Jae-Yol Lim

Distributions of cervical lymph node metastases in oropharyngeal carcinoma: therapeutic implications for the N0 neck.

Objectives: This study sought to investigate the patterns and distributions of lymph node metastases in oropharyngeal squamous cell carcinoma (SCC) and improve the rationale for elective treatment of N0 neck.

Quality of life in Korean patients with inflammatory bowel diseases : ulcerative colitis, Crohn's disease and intestinal Behçet's disease

Abstract Health-related quality of life (HRQOL) is an important outcome factor in chronic diseases such as inflammatory bowel disease (IBD). This study used the Korean translation of the disease-specific, self-administered Inflammatory Bowel Disease Questionnaire (IBDQ) to compare HRQOL in ulcerative colitis (UC; n=98), Crohns disease (CD; n = 49), and intestinal Behçets disease (BD; n = 34). In addition to the current status, patients were asked retrospectively to recall their symptoms at the beginning and during the worst period of their disease. Disease activity was measured by St. Marks Activity Index, Crohns disease Activity Index (CDAI), and the Harvey-Bradshaw Index (HBI). In all IBD patients, including those with BD, the IBDQ total score during the worst period was significantly lower than that at present and that at the beginning of the disease. However, there were no significant differences between groups regarding the total IBDQ score or its various dimensions. In UC a strong correlation between IBDQ scores and St. Marks Activity Index was observed (r = –0.708, P<0.001). IBDQ scores were also highly correlated with CDAI and HBI in both CD (r=–0.506, P<0.001 for CDAI; r = –0.600, P<0.001 for HBI) and BD (r = –0.687, P<0.001 for CDAI; r = –0.531, P<0.001 for HBI). However, the current IBDQ score was not related to demographic parameters such as gender, age, educational status, economic status, and marital status as well as disease factors such as duration of disease, history of operation or hospital admission, extent of disease in UC, involved region in CD, and clinical type in BD. We conclude that the Korean IBDQ is a responsive and promising instrument for measuring HRQOL of IBD patients in clinical trials. In addition, the IBDQ can be helpful in developing a disease-specific activity index in BD.

Systemic Transplantation of Human Adipose Tissue-Derived Mesenchymal Stem Cells for the Regeneration of Irradiation-Induced Salivary Gland Damage

Objectives Cell-based therapy has been reported to repair or restore damaged salivary gland (SG) tissue after irradiation. This study was aimed at determining whether systemic administration of human adipose-derived mesenchymal stem cells (hAdMSCs) can ameliorate radiation-induced SG damage. Methods hAdMSCs (1×106) were administered through a tail vein of C3H mice immediately after local irradiation, and then this infusion was repeated once a week for 3 consecutive weeks. At 12 weeks after irradiation, functional evaluations were conducted by measuring salivary flow rates (SFRs) and salivation lag times, and histopathologic and immunofluorescence histochemistry studies were performed to assay microstructural changes, apoptosis, and proliferation indices. The engraftment and in vivo differentiation of infused hAdMSCs were also investigated, and the transdifferentiation of hAdMSCs into amylase-producing SG epithelial cells (SGCs) was observed in vitro using a co-culture system. Results The systemic administration of hAdMSCs exhibited improved SFRs at 12 weeks after irradiation. hAdMSC-transplanted SGs showed fewer damaged and atrophied acinar cells and higher mucin and amylase production levels than untreated irradiated SGs. Immunofluorescence TUNEL assays revealed fewer apoptotic cells in the hAdMSC group than in the untreated group. Infused hAdMSCs were detected in transplanted SGs at 4 weeks after irradiation and some cells were found to have differentiated into SGCs. In vitro, a low number of co-cultured hAdMSCs (13%–18%) were observed to transdifferentiate into SGCs. Conclusion The findings of this study indicate that hAdMSCs have the potential to protect against irradiation-induced cell loss and to transdifferentiate into SGCs, and suggest that hAdMSC administration should be viewed as a candidate therapy for the treatment of radiation-induced SG damage.

