Enhancement of THz generation by feedback-optimized wavefront manipulation.

We apply active feedback optimization methods to pyroelectric measurements of a THz signal generated by four wave mixing in air using 1 mJ to 12 mJ, 35 fs laser pulses operating at 12 kHz repetition rate. A genetic algorithm, using the THz signal as a figure of merit, determines the voltage settings to a deformable mirror and results in up to a 6 fold improvement in the THz signal compared with settings optimized for the best focus. It is possible to optimize for different THz generation processes using this technique.

Radiofrequency ablation of low-risk small papillary thyroidcarcinoma: preliminary results for patients ineligible for surgery.

PURPOSE: The purpose of this study is to retrospectively evaluate the outcomes of radiofrequency ablation (RFA) of low-risk small papillary thyroid carcinomas (PTCs) in patients who were ineligible for surgery. MATERIALS AND METHODS: Between 2005 and 2009, six PTCs (mean diameter, 0.92 cm; range, 0.6-1.3 cm) in six patients were treated with RFA by three radiologists in two hospitals. The inclusion criteria for this study were (1) pathologically confirmed PTC without cytological aggressiveness, (2) single PTC without extrathyroidal extension, (3) no metastatic tumours and (4) ineligibility for surgery. RFA was performed using a radiofrequency generator and an 18-gauge internally cooled electrode. The medical records were reviewed and analysed, focussing on the procedural profiles of RFA, symptoms and complications during and after RFA, and changes in tumours on follow-up ultrasonography. RESULTS: Before and after RFA, the results of thyroid function tests were normal in all patients. During 48.5 ± 12.3 months (range, 36-65 months) of follow-up, along with a significant reduction in the mean volume (98.5 ± 3.3%), four ablation zones (4/6, 66.7%) completely disappeared. Two ablation zones exhibited only small calcified residues with nearly complete disappearance of the corresponding non-calcified solid portions, and in one of them, malignant cells were absent as assessed by fine-needle aspiration and core-needle biopsy. Transient hypertension with mild headache (n = 1) and mild neck pain (n = 1) developed during the procedure and subsided without any treatment. CONCLUSION: Besides surgery and active surveillance, which are conflicting currently used management plans, RFA might represent an effective and a safe alternative for managing low-risk small PTCs, especially in patients ineligible for surgery.

Clinical outcomes after local anesthesia with monitored anesthesia care during thyroidectomy and selective neck dissection: a randomized study.

Although thyroidectomy under local anesthesia with monitored anesthesia care (LA-MAC) has been reported, reports of neck dissections beyond level VI under LA-MAC in patients with thyroid cancer are rare. We aimed to analyze clinical data and patient satisfaction levels during thyroidectomy and selective neck dissection by comparing LA-MAC and general anesthesia (GA) in adult patients undergoing these surgeries for thyroid cancer. The 60 enrolled patients comprised 50 patients that underwent thyroidectomy and 10 that underwent selective neck dissection; 30 underwent thyroidectomy (n = 25) or selective neck dissection (n = 5) under LA-MAC and 30 (matched patients) underwent thyroidectomy (n = 25) or selective neck dissection (n = 5) under GA. Complaints of postoperative nausea, vomiting, throat discomfort, and voice changes were significantly fewer in the LA-MAC group than in the GA group. Postoperative pain, odynophagia, dyspnea, and patient satisfaction levels were not significantly different between groups. In the thyroidectomy group, postoperative nausea, vomiting, throat discomfort, and voice changes were less common with LA-MAC, whereas postoperative pain, odynophagia, dyspnea, and patient satisfaction levels were similar for both anesthesia methods. The selective neck dissection group showed no differences between the two anesthesia methods. No postoperative complications were reported in all patients. Our results suggest that LA-MAC can be routinely used for select cases of thyroidectomy and is feasible for selective neck dissection beyond level VI with regard to postoperative discomfort, patient satisfaction levels, and safety. However, further investigations are necessary to clarify these findings.

