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.

Effect of postoperative radiotherapy for patients with differentiated thyroid cancer.

OBJECTIVE: We evaluated the efficacy and safety of postoperative radiotherapy (PORT) for differentiated thyroid cancer (DTC) with high risk features. MATERIALS AND METHODS: This retrospective study analyzed 187 patients treated for DTC from 1985 to 2019. DTC referred to nonanaplastic thyroid cancer originating from follicular cells. PORT was defined as the administration of external beam radiation to the thyroid and regional lymph nodes following surgery for initially diagnosed DTC. The patients were included in the analysis if they received PORT or exhibited any of the following features: (a) pT4 or pN1b according to the 8th American Joint Committee on Cancer, (b) poorly differentiated thyroid cancer (PDTC), or (c) unfavourable variants such as anaplastic foci and etc. After 1:1 propensity matching, a total of 108 patients were analyzed according to PORT receipt. The median follow-up duration of the matched group was 10.4 years. RESULTS: After matching, most of the variables became balanced, but the PORT group still had more PDTC and DTC with anaplastic foci. Radioactive iodine (RAI) was less frequently administered in the PORT group. PORT yielded a significantly higher 5-year locoregional recurrence free survival (LRFS) than the No PORT group (5-year LRFS 86.1% vs. 72.7%, p = 0.022), but the 10-year cancer specific survival (CSS) was similar between them (97.8% vs. 85.9%, p = 0.122). The multivariable analysis indicated that PORT was a favourable prognostic factor (Hazard ratio 0.3, 95% Confidence interval 0.1-0.8, p = 0.02) for LRFS, but not for CSS. Among 133 patients without PORT for initial disease, 39 of them received salvage surgery followed by salvage PORT. No severe toxicity after PORT was reported. CONCLUSION: PORT reduced locoregional recurrence in DTC patients without severe toxicity. PORT can be an effective and safe treatment to improve locoregional control in DTC with high risk features. However, further study is warranted to identify those who can benefit from PORT.

Thyroid nodules in childhood-onset Hashimoto's thyroiditis: Frequency, risk factors, follow-up course and genetic alterations of thyroid cancer.

OBJECTIVE: We evaluated the frequency, risk factors and the follow-up outcomes of thyroid nodules, and genetic alterations in thyroid cancer, in youth with childhood-onset Hashimoto thyroiditis (HT) residing in an iodine-sufficient country. DESIGN: A retrospective cohort study. PATIENTS AND MEASUREMENTS: A total of 213 patients (194 females, mean age 10.6 years at the time of HT diagnosis) were ultrasonographically evaluated. Thyroid nodules were categorized using the Korean Thyroid Imaging Reporting and Data System (K-TIRADS) and the American College of Radiology Thyroid Imaging Reporting and Data System (ACR-TI-RADS). RESULTS: Thyroid nodules were detected in 40 (18.8%) patients over a median follow-up period of 3.4 years, usually after the onset of puberty. A family history of thyroid disease (hazard ratio 2.1, p = .031) was predictive of thyroid nodule detection. Papillary thyroid carcinoma (PTC) was diagnosed in 9 (4.2% of all and 22.5% of nodule-positive patients). The malignant nodules had a higher K-TIRADS or ACR-TI-RADS risk level compared with benign nodules (p < .01 for both). Genetic alterations were revealed in 7 (BRAFV600E in 6 and RET-ERC1 fusion in 1) of the eight available tumour tissue samples. None showed evidence of disease over a median follow-up period of 3.4 years. CONCLUSIONS: The nodule detection rate was 18.8%, with a 22.5% risk of malignancy among the detected nodules in childhood-onset HT patients, showing increased risk in those with a family history. Additional large-scale studies are required to evaluate the usefulness of K-TIRADS or ACR-TI-RADS risk level for the differentiation of paediatric thyroid nodules.

Immunological and Clinical Phenotyping in Primary Antibody Deficiencies: a Growing Disease Spectrum.

