The Efficacy and Safety of an Indocyanine Green-Macroaggregated Albumin-Hyaluronic Acid Mixture (LuminoMark™) for Surgical Localization of Recurrent Thyroid Cancer.

BACKGROUND: The recurrence of thyroid cancer poses challenges compounded by postoperative fibrosis and anatomic changes. By overcoming the limitations of current localizing dye techniques, indocyanine green-macroaggregated albumin-hyaluronic acid (ICG-MAA-HA) mixture dye promises improved localization. This study aimed to evaluate the efficacy and safety of the dye for recurrent thyroid cancer. METHODS: The nine patients in this study underwent surgery and postoperative ultrasonography. The dye was injected into recurrent lesions in all the patients preoperatively. During surgery, the lesions were confirmed with an imaging system before and after excision. If the lesion was unidentifiable with the naked eye, surgical excision was performed under the corresponding fluorescent guide. Side effects related to the dye injection and completeness of the surgery were evaluated. RESULTS: No side effects such as bleeding, skin tattooing, or pain during or after the dye injection were reported, and no discoloration occurred that interfered with the surgical field of view during surgery. In three cases (33.3 %), because it was difficult to localize metastatic lesions with the naked eye, the operation was successfully completed using an imaging system. The completeness of the surgical resection was confirmed by ultrasonography after an average of 5 months postoperatively. CONCLUSION: The study found that ICG-MAA-HA dye effectively located metastatic and recurrent thyroid cancer and had favorable results in terms of minimal procedural side effects and potential for assisting the surgeon. A large-scale multi-institutional study is necessary to prove the clinical significance regarding patient survival and disease control.

Evaluation and Classification of Supraorbital Nerve Emerging Patterns.

BACKGROUND: Numerous significant variations in the supraorbital nerve (SON) pass through the notches and foramina. During endoscopic forehead lifting, the passage and the location of the nerve against the frontal bone render it susceptible to injury, resulting in diminished or absent sensation in the corresponding location. We attempted to obtain accurate knowledge of the SON emergence routes. METHODS: Data of patients who underwent an endoscopic forehead lift in a plastic surgery clinic between November 2015 and August 2021 were retrospectively analyzed. Deep and superficial branch pathways of SONs were identified and compared according to side and gender. We also classified the nerve patterns into six types. RESULTS: Altogether, 942 patients (1884 SON cases) were evaluated. Out of the patients, 86 patients were male, and 856 were female. The overall mean age was 48.6 (± 13.1) years. In the deep branches, 49% came from the notch, and 51% came from the foramen. In the superficial branches, 67% came from the notch, and 33% of superficial branches came from the foramen. Unlike the deep branch, superficial branches from the notch were significant. Deep and superficial branches of male patients were much more notched than those of female patients. Branches emerged together in 56% and separately in 44% of the cases. CONCLUSION: The absolute number of SON notches was higher than that of SON foramina. This study with the largest number of SON cases will help surgeons understand the variation and course of SON. LEVEL OF EVIDENCE IV: This journal requires that authors 38 assign a level of evidence to each article. For a full 39 description of these Evidence-Based Medicine ratings, 40 please refer to the Table of Contents or the online 41 Instructions to Authors www.springer.com/00266 .

Surgical Outcomes in Patients With Low-risk Papillary Thyroid Microcarcinoma From MAeSTro Study: Immediate Operation Versus Delayed Operation After Active SurveillanceA Multicenter Prospective Cohort Study.

