GPR41 and GPR43: From development to metabolic regulation.

G-protein-coupled receptors are a diverse class of cell surface receptors that orchestrate numerous physiological functions. The G-protein-coupled receptors, GPR41 and GPR43, sense short-chain fatty acids (SCFAs), which are metabolites of dietary fermentation by the host's intestinal bacteria. These receptors have gained attention as potential therapeutic targets against various diseases because of their SCFA-mediated beneficial effects on the host's intestinal health. Mounting evidence has associated the activity of these receptors with chronic metabolic diseases, including obesity, diabetes, inflammation, and cardiovascular disease. However, despite intensive research using various strategies, including gene knockout (KO) mouse models, evidence about the precise roles of GPR41 and GPR43 in disease treatment remains inconsistent. Here, we comprehensively review the latest findings from functional studies of the signaling mechanisms that underlie the activities of GPR41 and GPR43, as well as highlight their multifaceted roles in health and disease. We anticipate that this knowledge will guide future research priorities and the development of effective therapeutic interventions.

Garcinia Cambogia Improves High-Fat Diet-Induced Glucose Imbalance by Enhancing Calcium/CaMKII/AMPK/GLUT4-Mediated Glucose Uptake in Skeletal Muscle.

SCOPE: Garcinia cambogia (G. cambogia) is known to have antiobesity effects. In this study, the therapeutic effects of G. cambogia on glucose homeostasis in obesity-induced diabetes are explored and the underlying mechanisms are investigated. METHODS AND RESULTS: C2C12 myotubes are treated with G. cambogia; glucose uptake, intracellular Ca2+ levels, and related alterations in signaling pathways are examined. High-fat diet (HFD)-fed mice are administered G. cambogia for 8 weeks; oral glucose tolerance is evaluated, and the regulation of identified targets of signaling pathways in quadriceps skeletal muscle are examined in vivo. G. cambogia increases glucose uptake in C2C12 myotubes and induces the upregulation of AMPK, ACC, and p38 MAPK phosphorylation. Notably, G. cambogia markedly elevates both intracellular Ca2+ levels, activating CaMKII, a Ca2+ -sensing protein, and TBC1D4-mediated GLUT4 translocation, to facilitate glucose uptake. Furthermore, high-glucose-induced inhibition of glucose uptake and signal transduction is reverted by G. cambogia. In an HFD-induced diabetes mouse model, G. cambogia administration results in significant blood glucose-lowering effects, which are attributed to the regulation of targets that have been identified in vitro, in quadricep skeletal muscle. CONCLUSION: These findings provide new insights into the mechanism by which G. cambogia regulates glucose homeostasis in obesity-induced diabetes.

Treatment With Glycogen Synthase Kinase 3ß Inhibitor Decreases Apoptotic and Autophagic Reactions in Rat Rotator Cuff Tears.

BACKGROUND: Apoptosis and autophagy are known to be correlated with the extent of damage in torn rotator cuffs, and there is no biological evidence for self-recovery or healing of the rotator cuff tear. PURPOSE: To establish in a rat model of partial- and full-thickness rotator cuff tears how a glycogen synthase kinase 3ß (GSK-3ß) inhibitor affects the expression of apoptotic and autophagic markers. STUDY DESIGN: Controlled laboratory study. METHODS: Twelve-week-old Sprague Dawley rats were divided into 3 groups (n = 16 per group). Group 1 acted as the control, with no treatment; group 2 received partial-thickness (right side) and full-thickness (left side) rotator cuff tears only; and group 3 received the same rotator cuff injuries, with GSK-3ß inhibitor injected afterward. The tendons from each group were harvested 42 days after surgery. Evaluation of gene expression, immunohistochemistry, and TUNEL staining (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) were performed for the following markers: caspases 3, 8, and 9 as well as Bcl-2 (B-cell lymphoma 2); BAX (Bcl-2-associated X protein); beclin 1; p53; and GSK-3ß; which represented apoptotic and autophagic reactions. Statistical analysis was performed using 1-way analysis of variance. RESULTS: In the group 2 rats with partial- and full-thickness tears, there were significant increases in the mRNA levels (fold changes) of all 8 markers as compared with group 1 (control). All these increased markers showed significant downregulation by the GSK-3ß inhibitor in partial-thickness tears. However, the response to the GSK-3ß inhibitor in full-thickness tears was not as prominent as in partial-thickness tears. The number of TUNEL-positive cells in group 2 (partial, 35.08% ± 1.625% [mean ± SE]; full, 46.92% ± 1.319%) was significantly higher than in group 1 (18.02% ± 1.036%; P < .01) and group 3 (partial, 28.04% ± 2.607% [P < .01]; full, 38.97% ± 2.772% [P < .01]), and immunohistochemistry revealed increased expression of all the markers in group 2 as compared with control. CONCLUSION: The apoptotic and autophagic activity induced in a rat model of an acute rotator cuff tear was downregulated after treatment with a GSK-3ß inhibitor, particularly with partial-thickness rotator cuff tears. CLINICAL RELEVANCE: A GSK-3ß inhibitor may be able to modulate deterioration in a torn rotator cuff.