PURPOSE: Although common variable immunodeficiency (CVID) is considered the most prevalent symptomatic primary antibody deficiency (PAD), there is a population with symptomatic PADs that do not meet criteria for CVID. We analyzed clinical and immunological profiles of patients with different PADs to better understand the differences and similarities between CVID and other PADs. METHODS: We extracted clinical and laboratory data of patients with PADs from electronic medical records. Patients were categorized into CVID, IgG subclass 2 deficiency (IgG2D), IgG deficiency (IgGD), and specific antibody deficiency (sAbD) based on basal immunoglobulin levels and pneumococcal vaccine responses. We compared clinical and immunological characteristics in these groups. RESULTS: All patients, regardless of PAD types, showed similar frequencies of infections, bronchiectasis, and interstitial lung disease (ILD). Hematopoietic malignancies were more frequently found in the CVID than in the IgG2D, IgGD, and sAbD groups, while the latter groups trended towards an increased frequency of connective tissue diseases (CTD). Low counts of natural killer (NK) cells were associated with malignancy, autoimmunity, and ILD in CVID but not in other PAD groups. CONCLUSIONS: Higher frequency of hematopoietic malignancy in CVID than in the other PADs and association of lower NK cell counts with non-infectious complications in CVID suggest a relationship between immune alterations and the development of non-infectious manifestations in PADs.

Prognostic value of the posterior cricoarytenoid muscle atrophy in computerized tomography scans for unilateral vocal fold paralysis recovery.

OBJECTIVES: To evaluate the prognostic value of the posterior cricoarytenoid (PCA) muscle atrophy observed on neck computed tomography (CT) in patients with unilateral vocal fold paralysis. METHODS: CT images of 87 subjects with unilateral vocal fold paralysis (UVFP) were evaluated to analyze the PCA muscle atrophy and to measure the severity of the PCA muscle atrophy in semi-quantitative manner. The grading of the PCA muscle atrophy was compared with the recruitment pattern of laryngeal electromyography (LEMG) and restoration of vocal fold movement. RESULTS: The PCA muscle was identifiable on CT in 73 subjects. Using the PCA muscle atrophy as an indicator of UVFP, we correctly predicted the paralysis in 69 (94.5%). Grade of the PCA muscle atrophy is significantly correlated with recruitment pattern of LEMG. If the positive result is defined as the PCA muscle showed moderate to severe degree of atrophy, we could predict the persistent UVFP in 88% of patients. CONCLUSIONS: PCA muscle atrophy identified on CT scan in patients with UVFP, is associated with low rates of return of mobility in the affected vocal fold.

A Phase II Study of Genexol-PM and Cisplatin as Induction Chemotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma.

LESSONS LEARNED: Induction chemotherapy with Genexol-PM and cisplatin demonstrated modest tumor response in locally advanced head and neck squamous cell carcinoma.Considering favorable toxicity profiles and promising survival data, further studies on this regimen are warranted in patients with head and neck squamous cell carcinoma. BACKGROUND: Genexol-PM is a polymeric micellar formulation of paclitaxel without Cremophor EL. We investigated the efficacy and safety of Genexol-PM plus cisplatin as induction chemotherapy (IC) in patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC). METHODS: Patients received Genexol-PM (230 mg/m2) and cisplatin (60 mg/m2) every 3 weeks as IC. After three cycles of IC, definitive treatment of either concurrent chemoradiotherapy (CCRT) with weekly cisplatin (30 mg/m2) or surgery was performed. The primary endpoint was overall response rate (ORR) after IC. RESULTS: Of 52 patients enrolled, 47 completed three cycles of IC, and the ORR was 55.8% (95% confidence interval, 42.3-69.3). Although there was one treatment-related death, toxicity profiles to Genexol-PM and cisplatin were generally favorable, and the most common grade 3 or 4 toxicities were neutropenia (15.4%), anorexia (7.7%), and general weakness (7.7%). Fifty-one patients received definitive treatment (CCRT [n = 44] or radical surgery [n = 7]). The rate of complete response following CCRT was 81.8% (36/44). After a median follow-up of 39 months, estimates of progression-free survival (PFS) and overall survival (OS) at 3 years were 54.3% and 71.3%, respectively. CONCLUSION: IC with Genexol-PM and cisplatin demonstrated modest tumor response with well-tolerated toxicity profiles for patients with LA-HNSCC.

Bioartificial Esophagus: Where Are We Now?