OBJECTIVE: To investigate surgical, and clinical outcomes in patients with low-risk papillary thyroid microcarcinoma (PTMC) according to treatment options [immediate operation (IOP) vs delayed operation after active surveillance (AS) (DOP)]. BACKGROUND: AS has been adopted as an alternative to immediate surgery in patients with low-risk PTMC. Although some patients undergo surgery during AS, there is little information on surgical, and clinical outcomes after delayed operation after AS. METHODS: A multicenter prospective cohort study including 1177 patients was conducted at 3 tertiary hospitals in Korea from June 2016 to January 2020. Patients with low-risk PTMC were enrolled. The participants were self-assigned into AS or IOP, and during AS, the patients underwent surgery if there were signs of disease progression or if the patient's choice changed. RESULTS: A total of 516 patients underwent operation; 384 (74.4%) in the IOP group and 132 (25.6%) in the DOP group. Compared with the IOP group, the DOP group was significantly associated with a larger tumor size ( P =0.002), higher rates of lymphatic invasion ( P =0.002), and multifocality ( P =0.008). However, the rates of total thyroidectomy, postoperative hypoparathyroidism and vocal cord palsy did not differ significantly between the groups ( P = 0.283, P =0.184, and P =0.284, respectively). Of the 132 patients in the DOP group, disease progression was present in 39 (29.5%) patients. The DOP group with disease progression had a significantly higher rate of lymph node metastasis ( P =0.021) and radioiodine therapy ( P =0.025) than the DOP group without disease progression. CONCLUSIONS: These results suggest that AS might be considered an alternative treatment option for patients with low-risk PTMC regarding the extent of thyroidectomy and postoperative complications in the DOP group. To assess oncologic outcomes, long-term follow-up will be needed. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02938702.

Ergonomic effects of medical augmented reality glasses in video-assisted surgery.

BACKGROUND: The aim of this study was to objectively compare medical augmented reality glasses (ARG) and conventional monitors in video-assisted surgery and to systematically analyze its ergonomic benefits. METHODS: Three surgeons (thoracic, laparoscopic, and thyroid surgeons) participated in the study. Six thoracoscopic metastasectomies, six subtotal laparoscopic gastrectomies, and six thyroidectomies were performed with and without ARG. The subjective experience was evaluated using a questionnaire-based NASA-Task Load Index (NASA-TLX). Postures during surgeries were recorded. The risk of musculoskeletal disorders associated with video-assisted surgery was assessed using rapid entire body assessment (REBA). Surface electromyography (EMG) was recorded. Muscle fatigue was objectively measured. RESULTS: NASA-TLX scores of three surgeons were lower when ARG was used compared to those with conventional monitor (66.4 versus 82.7). Less workload during surgery was reported with ARG. The laparoscopic surgeon exhibited a substantial decrease in mental and physical demand [- 21.1 and 12.5%)] and the thyroid surgeon did (- 40.0 and - 66.7%).Total REBA scores decreased with ARG (8 to 3.6). The risk of musculoskeletal disorders was improved in regions of the neck and shoulders. Root mean square (RMS) of the EMG signal decreased from 0.347 ± 0.150 to 0.286 ± 0.130 (p = 0.010) with usage of ARG; a decrease was observed in all surgeons. The greatest RMS decrease was observed in trapezius and sternocleidomastoid muscles. The decrease in brachioradialis muscle was small. CONCLUSION: ARG assisted with correction of bad posture in surgeons during video-assisted surgery and reduced muscular fatigue of the upper body. This study highlights the superior ergonomic efficiency of ARG in video-assisted surgery.

The emergence of oral cavity cancer and the stabilization of oropharyngeal cancer: Recent contrasting epidemics in the South Korean population.

