Prognostic significance of the harmonized maximum standardized uptake value of 18F-FDG-PET/CT in patients with resectable oral tongue squamous cell carcinoma: a multicenter study.

OBJECTIVES: To investigate the usefulness of harmonized 18F-FDG-PET/CT parameters for predicting the postoperative recurrence and prognosis of oral tongue squamous cell carcinoma (OTSCC). METHODS: We retrospectively analyzed the cases of 107 OTSCC patients who underwent surgical resection at four institutions in Japan in 2010-2016 and evaluated the harmonized PET parameters of the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) for the primary tumor as the pSUVmax, pMTV, and pTLG. For lymph node metastasis, we used harmonized PET parameters of nodal-SUVmax, nodal-total MTV (tMTV), and nodal-total TLG (tTLG). The associations between the harmonized PET parameters and the patients' relapse-free survival (RFS) and overall survival (OS) were evaluated by the Kaplan-Meier method and Cox proportional hazard regression analysis for model 1 (preoperative stage) and model 2 (preoperative + postoperative stages). RESULTS: The harmonized SUVmax values were significantly lower than those before harmonization (p=0.012). The pSUVmax was revealed as a significant preoperative risk factor for RFS and OS. Nodal-SUVmax, nodal-tMTV, and nodal-tTLG were significant preoperative risk factors for OS. The combination of pSUVmax + nodal-SUVmax significantly stratified the patients into a low-risk group (pSUVmax <3.97 + nodal-SUVmax <2.85 or ≥2.85) and a high-risk group (pSUVmax ≥3.97 + nodal-SUVmax <2.85 or pSUVmax ≥3.97 + nodal-SUVmax ≥2.85) for recurrence and prognosis (RFS: p=0.001; OS: p<0.001). CONCLUSIONS: The harmonized pSUVmax is a significant prognostic factor for the survival of OTSCC patients. The combination of pSUVmax and nodal-SUVmax identified OTSCC patients at high risk for recurrence and poor prognosis at the preoperative stage.

Incidence and spread pattern of lymph node metastasis from submandibular gland cancer.

OBJECTIVES: To clarify the indication of neck dissection (ND) for patient with submandibular gland (SMG) cancer. METHODS: A total of 43 patients with SMG cancer were retrospectively analyzed. Forty-one patients underwent ND: Levels I-V in 19 patients, Levels I-III in 18 patients, and Level Ib in 4 patients. The other two patients did not undergo ND, since preoperative diagnoses were benign. Postoperative radiotherapy was performed in 19 patients with positive surgical margin, high grade cancer or stage IV disease. RESULTS: LN metastases were pathologically confirmed in all patients with cN + and 6 out of 31 patients with cN-. No patients developed regional recurrence during follow-up periods. Ultimately, LN metastases were pathologically confirmed in 17 of 27 high grade, one out of 9 intermediate grade, but not in 7 low grade. CONCLUSIONS: Prophylactic neck dissection should be considered in T3/4 and high grade SMG cancers.

COVID-19 presenting as acute epiglottitis: A case report and literature review.

Coronavirus disease 2019 (COVID-19) occasionally causes acute laryngitis, requiring emergency treatment. Understanding the characteristic laryngeal findings can help diagnose COVID-19 earlier, prevent worsening infection, and properly manage airway obstruction. Herein, we report the case of a 44-year-old male with acute epiglottitis likely caused by COVID-19. On presentation, chest computed tomography (CT) showed no signs of pneumonia. However, the larynx had extensive necrotic-like erosive lesions resembling those of tuberculous laryngitis. COVID-19 was diagnosed by reverse-transcription polymerase chain reaction, and secondary bacterial superinfections were suspected after blood testing. The symptoms improved after administration of antibiotics (sulbactam sodium/ampicillin sodium), steroids (dexamethasone), and favipiravir. The patient developed a high fever on the sixth day of hospitalization, and pneumonia was identified on CT. Various culture tests, including tuberculosis, were negative. Thus, remdesivir was administered for COVID-19-induced pneumonia. The patient gradually recovered, was transferred to another hospital, and was discharged on the 35th day of hospitalization. Six previous case reports of COVID-19-induced acute epiglottitis suggested that acute epiglottitis preceded the onset of pneumonia. The laryngeal findings from this report may be useful for diagnosing COVID-19 that does not cause pneumonia and for bringing attention to pneumonia after a COVID-19 diagnosis.