The current treatments for esophageal diseases, such as carcinomas, trauma or congenital malformations, require surgical intervention and esophageal reconstruction using redundant parts of the gastrointestinal tract. However, the use of gastrointestinal segments can cause various surgical morbidities and mortality because additional abdominal surgery may be required at the expense of other anatomic structures. Therefore, tissue engineering using various biomaterial or cell sources has emerged as an alternative strategy of biomimicking the native esophageal tissue that could be implanted as an artificial graft. Although tissue engineering techniques have promise as an effective regenerative strategy, no functional solution currently exists for esophageal reconstruction. Here, we present a review of the progress made in the field of regenerative medicine for esophageal reconstruction from bench to bedside.

Clinicopathological factors influencing the outcomes of surgical treatment in patients with T4a hypopharyngeal cancer.

BACKGROUND: The purpose of this study was to determine prognostic factors influencing outcomes of surgical treatment in patients with T4a hypopharyngeal cancer. METHODS: The present study enrolled 93 patients diagnosed with T4a hypopharyngeal cancer who underwent primary surgery between January 2005 and December 2015 at six medical centers in Korea. Primary tumor sites included pyriform sinus in 71 patients, posterior pharyngeal wall in 14 patients, and postcricoid region in 8 patients. Seventy-two patients received postoperative radio(chemo)therapy. RESULTS: Five-year disease-free survival (DFS) and disease-specific survival (DSS) rates were 38% and 45%, respectively. In univariate analysis, 5-year DFS was found to have significant and positive correlations with margin involvement (p < 0.001) and extracapsular spread (p = 0.025). Multivariate analysis confirmed that margin involvement (hazard ratio (HR): 2.81; 95% confidence interval (CI): 1.49-5.30; p = 0.001) and extracapsular spread (HR: 2.08; 95% CI: 1.08-3.99; p = 0.028) were significant factors associated with 5-year DFS. In univariate analysis, cervical lymph node metastasis (p = 0.048), lymphovascular invasion (p = 0.041), extracapsular spread (p = 0.015), and esophageal invasion (p = 0.033) were significant factors associated with 5-year DSS. In multivariate analysis, extracapsular spread (HR: 2.98; 95% CI: 1.39-6.42; p = 0.005) and esophageal invasion (HR: 2.87; 95% CI: 1.38-5.98; p = 0.005) remained significant factors associated with 5-year DSS. CONCLUSION: Margin involvement and extracapsular spread are factors influencing recurrence while extracapsular spread and esophageal invasion are factors affecting survival in patients with T4a hypopharyngeal cancer treated by primary surgery.

Usefulness of radiologic examinations for diagnosing level VI lymph node metastasis in patients with laryngohypopharyngeal carcinoma.

The aim of this study was to estimate the usefulness of imaging modalities for diagnosing level VI lymph node metastasis in patients with laryngohypopharyngeal cancer. A retrospective review of 138 patients with squamous cell carcinoma of the larynx or hypopharynx who underwent central compartment neck dissection (CCND) was performed. Level VI metastasis occurred in 29 of 138 (21 %) patients. CT accuracy and sensitivity for level VI lymph node was 85.5 and 48.3 %, respectively. Respective values for MRI, US, and PET were 84.4 and 41.4 %, 87.7 and 44.8 %, and 81.2 and 34.5 %. CT combined with US demonstrated the best result in sensitivity (51.7 %) and negative predictive value (NPV) (88.1 %) compared to those of other imaging techniques. CT combined with US could improve sensitivity and NPV compared to CT or US alone. Considering cost-effectiveness and the highest results in all parameters compared to those of other combinations of imaging techniques, CT combined with US could be the best preoperative imaging modalities for evaluating laryngohypopharyngeal cancer. However, these imaging techniques are not absolutely reliable methods for detecting occult metastasis in the level VI due to high false-negative rates. Elective CCND should be considered in indicated patients (>N2b, T4), even if physical examinations and the radiologic findings of level VI nodes are negative.

Retropharyngeal lymph node metastasis in 54 patients with oropharyngeal squamous cell carcinoma who underwent surgery-based treatment.