5-lipoxygenase mediates docosahexaenoyl ethanolamide and N-arachidonoyl-L-alanine-induced reactive oxygen species production and inhibition of proliferation of head and neck squamous cell carcinoma cells.

BACKGROUND: Endocannabinoids have recently drawn attention as promising anti-cancer agents. We previously observed that anandamide (AEA), one of the representative endocannabinoids, effectively inhibited the proliferation of head and neck squamous cell carcinoma (HNSCC) cell lines in a receptor-independent manner. In this study, using HNSCC cell lines, we examined the anti-cancer effects and the mechanisms of action of docosahexaenoyl ethanolamide (DHEA) and N-arachidonoyl-L-alanine (NALA), which are polyunsaturated fatty acid (PUFA)-based ethanolamides like AEA. METHODS AND RESULTS: DHEA and NALA were found to effectively inhibit HNSCC cell proliferation. These anti-proliferative effects seemed to be mediated in a cannabinoid receptor-independent manner, since the antagonist of cannabinoid receptor-1 (CB1) and vanilloid receptor-1 (VR1), two endocannabinoid receptors, did not reverse the ability of DHEA and NALA to induce cell death. Instead, we observed an increase in reactive oxygen species (ROS) production and a decrease of phosphorylated Akt as a result of DHEA and NALA treatment. Antioxidants efficiently reversed the inhibition of cell proliferation and the decrease of phosphorylated Akt induced by DHEA and NALA; inhibition of 5-lipoxygenase (5-LO), which is expected to be involved in DHEA- and NALA-degradation pathway, also partially blocked the ability of DHEA and NALA to inhibit cell proliferation and phosphorylated Akt. Interestingly, ROS production as a result of DHEA and NALA treatment was decreased by inhibition of 5-LO. CONCLUSIONS: From these findings, we suggest that ROS production induced by the 5-LO pathway mediates the anti-cancer effects of DHEA and NALA on HNSCC cells. Finally, our findings suggest the possibility of a new cancer-specific therapeutic strategy, which utilizes 5-LO activity rather than inhibiting it.

Predictive and prognostic value of PET/CT imaging post-chemoradiotherapy and clinical decision-making consequences in locally advanced head & neck squamous cell carcinoma: a retrospective study.

BACKGROUND: The accuracy of (18)F-fluorodeoxygluocose positron emission tomography/computed tomography (PET/CT) in predicting immediate failure after radical chemoradiotherapy (CRT) for HNSCC is poorly characterized at present. The purpose of this study was to examine PET/CT as a predictive and prognostic gauge of immediate failure after CRT and determine the impact of these studies on clinical decision making in terms of salvage surgery. METHODS: Medical records of 78 consecutive patients receiving radical CRT for locally advanced HNSCC were reviewed, analyzing PET/CTs done before and 3 months after CRT. Immediate failure was defined as residual disease or locoregional and/or systemic relapse within 6 months after CRT. RESULTS: Maximum standard uptake value (SUV) of post CRT PET/CT (postSUVmax) was found optimal for predicting immediate failure at a cutpoint of 4.4. Sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) were 90.0%, 83.8%, 98.3%, and 45.0%, respectively. Of 78 patients studied, postSUVmax ≥ 4.4 prevailed in 20 (25.6%), with postSUVmax <4.4 in 58 (74.4%). At postSUVmax ≥ 4.4 (vs. postSUVmax <4.4) OS was poorer by comparison (3-year OS: 56.9 vs. 87.7%; P = 0.005), as was progression-free survival (3-year PFS: 42.9 vs. 81.1%; P < 0.001). At postSUVmax ≥ 4.4, OS with and without immediate salvage surgery did not differ significantly (3-year OS: 60.0 vs. 55.6%; Log-rank P = 0.913). CONCLUSION: Post CRT PET/CT imaging has prognostic value in terms of OS and PFS and is useful in predicting immediate therapeutic failure, given its high NPV. However, OS was not significantly altered by early salvage surgery done on the basis of post CRT PET/CT findings.