Three Cases of Hematoma in the Retropharyngeal Space.

OBJECTIVES: Hematoma in the retropharyngeal space (RPS) is a life-threatening condition that leads to rapid airway obstruction. However, the indication for airway management remains unclear. Additionally, the requirement for surgical hematoma evacuation remains undetermined. Therefore, we attempt to suggest some criteria for the management of hematoma in such cases. METHODS: We report three cases of hematoma in the RPS wherein one patient was treated without surgery and the other two underwent tracheotomy followed by hematoma evacuation. RESULTS: We found that airway management should be based on whether the glottis could be visible on laryngoscopy and dyspnea severity. The degree of hematoma, swelling, subcutaneous bleeding in the anterior neck, and emotional stability should also be considered. Proper management during the acute phase may allow for conservative treatments. Hematomas extending below the tracheal bifurcation may help ease upper airway obstruction due to pressure distribution, allowing for conservative treatment. When hematomas are surgically evacuated, tracheotomy should be performed simultaneously. Our report suggests that mediastinal hematoma evacuation could be avoided. CONCLUSION: We should determine a therapeutic strategy for hematoma in RPS based on glottis visualization, patient's condition, and extent of hematoma growth under careful observation.

Intraoperative quantitative assessment of parathyroid blood flow during total thyroidectomy using indocyanine green fluorescence imaging - surgical strategies for preserving the function of parathyroid glands.

Objective: We investigated the factors affecting postoperative parathyroid gland (PTG) function and devised an objective index to predict the postoperative PTG function during total thyroidectomy. Method: This was a retrospective clinical review of 21 consecutive patients who were diagnosed with papillary thyroid carcinoma and underwent total thyroidectomy. The maximum intensity ratio (MIR) was determined as the maximum fluorescence intensity after ICG injection divided by the intensity before ICG injection. Results: Postoperative hypoparathyroidism is significantly associated with simultaneous central neck dissection (CND) and lateral neck dissection (LND) (p = .032). The Spearman correlation test showed a moderate correlation between the MIR and iPTH levels (p = .0047). The optimal MIR cutoff value for predicting postoperative hypoparathyroidism was 2.14 with area under the curve = 0.904 (sensitivity: 0.769 and specificity: 1.00). Conclusion: CND + LND was significantly associated with postoperative hypoparathyroidism. MIR was found useful in predicting the postoperative PTG function.

Predictive factors for malignant neoplasms veiled in deep neck infections.

Background: Malignant neoplasms (MNs) in the head and neck are occasionally hidden in deep neck infections (DNIs) that require emergency treatment, which potentially leads to delayed diagnosis of MNs.Objectives: This study aimed to identify predictive factors that can prevent delays in diagnosing MNs in patients with DNIs.Methods: We retrospectively analysed data from 83 patients admitted to our hospital who were diagnosed with DNIs.Results: Four patients (4.8%) had DNIs veiling MNs in the head and neck. Statistical analyses revealed a significant association (p = .0481) of platelet to albumin ratio (PAR; ≥ 98.9 × 103) with hidden MNs in DNIs. Furthermore, concomitant cervical lymphadenopathy, especially multiple lymphadenopathies and excluding abscesses, was higher in patients with DNIs veiling MNs (p = .0142 and p = .0023, respectively).Conclusions and Significance: The PAR, which can be easily measured and readily detected, was a potential predictive factor. Moreover, performing fine-needle aspiration for lymphadenopathies could help diagnose hidden MNs in DNIs.

A novel parotid carcinoma with a prominent ghost cell population: a masquerading tumor or "salivary ghost cell carcinoma"?