BACKGROUND: By analyzing the recent epidemiologic trajectory of head and neck squamous cell carcinoma (HNSCC) in South Korea, we tracked 2 findings that have been reported recently in other countries: the stabilization of human papillomavirus (HPV)-related HNSCC incidence and the acceleration of oral cavity cancer incidence. METHODS: We analyzed data from the comprehensive population-based Korean Central Cancer Registry for the period 1999 to 2017. The age-standardized incidence rate (ASR), annual percent change (APC), and relative survival were calculated. RESULTS: The ASR of total HNSCC decreased from 1999 to 2017 (APC, -0.2 [95% CI, -0.3 to -0.0]), as did the ASR of HPV-unrelated HNSCC (APC, -0.6 [95% CI, -0.8 to -0.5]); however, the ASR of HPV-related HNSCC increased (APC, 2.9 [95% CI, 2.5 to 3.2]). The rapidly increasing incidence of tonsil squamous cell carcinoma, which was the main subsite of HPV-related HNSCC, stabilized after 2011 (APC pre-2011, 6.8 [95% CI, 5.0 to 8.3]; APC post-2011, 1.6 [95% CI, -2.1 to 5.5]), and the difference was significant (P = .017). In contrast, oral cavity cancer incidence demonstrated the only increase among HPV-unrelated subsites, with the increase occurring after 2006 (APC pre-2006, 1.6 [95% CI, 0.3 to 2.8]; APC post-2006, 2.8 [95% CI, 2.2 to 3.5]); the main cause of this change was an increase in the ASR of tongue cancer. CONCLUSION: This study demonstrates the recent stabilization of tonsil cancer incidence and the contrasting increase in oral cavity cancer incidence, unlike other HPV-unrelated cancers. These trends require further surveillance and understanding in terms of tumor biology and prevention.

Oral Commissure Lift: A Retrospective Analysis of Complication Rates and Overall Outcomes.

BACKGROUND: Downward-turning oral commissures and sagging mouth corners can present an unfavorable impression. We introduced a new oral commissure lift procedure and investigated its effectiveness and complication rates. METHODS: Patients who underwent oral commissure lift in the plastic surgery clinic between January 2010 and December 2017 were enrolled retrospectively. Pre-and postoperative photographs were evaluated to measure oral commissure angles and analyze surgical complications, including visible scarring, unnatural appearance, and asymmetry. Many patients underwent a oral commissure lift with a simultaneous facelift. To exclude potential bias, we compared angular changes between patients receiving both oral commissure lift and facelift, with those receiving only oral commissure lift. Moreover, oral commissure angles of patients only receiving facelift were also measured. Statistical significance was set at p < 0.05. RESULTS: Oral commissure lift was performed in 51 patients. The mean ages and follow-up periods were 46.7 ± 11.9 years, and 25.2 ± 22.9 months, respectively. The preoperative mean angles of the right and left oral commissures measured - 3.1 ± 4.0° and - 3.4 ± 3.7°, respectively, and postoperative mean angles measured 3.6 ± 3.2° and 3.3 ± 3.5°, respectively. Postoperative changes in oral commissure angles were statistically significant (p < 0.05). The low complication rate included undercorrection in one patient, asymmetry in one patient, and visible scarring in three patients. We found no statistically significant differences in the studies excluding bias. CONCLUSIONS: The new oral commissure lift procedure for correcting sagging oral commissures was simple, safe, and effective with a low complication rate. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Singing voice range profile: New objective evaluation methods for voice change after thyroidectomy.

BACKGROUND: After surgery in the thyroid region, patients may present with phonation or singing difficulty, even within their vocal range. We designed a novel voice evaluation method that reflects subjective and objective voice complications of the surgery. METHODS: This tool recorded patients' voice ranges while singing, which was named the singing voice range profile (singing VRP). Patients were asked to sing "Happy Birthday," which has a one-octave scale, at a comfortable tone and intensity. The singing VRP, standard VRP and voice handicap index-10 (VHI-10) results were recorded before thyroidectomy and 1 and 3 months after thyroidectomy for 128 patients. For subgroup analysis, a group where the maximum F0 of standard VRP in 1 month postoperatively was lower than the highest singing F0 of the preoperative singing VRP was defined as "Collapsed group" and the other group was "Preserved group." RESULTS: The changes in the highest, lowest and range of singing fundamental frequency (F0 ) had decreased at 1 month postoperatively. Subsequently, they had improved significantly at 3 months postoperatively but were lower than those preoperatively (all P < .05, except for the change in the lowest singing F0 between 1 and 3 months postoperatively, P = .274). In the subgroup analysis, the singing range of the collapsed group (n = 65) showed significantly lower VHI-10 scores, range of vocal F0 and singing F0 than those of the preserved group (n = 63) at 1 and 3 months postoperatively (all P < .001). At 3 months postoperatively, the singing F0 range in the preserved group had recovered to the range before surgery (13.0 ± 1.3 vs. 13.1 ± 1.4, P = .746 for the preserved group, and 13.0 ± 1.3 vs 11.5 ± 2.4, P < .001 for the collapsed group). CONCLUSIONS: Parameters measured by singing VRP showed a trend similar to the change in VHI-10 and the maximum F0 of standard VRP. In addition, singing VRP allowed a qualitative classification of the postoperative voice function when combined with standard VRP. Therefore, it can be used as a supplementary voice evaluation tool to reflect the physiologic and functional aspects of voice.