Machine Learning for Recurrence Prediction of Gynecologic Cancers Using Lynch Syndrome-Related Screening Markers.

To support the implementation of genome-based precision medicine, we developed machine learning models that predict the recurrence of patients with gynecologic cancer in using immune checkpoint inhibitors (ICI) based on clinical and pathologic characteristics, including Lynch syndrome-related screening markers such as immunohistochemistry (IHC) and microsatellite instability (MSI) tests. To accomplish our goal, we reviewed the patient demographics, clinical data, and pathological results from their medical records. Then we identified seven potential characteristics (four MMR IHC [MLH1, MSH2, MSH6, and PMS2], MSI, Age 60, and tumor size). Following that, predictive models were built based on these variables using six machine learning algorithms: logistic regression (LR), support vector machine (SVM), naive Bayes (NB), random forest (RF), gradient boosting (GB), and extreme gradient boosting (EGB) (XGBoost). The experimental results showed that the RF-based model performed best at predicting gynecologic cancer recurrence, with AUCs of 0.818 and 0.826 for the 5-fold cross-validation (CV) and 5-fold CV with 10 repetitions, respectively. This study provides novel and baseline results about predicting the recurrence of gynecologic cancer in patients using ICI by using machine learning methods based on Lynch syndrome-related screening markers.

Therapeutic effect of local photothermal heating of gold nanoparticle-coated self-expandable metallic stents for suppressing granulation tissue formation in the mouse colon.

PURPOSE: To investigate the therapeutic effect of local photothermal (PT) heating on suppression of stent-induced granulation tissue formation in mouse colon. MATERIALS AND METHODS: A gold nanoparticle (GNP)-coated self-expandable metallic stent (SEMS) was prepared using a two-step synthesis process for local PT heating under near-infrared laser irradiation. Twenty-four mice were randomly divided into two groups of 12 and subjected to SEMS placement in the colon. Group A received a GNP-coated SEMS without local heating and Group B received a GNP-coated SEMS and underwent local heating at 55°C after SEMS placement. The therapeutic effect of local heating was assessed by comparing the histopathological, immunohistochemical, and endoscopic results. RESULTS: Four mice were excluded because of stent migration (n = 3, group B) or death (n = 1, group A). Stent-induced granulation tissue-related variables were significantly lower in group B than in group A (p < 0.001). In vivo endoscopic images, 4 weeks after stent placement, showed granulation tissue formation over the wire mesh in group A and relatively good patency of the stented colon with no definite irregularities in group B. There was more vascular endothelial growth factor (VEGF) positivity in group A than in group B. CONCLUSION: Local PT heating suppresses granulation tissue formation after stent placement in mouse colon.

Estrogen Replacement Reduces Hearing Threshold Shifts and Cochlear Hair Cell Loss After Acoustic Overexposure in Ovariectomized Rats.

OBJECTIVES: The relationship of estrogen (the primary female sex hormone) with hearing function has been studied in both humans and animals. However, whether estrogen levels affect hearing remains uncertain. Therefore, in this study, we investigated changes in the vulnerability of hearing to acoustic overexposure in ovariectomized female rats. METHODS: Eighteen 8-week-old female Sprague-Dawley rats were separated into four groups as follows: sham ovariectomy (OP), OP only, and OP treated with low (10 µg/kg) or high doses (100 µg/kg) of estrogen. Rats in the estrogen replacement groups were given two intraperitoneal injections. Hearing thresholds were measured before noise exposure, and at 1 day and 2 weeks after exposure. RESULTS: The hearing thresholds of the sham OP and OP-only groups were not significantly different. However, both estrogen groups showed a lower threshold shift than the OP-only group. Histological immunostaining analyses showed that hair cell loss in the 32 kHz region was more severe in the sham OP group than in the OP-only group. Furthermore, there was little or no hair cell loss in either estrogen replacement group and significantly more hair cell loss in the OP-only group. CONCLUSION: These results suggest that estrogen replacement may reduce the vulnerability of hearing to noise exposure in menopausal women.