Ghost cell is one of several unique cellular morphologies associated with aberrant keratinization. We encountered a novel parotid tumor containing numerous ghost cells and herein describe its histological features and discuss diagnostic problems. The patient was a 90-year-old Japanese male, who complained of swelling of the left parotid area for four months. Positron emission tomography indicated no cervical lymph node metastasis or distant metastasis. The tumor was successfully resected with no signs of recurrence or metastasis for six months after surgery. Histologically, the tumor was mainly composed of squamous cells forming irregularly shaped nests with a mixture of pleomorphic giant or multinucleated cells and bland basaloid cell. Keratinized areas were occupied by a prominent ghost cell population. Immunohistochemically, CK5/6 and CK19 were widely positive as well as AE1/AE3, p40 and p63. Nuclear expression of ß-catenin was also observed. The present case can be regarded as a particular form of squamous cell carcinoma and is believed to contain a large number of ghost cells resulting from an unclear mechanism. However, it seems difficult to consider such tumors as a clinicopathologically independent entity at present. Applying a term such as "salivary ghost cell carcinoma" would be premature.

Blowing time ratio and high-resolution manometry to evaluate swallowing function of patients with oral and oropharyngeal cancer.

OBJECTIVE: The blowing time ratio, which is the ratio of the blowing time when the nostrils are open and closed, is significantly correlated with velopharyngeal pressure, not only during speech but also during swallowing. This study aimed to further evaluate the usefulness of the blowing time ratio as a screening tool to evaluate the swallowing pressure of patients treated for oral and oropharyngeal cancers using high-resolution manometery (HRM). METHODS: Ten patients treated for oral or oropharyngeal cancer were recruited for this study. Swallowing pressures at the velopharynx, oropharynx, and upper esophageal sphincter (UES) were measured using HRM. Their correlations with the blowing time ratio were analyzed. RESULTS: The blowing time ratio was significantly correlated with the swallowing pressures of the oropharynx (CC = 0.815, p = 0.004) and the velopharynx (CC = 0.657, p = 0.039), but not of the UES. CONCLUSIONS: The present results further support our previous finding that the blowing time ratio is a useful screening tool to evaluate velopharyngeal and oropharyngeal swallowing pressures in patients treated for oral and oropharyngeal cancer.

Docetaxel plus cisplatin in recurrent and/or metastatic non-squamous-cell head and neck cancer: a multicenter phase II trial.

The clinical utility of systemic therapy and genomic profiling in non-squamous-cell head and neck cancer (NSCHNC) has not been fully elucidated. This phase II trial evaluated the efficacy and safety of docetaxel and cisplatin combination in the first-line setting. Eligibility criteria were recurrent and/or metastatic NSCHNC; progressive disease within the last 6 months; no prior systemic therapy; and ECOG performance status of 0-1. Patients received docetaxel (75 mg/m2 on day 1) and cisplatin (75 mg/m2 on day 1), repeated every 21 days for 6 cycles. The primary endpoint was confirmed objective response rate (ORR). The secondary endpoints included progression-free survival (PFS), overall survival (OS), and adverse events. Next-generation sequencing (NGS) was performed using the Ion AmpliSeq Cancer Hotspot Panel v2. Twenty-three patients were enrolled from November 2012 to October 2016, of whom 8 were male. Median age was 57 years. Ninety-six percent of cases were metastatic. Among 22 evaluable patients, confirmed ORR was 45% (95% confidential interval 24-68%). With a median follow-up period of 18.8 months, median PFS and OS were 6.7 and 20.1 months, respectively. Grade 3/4 adverse events included febrile neutropenia (39%) and anemia (22%). No treatment-related deaths were observed. NGS analysis revealed potential treatment targets, including ERBB2, KIT, and ALK. The docetaxel and cisplatin combination regimen can be considered a new treatment option in recurrent and/or metastatic NSCHNC, although primary prophylaxis for febrile neutropenia should be considered. Diverse genomic alterations may lead novel treatment options.This trial was registered with the UMIN Clinical Trials Registry as UMIN000008333 on [September 1st, 2012].