Anti-proliferative activity of A. Oxyphylla and its bioactive constituent nootkatone in colorectal cancer cells.

BACKGROUND: A. oxyphylla extract is known to possess a wide range of pharmacological activites. However, the molecular mechanism of A. oxyphylla and its bioactive compound nootkatone in colorectal cancer is unknown. METHODS: Our study aims to examine the role of A. oxyphylla and its bioactive compound nootkatone, in tumor suppression using several in vitro assays. RESULTS: Both A. oxyphylla extract and nootkatone exhibited antiproliferative activity in colorectal cancer cells. A. oxyphylla displayed antioxidant activity in colorectal cancer cells, likely mediated via induction of HO-1. Furthermore, expression of pro-apoptotic protein NAG-1 and cell proliferative protein cyclin D1 were increased and decreased respectively in the presence of A. oxyphylla. When examined for anticancer activity, nootkatone treatment resulted in the reduction of colony and spheroid formation. Correspondingly, nootkatone also led to increased NAG-1 expression and decreased cyclin D1 expression. The mechanism by which nootkatone suppresses cyclin D1 involves protein level regulation, whereas nootkatone increases NAG-1 expression at the transcriptional level. In addition to having PPARγ binding activity, nootkatone also increases EGR-1 expression which ultimately results in enhanced NAG-1 promoter activity. CONCLUSION: In summary, our findings suggest that nootkatone is an anti-tumorigenic compound harboring antiproliferative and pro-apoptotic activity.

Prognostic significance of smoking and alcohol history in young age oral cavity cancer.

OBJECTIVE: To assess prognostic factors of patients with operable oral cavity squamous cell carcinoma (OSCC), focusing on the associations with smoking/alcohol exposure and age. MATERIALS AND METHODS: A total of 247 patients with OSCC who received curative surgery ± adjuvant radiotherapy were analyzed. The patient subgroups were divided according to pretreatment smoking/alcohol exposure. Individuals aged 45 years or less were classified as younger patients. RESULTS: The median follow-up was 52.2 months. The 5-year locoregional progression-free survival (LRFFS), distant metastasis-free survival (DMFS), overall survival (OS), and cancer-specific survival (CSS) rates were 85.2%, 88.3%, 78.1%, and 83.5%, respectively. An advanced stage, differentiation, and lympho-vascular space invasion were significantly associated with lower OS and CSS. In a subgroup analysis of younger patients (n = 49), more smoking/alcohol exposure was significantly associated with better OS (hazard ratio [HR]: 0.21, 95% confidence interval [CI]: 0.05-0.95, p = .043). With increasing age, the HR for smoking/alcohol exposure with respect to OS increased up to 11.59 (95% CI: 1.49-89.84, p = .019) in older patients. CONCLUSION: Younger OSCC patients with non- or less smoking/alcohol exposure showed unfavorable outcomes. The prognostic significance of pretreatment smoking/alcohol exposure changed from favorable to detrimental with increasing age in operable OSCC.

Attitudes towards second opinion services in cancer care: a nationwide survey of oncologists in Korea.