Is There Any Age Cutoff to Treat Elderly Patients with Head and Neck Cancer? Comparing with Septuagenarians and Octogenarians.

With the increase in life expectancy, age is no longer considered as a limitation for treatment. Nevertheless, the treatment of elderly patients with head and neck cancer (HNC) remains controversial. Here, we aimed to review our experience with the treatment for elderly patients, while particularly focusing on the differences among older old patients (septuagenarians vs. octogenarians). We retrospectively reviewed the records of 260 elderly patients who were assigned to 3 groups according to age: 70 years old ≤ group 1 < 75 years old, 75 years old ≤ group 2 < 80 years old, and group 3 ≥ 80 years old. The patients were assessed for comorbidities using the Adult Comorbidity Evaluation (ACE)-27, and the American Society of Anesthesia (ASA) physical status was also compared. Group 1, 2, and 3, consisted of 97, 102, and 61 patients, respectively. No significant difference in demographic data was noted among the groups. However, group 3 showed more comorbidities than groups 1 and 2. With regard to the initial treatment for HNC, radiation therapy (RT) was more frequently performed in group 3 than in groups 1 and 2. Among 7 patients of non-compliant to treatment in group 3, 6 patients had have performed RT. In group 3, a total of 18 patients underwent surgery, including microvascular free flap reconstruction and no significant difference in complications was observed postoperatively compared with group 1 and 2. Moreover, no significant difference was noted in overall survival between the groups, regardless of the treatment modality chosen. In conclusion, octogenarians with HNC should be more carefully managed than septuagenarians with HNC. Surgical treatment can be considered in octogenarians with HNC, if it can be tolerated.

Prognostic factors of locally invasive well-differentiated thyroid carcinoma involving the trachea.

To report our experience with tracheal invasive thyroid carcinoma with emphasis on clinical characteristics and treatment modalities, and to identify the prognostic factors for tracheal invasive thyroid carcinoma. Totally 1919 patients underwent surgical extirpation of thyroid cancer from 1990 to 2010. Among them, 65 patients had well-differentiated thyroid cancer with tracheal invasion. The incidence was higher in male and older patients. Patients were treated with tracheal shave excision (n = 18), tracheal resection (n = 37) and total laryngectomy (n = 10). Locoregional recurrence occurred in 39 patients, and metastasis occurred in 25 patients. Simultaneous involvement of the trachea and the esophagus was associated with locoregional recurrence (p = 0.039) in univariate analysis, but not confirmed by multivariate analysis. There was significant difference in the disease-specific survival (DSS) according to laryngeal involvement (p = 0.002). All the patient in the shave excision group survived until the end of the study period. Although it is categorized in same classification of T4a, simultaneous involvement of the trachea and the esophagus showed higher locoregional recurrence and laryngeal involvement showed lower DSS. Despite the invasion of thyroid cancer into the adjacent aerodigestive tract, many patients showed long survival when they underwent appropriate surgery.

Activation of K(+) channel by 1-EBIO rescues the head and neck squamous cell carcinoma cells from Ca(2+) ionophore-induced cell death.

Ion channels in carcinoma and their roles in cell proliferation are drawing attention. Intracellular Ca(2+) ([Ca(2+)]i)-dependent signaling affects the fate of cancer cells. Here we investigate the role of Ca(2+)-activated K(+) channel (SK4) in head and neck squamous cell carcinoma cells (HNSCCs) of different cell lines; SNU-1076, OSC-19 and HN5. Treatment with 1 µM ionomycin induced cell death in all the three cell lines. Whole-cell patch clamp study suggested common expressions of Ca(2+)-activated Cl(-) channels (Ano-1) and Ca(2+)-activated nonselective cation channels (CAN). 1-EBIO, an activator of SK4, induced outward K(+) current (ISK4) in SNU-1076 and OSC-19. In HN5, ISK4 was not observed or negligible. The 1-EBIO-induced current was abolished by TRAM-34, a selective SK4 blocker. Interestingly, the ionomycin-induced cell death was effectively prevented by 1-EBIO in SNU-1076 and OSC-19, and the rescue effect was annihilated by combined TRAM-34. Consistent with the lower level of ISK4, the rescue by 1-EBIO was least effective in HN5. The results newly demonstrate the role of SK4 in the fate of HNSCCs under the Ca(2+) overloaded condition. Pharmacological modulation of SK4 might provide an intriguing novel tool for the anti-cancer strategy in HNSCC.