Up-front neck dissection followed by chemoradiotherapy for T1-T3 hypopharyngeal cancer with advanced nodal involvement.

BACKGROUND: The advantage of up-front neck dissection (UFND) followed by chemoradiotherapy (CRT) for hypopharyngeal cancer (HPC) with advanced neck involvement remains controversial. We aimed to determine the indications. METHODS: The data of 41 and 14 patients with stage IVA/B (T1-T3 and ≥N2a) HPC who underwent UFND followed by CRT and received CRT, respectively, were retrospectively analyzed and compared. RESULTS: The 5-year overall survival (OS) and disease-specific survival rates for the UFND and CRT groups were 61% and 52% (p = 0.1019), and 89% and 74% (p = 0.2333), respectively. Moreover, patients aged ≥70 years or those with a pulmonary disease history had a significantly poorer prognosis due to aspiration pneumonia in the UFND group. The 5-year regional control (RC) for the UFND and CRT groups were 92% and 57%, respectively (p = 0.0001). CONCLUSIONS: UFND followed by CRT was feasible with satisfactory RC. To further improve OS, aspiration pneumonia prevention is essential.

Prognostic factors after transoral resection of early hypopharyngeal cancer.

OBJECTIVE: This study aimed to investigate risk factors predictive of local recurrence and/or lymph node metastasis after transoral resection of early hypopharyngeal cancer. METHODS: Forty-nine consecutive patients who underwent transoral videolaryngoscopic surgery (TOVS) as an initial treatment for hypopharyngeal cancer were evaluated. On univariate and multivariate analysis, local recurrence rates were assessed respectively using log-rank test and cox regression analysis according to the following parameters: subsite, pT, mucosal margin, lymphatic invasion, vessel invasion, tumor thickness (> 4 mm vs ≤4 mm), history of esophageal cancer, and multiple Lugol-voiding lesions (LVLs) in the esophagus. Categorical variables were evaluated for their associations with lymph node metastasis using chi-squared test or Fisher's exact test. RESULT: The subsites of primary lesions were piriform sinus in 24 patients, posterior wall in 15 patients, and postcricoid in 10 patients. Thirty patients had esophageal cancer. Local recurrence occurred in 14 patients. Three patients had lymph node metastasis at the time of diagnosis and four patients developed lymph node metastasis after the initial treatment, resulting a total of seven patients having lymph node metastasis. While mucosal margin and LVLs showed significant associations with local recurrence on univariate analysis, only LVLs remained as a significant risk factor on multivariate analysis (P = .0395; hazard ratio = 8.897; 95% confidence interval, 1.113-71.15). Most cases of local recurrence were satisfactorily controlled by repeated TOVS. While multivariate analysis could not be performed due to the small number of the patients with lymph node metastases, venous invasion (P = .0166) and tumor thickness (P = .0092) were significantly associated with lymph node metastasis on univariate analysis. CONCLUSIONS: Local recurrence was more frequent in patients with LVLs, but most of them were salvaged by repeated TOVS. Patients with venous invasion and/or tumor thickness greater than 4 mm should be followed up with special attention to lymph node metastasis.Level of Evidence: 3.

Exploratory Analysis to Predict Optimal Tumor Burden for Starting Lenvatinib in Patients With Radioiodine-Refractory Differentiated Thyroid Cancer.

BACKGROUND: We previously reported that a high tumor burden is a prognostic factor based on an analysis of 26 patients with radioactive iodine-refractory differentiated thyroid cancer (RR-DTC) who were treated with lenvatinib. However, the optimal tumor burden for starting lenvatinib still remains to be defined. The aim of this retrospective study was to further explore in the same patient cohort the optimal timing for the start of lenvatinib by focusing on the pre- and post-treatment tumor burden. METHODS: The 26 patients were treated with lenvatinib from 2012 to 2017. We explored the optimal timing for the start of lenvatinib by comparing the characteristics of long-term responders who were defined as patients with progression-free survival ≥ 30 months and non-long-term responders. RESULTS: Long-term responders had a smaller post-treatment tumor burden at maximum shrinkage than non-long-term responders. Further, post-treatment tumor burden had a strong linear correlation with baseline tumor burden. We created an estimation formula for baseline tumor burden related to prognosis, using these regression lines. Patients with a sum of diameters of target lesions < 60 mm or maximum tumor diameter < 34 mm at baseline were estimated to have significantly better survival outcomes. CONCLUSIONS: We found a strong linear correlation between pre- and post-treatment tumor burden. Our results suggested a cut-off value for baseline tumor burden for long-term prognosis among patients treated with lenvatinib.

