Imaging findings of granular cell tumours of the head and neck.

AIM: To review the imaging characteristics of granular cell tumours in the head and neck and assess their associations with pathological findings. MATERIALS AND METHODS: Eleven patients (10 [91%] women, mean age 43 years) with histopathologically confirmed granular cell tumours were included in this study. Preoperative imaging studies were performed, including computed tomography (CT), magnetic resonance imaging (MRI), or ultrasound. The location of the tumours, their imaging features, and histopathological findings were analysed. RESULTS: Among the 11 granular cell tumours, four (36%), three (27%), and two (18%) tumours were found in the submucosal layer, subcutaneous layer, and intramuscular area, respectively. On CT, all tumours exhibited homogeneous iso-attenuating enhancement compared with adjacent muscle, and nine out of the 11 tumours (81%) demonstrated well-defined margins. On T2-weighted imaging (T2WI), four out of five tumours (80%) demonstrated iso-signal intensity compared with adjacent muscles, and four tumours (80%) exhibited homogeneous signal intensity. The apparent diffusion coefficient (ADC) values ranged from 0.68-0.81 × 10-3 mm2/s. Histopathological examination revealed densely packed tumour cells with variable amounts of fibrous stroma. CONCLUSION: Granular cell tumours were characterised by well-defined and iso-signals on T2WI and low mean ADC values, and were predominantly located in the submucosal, subcutaneous, or intramuscular areas in middle-aged women. The characteristic locations, demographic characteristics, and imaging findings can help to differentiate granular cell tumours from other soft-tissue tumours in the head and neck.

Image findings of anti-neutrophil cytoplasmic antibody-associated vasculitis involving the skull base.

AIM: To investigate computed tomography (CT) and magnetic resonance imaging (MRI) features of skull bases involving anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV). MATERIALS AND METHODS: A retrospective review was undertaken to identify an institutional historical cohort of 17 patients with confirmed AAV who underwent CT or MRI and had skull base involvement between 2002 and 2021. Two radiologists reviewed the extent and features of the lesions, bone changes, and other MRI findings. RESULTS: A total of 17 patients (12 men; mean age ± standard deviation, 46.5 ± 17.1 years) were selected. AAV presented as infiltrative lesions with involvement at various sites. Most cases involved the paranasal sinuses (PNS; 88%, 15/17), nasopharynx (88%, 15/17), pterygopalatine fossa (82%, 14/17), and parapharyngeal space (82%, 14/17), frequently accompanied by mucosal irregularity of the PNS and nasopharynx (71%, 12/17). Central skull base and temporal bone involvement were seen in 53% (9/17) and 38% (6/16) of cases, respectively. On T1-weighted imaging (WI) and T2WI MRI, all lesions (15/15) showed predominant signal iso-intensity to grey matter. CONCLUSIONS: Although radiological findings of AAV are non-specific and skull base involvement is less common, AAV may be considered if infiltrative lesions predominantly involving the PNS, nasopharynx, pterygopalatine fossa, and parapharyngeal space with combined bone changes of skull base are seen.

Temporal change in the diagnosis and treatment rates of osteoporosis: results from the Korea National Health and Nutrition Examination Survey.

To compare the diagnosis andtreatment rates of osteoporosis and diabetes in Korea, a nationwide database was used. The results showed that although osteoporosis management is improving, it is still lower compared with that of diabetes; thus, further efforts are needed in this regard. INTRODUCTION: This study aimed to re-evaluate the diagnosis and treatment of osteoporosis from the KNHANES 2016-2017 and compare the temporal change of the rate with those of diabetes as another prevalent chronic disease in South Korea. METHODS: The prevalence of osteoporosis in 2016 was estimated using the previous data classified by age groups (50-59,60-69, and ≥70years) and the 2016 Korean census data. The physician diagnosis and treatment rates of osteoporosis in adults aged ≥50years were estimated using the 2016-2017 KNHANES data. The physician diagnosis and treatment rates of diabetes were evaluated using the KNHANES 2008-2009 and 2016-2017 data. RESULTS: The estimated physician diagnosisrate of osteoporosis increased from 29.9% in females and 5.8% in males in 2008-2009 to 62.8% in females and 22.8% in males in 2016-2017. The treatment rate for the estimated total number of patients with osteoporosis increased from 14.4% in females and 3.8% in males in 2008-2009 to 32.2% in females and 9.0% in males in 2016-2017. An increasing trend in the estimated treatment rateof physician-diagnosed osteoporosis patients was not observed (48.3% [2008-2009] vs 51.5% [2016-2017] in females; 42.6% [2008-2009] vs 42.2% [2016-2017] in males). The physician diagnosis and treatment rates of diabetes were considerably better and more stable than those of osteoporosis. CONCLUSION: Osteoporosis management in South Korea is improving but is insufficient compared with diabetes management. More extensive efforts are needed to improve the diagnosis and treatment rates of osteoporosis.