Intraglandular transplantation of bone marrow-derived clonal mesenchymal stem cells for amelioration of post-irradiation salivary gland damage

OBJECTIVES External irradiation in head and neck cancers may induce irreversible hyposalivation and consequent xerostomia, stemming from radiation damage to salivary glands (SGs). As cell-based therapy has been reported to be able to repair or restore damaged SG tissues, we attempted to determine whether bone marrow-derived clonal mesenchymal stem cells (BM-cMSCs) can ameliorate irradiation-induced salivary gland damage via a murine model. METHODS External irradiation at a dose of 15Gy was delivered to the neck fields of C57BL/6 mice. We directly administered either homologous mouse BM-cMSCs labeled with PKH26 (treatment group) or PBS (control group) into SGs 24h after irradiation. Salivary flow rate (SFR) and lag time of salivation were measured at 12weeks after transplantation. At 4 and 12weeks post-transplantation, we performed morphological, histological, and immunofluorescent examinations. Transdifferentiation of administered BM-cMSCs into salivary epithelial cells was observed by confocal microscopy. RESULTS SFR was significantly increased in BM-cMSCs-transplanted mice compared with PBS-injected mice at 12weeks after transplantation. Administration of BM-cMSCs preserved the microscopic morphologies of SGs, with more functional acini in BM-cMSC-transplanted SGs than in PBS-injected SGs. Immunofluorescent staining revealed less apoptotic cells and increased microvessel density in BM-cMSC-transplanted SGs compared with PBS-injected SGs. PKH-26 labeled BM-cMSCs were detected in transplanted SGs at 4weeks after transplantation and in vivo transdifferentiation of BM-cMSCs into acinar cells was also observed. CONCLUSION This study suggests that BM-cMSCs can ameliorate salivary damage following irradiation and can be used as a source of cell-based therapy for restoration of irradiation-induced salivary hypofunction.

Management of Contralateral N0 Neck in Tonsillar Squamous Cell Carcinoma

Objectives: It is well established that tonsillar squamous cell carcinomas have a high probability of disseminating to the neck. An ipsilateral neck treatment is mandatory during initial treatment of stages II to IV tonsillar carcinomas. However, as of yet, no consensus exists whether to perform elective contralateral neck management.

Analysis of age-related changes in the functional morphologies of salivary glands in mice

BACKGROUND AND OBJECTIVES Salivary glands in the elderly commonly exhibit salivary dysfunction resulting dry mouth, poor oral hygiene, and dental caries. However, in vivo changes of salivary glands during aging have not been well documented in the literature. This study was undertaken to determine age-related morphometric and functional changes of salivary glands using an aging mouse model. METHODS Male C57BL/6 mice were divided into three groups, group A (10 weeks old; n=10), group B (30 weeks old; n=10), and group C (90 weeks old; n=10). Body weights, salivary gland weights, salivary flow rates, and salivary lag times were measured and compared. Histomorphometric examinations and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays were performed. In addition, changes in salivary uptake and excretion were observed by single-photon emission computed tomography (SPECT). RESULTS Body and gland weights increased with age. Gland weight was significantly higher in group B than in groups A and C. Salivary lag time was significantly greater in group C than in groups A and B, and salivary flow rate was significantly greater in group B than in groups A and C. Histologic evaluations exhibited acinar cell atrophy, cytoplasmic vacuolization, lymphocyte infiltration, small mucin component and more periductal fibrosis in salivary glands of group C. TUNEL assays revealed that apoptotic salivary epithelial cells were significantly more numerous in group C than in groups A and B. (99m)Tc-pertechnetate excretion rate was significantly lower in group C than in groups A and B in SPECT. CONCLUSION Various morphometric and histopathological changes were observed in the salivary glands of aging mouse as well as relevant functional alterations, such as, decreased saliva production and excretion. Increased number of apoptotic salivary epithelial cells may contribute to the observed functional deterioration.