OBJECTIVE: Second opinion is a common phenomenon in many health systems, especially in the care of patients with cancer. However, it is not clear whether second opinion seeking should be promoted or discouraged and how second opinion services and policies can be better formalized to maximize the benefits and minimize the disadvantages. METHODS: A nationwide survey was conducted with a representative sample of 678 physicians involved in cancer care (75.5% participation rate) recruited in 13 cancer centres. RESULTS: Most physicians involved with cancer care perceived patients' second opinion seeking as a legitimate right (96.0%) and they acknowledged the need for second opinion services under certain conditions (98.2%). Many believed that second opinions can enhance patient satisfaction (77.3%) and quality of care (74.3%), but they also had concerns about increase in healthcare and societal costs (91.3%) and concentration in a high-volume centre (90.7%). While the majority agreed with the involvement of the first opinion physicians in the second opinion services (69.5%), there were mixed opinions regarding the desirability of remote (teleconsultation) second opinion services (49.0%) and coverage by national health insurance (51.9%). CONCLUSION: Physicians were generally positive to second opinion services and expected positive consequences in terms of patient satisfaction and quality of care. However, they had concerns about the consequences regarding cost and equity, and disagreements were observed regarding the way to improve second opinion services. The physicians' opinions revealed in our study will be helpful in developing clearer guidelines used to maximize the benefits of second opinion services.

Elevated risks of subsequent primary malignancies in patients with thyroid cancer: a nationwide, population-based study in Korea.

BACKGROUND: Thyroid cancer affects relatively young adults, and its overall survival is excellent. With long life expectancy, the development of subsequent cancers is an important concern for survivors of thyroid cancer. The objective of this study was to investigate the incidence and types of second primary malignancies in Korean patients with thyroid cancer. METHODS: The study cohort included 178,844 registrants with thyroid cancer from the Korea Central Cancer Registry (KCCR) database between 1993 and 2010. Standardized incidence ratios (SIRs) were calculated using a statistical software program (SEER*Stat 8.0.4). RESULTS: Among 178,844 patients with thyroid cancer, 2895 (1.6%) were diagnosed with subsequent second primary malignancies. The overall risks of a second primary cancer were elevated by 6% in patients who had thyroid cancer compared with the general population during the same period. The elevated risks for developing second cancers were observed in all sites except the stomach and cervix. The elevated risk of second primary cancers was observed within the first 10 years of follow-up. Leukemia and cancers of the salivary gland, kidney, prostate, lung, and breast had the most significantly elevated risks as secondary cancers and presented as early as during the first 5 years after the initial diagnosis of thyroid cancer. CONCLUSIONS: This is the largest, standardized, population-based study to date using nationwide data from the entire Korean population. The risks of several cancers were elevated significantly during follow-up, thus alerting physicians to pay special attention in their care of patients with thyroid cancer and long-term survivors.

Risk factors for recurrence after therapeutic lateral neck dissection for primary papillary thyroid cancer.

BACKGROUND: Lateral lymph node metastasis is an important prognostic factor and is predictive of tumor recurrence and cause-specific survival in patients with papillary thyroid cancer (PTC). However, the factors predicting recurrence and clinical outcomes after therapeutic lateral neck dissection are not well established. The aims of this study were to evaluate the incidence, pattern, and factors predictive of PTC recurrence after therapeutic lateral neck dissection. MATERIALS AND METHODS: The records of 126 consecutive patients who underwent total thyroidectomy with therapeutic lateral neck dissection for primary PTC at the National Cancer Center were retrospectively reviewed. The factors predictive of recurrence were determined using both univariate and multivariate analyses considering several clinicopathologic variables. RESULTS: The median follow-up period was 61.2 months, during which 22 patients (17.5 %) experienced recurrence with 1 death (0.8 %) due to disease. Locoregional recurrence and distant metastasis were found in 20 cases (15.9 %) and 2 cases (1.6 %), respectively. Male gender, aggressive histology, number of lymph node metastases, initial level of T4-off Tg per ng/mL, and ATA risk categories (high risk) were independent risk factors for recurrence. Of note, initial T4-off Tg levels greater than 4.2 ng/mL showed highest sensitivity and specificity in predicting recurrence. CONCLUSIONS: These results provide useful information regarding the clinical outcomes after therapeutic lateral neck dissection for primary PTC and can be used to identify at-risk patients who need aggressive treatment and intensive surveillance for postoperative recurrence.