Phthalyl starch nanoparticles as prebiotics enhanced nisin production in Lactococcus lactis through the induction of mild stress in probiotics.

AIM OF THE STUDY: Effect of internalized phthalyl starch nanoparticles (PSNs) on the antimicrobial ability of Lactococcus lactis (LL) KCTC 2013. METHODS AND RESULTS: Phthalyl starch nanoparticles were prepared by self-assembly of phthalyl starch and the amount of the hydrophobic phthalic moieties were characterized by nuclear magnetic resonance: PSN1 (DS: 14·3 mol.%), PSN2 (DS: 17·8 mol.%) and PSN3 (DS: 30·4 mol.%). The sizes of PSN1, PSN2 and PSN3 measured by dynamic light scattering were 364·7, 248·4 and 213·4 nm, respectively, and the surface charges of PSNs measured by electrophoretic light scattering were negative charges and PSNs were spherical in shape according to scanning electron microscope. It was found that when PSNs were treated with LL, the PSNs were internalized into LL through nanoparticle size-, energy- and glucose transporter-dependent mechanisms. The internalization was confirmed by confocal laser scanning microscopy and fluorescence-activated cell sorting. Nisin was isolated and identified by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. Also, more nisin was produced from PSNs-treated LL than untreated- or starch-treated LL. Co-culture assay and agar diffusion test were performed to test the antimicrobial ability. Antimicrobial ability against Gram-negative Escherichia coli k88, Salmonella gallinarum and Gram-positive Listeria monocytogenes of LL treated with PSNs was higher than that of untreated or starch-treated group. Finally, it was found that the expression level of stress response genes dnaK, dnaJ and groES was significantly higher in PSNs-treated groups compared with starch-treated group or LL alone. CONCLUSION: The internalization of PSNs into LL enhanced the production of nisin through mild intracellular stimulation, resulting in enhanced antimicrobial ability. SIGNIFICANCE AND IMPACT OF THE STUDY: This study shows the promising potential of PSNs as new prebiotics for increasing the production of nisin, thus demonstrating a new method for the biological production of such antimicrobial peptides.

Diagnostic performance of MRI to detect metastatic cervical lymph nodes in patients with thyroid cancer: a systematic review and meta-analysis.

AIM: To evaluate the diagnostic performance of magnetic resonance imaging (MRI) in the diagnosis of metastatic cervical lymph nodes. MATERIALS AND METHODS: Ovid-MEDLINE and EMBASE databases were searched up until 12 June 2018. Eleven articles were included in the qualitative systematic review and nine of the 11 in the quantitative analysis. Two radiologists independently performed data extraction and methodological quality assessment using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. A qualitative systematic review and quantitative analysis were performed, followed by a meta-regression analysis to determine factors causing heterogeneity. RESULTS: The pooled sensitivity and specificity in the diagnosis of metastatic cervical lymph nodes were 80% (95% confidence interval [CI]: 68-88%) and 85% (95% CI: 63-95%), respectively. The sensitivity and false-positive rate (correlation coefficient, 0.655) showed a positive correlation due to a threshold effect, which was responsible for heterogeneity across the studies, as indicated by a Q-test (p<0.01) and Higgins I2 statistic (sensitivity, I2=90.11%; specificity, I2=92.49%). In the meta-regression analysis, fat-suppressed imaging, and the analysis method were significant factors influencing the heterogeneity in diagnostic performance. CONCLUSIONS: MRI shows moderate diagnostic performance in the diagnosis of metastatic lymph nodes in patients with thyroid cancer in the neck. MRI may be an optional or complementary imaging method to ultrasound or computed tomography (CT) in thyroid cancer patients.