Prevalence and prognostic value of human papillomavirus genotypes in tonsillar squamous cell carcinoma: a Korean multicenter study.

BACKGROUND: This study was aimed at investigating the change in the prevalence of human papillomavirus (HPV) genotypes in tonsillar squamous cell carcinoma (TSCC) and the association of the HPV genotype with the prognosis. METHODS: This multicenter study included 175 patients with TSCC from 3 general hospitals between 1991 and 2009. HPV DNA was detected in paraffin-embedded tissues with genotyping chips. A survival analysis that considered clinicopathological factors, the HPV genotype, and the expression of p53, retinoblastoma protein, p16, and epidermal growth factor receptor (assessed with immunohistochemistry) was performed with Cox regression analysis. RESULTS: High-risk HPV types were found in 23.4% of the cases. The prevalence of HPV-18 (10.3%) was as high as that of HPV-16 (10.3%). The proportion of high-risk HPV-positive tumors increased from 5.9% in 1991 to 31.6% in 2009. HPV-16 positivity was associated with an advanced stage and lymph node metastasis, whereas HPV-18 positivity was associated with old age and an advanced T stage. The survival analysis showed that old age and T classification were poor prognostic factors, whereas the expressions of various biomarkers were not associated with prognosis. HPV-18-positive cases had a poorer prognosis than HPV-16-positive cases and non-HPV-related TSCC cases. A multivariate analysis revealed that HPV-18 positivity, old age, and an advanced T stage were independent prognostic factors for predicting poor outcomes for patients with TSCC. CONCLUSIONS: The proportion of HPV-positive tonsillar cancer cases has increased during the last 20 years in the Republic of Korea. The presence of HPV-18 may serve as a biomarker for a poor prognosis.

A Randomized, Multicenter, Phase II Study of Cetuximab With Docetaxel and Cisplatin as Induction Chemotherapy in Unresectable, Locally Advanced Head and Neck Cancer.

BACKGROUND: We investigated the efficacy of cetuximab when added to induction chemotherapy followed by concurrent chemoradiotherapy (CCRT) in patients with locally advanced head and neck squamous cell carcinoma. METHODS: Patients were randomized to receive three cycles of docetaxel and cisplatin (TP regimen) with or without cetuximab (TP plus cetuximab [CTP] vs. TP) as induction chemotherapy. Patients in the CTP arm received CCRT with cetuximab and cisplatin, whereas patients in the TP arm received cisplatin alone. The primary endpoint was the objective response rate (ORR) after induction chemotherapy. RESULTS: Overall, 92 patients were enrolled. The ORRs for induction chemotherapy in the CTP and TP arms were not different (81% vs. 82%). Adding cetuximab lowered the completion rate of induction chemotherapy and CCRT and resulted in more frequent dose reductions of the induction chemotherapy, although this did not reach statistical significance. In the CTP and TP arms, respectively, the 3-year progression-free survival (PFS) rates were 70% and 56% (p = .359), and the overall survival (OS) rates were 88% and 74% (p = .313). When limited to patients who completed induction chemotherapy, 3-year PFS rates of 78% and 59% (p = .085) and OS rates of 94% and 73% (p = .045) were observed in the CTP and TP arms, respectively. CONCLUSION: Adding cetuximab to sequential treatment did not increase the treatment efficacy and resulted in greater toxicity. In the intent-to-treat population, neither PFS nor OS was improved by the addition of cetuximab to sequential treatment; however, a suggestion of improved survival outcomes was observed in patients completing cetuximab-containing induction chemotherapy.

Practical use of povidone-iodine antiseptic in the maintenance of oral health and in the prevention and treatment of common oropharyngeal infections.

