Robot-Assisted Total Thyroidectomy with or without Robot-Assisted Neck Dissection in Pediatric Patients with Differentiated Thyroid Cancer

Pediatric thyroid cancer more frequently develops cervical node metastasis than adult thyroid cancer, even in differentiated thyroid carcinoma (DTC). Thus, cervical neck dissection often needs to be performed simultaneously with thyroidectomy in pediatric patients. Herein, we describe our experience with robot-assisted total thyroidectomy with/without robot-assisted neck dissection in pediatric patients compared with the conventional operated group. A total of 30 pediatric patients who underwent thyroidectomy for DTC between July 2011 and December 2019 were retrospectively reviewed. Among them, 22 underwent robot-assisted operation, whereas 8 underwent conventional operation. There was no statistical difference in the mean operation times, blood loss, drainage amounts, and hospital stay length between the robot-assisted and conventional operation groups; however, the operation time was less in the retroauricular approach subgroup (robot-assisted operation group) with better satisfaction on cosmesis. No postoperative complications, such as seromas, hemorrhages, or hematomas were observed. Our experience suggested that robot-assisted thyroidectomy with or without neck dissection through the retroauricular approach is a feasible and safe alternative treatment, producing outstanding esthetic results compared to the conventional approach, especially in pediatric patients with DTC.ope

Analysis of low-level somatic mosaicism reveals stage and tissue-specific mutational features in human development

Most somatic mutations that arise during normal development are present at low levels in single or multiple tissues depending on the developmental stage and affected organs. However, the effect of human developmental stages or mutations of different organs on the features of somatic mutations is still unclear. Here, we performed a systemic and comprehensive analysis of low-level somatic mutations using deep whole-exome sequencing (average read depth ~500×) of 498 multiple organ tissues with matched controls from 190 individuals. Our results showed that early clone-forming mutations shared between multiple organs were lower in number but showed higher allele frequencies than late clone-forming mutations [0.54 vs. 5.83 variants per individual; 6.17% vs. 1.5% variant allele frequency (VAF)] along with less nonsynonymous mutations and lower functional impacts. Additionally, early and late clone-forming mutations had unique mutational signatures that were distinct from mutations that originated from tumors. Compared with early clone-forming mutations that showed a clock-like signature across all organs or tissues studied, late clone-forming mutations showed organ, tissue, and cell-type specificity in the mutation counts, VAFs, and mutational signatures. In particular, analysis of brain somatic mutations showed a bimodal occurrence and temporal-lobe-specific signature. These findings provide new insights into the features of somatic mosaicism that are dependent on developmental stage and brain regions.ope

Salivary gland organoid culture maintains distinct glandular properties of murine and human major salivary glands

Salivary glands that produce and secrete saliva, which is essential for lubrication, digestion, immunity, and oral homeostasis, consist of diverse cells. The long-term maintenance of diverse salivary gland cells in organoids remains problematic. Here, we establish long-term murine and human salivary gland organoid cultures. Murine and human salivary gland organoids express gland-specific genes and proteins of acinar, myoepithelial, and duct cells, and exhibit gland functions when stimulated with neurotransmitters. Furthermore, human salivary gland organoids are established from isolated basal or luminal cells, retaining their characteristics. Single-cell RNA sequencing also indicates that human salivary gland organoids contain heterogeneous cell types and replicate glandular diversity. Our protocol also enables the generation of tumoroid cultures from benign and malignant salivary gland tumor types, in which tumor-specific gene signatures are well-conserved. In this study, we provide an experimental platform for the exploration of precision medicine in the era of tissue regeneration and anticancer treatment.ope

