resection and glossectomy were also independently associated with poor oral intake after surgery. CONCLUSION: The present study showed the positive impact of CAD/CAM mandibular reconstruction on chewing and swallowing function after surgery for locally advanced oral cancer for the first time.

Whole exome sequencing and establishment of an organoid culture of the carcinoma showing thymus-like differentiation (CASTLE) of the parotid gland.

Carcinoma showing thymus-like differentiation (CASTLE) is a rare tumor, especially in the parotid gland. We encountered a CASTLE of the parotid gland and analyzed its clinicopathological features, as well as the genotype using whole exome sequencing (WES). Moreover, we successfully established an organoid culture cell line from the primary tumor tissue. The patient was a 23-year-old woman who underwent superficial parotidectomy with peripheral neck dissection, followed by radiotherapy. Pathologically, the resected specimen showed atypical epithelioid nests and trabeculae with squamous differentiation, separated by thick fibrous septa, accompanied by dense lymphocytes and plasma cell infiltration. Immunohistochemistry revealed that the tumor cells were positive for AE1/AE3, p40, p63, p16, CK5/6, and CD5, and the background lymphocytes were positive for CD5 and CD99. Based on these findings, the tumor was diagnosed as CASTLE. WES uncovered five nonsynonymous and splicing somatic mutations, namely, FREM2 p.Val861Phe, CLK3 p.Phe376Leu, DLGAP1 p.Lys294Asn, NOX1 p.Val165Met, and PSG9 c.430 + 4A > T. Organoid culture cells preserved the histopathological characteristics of the epithelioid component of CASTLE and harbored all five somatic mutations detected in the primary tumor. In conclusion, for the first time to the best of our knowledge, we successfully analyzed a comprehensive genotype and established an organoid culture cell line of a parotid gland CASTLE, which should serve for analyzing the nature of this rare tumor.

Serum selenium predicts achievement of full-dose cisplatin in concurrent chemoradiotherapy for locally advanced head and neck squamous cell carcinoma: A prospective, observational study.

OBJECTIVE: Concurrent chemoradiotherapy (CCRT) with three-weekly high-dose cisplatin (100 mg/m2) is a standard treatment for locally advanced head and neck squamous cell carcinoma (HNSCC), but compliance with cisplatin is often poor due to various adverse events. The aim of this prospective, observational study was to determine the predictors of achievement of full-dose cisplatin. METHODS: A prospective, observational study was conducted involving 60 patients who received CCRT with three-weekly high-dose cisplatin (100 mg/m2) for locally advanced HNSCC. Possible predictors affecting compliance with cisplatin were subjected to univariate and multivariate logistic regression analyses. Age, sex, primary site, clinical stage, treatment intent, history of hypertension, diabetes mellitus, smoking and drinking habits, body mass index, creatinine clearance, serum albumin, controlling nutrition status, trace elements (Fe, Zn, Cu, Se), acute kidney injury, white blood cell count decrease, neutrophilia, and weight loss were the variables evaluated. RESULTS: Twenty-seven patients achieved full-dose cisplatin (300 mg/m2), and the other 33 patients did not. Multivariate logistic regression analysis showed that both mild renal dysfunction and selenium deficiency before treatment independently had negative impacts on achievement of full-dose cisplatin. CONCLUSIONS: As well as renal function, selenium deficiency is a potential therapeutic target for CCRT with high-dose cisplatin in HNSCC patients.