BACKGROUND: This study aimed to determine the incidence, risk factors, and prognostic significance of retropharyngeal lymph node (RPLN) metastasis from malignancies of the oropharynx. METHODS: The study retrospectively analyzed 54 patients with oropharyngeal squamous cell carcinoma who underwent primary surgery-based treatment. Most of the patients had advanced stage (stage 3 or 4, 96.3 %) oropharyngeal cancer. Surgery alone was performed for 14 patients. Postoperative radiotherapy was administered to 14 patients and chemoradiation to 26 patients. Genotyping and detection of human papillomavirus (HPV) was available for 52 patients. RESULTS: Using pathologic analysis, RPLN metastasis was confirmed in 22 subjects. The patients with RPLN metastasis had a significantly lower disease-specific survival rate than the non-RPLN metastasis group (54.5 vs 75 %; p = 0.05). The pN+ (RPLN) yield of these cases was 18/22 (81.8 %) for cN+ (RPLN) versus 4/32 (7.4 %) for cN0 (RPLN). Multivariate analysis identified the independent factors associated with RPLN metastasis as radiographically positive retropharyngeal node (p = 0.012; odds ratio [OR] 53.920) and posterior pharyngeal wall invasion (p = 0.021; OR 33.014). A high-risk HPV-positive result was not significantly correlated with RPLN metastasis. CONCLUSIONS: Elective RPLN dissection should be considered for patients with advanced neck and primary tumor, particularly those with posterior pharyngeal wall invasion.

A prospective 1-year comparative study of endoscopic thyroidectomy via a retroauricular approach versus conventional open thyroidectomy at a single institution.

OBJECTIVE: The objective of this study was to evaluate the feasibility and safety of performing an endoscopic thyroidectomy (ETE) via a retroauricular approach. METHODS: Forty-seven patients who underwent ETE via a retroauricular approach were included, and a total of 47 patients who underwent conventional open thyroid lobectomy in the same period were analyzed as a control group. All patients underwent prospective functional evaluations before the operation and 1 week, and 1, 3, 6, and 12 months postoperatively using a comprehensive battery of functional assessments. RESULTS: The mean total operative time was 152 ± 48 min, with a mean endoscopic procedure time of 58 ± 18 min. One patient developed temporary vocal fold paralysis. Although most of the parameters for the functional outcome were worse in the ETE group, these differences were transient. Subjective worsening on the voice handicap index and dysphagia handicap index normalized by 3 months postoperatively. The average pain score on a visual analog scale at 1 week after surgery was 2.84, representing a tolerable range of discomfort. The mean paresthesia/hyperesthesia score was worse in the ETE group than the open surgery group by postoperative month 6; however, these differences eventually disappeared. Thirty-six of the 47 patients in the ETE group were satisfied or extremely satisfied with the retroauricular incision by 6 months after surgery. CONCLUSIONS: ETE via a retroauricular approach is a safe, feasible, and cosmetically desirable treatment option, with outcomes comparable to conventional open thyroidectomy in the longer term.

Incidental focal FDG uptake in the parotid glands on PET/CT in patients with head and neck malignancy.

OBJECTIVES: To evaluate the prevalence and clinical significance of focal parotid lesions identified by (18)F- FDG PET/CT in patients with nonparotid head and neck malignancies. METHODS: From 3,638 PET/CT examinations using (18)F-FDG conducted on 1,342 patients with nonparotid head and neck malignancies, we retrospectively identified patients showing incidental focal FDG uptake in the parotid glands. The diagnosis of parotid lesions was confirmed histopathologically or on imaging follow-up. Patient demographics, clinical features, maximum standardized uptake value (SUV(max)) on PET images, size and attenuation on corresponding contrast-enhanced CT images were assessed and correlated with the final diagnosis. RESULTS: The prevalence of incidental focal parotid FDG uptake on PET/CT was 2.1% (95% CI 1.4 - 3.0%). Among 21 patients with focal parotid lesions confirmed histologically or on imaging follow-up, 7 (33.3%) had malignant lesions (all metastases) and 14 (66.7%) had benign lesions (four pleomorphic adenomas, two Warthin's tumours, one benign lymph node, one granulomatous lesion, six lesions without histopathological confirmation). There were no significant differences in age, sex, SUV(max) or CT findings between patients with benign and those with malignant lesions. CONCLUSION: Focal parotid FDG uptake on PET/CT in patients with head and neck malignancy warrants further investigations to ensure adequate therapy for incidental parotid lesions. KEY POINTS: • The prevalence of parotid incidentaloma on PET in head and neck malignancy was 2.1% • The malignancy rate of incidental focal parotid FDG uptake was 33.3% • SUV max could not reliably differentiate malignant from benign incidental parotid lesions.