The Time Course of Monocytes Infiltration After Acoustic Overstimulation

Cochlea macrophages regulate cochlea inflammation and may harbors the potentials to protect hearing function from injury, including acoustic overstimulation. Cochlea macrophage numbers increase at 3-7 days after acoustic stimulation. However, the exact timing of macrophage infiltration and maturation from inflammatory monocytes is unclear. Furthermore, neutrophils may also be involved in this process. Therefore, in this study, we investigated time-dependent immune cell infiltration, macrophage transformation, and neutrophil involvement following acoustic stimulation. Flow cytometry and immunofluorescence were conducted in C-X3-C motif chemokine receptor 1 (CX3CR1)+/GFP mice after acoustic overstimulation (at baseline and at 1, 2, 3, and 5 days after exposure to 120 dB for 1 h) to identify inflammatory monocytes in the cochlea. RNA-sequencing and quantitative polymerase chain reaction were performed to identify differentially expressed genes. Inflammatory monocytes infiltrated into the lower portion of the lateral wall within 2 days after acoustic overstimulation (dpn), followed by transformation into macrophages at 3-5 dpn via CX3CR1 upregulation and Ly6C downregulation. In addition, inflammatory monocytes were aggregated inside the collecting venule only at 1 dpn. Neutrophils were not a major type of phagocyte during this response. The gene encoding C-C motif chemokine ligand 2 gene was significantly upregulated as early as 3 h after acoustic overstimulation. Given these results, treatment to control immune response after a noise-induced hearing loss should be applied as soon as possible.ope

Protective Effect of Locally Injected Polydeoxyribonucleotide in Ischemic Murine Random Skin Flaps

Background and Objectives This study aimed to investigate the protective effect of polydeoxyribonucleotide (PDRN) against skin flap necrosis in a murine skin flap model.Materials and Method Twenty mice with rectangular skin flaps on the dorsum were randomly divided into the PDRN (n=10) and pentobarbital sodium (PBS) (n=10) injection groups. PDRN (8 mg/kg) was subdermally injected at 12 different points immediately after the operation. After 7 days, the flap perfusions were evaluated using a laser speckle contrast imaging (LSCI) system, and specimens were collected for immunohistochemistry analysis. Results The percentage of survival area relative to the total flap area was significantly higher in the PDRN group (60.87%±7.63%) than in the PBS group (45.23%±10.72%) (p<0.05). The mean LSCI perfusion signal of the distal part of the skin flap in the PBS group was 0.57±0.12, and that in the PDRN group was 0.74±0.13 (p<0.05). The PDRN group had a significantly lower interleukin 1 beta expression than the PBS group and higher vascular endothelial growth factor α expression than the PBS group (p<0.05). Conclusion These findings suggest that subdermally injected PDRN is more effective in enhancing flap survival during necrosis.ope

Phase II Clinical Trial of Eribulin-Gemcitabine Combination Therapy in Previously Treated Patients With Advanced Liposarcoma or Leiomyosarcoma

Purpose: Monotherapy with eribulin or gemcitabine has been found to be moderately effective in treating soft-tissue sarcomas (STS). In this study, we evaluated the efficacy and safety of eribulin-gemcitabine combination therapy for the two most common histologic types of STS, liposarcoma and leiomyosarcoma. Patients and methods: In this nonrandomized, multicenter, phase II study, we included patients with progressive disease who had received one or two courses of chemotherapy that included doxorubicin. Patients were administered 1.4 mg/m2 eribulin and 1,000 mg/m2 gemcitabine on days 1 and 8 every 3 weeks. The primary endpoint was progression-free survival rate at 12 weeks (PFSR12wks), with null and alternative hypotheses of PFSR12wks ≤20.0% and ≥40.0%, respectively. Exploratory biomarker analyses with next-generation sequencing (NGS) were performed on pretreatment tumor samples. Results: Among the 37 patients included, the overall PFSR12wks was 73.0%, achieving the primary endpoint. The objective response rate, disease control rate, median progression-free survival, and median overall survival were 16.2%, 78.4%, 5.6 months, and 31.9 months, respectively, without differences according to histologic type. New safety signals and treatment-related deaths were not documented. NGS-based transcriptome analysis revealed that functional enrichment in the TGFβ pathway was mostly associated with a poor outcome, whereas single genetic alterations largely failed to predict treatment outcome. Conclusions: Eribulin-gemcitabine combination therapy showed promising activity and an acceptable safety profile in patients with liposarcoma or leiomyosarcoma. Gene expression profiling with pathway enrichment analysis would have possibilities to have predictive value for survival outcome, necessitating further investigation to confirm.restrictio