Preoperative evaluation of mammographic microcalcifications after neoadjuvant chemotherapy for breast cancer.

AIM: To assess the predictive value of preoperative residual mammographic microcalcifications for residual tumours after neoadjuvant chemotherapy (NAC) for breast cancer. MATERIALS AND METHODS: This single-centre retrospective study included breast cancer patients who underwent NAC and demonstrated suspicious microcalcifications within or near the tumour bed on mammography from June 2015 to August 2018. The residual microcalcifications and remnant lesion on magnetic resonance imaging (MRI) were correlated with histopathological findings of residual tumours and immunohistochemical markers. RESULTS: A total of 96 patients were included. Ten patients achieved pathological complete response (pCR) and previous suspicious microcalcifications were associated with benign pathology in 10.4% (10/96) of the patients. In the remaining 86 patients who did not achieve pCR, 61.5% (59/96) of the residual microcalcifications were associated with invasive or in situ carcinoma and 28.1% (27/96) with benign pathology. Hormone receptor-positive (HR+) patients had the highest proportion of residual malignant microcalcifications compared to HR- patients (48.9% versus 13.5%, respectively; p=0.019). MRI correlated better than residual microcalcifications on mammography in predicting residual tumour extent in all subtypes (ICC=0.709 versus 0.365). MRI also showed higher correlation with residual tumour size for the HR-/HER2+ and HR-/HER2- subtype (ICC=0.925 and 0.876, respectively). CONCLUSION: The extent of microcalcifications on mammography after NAC did not correlate with the extent of residual cancer in 38.5% of women. Regardless of the extent of microcalcifications, residual tumour extent on MRI after NAC and molecular subtype could be an accurate tool in evaluating residual cancer after NAC.

High-resolution MRI using compressed sensing-sensitivity encoding (CS-SENSE) for patients with suspected neurovascular compression syndrome: comparison with the conventional SENSE parallel acquisition technique.

AIM: To retrospectively compare sensitivity encoding (SENSE) and compressed sensing-sensitivity encoding (CS-SENSE) for high resolution (HR) cranial nerve magnetic resonance imaging (MRI) in a clinical population. MATERIAL AND METHODS: Twenty consecutive patients who were clinically suspected of neurovascular compression syndrome (NVCS) were enrolled in this study. HR three-dimensional isotropic T2-weighted fast spin-echo (T2 VISTA) sequences with SENSE or CS-SENSE, and contrast-enhanced three-dimensional T1-turbo field-echo (CE 3D T1 TFE) with SENSE or CS-SENSE, were compared using quantitative and qualitative methods by two board-certified neuroradiologists. RESULTS: For the T2 VISTA, CS-SENSE was significantly superior to SENSE in terms of cerebrospinal fluid homogeneity. For CE 3D T1 TFE, CS-SENSE was significantly superior to SENSE in terms of the existence of ghost artefact and the signal-to-noise ratio (SNR) of the pontine parenchyma. There was no significant difference in overall image quality between the two techniques. Compared with SENSE, CS-SENSE reduced the scan time to 44.2% of that with SENSE on T2 VISTA, and to 66.1% of that with SENSE of the CE 3D T1 TFE, with the differences being statistically significant (p<0.01, both). CONCLUSION: For T2 VISTA and CE 3D T1 TFE imaging of patients with suspected NVCS, CS-SENSE appears to offer superior reductions in motion artefact and scan time relative to SENSE, without a loss of overall image quality.

Prostate cancer detection rate according to lesion visibility using ultrasound and MRI.