Human papillomavirus-related cell cycle markers can predict survival outcomes following a transoral lateral oropharyngectomy for tonsillar squamous cell carcinoma.

OBJECTIVES: To identify the prognostic implications of human papillomavirus (HPV)-related cell cycle marker profiles in patients who have received a transoral lateral oropharyngectomy (TLO) as a primary treatment for tonsillar squamous cell carcinoma (TSCC). PATIENTS AND METHODS: Immunohistochemical profiles of HPV-related cell cycle markers, including p16, pRb, cyclin D1, p53, and the HPV DNA status of 42 consecutive TSCC patients who underwent TLO-based treatments were analyzed. The prognostic value of each marker was evaluated. RESULTS: Univariate analysis indicated that high p16, low pRb, and low p53 expression levels are significantly associated with a good disease-free and overall survival outcome. Clinicopathological parameters and the HPV DNA status did not show prognostic significance. When adjusted for age, overall stage and treatment strategy, a high p16 and low pRb level remained an effective prognostic marker for good survival outcomes. A high p16/low pRb combination showed superior survival prediction ability over high p16 or low pRb alone. CONCLUSION: HPV-related cell cycle markers may also be good indicators for predicting survival after TLO for TSCC. The de-escalation TLO surgery approach would be more effective if performed under the stringent guidance of these markers.

Surgical targeting of recurrent thyroid cancer using a novel mixture of 99m-technetium macroaggregated albumin and indocyanine green.

BACKGROUND: Precise targeting has played a pivotal role in the success of surgery for recurrent differentiated thyroid cancers (DTCs). To improve on current targeting methods, we developed a novel technique using (99m)Tc-macroaggregated human serum albumin and indocyanine green (TIGMA), with which surgeons effectively target lesions in real time by radiofluorescence dual guidance. METHODS: Seven patients with 10 recurrent DTC lesions were retrospectively enrolled in the study. Prior to the operation, we injected TIGMA into the target lesion under the guidance of ultrasonography. Resection was concurrently monitored using a gamma probe and a specially designed near infrared fluorescence camera. Outcomes were evaluated using imaging, surgical, and pathological records. RESULTS: In all enrolled cases, both injection of TIGMA and radiofluorescence dual guidance were well tolerated and easy to implement. The technical success rates were 100%, confirmed by final pathological examination, postoperative ultrasonography, and I-131 scan clearance. Complications such as temporary postoperative neck pain (n = 2) were minimal. CONCLUSIONS: TIGMA using radiofluorescence dual guidance facilitated the precise targeting of recurrent lesions. The entire procedure was feasible, safe, and successful. This method would help enhance surgical outcomes for recurrent DTCs.

Effect of thyroid-stimulating hormone suppression on quality of life in thyroid lobectomy patients: interim analysis of a multicenter, randomized controlled trial in low- to intermediate-risk thyroid cancer patients (MASTER study).

Purpose: Current clinical practices favor less or no thyroid-stimulating hormone (TSH) suppression for low- to intermediate-risk thyroid cancer patients who receive thyroid lobectomy. The association of TSH suppression on health-related quality of life (HR-QoL) in patients after thyroid lobectomy is not well studied. This study aimed to evaluate the effect of TSH suppression on patient HR-QoL after thyroid lobectomy. Methods: This study included patients enrolled in an ongoing, multicenter, randomized controlled study investigating the effects of TSH suppression. Patients were randomized to either the low-TSH group (TSH target range, 0.3-1.99 µIU/mL) or the high-TSH group (TSH target range, 2.0-7.99 µIU/mL). The HR-QoL, hyperthyroidism symptom, and depression symptom questionnaires performed preoperatively and 2 weeks and 3 months postoperatively were evaluated. Results: Total of 669 patients (low-TSH group, 340; high-TSH group, 329) were included. Although total HR-QoL score changes were not different between the 2 groups, the high-TSH group had a significantly higher score in the physical domain at postoperative 3 months (P = 0.046). The 2 groups did not have significant differences in hyperthyroidism and depression scores. Conclusion: In the short-term postoperative period, the physical HR-QoL scores in thyroid lobectomy patients were better when they did not receive TSH suppression. This study suggests the importance of considering HR-QoL when setting TSH suppression targets in thyroid lobectomy patients.