AIMS: To better inform medical practitioners on the role of antiseptics in oropharyngeal health and disease, this article focuses on povidone-iodine (PVP-I), an established and widely-available antiseptic agent. METHODOLOGY: Review of the anti-infective profile, efficacy and safety of PVP-I in managing common upper respiratory tract infections such as the common cold, influenza and tonsillo-pharyngitis, as well as oral complications resulting from cancer treatment (oral mucositis), and dental conditions (periodontitis, caries). RESULTS: Antiseptics with broad-spectrum anti-infective activity and low resistance potential offer an attractive option in both infection control and prevention. While there is some evidence of benefit of antiseptics in a variety of clinical settings that include dental and oral hygiene, dermatology, oncology, and pulmonology, there appears to be discordance between the evidence-base and practice. This is especially apparent in the management and prevention of oropharyngeal infections, for which the use of antiseptics varies considerably between clinical practices, and is in marked contrast to their dermal application, where they are extensively used as both a prophylaxis and a treatment of skin and wound infections, thus minimising the use of antibiotics. CONCLUSION: The link between oral and oropharyngeal health status and susceptibility to infection has long been recognised. The high rates of antibiotic misuse and subsequent development of bacterial resistance (e.g. increasing vancomycin-resistant enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA)) in large parts of the world, especially across Asia Pacific, highlight the need for identifying alternative antimicrobials that would minimise the use of these medications. This, together with recent large-scale outbreaks of, for example, avian and swine influenza virus, further underline the importance of an increasing armamentarium for infection prevention and control.

Neck computed tomography in pediatric neck mass as initial evaluation in ED: is it malpractice?

BACKGROUND: Although ultrasound is regarded as the first choice imaging modality for evaluating a pediatric neck mass, neck computed tomography (CT) is necessary for urgent surgical conditions such as deep neck infections. Our aim was to evaluate the diagnostic effectiveness of and proper patient selection for neck CT as a method for the initial evaluation of pediatric neck masses in the emergency department. METHODS: We analyzed the medical records of 105 pediatric patients who visited the emergency department with neck mass whose initial imaging work-up was a neck CT and who visited the emergency department with a neck mass. The parameters investigated included the patient's age, sex, symptom duration, clinical impression, CT interpretation, final diagnosis, and treatment. The positive predictive value (PPV) for CT was calculated, and the parameters that correlated with an urgent surgical condition post-CT were evaluated. RESULTS: The median age was 6.5 years (1 month to 12 years), and the male-to-female ratio was 2:1. The most common initial impression was acute cervical lymphadenopathy. A comparison of the final diagnosis and CT scan demonstrated that the overall PPV was 96.2%. If the initial impression was a deep neck infection, a salivary gland infection, or tonsillitis, the PPV for CT was 100%. Fever (>38.0°C) and severe tenderness were significant between patients with and without urgent surgical conditions on CT. CONCLUSIONS: Computed tomography could be considered as the first diagnostic modality when an urgent surgical condition such as a deep neck infection is highly suspected.

Influences of demographic changes and medical insurance status on tonsillectomy and adenoidectomy rates in Korea.