AIM: To evaluate the difference in prostate cancer detection rates according to lesion visibility using transrectal ultrasound (TRUS) and magnetic resonance imaging (MRI) before biopsy. MATERIALS AND METHODS: Patients who underwent TRUS-guided prostate biopsy in 2016 and 2017 (n=1,022) were divided into three groups: (1) patients who did not undergo a prebiopsy MRI (group 1, n=622); (2) patients without visible lesions on the prebiopsy MRI (group 2, n=77); and (3) patients with visible lesions on the prebiopsy MRI (group 3, n=323). Biopsy results were compared using chi-square tests or independent t-tests between patients with and without TRUS-visible lesions in each group. A logistic regression test was used to determine the variables independently associated with the detection of clinically significant cancer. RESULTS: Focal lesions were visible on TRUS in 710 patients. Clinically significant cancers were detected in 39.4% and 13.1% of patients with and without TRUS-visible lesions, respectively (p<0.001). The cancer detection rate was significantly higher in patients with TRUS-visible lesions in groups 1 and 3 (p<0.001). Within group 1, the Gleason scores, number of positive cores, and the cancer involvement ratios were significantly greater in patients with TRUS-visible lesions than in patients without TRUS-visible lesions. MRI- and TRUS visibility were positively associated with the detection of clinically significant prostate cancer (p=0.002 and p<0.001, respectively). CONCLUSION: TRUS- and MRI-visible focal lesions in the prostate were significantly associated with the detection of clinically significant cancer.

Identification of predictive variables for the recurrence of oral mucocele.

BACKGROUND: Oral mucocele is the most common minor salivary gland lesion with good prognosis after surgical removal. However, its recurrence is not rare, sometimes bothersome. This study aimed to identify the possible predictive variables affecting the recurrence rate of oral mucocele. MATERIAL AND METHODS: The histoclinical data of 164 patients diagnosed with oral mucocele were retrospectively obtained by reviewing dental records. The predictive variables for its recurrence were identified by analyzing its recurrence rate according to clinical variables. RESULTS: The recurrence rate showed the significant differences according to location and age. Oral mucocele recurred with significantly higher frequency on the ventral mucosa of tongue (50.0%) than on the labial/buccal mucosa (8.8%). Its recurrence was significantly more common in the younger patients (aged < 30 years, 16.0%) than in the older patients (aged > 30 years, 4.4%). However, there was no significant difference in recurrence rates between surgical procedures using scalpels and those using lasers. CONCLUSIONS: Patients with oral mucocele should be more carefully informed of its possible recurrence, especially when it is found on the ventral surface of the tongue or in a younger population.

Urinary Pentosidine levels negatively associates with trabecular bone scores in patients with type 2 diabetes mellitus.

Pentosidine levels were higher in diabetic patients with vertebral fractures. Trabecular bone scores were negatively associated with pentosidine levels in diabetic patients only. Our results provide further evidence that AGEs are associated with the pathogenesis of bone fragility in patients with T2DM. INTRODUCTION: Type 2 diabetes mellitus (T2DM) is associated with fracture risk. Pentosidine, an advanced glycation end product (AGE), is associated with prevalent vertebral fractures (VFs) in patients with T2DM. Trabecular bone score (TBS) has been proposed as an index of bone microarchitecture associated with bone quality. This study evaluated the associations of urine pentosidine and TBS in T2DM and non-T2DM groups. METHODS: A total of 112 T2DM patients and 62 non-T2DM subjects were enrolled. TBS was calculated using TBS insight® software (version 2.1). Pentosidine levels were measured using high-performance liquid chromatography method. We compared the BMD, TBS, and pentosidine levels between those with and without VFs with or without adjustment for age and sex. The association with TBS, lumbar spine BMD, and pentosidine levels were also evaluated in both T2DM and non-T2DM groups. RESULTS: Pentosidine levels were significantly higher in T2DM patients with VFs. TBSs were significantly lower in patients with T2DM and VFs. In non-diabetic patients, there were no significant differences in TBS and pentosidine levels for those with and without VFs after adjustment for age and sex. Pentosidine levels were negatively associated with TBS only in patients with T2DM. In multivariate stepwise regression analysis, pentosidine levels were significantly associated with TBS in patients with T2DM. CONCLUSIONS: TBS and pentosidine could be used as a method to assess bone quality to identify T2DM patients at risk of VFs. Our results also provide further evidence that AGEs are associated with the pathogenesis of bone fragility in patients with T2DM.