Quercetin induces dual specificity phosphatase 5 via serum response factor.

The phytochemical quercetin has gained attention for its antiinflammatory and anti-tumorigenic properties in various types of cancer. Tumorigenesis involves the aberrant regulation of kinase/phosphatase, highlighting the importance of maintaining homeostasis. Dual Specificity Phosphatase (DUSP) plays a crucial role in controlling the phosphorylation of ERK. The current study aimed to clone the DUSP5 promoter, and investigate its transcriptional activity in the presence of quercetin. The results revealed that quercetin-induced DUSP5 expression is associated with the serum response factor (SRF) binding site located in the DUSP5 promoter. The deletion of this site abolished the luciferase activity induced by quercetin, indicating its vital role in quercetin-induced DUSP5 expression. SRF protein is a transcription factor that potentially contributes to quercetin-induced DUSP5 expression at the transcriptional level. Additionally, quercetin enhanced SRF binding activity without changing its expression. These findings provide evidence of how quercetin affects anti-cancer activity in colorectal tumorigenesis by inducing SRF transcription factor activity, thereby increasing DUSP5 expression at the transcriptional level. This study highlights the importance of investigating the molecular mechanisms underlying the anti-cancer properties of quercetin, and suggests its potential use in cancer therapy. [BMB Reports 2023; 56(9): 508-513].

Tolfenamic acid negatively regulates YAP and TAZ expression in human cancer cells.

Several diseases are associated with improper regulation of the Hippo pathway, which plays an important role in cell proliferation and cancer metastasis. Overactivation of the YAP and TAZ proteins accelerates cell proliferation, invasion, and migration during tumorigenesis. Tolfenamic acid (TA) is a non-steroidal anti-inflammatory drug (NSAID) that exhibits activity against various types of cancer. In this study, we observed that TA decreased YAP and TAZ protein levels in cancer cells. TA increased the phosphorylation of YAP and TAZ, leading to the degradation of YAP and TAZ in the cytoplasm and nucleus. TA predominantly affected multiple phosphodegron sites in the YAP and TAZ and lowered 14-3-3ß protein expression, causing YAP and TAZ to enter the ubiquitination pathway. Proteins that affect YAP and TAZ regulation, such as NAG-1 and several YAP/TAZ E3 ligases, were not involved in TA-mediated YAP/TAZ degradation. In summary, our results indicate that TA affects phosphodegron sites on YAP/TAZ, demonstrating a novel effect of TA in tumorigenesis.

Novel thrombospondin-1 transcript exhibits distinctive expression and activity in thyroid tumorigenesis.

Thrombospondin 1 (TSP1) is known for its cell-specific functions in cancer progression, such as proliferation and migration. It contains 22 exons that may potentially produce several different transcripts. Here, we identified TSP1V as a novel TSP1-splicing variant produced by intron retention (IR) in human thyroid cancer cells and tissues. We observed that TSP1V functionally inhibited tumorigenesis contrary to TSP1 wild-type, as identified in vivo and in vitro. These activities of TSP1V are caused by inhibiting phospho-Smad and phospho-focal adhesion kinase. Reverse transcription polymerase chain reaction and minigene experiments revealed that some phytochemicals/non-steroidal anti-inflammatory drugs enhanced IR. We further found that RNA-binding motif protein 5 (RBM5) suppressed IR induced by sulindac sulfide treatment. Additionally, sulindac sulfide reduced phospho-RBM5 levels in a time-dependent manner. Furthermore, trans-chalcone demethylated TSP1V, thereby preventing methyl-CpG-binding protein 2 binding to TSP1V gene. In addition, TSP1V levels were significantly lower in patients with differentiated thyroid carcinoma than in those with benign thyroid nodule, indicating its potential application as a diagnostic biomarker in tumor progression.