Pathological evaluation of tumor grade for salivary adenoid cystic carcinoma: A proposal of an objective grading system.

Three pathological grading systems advocated by Perzin/Szanto, Spiro, and van Weert are currently used for adenoid cystic carcinoma (AdCC). In these systems, the amount or presence of the solid tumor component in AdCC specimens is an important index. However, the "solid tumor component" has not been well defined. Salivary AdCC cases (N = 195) were collected after a central pathology review. We introduced a novel criterion for solid tumor component, minAmax (minor axis maximum). The largest solid tumor nest in each AdCC case was histologically screened, the maximum oval fitting the solid nest was estimated, and the length of the minor axis of the oval (minAmax) was measured. The prognostic cutoff for the minAmax was determined using training and validation cohorts. All cases were evaluated for the four grading systems, and their prognostic impact and interobserver variability were examined. The cutoff value for the minAmax was set at 0.20 mm. Multivariate prognostic analyses showed the minAmax and van Weert systems to be independent prognostic tools for overall, disease-free, and distant metastasis-free survival while the Perzin/Szanto and Spiro systems were selected for overall survival but not for disease-free or distant metastasis-free survival. The highest hazard ratio for overall survival (11.9) was obtained with the minAmax system. The reproducibility of the minAmax system (kappa coefficient of 0.81) was scored as very good while those of the other three systems were scored as moderate. In conclusion, the minAmax is a simple, objective, and highly reproducible grading system useful for prognostic stratification for salivary AdCC.

Left non-recurrent inferior laryngeal nerve in a patient with right-sided aortic arch and aberrant left subclavian artery.

Non-recurrent inferior laryngeal nerve (NRILN) is rare but one of the important anatomical variations in thyroid and parathyroid surgery. Almost all cases were observed on the right side with aberrant right subclavian artery and left NRILN have been reported in only five cases so far. Here, we reported a 38 year-old Japanese male with left NRILN accompanying adenomatous goiter. He was referred to our hospital for the surgical treatment of left thyroid goiter. Preoperative computed tomography revealed right-sided aortic arch and aberrant left subclavian artery with no signs of complete situs inversus viscerum, suggesting possible left NRLN. Left hemithyroidectomy was performed using nerve monitoring system. Intraoperatively, left recurrent laryngeal nerve was not identified along tracheoesophageal groove, but directly originated from vagal nerve and was running horizontally to larynx. Mobility of vocal cords were not impaired and postoperative course was uneventful. During thyroid surgery for the patients with right-sided aortic arch, meticulous care should be taken using nerve monitoring system to avoid nerve injury.

Two cases of glottic closure for refractory aspiration pneumonia after vertical partial laryngectomy.

Vertical partial laryngectomy is a well-established surgical procedure for early glottic cancers with acceptable functional and oncological outcomes. However, on a long-term basis, aspiration might be a serious problem with aging. Here we presented two cases of refractory aspiration pneumonia after vertical laryngectomy. Case 1: A 76-year old gentleman with a past history of malignant lymphoma treated by chemotherapy and radiotherapy had glottic cancer, which was treated by repeated vertical partial laryngectomies. Although glottic caner had been well controlled, he started to suffer from refractory aspiration pneumonia. Since his cervical skin was very thin and hard and his general condition was poor, we employed modified Kano's method for glottic closure. Case 2: A 87-year old Japanese male had a past history of glottic cancer treated by radiotherapy and vertical partial laryngectomy. He was repeatedly hospitalized for severe aspiration pneumonia. At the age of 87, he had second primary oropharyngeal cancer. Kano's method was simultaneously performed at the time of resection of oropharyngeal cancer. Postoperative courses were uneventful without sign of leakage in both cases. The patients started oral intake 2 weeks after the surgery. They have been alive without aspiration pneumonia and takes normal diet.