Unraveling the role of the mitochondrial one-carbon pathway in undifferentiated thyroid cancer by multi-omics analyses.

The role of the serine/glycine metabolic pathway (SGP) has recently been demonstrated in tumors; however, the pathological relevance of the SGP in thyroid cancer remains unexplored. Here, we perform metabolomic profiling of 17 tumor-normal pairs; bulk transcriptomics of 263 normal thyroid, 348 papillary, and 21 undifferentiated thyroid cancer samples; and single-cell transcriptomes from 15 cases, showing the impact of mitochondrial one-carbon metabolism in thyroid tumors. High expression of serine hydroxymethyltransferase-2 (SHMT2) and methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is associated with low thyroid differentiation scores and poor clinical features. A subpopulation of tumor cells with high mitochondrial one-carbon pathway activity is observed in the single-cell dataset. SHMT2 inhibition significantly compromises mitochondrial respiration and decreases cell proliferation and tumor size in vitro and in vivo. Collectively, our results highlight the importance of the mitochondrial one-carbon pathway in undifferentiated thyroid cancer and suggest that SHMT2 is a potent therapeutic target.

CT differentiation of abscess and non-infected fluid in the postoperative neck.

BACKGROUND: Differentiation of postoperative neck abscess from non-infected fluid is important because the treatment is different. PURPOSE: To determine specific CT findings that might help to differentiate abscesses from non-infected fluid collections in the postoperative neck. MATERIAL AND METHODS: We retrospectively reviewed CT scans of 50 patients (43 men and 7 women; mean age, 62.5 ± 8.9 years) who had postoperative fluid collections in the neck (26 abscesses and 24 non-infected fluid collections). Diagnosis of an abscess was determined by a positive bacteria culture from the fluid collection. Diagnoses were correlated with the following CT findings: anatomic spaces involved, the maximum transverse diameter, margin, attenuation, rim enhancement, gas bubbles, and manifestations of soft tissue adjacent to a fluid collection. RESULTS: Rim enhancement pattern and soft tissue manifestations showed significant differences between abscess and non-infected fluid. The reliable CT findings for abscess were: (i) rim enhancement > 50% of the circumference, 54% sensitive, 71% specific, and 62% accurate; and (ii) severe soft tissue manifestations, 39% sensitive, 92% specific, and 64% accurate. There were no significant differences in the anatomic spaces involved, the maximum transverse diameter, margin, attenuation, and gas bubbles between abscess and non-infected fluid. CONCLUSION: CT findings that may help differentiate postoperative neck abscess from non-infected fluid were rim enhancement > 50% of the circumference and severe soft tissue manifestations.

Incidental thyroid lesions identified by ultrasound in patients with non-thyroidal head and neck cancer.

BACKGROUND: Thyroid cancer is one of the common head and neck malignancies and may be found incidentally with other head and neck cancers. PURPOSE: To evaluate the prevalence and risk of malignancy in incidental thyroid lesions identified by ultrasound (US) in patients with head and neck cancer. MATERIAL AND METHODS: We retrospectively reviewed medical records of all patients with head and neck cancer other than of thyroid origin between January 2004 and December 2011. A total of 690 patients (537 men and 153 women; mean age, 58.9 ± 12.9 years) underwent US of the neck for the evaluation of cervical lymph node status (including thyroid gland). We evaluated the prevalence of patients with incidental thyroid lesions identified by US and the risk of malignancy in these patients. RESULTS: Of the 690 patients with head and neck cancer, 234 (33.9%) had incidental thyroid lesions on US. Based on US findings, 61 patients underwent fine-needle aspiration, with 39 eventually undergoing thyroidectomy. Among these thyroid lesions, 24 incidental thyroid lesions of 22 patients were histologically proven to be malignant (23 papillary and 1 follicular carcinomas). The risk of malignancy was 9.4% on a patient-by-patient basis. CONCLUSION: Screening of the thyroid gland should be included in the preoperative US examination for cervical lymph node metastases in patients with non-thyroidal head and neck cancer.

Risk factors of postoperative hypoparathyroidism after total thyroidectomy in pediatric patients with thyroid cancer.