Comparative Study of Gasless Transaxillary, Bilateral Axillo-Breast, Unilateral Axillo-Breast With Carbon Dioxide Insufflation, Retroauricular, and Transoral Vestibular Endoscopic Thyroidectomy Approaches at a Single Institution: A Retrospective Analysis and Lessons Learned.

OBJECTIVES: This study aimed to present our experiences with various approaches for endoscopic thyroidectomy (ET) and to offer lessons for choosing an approach. METHODS: The medical records of 701 patients who underwent ET via the transaxillary (TA), bilateral axillo-breast (BABA), unilateral axillo-breast with carbon dioxide insufflation (UABA), retroauricular (RA), or transoral vestibular (TO) approach between May 2008 and March 2020 were retrospectively reviewed. Postoperative pain and cosmetic outcomes were evaluated using visual analog scales. RESULTS: The mean operative time of UABA was the shortest among the five approaches (TA, 194.65±51.13 minutes; BABA, 189.11±61.53 minutes; UABA, 118.62±30.23 minutes; RA, 168.22±45.63 minutes; TO, 196.10±40.19 minutes; P=0.02). BABA was the most painful approach, while TO was the least painful on postoperative day 1 (TA, 3.09±0.96; BABA, 3.59±0.92; UABA, 2.39±0.54; RA, 3.49±0.93; TO, 2.01±0.37; P=0.04) and day 3 (TA, 2.10±0.77; BABA, 2.59±0.88; UABA, 1.84±0.37; RA, 3.01±0.67; TO, 1.49±0.45; P=0.04). The TO group had the best cosmetic outcomes at 3 months (TA, 3.91±1.21; BABA, 4.52±1.13; UABA, 4.49±0.74; RA, 4.28±0.74; TO, 4.81±0.48; P=0.04). CONCLUSION: We present a single-surgeon experience of five distinctive ET approaches and the lessons from each approach, together with a literature review. This data may aid endoscopic thyroid surgeons in choosing from various ET approaches.

Spade-Shaped Anastomosis after Laparoscopic Proximal Gastrectomy Using Double Suture Anchoring between the Posterior Wall of the Esophagus and the Anterior Wall of the Stomach (SPADE Operation): A Case Series.

We introduced SPADE operation, a novel anastomotic method after laparoscopic proximal gastrectomy (PG). Technical modifications were performed and settled. This report aimed to demonstrate the short-term clinical outcomes after settlement. Data from 34 consecutive patients who underwent laparoscopic PG with SPADE between June 2017 and March 2020 were retrospectively reviewed. Reflux was evaluated based on the patients' symptoms and follow-up endoscopy using Los Angeles (LA) classification and RGB Classification (Residue, Gastritis, Bile). Other complications were classified using the Clavien-Dindo method. The incidence of reflux esophagitis was 2.9% (1/34). Bile reflux was observed in six patients (17.6%), and residual food was observed in 16 patients (47.1%) in the endoscopy. Twenty-eight patients had no reflux symptoms (82.4%), while five patients (14.7%) and one patient (2.9%) had mild and moderate reflux symptoms, respectively. The rates of anastomotic stricture and ileus were 14.7% (5/34) and 11.8% (4/34), respectively. No anastomotic leakage was observed. The incidence of major complications (Clavien-Dindo grade III or higher) was 14.7%. The SPADE operation following laparoscopic PG is effective in reducing gastroesophageal reflux. Its clinical usefulness should be validated using prospective clinical trials.