Safety and efficacy of cetuximab-containing chemotherapy after immune checkpoint inhibitors for patients with squamous cell carcinoma of the head and neck: a single-center retrospective study.

Immunotherapy has been shown to prolong survival in recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) in front-line use; however, subsequent systemic therapy has not been optimized. This study aimed to evaluate the safety and efficacy of cetuximab-containing chemotherapy after immunotherapy. We retrospectively analyzed patients with recurrent or metastatic SCCHN who underwent cetuximab-containing regimens after progression on immunotherapy. Of the 22 patients who met the inclusion criteria, 21 received paclitaxel and cetuximab, and 1 carboplatin and fluorouracil and cetuximab after immunotherapy. Nine patients achieved a partial response, 10 patients had stable disease as their best response on cetuximab-containing chemotherapy, yielding an overall response rate and disease control rate of 40.9 and 86.4%, respectively. The median progression-free survival was 5.2 months, and the median overall survival was 14.5 months. Ten patients developed grade 3-4 adverse events, including neutropenia (31.8%), acneiform rash (9.1%), anemia (4.5%), hypertransaminasemia (4.5%) and stomatitis (4.5%). The most frequent cetuximab-related toxicities across all grades were skin reactions (77.3%), hypomagnesemia (40.9%), stomatitis (27.3%), paronychia (13.6%) and keratitis (4.5%). There was no treatment-related death. Taken together, cetuximab-containing chemotherapy was effective and feasible even after immunotherapy.

Boron neutron capture therapy using cyclotron-based epithermal neutron source and borofalan (10B) for recurrent or locally advanced head and neck cancer (JHN002): An open-label phase II trial.

BACKGROUND AND PURPOSE: Boron neutron capture therapy (BNCT) can be performed without reactors due to development of cyclotron-based epithermal neutron source (C-BENS), which is optimized for treatment for deeper-seated tumors. The purpose of this study was to evaluate efficacy and safety of cyclotron-based BNCT with borofalan (10B) for recurrent or locally advanced head and neck cancer. MATERIALS AND METHODS: In this open-label, phase II JHN002 trial of BNCT using C-BENS with borofalan (10B), patients with recurrent squamous cell carcinoma (R-SCC) or with recurrent/locally advanced non-squamous cell carcinoma (R/LA-nSCC) of the head and neck were intravenously administered 400 mg/kg borofalan (10B), followed by neutron irradiation. The tumor dose was determined passively as the mucosal maximum dose of 12 Gy-Eq. The primary endpoint was the objective response rate (ORR). Post-trial observational JHN002 Look Up study was planned for evaluating locoregional progression-free survival (LRPFS). RESULTS: Eight R-SCC and 13 R/LA-nSCC patients were enrolled. All R-SCC patients had prior radiotherapy with a median dose of 65.5 Gy (range, 59.4-76.0 Gy). The ORR for all patients was 71%, and complete response/partial response were 50%/25% in R-SCC and 8%/62% in R/LA-nSCC. The 2-year overall survival for R-SCC and R/LA-nSCC were 58% and 100%, respectively. The median LRPFS was 11.5 months for R-SCC. Frequently observed adverse events included alopecia (95%), hyperamylasemia (86%), and nausea (81%). CONCLUSION: These data suggest that BNCT using C-BENS with borofalan (10B) is a promising treatment option for patients with R-SCC or R/LA-nSCC of the head and neck.

Diagnostic accuracy of deep-learning with anomaly detection for a small amount of imbalanced data: discriminating malignant parotid tumors in MRI.