Comparison of injectate spread and nerve involvement between retrolaminar and erector spinae plane blocks in the thoracic region: a cadaveric study.

Although different injection locations for retrolaminar and erector spinae plane blocks have been described, the two procedures have a similar anatomical basis. In this cadaveric study we compared anatomical spread of dye in the thoracic region following these two procedures. Following randomisation, 10 retrolaminar blocks and 10 erector spinae plane blocks were performed on the left or right sides of 10 unembalmed cadavers. For each block, 20 ml of dye solution was injected at the T5 level. The back regions were dissected and the involvement of the thoracic spinal nerve was also investigated. Twenty blocks were successfully completed. A consistent vertical spread, with deep staining between the posterior surface of the vertebral laminae and the overlaying transversospinalis muscle was observed in all retrolaminar blocks. Moreover, most retrolaminar blocks were predominantly associated with fascial spreading in the intrinsic back muscles. With an erector spinae plane block, dye spread in a more lateral pattern than with retrolaminar block, and fascial spreading in the back muscles was also observed. The number of stained thoracic spinal nerves was greater with erector spinae plane blocks than with retrolaminar blocks; median 2.0 and 3.5, respectively. Regardless of technique, the main route of dye spread was through the superior costotransverse ligament to the ipsilateral paravertebral space. Although erector spinae plane blocks were associated with a slightly larger number of stained thoracic spinal nerves than retrolaminar blocks, both techniques were consistently associated with posterior spread of dye and with limited spread to the paravertebral space.

Increased propionate concentration in Lactobacillus mucosae-fermented wet brewers grains and during in vitro rumen fermentation.

AIMS: This study was conducted to isolate and identify propionate-producing bacteria that can be used as an inoculum in improving wet brewers grains and rumen fermentation via increasing propionate concentration. METHODS AND RESULTS: A strain of Lactobacillus that exhibits high levels of propionate production was identified and characterized as Lactobacillus mucosae 521129 by 16S rRNA gene sequencing and phylogenetic analyses. Wet brewers grains were fermented through L. mucosae inoculation and resulted in an increase in propionate concentration. Fermented wet brewers grains were used in in vitro rumen fermentation and revealed that L. mucosae-fermented wet brewers grains produced more gas and had higher accumulations propionate and total volatile fatty acid (VFA) than the control. The fewest methanogen DNA copies were detected in L. mucosae-fermented wet brewers grains. CONCLUSION: Identified L. mucosae improved the fermentation of wet brewers grains and the in vitro rumen fermentation via increasing propionate and total VFA concentrations. SIGNIFICANCE AND IMPACT OF THE STUDY: The presented research provided the identification of L. mucosae 521129 as a propionate producer and was metabolically profiled. Furthermore, data present the putative application of this organism in improving the fermentation of wet brewers grains and in vitro rumen fermentation.

Reduced metallic artefacts in 3 T knee MRI using fast spin-echo multi-point Dixon compared to fast spin-echo T2-weighted sequences.

AIM: To compare multi-point Dixon magnetic resonance imaging (MRI) and fast spin-echo (FSE) T2-weighted imaging (WI) with regard to the size of metallic artefacts when imaging the knee joint. MATERIALS AND METHODS: A total of 42 patients who underwent anterior cruciate ligament (ACL) reconstruction and follow-up imaging with 3 T MRI using the multi-point Dixon technique was included in this retrospective study. The maximal distance of the image distortion area around the metallic artefact was measured (interference screw of femoral tunnel area) on sagittal images of both FSE T2WI (T2WI and fat-suppressed [FS] T2WI) and multi-point Dixon (water only image and in-phase image) sequences. The maximal distance of the image distortion were compared using paired t-tests across the image sequences (multi-point Dixon water only image versus FS T2WI and multi-point Dixon in-phase image versus T2WI). RESULTS: The mean distance of the image distortion from metallic artefacts regardless of the image sequence ranged from 16.6 mm to 24.5 mm (Table 2). The mean distances measured by two readers on multi-point Dixon (water only image) sequences were significantly shorter than those in FS T2WI sequences (p<0.001). In contrast, the mean distances measured by two readers on multi-point Dixon (in-phase image) sequences did not differ from those of T2WI (p>0.05) sequences. CONCLUSION: The water-only image of multi-point Dixon technique reduces the amount of metallic artefacts compared to that in FS FSE T2WI sequences; however, the metallic artefacts were not significantly different between in-phase images of multi-point Dixon and FSE T2WI.