Voice analysis of patients with diverse types of Reinke's edema and clinical use of electroglottographic measurements

Conclusions. Reinkes edema shows a variety of clinical patterns and differences in voice analysis depending on its type. Electroglottographic measurements help to objectively assess the severity of edema and voice quality before and after surgery. Objectives. Reinkes edema manifests various clinical findings and different voice characteristics depending on the degree of swelling and the severity of voice impairment. The aim of this study was to compare the aerodynamic, acoustic and electroglottographic parameters for the different types of Reinkes edema according to its morphological, perceptual and histopathological classifications, and to assess voice quality in patients with Reinkes edema before and after laryngomicrosurgery. We also aimed to determine which parameter was most associated with the improvement in postoperative voice quality and to investigate the clinical usefulness of electroglottographic analysis in Reinkes edema. Material and methods. The clinical and voice records of 61 patients with Reinkes edema were reviewed. All the patients were classified according to stroboscopic findings (Yonekawas classification), perceptual grade and histopathological findings. Voice analysis of the perceptual, acoustic, aerodynamic and electroglottographic measurements was carried out using various classifications, and the voices of 23 patients who underwent laryngomicrosurgery were evaluated 2 months after surgery. Furthermore, the voices of 30 normal speakers (controls) were recorded and analyzed. Results. The fundamental frequency (FxM) of Yonekawa Type III was significantly lower than those of the other types of Reinkes edema, and the SD of the FxM, the percentage irregularity of the FxM (CFx) and the percentage irregularity of the amplitude were larger than those of the other types of Reinkes edema. The closed quotient was significantly higher in Yonekawa Type III. In addition, the mean flow rate (MFR), maximum phonation time and harmonics:noise ratio (HNR) differed significantly among the different types of Reinkes edema. The postoperative results showed an increase in the FxM and an improvement in the MFR, subglottic pressure, shimmer and HNR. Correlation analysis showed that jitter, the HNR, the mean closed quotient and the irregularity of the frequency were the parameters that had the best correlation with improvement in postoperative voice quality.

Adipose Mesenchymal Stem Cell Secretome Modulated in Hypoxia for Remodeling of Radiation-Induced Salivary Gland Damage

Background and Purpose This study was conducted to determine whether a secretome from mesenchymal stem cells (MSC) modulated by hypoxic conditions to contain therapeutic factors contributes to salivary gland (SG) tissue remodeling and has the potential to improve irradiation (IR)-induced salivary hypofunction in a mouse model. Materials and Methods Human adipose mesenchymal stem cells (hAdMSC) were isolated, expanded, and exposed to hypoxic conditions (O2 < 5%). The hypoxia-conditioned medium was then filtered to a high molecular weight fraction and prepared as a hAdMSC secretome. The hAdMSC secretome was subsequently infused into the tail vein of C3H mice immediately after local IR once a day for seven consecutive days. The control group received equal volume (500 μL) of vehicle (PBS) only. SG function and structural tissue remodeling by the hAdMSC secretome were investigated. Human parotid epithelial cells (HPEC) were obtained, expanded in vitro, and then irradiated and treated with either the hypoxia-conditioned medium or a normoxic control medium. Cell proliferation and IR-induced cell death were examined to determine the mechanism by which the hAdMSC secretome exerted its effects. Results The conditioned hAdMSC secretome contained high levels of GM-CSF, VEGF, IL-6, and IGF-1. Repeated systemic infusion with the hAdMSC secretome resulted in improved salivation capacity and increased levels of salivary proteins, including amylase and EGF, relative to the PBS group. The microscopic structural integrity of SG was maintained and salivary epithelial (AQP-5), endothelial (CD31), myoepithelial (α-SMA) and SG progenitor cells (c-Kit) were successfully protected from radiation damage and remodeled. The hAdMSC secretome strongly induced proliferation of HPEC and led to a significant decrease in cell death in vivo and in vitro. Moreover, the anti-apoptotic effects of the hAdMSC secretome were found to be promoted after hypoxia-preconditioning relative to normoxia-cultured hAdMSC secretome. Conclusion These results show that the hAdMSC secretome from hypoxic-conditioned medium may provide radioprotection and tissue remodeling via release of paracrine mediators.

Adipose-derived stem cell-containing hyaluronic acid/alginate hydrogel improves vocal fold wound healing

The purpose of this study was to investigate the regenerative efficacy of an injectable hyaluronic acid/mildly cross‐linked alginate hydrogel (HA/ALG hydrogel) containing human adipose‐derived mesenchymal stem cells (hAdMSCs) for vocal fold (VF) wound healing.

Salivary gland function after sialendoscopy for treatment of chronic radioiodine-induced sialadenitis

The purpose of this study was to determine whether sialendoscopy could ameliorate radioactive iodine‐induced obstructive sialadenitis and restore the salivary gland dysfunction in recalcitrant radioactive iodine sialadenitis.