In Korea, the proportion of the pediatric population is decreasing due to low fertility rates and aging of the society. It is hypothesized that this change in population structure and medical insurance status may affect rates of elective surgeries more significantly than clinical factors. An observational study conducted using data from the Health Insurance Review and Assessment Service for tonsillectomy and adenoidectomy, with 403,924 registered patients from 2007 through 2011. We analyzed longitudinal changes in crude and age-adjusted surgery rates of three surgeries-tonsillectomy without adenoidectomy (T), adenoidectomy without tonsillectomy (A), and tonsillectomy with adenoidectomy (T&A)-according to medical insurance status: health insurance (HI) group (better economic status) versus health aid (HA) group (poorer economic status). Most of the surgeries (51.8 % of T, 93.7 % of A, and 95.1 % of T&A) were performed in patients younger than 15. Over 5 years, the proportion of the child population numbers decreased, from 17.43 to 15.41 % in the HI group and from 21.20 to 13.15 % in the HA group. Thus, crude surgery rates for T, A, and T&A decreased more rapidly in the HA group (7.50, 14.79, and 15.55 %) than the HI group (1.69, 1.49, and 0.90 %) each year. Adjusted surgery rates for T, A, and T&A increased in the HI group (1.01, 2.64, and 3.36 %) and decreased in the HA group (1.39, 2.86, and 2.76 %) each year. These adjusted surgery rates partially explains the sharper decrease in crude surgery rates in the HA group than the HI group. The crude and adjusted rates of surgeries were usually higher in lower economic status groups. In conclusion, surgery rates were affected by changes in the population structure, but by other factors as well. Predictable socioeconomic factors could be used to calculate and predict the rates for other well-established surgeries.

Long-term subjective tongue function after partial glossectomy.

There have been limited studies of subjective tongue function over long-term follow-up in spite of swallowing and articulation disorders are common complications of glossectomy. To assess long-term subjective swallowing and articulation function after partial glossectomy. A total of 63 patients with the mobile tongue cancer who underwent partial glossectomy without reconstruction were interviewed to score their swallowing and articulation function on a 100-point scale. The relation of this subjective scoring to the perioperative data was subjected to multivariate analysis. The mean patient age was 53·4 (19-81) years, and the mean follow-up duration was 78·9 (14-277) months. Mean swallowing and articulation function score was 87·7 ± 6·1 and 88·6 ± 5·4. Age, follow-up duration, T stage and resection volume were significantly correlated with swallowing function (P = 0·026, 0·029, 0·016, 0·002, respectively); follow-up duration was correlated with articulation function (P = 0·039). Patients who undergo partial glossectomy without reconstruction generally demonstrate good function on long-term follow-up. Subjective dysfunction was correlated with larger resection volume, older age and shorter follow-up duration.

The Expression of Defensin-Associated Genes May Be Correlated With Lymph Node Metastasis of Early-Stage Tongue Cancer.

OBJECTIVES: We aimed to assess the genetic differences between cases of early-stage tongue cancer that were positive or negative for lymph node metastasis. METHODS: In total, 35 cases of tongue cancer with RNA sequencing data were enrolled in this study. The gene expression profile of the following two groups was compared: N0 group (T stage 1 or 2 with N0 stage) and N+ group (T stage 1 or 2 with N+ stage). Using the R and limma packages in the Bioconductor program, we extracted the differentially expressed genes (DEGs). Gene ontology and pathway enrichment analysis were performed using the Database for Annotation, Visualization and Integration Discovery (DAVID) online tool. Immune cell infiltration was analyzed using the CIBERSORT online program. Immunochemical staining of the cancer tissue was evaluated and The Cancer Genome Atlas (TCGA) data were analyzed to validate the identified DEGs. RESULTS: No significant differences were found in the infiltration of 22 types of immune cells. Among a total of 51 identified DEGs, 14 genes were significantly upregulated, while 37 genes were significantly downregulated (P<0.01; fold change >2). Pathway analysis revealed significant associations with the arachidonic acid metabolism-related pathway, calcium signaling, and the muscle contraction pathway. The following DEGs were the most significantly different between the two groups: DEFB4A, SPRR2B, DEFB103B, SPRR2G, DEFB4B, and FAM25A. TCGA data showed that DEFB4A and DEFB103B were more highly expressed in the N0 group than in the N+ group, although the difference did not achieve statistical significance. Immunochemical staining of cancer tissue revealed significantly higher expression of defensin in the N0 group. CONCLUSION: . Defensin (DEFB4A, DEFB103B, DEFB4B) may be a novel biomarker for early regional metastasis in T1/2 tongue cancer.

NTRK and RET fusion-directed therapy in pediatric thyroid cancer yields a tumor response and radioiodine uptake.