Interobserver reproducibility of maximal axial diameter and tumour volume measurements from CT of patients with head and neck squamous cell carcinoma.

AIM: To evaluate the interobserver reproducibility of computed tomography (CT) measurements of maximum tumour diameter and tumour volume for head and neck squamous cell carcinoma. MATERIALS AND METHODS: Eighty consecutive patients who underwent neck CT for the initial evaluation of head and neck squamous cell carcinoma were included in this retrospective study. Two radiologists independently measured the maximal axial diameter and volume of tumours. The reproducibility between the two observers was assessed using 95% Bland-Altman limits of agreement, reproducibility coefficient, within-subject coefficient of variation, and intraclass correlation coefficient with subgroup analysis according to tumour location. Logistic regression analysis was performed to identify the risk factors for high variability in tumour volume. RESULTS: The 95% limits of agreement for maximal axial diameter and tumour volume were ±22.3% and ±42.8%, respectively. The within-subject coefficient of variation and reproducibility coefficient were 7.9% and 0.564 for maximal axial diameter and 22.9% and 5.069 for tumour volume. All intraclass correlation coefficients for maximal axial diameter and tumour volume demonstrated excellent agreement (all intraclass correlation coefficients >0.9). Peritumoural infiltration (odds ratio: 7.189; confidence interval: 1.815-28.469; p=0.005) was an independent risk factor for high interobserver variability. CONCLUSION: Changes in maximum axial diameter and tumour volume of <22.3% and 42.8%, respectively, were in the range of measurement error on CT. The presence of peritumoural infiltration on CT increases the error in tumour volume measurement.

3D isotropic T2-weighted fast spin echo (VISTA) versus 2D T2-weighted fast spin echo in evaluation of the calcaneofibular ligament in the oblique coronal plane.

AIM: To investigate whether the image quality of three-dimensional (3D) volume isotropic fast spin echo acquisition (VISTA) magnetic resonance imaging (MRI) of the calcaneofibular ligament (CFL) view is comparable to that of 2D fast spin echo T2-weighted images (2D T2 FSE) for the evaluation of the CFL, and whether 3D VISTA can replace 2D T2 FSE for the evaluation of CFL injuries. MATERIALS AND METHODS: This retrospective study included 76 patients who underwent ankle MRI with CFL views of both 2D T2 FSE MRI and 3D VISTA. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of both techniques were measured. The anatomical identification score and diagnostic performances were evaluated by two readers independently. The diagnostic performances of 3D VISTA and 2D T2 FSE were analysed by sensitivity, specificity, and accuracy for diagnosing CFL injury with reference standards of surgically or clinically confirmed diagnoses. Surgical correlation was performed in 29% of the patients, and clinical examination was used in those who did not have surgery (71%). RESULTS: The SNRs and CNRs of 3D VISTA were significantly higher than those of 2D T2 FSE. The anatomical identification scores on 3D VISTA were inferior to those on 2D T2 FSE, and the differences were statistically significant (p<0.05). There were no significant differences in diagnostic performance between the two sequences when diagnoses were classified as normal or abnormal. CONCLUSION: Although the image quality of 3D VISTA MRI of the CFL view is not equal to that of 2D T2 FSE for the anatomical evaluation of CFL, 3D VISTA has a diagnostic performance comparable to that of 2D T2 FSE for the diagnosis of CFL injuries.

Local myogenic pulp-derived cell injection enhances craniofacial muscle regeneration in vivo.