PURPOSE: Hypoparathyroidism (hypoPTH) is the most common complication following thyroidectomy. We investigated the frequency and risk factors of hypoPTH after total thyroidectomy (TT) in pediatric patients with thyroid cancer. METHODS: This retrospective study included 98 patients younger than 20 years who were diagnosed with thyroid cancer after T T during 1990-2018 and followed for more than 2 years at Seoul National University Hospital. HypoPTH was defined as receiving active vitamin D (1-hydroxycholecalciferol or 1,25-dihydroxycholecalciferol) after surgery. RESULTS: The study included 27 boys (27.6%) and 71 girls (72.4%). The mean age at diagnosis was 14.9±3.7 years. HypoPTH occurred in 43 patients (43.9%). Twenty-one patients (21.4%) discontinued active vitamin D less than 6 months after surgery, while 14 (14.3%) continued active vitamin D for more than 2 years. Tumor multifocality (odds ratio [OR], 3.7 vs. single tumor; P=0.013) and preoperative calcium level (OR, 0.2; P=0.028) were independent predictors of hypoPTH immediately after TT. In addition, age (OR, 0.8; P=0.011) and preoperative calcium level (OR, 0.04; P=0.014) significantly decreased the risk for persistent hypoPTH requiring active vitamin D for more than 2 years. CONCLUSION: HypoPTH occurred in 43.9% of pediatric thyroid cancer patients after TT in this study. Among them, one-third of patients continued active vitamin D medication for more than 2 years, which was predicted by young age and low preoperative calcium level.

Incorporation of Cell-Adhesive Proteins in 3D-Printed Lipoic Acid-Maleic Acid-Poly(Propylene Glycol)-Based Tough Gel Ink for Cell-Supportive Microenvironment.

In extrusion-based 3D printing, the use of synthetic polymeric hydrogels can facilitate fabrication of cellularized and implanted scaffolds with sufficient mechanical properties to maintain the structural integrity and physical stress within the in vivo conditions. However, synthetic hydrogels face challenges due to their poor properties of cellular adhesion, bioactivity, and biofunctionality. New compositions of hydrogel inks have been designed to address this limitation. A viscous poly(maleate-propylene oxide)-lipoate-poly(ethylene oxide) (MPLE) hydrogel is recently developed that shows high-resolution printability, drug-controlled release, excellent mechanical properties with adhesiveness, and biocompatibility. In this study, the authors demonstrate that the incorporation of cell-adhesive proteins like gelatin and albumin within the MPLE gel allows printing of biologically functional 3D scaffolds with rapid cell spreading (within 7 days) and high cell proliferation (twofold increase) as compared with MPLE gel only. Addition of proteins (10% w/v) supports the formation of interconnected cell clusters (≈1.6-fold increase in cell areas after 7-day) and spreading of cells in the printed scaffolds without additional growth factors. In in vivo studies, the protein-loaded scaffolds showed excellent biocompatibility and increased angiogenesis without inflammatory response after 4-week implantation in mice, thus demonstrating the promise to contribute to the printable tough hydrogel inks for tissue engineering.

Assessment of Esophageal Reconstruction via Bioreactor Cultivation of a Synthetic Scaffold in a Canine Model.

OBJECTIVES: Using tissue-engineered materials for esophageal reconstruction is a technically challenging task in animals that requires bioreactor training to enhance cellular reactivity. There have been many attempts at esophageal tissue engineering, but the success rate has been limited due to difficulty in initial epithelialization in the special environment of peristalsis. The purpose of this study was to evaluate the potential of an artificial esophagus that can enhance the regeneration of esophageal mucosa and muscle through the optimal combination of a double-layered polymeric scaffold and a custom-designed mesenchymal stem cell-based bioreactor system in a canine model. METHODS: We fabricated a novel double-layered scaffold as a tissue-engineered esophagus using an electrospinning technique. Prior to transplantation, human-derived mesenchymal stem cells were seeded into the lumen of the scaffold, and bioreactor cultivation was performed to enhance cellular reactivity. After 3 days of cultivation using the bioreactor system, tissue-engineered artificial esophagus was transplanted into a partial esophageal defect (5×3 cm-long resection) in a canine model. RESULTS: Scanning electron microscopy (SEM) showed that the electrospun fibers in a tubular scaffold were randomly and circumferentially located toward the inner and outer surfaces. Complete recovery of the esophageal mucosa was confirmed by endoscopic analysis and SEM. Esophagogastroduodenoscopy and computed tomography also showed that there were no signs of leakage or stricture and that there was a normal lumen with complete epithelialization. Significant regeneration of the mucosal layer was observed by keratin-5 immunostaining. Alpha-smooth muscle actin immunostaining showed significantly greater esophageal muscle regeneration at 12 months than at 6 months. CONCLUSION: Custom-designed bioreactor cultured electrospun polyurethane scaffolds can be a promising approach for esophageal tissue engineering.