BACKGROUNDMolecular characterization in pediatric papillary thyroid cancer (PTC), distinct from adult PTC, is important for developing molecularly targeted therapies for progressive radioiodine-refractory (131I-refractory) PTC.METHODSPTC samples from 106 pediatric patients (age range: 4.3-19.8 years; n = 84 girls, n = 22 boys) who were admitted to SNUH (January 1983-March 2020) were available for genomic profiling. Previous transcriptomic data from 125 adult PTC samples were used for comparison.RESULTSWe identified genetic drivers in 80 tumors: 31 with fusion oncogenes (RET in 21 patients, ALK in 6 patients, and NTRK1/3 in 4 patients); 47 with point mutations (BRAFV600E in 41 patients, TERTC228T in 2 patients [1 of whom had a coexisting BRAFV600E], and DICER1 variants in 5 patients); and 2 with amplifications. Fusion oncogene PTCs, which are predominantly detected in younger patients, were at a more advanced stage and showed more recurrent or persistent disease compared with BRAFV600E PTCs, which are detected mostly in adolescents. Pediatric fusion PTCs (in patients <10 years of age) had lower expression of thyroid differentiation genes, including SLC5A5, than did adult fusion PTCs. Two girls with progressive 131I-refractory lung metastases harboring a TPR-NTRK1 or CCDC6-RET fusion oncogene received fusion-targeted therapy; larotrectinib and selpercatinib decreased the size of the tumor and restored 125I radioiodine uptake. The girl with the CCDC6-RET fusion oncogene received 131I therapy combined with selpercatinib, resulting in a tumor response. In vitro 125I uptake and 131I clonogenic assays showed that larotrectinib inhibited tumor growth and restored radioiodine avidity.CONCLUSIONSIn pediatric patients with fusion oncogene PTC who have 131I-refractory advanced disease, selective fusion-directed therapy may restore radioiodine avidity and lead to a dramatic tumor response, underscoring the importance of molecular testing in pediatric patients with PTC.FUNDINGThe Ministry of Science, ICT and Future Planning (NRF-2016R1A2B4012417 and 2019R1A2C2084332); the Korean Ministry of Health and Welfare (H14C1277); the Ministry of Education (2020R1A6A1A03047972); and the SNUH Research Fund (04-2015-0830).TRIAL REGISTRATIONTwo patients received fusion-targeted therapy with larotrectinib (NCT02576431; NAVIGATE) or selpercatinib (LOXO-RET-18018).

Conditionally replicating adenovirus improves gene replication efficiency and anticancer effect of E1-deleted adenovirus carrying TRAIL in head and neck squamous cell carcinoma.

To overcome the low efficiency of gene therapy, we combined a conditionally replicating adenovirus (CRAd) and an adenoviral vector with a therapeutic gene. CRAd has an oncolytic activity in cancer cells with abnormal Rb activity and helps the replication of therapeutic genes incorporated in the E1-deleted adenovirus. We investigated the anticancer effect of a combination of CRAd and adenovirus carrying tumor necrosis factor-related apoptosis inducing ligand (ad-TRAIL). We expected to see increased gene expression in cancer cells as well as an antitumor effect. With the combined application of CRAd and ad-luciferase in head and neck cancer cell lines, we observed considerably increased luciferase activity that was 10- to 50-fold greater than with ad-luciferase alone. The combination of CRAd and ad-TRAIL showed significant suppression of growth in cell lines and increased the sub-G(1) portion of cells 30-fold compared to any single treatment. The expression of TRAIL was highly amplified by the combined treatment and was accompanied by expression of molecules related to apoptosis. In a xenograft animal model, mice treated with CRAd and ad-TRAIL showed complete regression of established tumors, whereas mice treated with CRAd or ad-TRAIL alone did not. In conclusion, this combined strategy using CRAd and adenovirus carrying a therapeutic gene increased the gene transfer rate and enhanced antitumor effects. We expect that this combination strategy could be extended to a multitarget cancer gene therapy by combining multiple adenoviruses and CRAd.

A combination treatment with SAHA and ad-p63/p73 shows an enhanced anticancer effect in HNSCC.