OBJECTIVES: To enhance myogenic differentiation in pulp cells isolated from extracted premolars by epigenetic modification using a DNA demethylation agent, 5-aza-2'-deoxycytidine (5-Aza), and to evaluate the potent stimulatory effect of 5-Aza-treated pulp cell injection for craniofacial muscle regeneration in vivo. SETTING AND SAMPLE POPULATION: Pulp cells were isolated from premolars extracted for orthodontic purposes from four adults (age range, 18-22.1 years). MATERIAL AND METHODS: Levels of myogenic differentiation and functional contraction response in vitro were compared between pulp cells with or without pre-treatment of 5-Aza. Changes in muscle regeneration in response to green fluorescent protein (GFP)-labelled myogenic pulp cell injection in vivo were evaluated using a cardiotoxin (CTX)-induced muscle injury model of the gastrocnemius as well as the masseter muscle in mice. RESULTS: Pre-treatment of 5-Aza in pulp cells stimulated myotube formation, myogenic differentiation in terms of desmin and myogenin expression, and the level of collagen gel contraction. The local injection of 5-Aza pre-treated myogenic pulp cells was engrafted into the host tissue and indicated signs of enhanced muscle regeneration in both the gastrocnemius and the masseter muscles. CONCLUSION: The epigenetic modification of pulp cells from extracted premolars and the local injection of myogenic pulp cells may stimulate craniofacial muscles regeneration in vivo.

Phase I study of safety and pharmacokinetics of the anti-MUC16 antibody-drug conjugate DMUC5754A in patients with platinum-resistant ovarian cancer or unresectable pancreatic cancer.

BACKGROUND: MUC16 is a tumor-specific antigen overexpressed in ovarian (OC) and pancreatic (PC) cancers. The antibody-drug conjugate (ADC), DMUC5754A, contains the humanized anti-MUC16 monoclonal antibody conjugated to the microtubule-disrupting agent, monomethyl auristatin E (MMAE). PATIENTS AND METHODS: This phase I study evaluated safety, pharmacokinetics (PK), and pharmacodynamics of DMUC5754A given every 3 weeks (Q3W, 0.3-3.2 mg/kg) or weekly (Q1W, 0.8-1.6 mg/kg) to patients with advanced recurrent platinum-resistant OC or unresectable PC. Biomarker studies were also undertaken. RESULTS: Patients (66 OC, 11 PC) were treated with DMUC5754A (54 Q3W, 23 Q1W). Common related adverse events (AEs) in >20% of patients (all grades) over all dose levels were fatigue, peripheral neuropathy, nausea, decreased appetite, vomiting, diarrhea, alopecia, and pyrexia in Q3W patents, and nausea, vomiting, anemia, fatigue, neutropenia, alopecia, decreased appetite, diarrhea, and hypomagnesemia in Q1W patients. Grade ≥3-related AE in ≥5% of patients included neutropenia (9%) and fatigue (7%) in Q3W patients, and neutropenia (17%), diarrhea (9%), and hyponatremia (9%) in Q1W patients. Plasma antibody-conjugated MMAE (acMMAE) and serum total antibody exhibited non-linear PK across tested doses. Minimal accumulation of acMMAE, total antibody, or unconjugated MMAE was observed. Confirmed responses (1 CR, 6 PRs) occurred in OC patients whose tumors were MUC16-positive by IHC (2+ or 3+). Two OC patients had unconfirmed PRs; six OC patients had stable disease lasting >6 months. For CA125, a cut-off of ≥70% reduction was more suitable for monitoring treatment response due to the binding and clearance of serum CA125 by MUC16 ADC. We identified circulating HE4 as a potential novel surrogate biomarker for monitoring treatment response of MUC16 ADC and other anti-MUC16 therapies in OC. CONCLUSIONS: DMUC5754A has an acceptable safety profile and evidence of anti-tumor activity in patients with MUC16-expressing tumors. Objective responses were only observed in MUC16-high patients, although prospective validation is required. CLINICAL TRIAL NUMBER: NCT01335958.

Assessment of clinical and MRI outcomes after mesenchymal stem cell implantation in patients with knee osteoarthritis: a prospective study.