Adjuvant radiotherapy in node-negative salivary malignancies of the parotid gland: A multi-institutional analysis.

BACKGROUND AND PURPOSE: To determine the role of adjuvant radiotherapy (ART) in parotid gland cancer without nodal metastasis, we evaluated the survival outcomes, prognostic factors, and dose-response relationships in patients with node-negative parotid gland cancer patients. MATERIALS AND METHODS: Patients who underwent curative parotidectomy and were pathologically diagnosed with parotid gland cancer without regional or distant metastases between 2004 and 2019 were reviewed. The benefit of ART in terms of locoregional control (LRC) and progression-free survival (PFS) were evaluated. RESULTS: In total, 261 patients were included in the analysis. Of them, 45.2 % received ART. The median follow-up period was 66.8 months. Multivariate analysis revealed that histological grade and ART were independent prognostic factors for LRC and PFS (all p <.05). For patients with high-grade histology, ART was associated with a significant improvement in 5-year LRC (p =.005) and PFS (p =.009). Among patients with high-grade histology who completed RT, higher biologic effective dose (≥77 Gy10) significantly increased PFS (adjusted hazard ratio [HR], 0.10 per 1-Gy increase; 95 % confidence interval [CI], 0.02-0.58; p =.010). ART significantly improved LRC (p =.039) in patients with low-to-intermediate histological grade as well per multivariate analysis, and subgroup analyses revealed patients with T3-4 stage and close/positive resection margins (<1 mm) would benefit from ART. CONCLUSION: ART should be strongly recommended for patients with node-negative parotid gland cancer with high-grade histology in terms of disease control and survival. In patients with low-to-intermediate-grade disease, those with high T stage and incomplete resection margin benefit with ART.

Predictors of Early and Late Response to Esomezol and Lifestyle Modification in Adults With Laryngopharyngeal Reflux Disease: A Prospective, Multicenter, Open-Label Cohort Study.

OBJECTIVES: This study aimed to assess predictors of the response to varying durations of proton pump inhibitor (PPI) use and lifestyle modification treatment for laryngopharyngeal reflux disease (LPRD). METHODS: Between October 2014 and June 2016, a prospective, multicenter, open-label, single-cohort, intention-to-treat, observational study was conducted at eight referral hospitals across the Republic of Korea to examine predictors of early and late response to treatment in adult patients (age ≥19 years) with LPRD. Participants underwent standard treatment (PPI [Esomezol] and lifestyle modification) for 3 months. Response to treatment was defined as greater than 50% improvement in reflux symptom index score. The primary outcome was potential predictors of treatment response at 1 and 3 months. The secondary outcome was potential predictors distinguishing early from late responders. RESULTS: In total, 394 patients were enrolled. Improved sleep habits was a positive predictor (odds ratio [OR], 1.785; 95% confidence interval [CI], 1.06-3.007; P=0.029), while initial alcohol consumption (OR, 0.587; 95% CI, 0.355-0.969; P=0.037) and past medication history (OR, 0.438; 95% CI, 0.215-0.891; P=0.005) were negative predictors of response after 1 month of treatment. High pre-reflux finding score was a positive predictor (OR, 1.187; 95% CI, 1.049- 1.344; P=0.007), while male sex (OR, 0.516; 95% CI, 0.269-0.987; P=0.046), higher depression score (OR, 0.867; 95% CI, 0.784-0.958; P=0.005), and past thyroid hormone medication history (OR, 0.161; 95% CI, 0.033-0.788; P=0.024) were negative predictors of response after 3 months of treatment. Past medication history (OR, 0.438; 95% CI, 0.215-0.891; P=0.023) was the only negative predictor for early responders compared to late responders. CONCLUSION: Adult patients with LPRD and a history of prior medication use may require longer treatment durations to achieve a therapeutic response. Future research should explore the incorporation of diverse treatment approaches to improve treatment outcomes for patients exhibiting negative prognostic indicators.