Suberoylanilide hydroxamic acid (SAHA) is one of the most widely used histone deacetylase inhibitors. However, the potential advantage of SAHA has not been sufficiently validated as an adjunct to gene therapy of head and neck squamous cell carcinoma (HNSCC). SAHA has been shown to boost the efficiency of gene transfer by upregulating the expression of coxsackie adenoviral receptor on treated cells. The p53 family genes, p63 and p73, have been shown to have characteristics similar to p53, and although they are not confirmed as tumor suppressors, DNA-damaging signals induce their overexpression. We previously reported that the adenovirus-mediated transfer of p63 or p73 showed an effective cancer-killing effect similar to that of p53. In this study, we combined SAHA with adenoviral delivery of p63 or p73 to enhance the efficiency of gene therapy. This combination resulted in a significantly enhanced cancer-killing effect in HNSCC cell lines but had no effect on normal human fibroblasts. SAHA treatment added to ad-p63/p73 gene delivery caused an increase in p21 expression and cleaved poly-ADP ribose polymerase. Our results indicate that adjuvant SAHA treatment could be developed as a therapeutic strategy to enhance the efficiency of adenoviral gene transfer in the treatment of cancer.

Class III beta-tubulin, but not ERCC1, is a strong predictive and prognostic marker in locally advanced head and neck squamous cell carcinoma.

BACKGROUND: Recent researches revealed that class III beta-tubulin (TUBB3) is a prognostic marker in various tumors and role of TUBB3 in head and neck squamous cell carcinoma (HNSCC) is not defined yet. We analyzed the significance of TUBB3 expression along with p53 and ERCC1 in locally advanced HNSCC patients receiving cisplatin-based induction chemotherapy. MATERIALS AND METHODS: Retrospective review of medical records at Seoul National University Hospital between 1998 and 2007 was carried out. Immunohistochemical stain of TUBB3, p53, and ERCC1 was done in paraffin-embedded tumor tissue. We assessed response to treatment, progression-free survival (PFS), overall survival (OS), and cancer-specific survival (CSS). RESULTS: Eighty-five patients with oropharyngeal, hypopharyngeal, and laryngeal cancers received induction chemotherapy with 5-fluorouracil (5-FU) and cisplatin (n = 55), or 5-FU, cisplatin, and docetaxel (Taxotere) (n = 30). Eighty-three received definitive treatment after induction chemotherapy, where 62 received radiotherapy and 21 received surgery. TUBB3-positive patients showed lower response rate than TUBB3-negative patients (69% versus 88%, P = 0.039). Shorter median PFS was observed in TUBB3-positive group (12 versus 47 months, P = 0.001). Shorter median OS was observed in TUBB-positive group not reaching statistical significance (30 versus 59 months, P = 0.072). TUBB3 status significantly influenced CSS (35 months versus not reached, P = 0.017). Positive p53 status was related to poorer OS and CSS. ERCC1 showed no influence on chemotherapy response, PFS, OS, and CSS. CONCLUSION: TUBB3 is a predictive and prognostic marker along with well-known p53 in HNSCC patients receiving cisplatin-based induction chemotherapy. Clinical impact of ERCC1 is not evident in this setting.

OK-432 sclerotherapy in head and neck lymphangiomas: long-term follow-up result.

INTRODUCTION: Nonsurgical treatments, such as sclerotherapy have been attempted for head and neck lymphagiomas. Of the available sclerosing agents, picibanil has shown satisfactory short-term treatment results in many studies, but no study has presented long-term treatment results. Accordingly, in the present study, the authors retrospectively reviewed the long-term treatment results of picibanil sclerotherapy. MATERIALS AND METHODS: Fifty-five lymphangioma patients who underwent picibanil sclerotherapy were enrolled. Data about initial and long-term response, recurrence, and excision rate were collected. RESULTS: Initial response rates were 83.5 percent and long-term response rates were 76.3 percent. CONCLUSION: Initial and the long-term response rate were equally good for lymphangioma.