OBJECTIVE: Cartilage regenerative procedures using the cell-based tissue engineering approach involving mesenchymal stem cells (MSCs) have been receiving increased interest because of their potential for altering the progression of osteoarthritis (OA) by repairing cartilage lesions. The aim of this study was to investigate the clinical and magnetic resonance imaging (MRI) outcomes of MSC implantation in OA knees and to determine the association between clinical and MRI outcomes. DESIGN: Twenty patients (24 knees) who underwent arthroscopic MSC implantation for cartilage lesions in their OA knees were evaluated at 2 years after surgery. Clinical outcomes were evaluated according to the International Knee Documentation Committee (IKDC) score and the Tegner activity scale, and cartilage repair was assessed according to the MRI Osteoarthritis Knee Score (MOAKS) and Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score. RESULTS: The clinical outcomes significantly improved (P < 0.001 for both). The cartilage lesion grades (as described in MOAKS [grades for size of cartilage-loss area and percentage of full-thickness cartilage loss]) at follow-up MRI were significantly better than the preoperative values (P < 0.001 for both). The clinical outcomes at final follow-up were significantly correlated with the MOAKS and MOCART score at follow-up MRI (P < 0.05 for all). CONCLUSIONS: Considering the encouraging clinical and MRI outcomes obtained and the significant correlations noted between the clinical and MRI outcomes, MSC implantation seems to be useful for repairing cartilage lesions in OA knees. However, a larger sample size and long-term studies are needed to confirm our findings.

Ethanol and/or radiofrequency ablation to treat venolymphatic malformations that manifest as a bulging mass in the head and neck.

AIM: To evaluate the efficacy of ultrasound (US)-guided ethanol ablation (EA) and radiofrequency ablation (RFA) for treating venolymphatic malformations (VLM) of the head and neck. MATERIALS AND METHODS: US-guided EA and/or RFA were performed on 17 patients with VLM of the head and neck. Computed tomography (CT) or magnetic resonance imaging (MRI) was used to locate the cranial nerves and salivary gland ducts that were close to targets, and these were avoided during the procedures. Treatment response was assessed using volume reduction and cosmetic grading scoring. RESULTS: Nine VLMs were located close to the functional structures: Stensen's duct (n=3), cranial nerve branch (n=3), or both (n=3). All patients demonstrated >50% volume reduction, except one patient with a microcystic lymphatic malformation that was abutting the facial nerve. Median cosmetic grading scores improved from 4 to 1 (p<0.001). CONCLUSION: US-guided EA and/or RFA are effective and safe treatment methods in patients with VLMs of the head and neck. Treatment selection of EA and/or RFA could be performed based on the composition of VLMs as assessed at CT and MRI.

Interobserver reproducibility of cervical lymph node measurements at CT in patients with head and neck squamous cell carcinoma.

AIM: To determine the interobserver reproducibility of measuring cervical lymph nodes at computed tomography (CT) in patients with head and neck squamous cell carcinoma (HNSCC) and to investigate the influence of finding extracapsular spread (ECS) at CT on measurement reliability. MATERIALS AND METHODS: The institutional review board approved the study protocol, and informed consent was obtained. A total of 146 patients with 224 suspicious lymph nodes underwent CT before treatment. Two observers independently measured the diameters (minimal axial, maximum axial, and maximum longitudinal diameter) and assessed the ECS using CT. The greatest diameter was defined as the largest among the three measured diameters. Interobserver variability was determined by the within-subject coefficient of variation, and interobserver agreement was determined by the intraclass correlation coefficient (ICC). RESULTS: The within-subject coefficients of variation were 7.8%, 7.6%, and 11.4% for the minimal axial, maximum axial, and greatest diameters, respectively. The ICC values for interobserver agreement were excellent for all diameter measurements (i.e., ICC >0.9). Minimum and maximum axial diameter measurements were statistically more reliable than the greatest diameter measurement (p=0.008 and p=0.0001, respectively). The presence of ECS on CT does not significantly affect the reliability of lymph node diameter measurements (p>0.05). CONCLUSION: Lymph node diameter measurement on CT is a highly reproducible and robust method. Additionally, imaging features of ECS do not affect reliability. Therefore, the measurement of lymph node diameter can be confidently performed in daily clinical practice or clinical trials.