We hypothesized that, in discrimination between benign and malignant parotid gland tumors, high diagnostic accuracy could be obtained with a small amount of imbalanced data when anomaly detection (AD) was combined with deep leaning (DL) model and the L2-constrained softmax loss. The purpose of this study was to evaluate whether the proposed method was more accurate than other commonly used DL or AD methods. Magnetic resonance (MR) images of 245 parotid tumors (22.5% malignant) were retrospectively collected. We evaluated the diagnostic accuracy of the proposed method (VGG16-based DL and AD) and that of classification models using conventional DL and AD methods. A radiologist also evaluated the MR images. ROC and precision-recall (PR) analyses were performed, and the area under the curve (AUC) was calculated. In terms of diagnostic performance, the VGG16-based model with the L2-constrained softmax loss and AD (local outlier factor) outperformed conventional DL and AD methods and a radiologist (ROC-AUC = 0.86 and PR-ROC = 0.77). The proposed method could discriminate between benign and malignant parotid tumors in MR images even when only a small amount of data with imbalanced distribution is available.

Oncolytic effect of Midkine promoter-based conditionally replicating adenoviruses expressing EGFR siRNA in head and neck squamous cancer cell line T891.

BACKGROUND: Epidermal growth factor receptor (EGFR) is overexpressed in head and neck squamous cell carcinomas (HNSCCs). Midkine expression is restricted in adult tissues but is increased in several malignant tumors, including HNSCCs. AIM: Here, we evaluated the antitumor effect of Midkine promoter-based conditionally replicative adenovirus expressing siRNA against EGFR for targeting HNSCCs expressing Midkine. METHODS AND RESULTS: A conditionally replicative adenovirus vector controlled by the Midkine promoter, Ad-MK-siEGFR, was generated by integrating gene-expressing siRNA against EGFR. Antitumor effect of Ad-MK-siEGFR was tested in vitro using established HNSCC cell line, T891 with strong Midkine expression. Expression of EGFR in T891 infected with Ad-MK-siEGFR was significantly lower than that of T891 infected with control. Cytotoxicity assays showed significant growth suppression of Ad-MK-siEGFR in T891 cells. CONCLUSIONS: This study demonstrated the possibility of oncolytic therapy using the Midkine promoter-based conditional replication-selective adenovirus containing siRNA against EGFR in HNSCC cell line T891. Further validation of the findings in more cell lines and in vivo should be performed to clarify the potential clinical application.

Salvage surgery for structural local recurrence of papillary thyroid cancer: recurrence patterns and surgical outcome.

To clarify the patterns of the recurrence and to assess the oncological and functional outcomes after salvage surgery for the patients with structural local recurrence of papillary thyroid cancer (PTC), twenty-five patients who underwent salvage surgery for structural local recurrence of PTC were retrospectively reviewed. Structural recurrences were observed in the tracheal lumen in 5 patients, intraluminal or intramuscular esophagus in 5 patients, trachea, and cricoid cartilage in 9 patients, cricoid and thyroid cartilage in 2 patients, intra-lumen of the larynx in 1 patient and soft tissue around thyroid in 3 patients, respectively. Although all local disease was resected with macroscopically negative margin, 10 patients diagnosed as microscopically positive margin. Major surgical complications occurred in 6 patients, including common carotid artery injury (n = 1), unintentional pharyngeal or esophageal injury (n = 2), recurrent laryngeal nerve paralysis (n = 2), and pharyngeal fistula resulting in common carotid artery rupture (n = 1), and were successfully managed. During the follow-up periods, 6 patients were alive without disease, 15 patients survived with distant metastases and/or locoregional recurrence, and 4 patients died of the disease. While tracheocutaneous fistula remained in 7 patients, the vocal function was preserved in all patients but one who underwent total laryngectomy. Normal oral intake was retained in all patients. In conclusion, although salvage surgery for structural recurrence of PTC has a high risk of complications, it may be worthwhile when macroscopic curative resection is available. The decision should be made considering various factors including curability, risk of surgical procedure, functional outcome, and life expectancy.