Local Heat Treatment for Suppressing Gastroduodenal Stent-Induced Tissue Hyperplasia Using Nanofunctionalized Self-Expandable Metallic Stent in Rat Gastric Outlet Model.

Despite the promising results from the placement of covered or uncovered self-expandable metallic stent (SEMS) as a nonsurgical therapeutic option for the malignant gastric outlet obstruction (GOO), the long patency of the stent is still limited because of stent-induced tissue hyperplasia. Here, a local heat treatment using a nanofunctionalized SEMS is proposed for suppressing stent-induced tissue hyperplasia during GOO treatment. Highly efficient photothermal gold nanoparticle (GNP) transducer-coated SEMSs (GNP-SEMSs) were prepared for local heat treatment in rat gastric outlet. The in vivo heating temperature in rat gastric outlet model was evaluated and compared with in vitro heating temperature. Three groups of our developed 45 rat gastric outlet models were used: group A, noncoated SEMS only; group B, GNP-SEMS plus local heating; and group C, GNP-SEMS only to investigate in vivo efficacy of GNP-SEMS mediated local heating. Ten rats per group were sacrificed for 4 weeks, and five rats per group were sacrificed immediately after local heat treatment. The in vivo heating temperature was found to be 10.8% lower than the in vitro heating temperatures. GNP-SEMSs were successfully placed through a percutaneous approach into the rat gastric outlet (n = 45). The therapeutic effects of GNP-SEMS were assessed by histologic examination including hematoxylin-eosin, Masson trichrome, immunohistochemistry (TUNEL and CD31), and immunofluorescence (Ki67), and the results showed significant prevention of tissue hyperplasia following stent placement without adjacent gastrointestinal tissue damage. GNP-SEMS-mediated local heating could be an alternative therapeutic option for the suppression of tissue hyperplasia following stent placement in benign and malignant GOOs.

Measurement of horizontal ocular deviation on magnetic resonance imaging in various disease with acute vertigo.

In our previous study, we found that horizontal ocular deviation (OD) was significantly increased in patients with unilateral vestibular neuritis (VN). This study is aimed to compare the measurements of horizontal OD in various diseases which can present as acute vertigo in the emergency department. We retrospectively reviewed patients who visited the emergency department and underwent brain MRI due to acute vertigo. We compared them to healthy controls who underwent brain MRI for a regular health examination. Among the study participants, 149 patients who were diagnosed with benign paroxysmal positional vertigo (BPPV), unilateral Ménière's disease (MD), vestibular migraine (VM), unilateral vestibular neuritis (VN), or posterior inferior cerebellar artery (PICA) infarction were enrolled. Absolute angles of horizontal OD were larger in the definite MD (19.1 ± 12.7°), possible and probable MD (15.5 ± 11.7°), and VN (22.2 ± 11.7°) groups compared to the control group (4.3 ± 3.7°). Most VN patients (83.3%) had horizontal OD toward the direction of the lesion. About half of the MD patients (46.2%) and half of the patients with PICA infarction (50.0%) had horizontal OD toward the opposite direction of the lesion. Regarding PICA infarction, horizontal OD was observed only in patients who immediately underwent an MRI after developing the PICA territory vestibulocerebellar infarction. Although the exact mechanism of horizontal OD is unclear, this study suggests that horizontal OD reflects a static vestibular imbalance, and that the eyeball is deviated to the weaker of the two vestibular nuclei during neural resting activity. Therefore, horizontal OD could be helpful in assessing for a prior vestibular imbalance.

Persistent static imbalance among acute unilateral vestibulopathy patients could be related to a damaged velocity storage system.

Background: Acute unilateral vestibulopathy (AUV) is common but, the course of disease recovery is variable. Moreover, the final recovery status might vary between subjects. The remaining symptoms of these patients indicate the poor recovery of static imbalance, which could limit social activities and decrease their quality of life. Objective: To determine the possible predictive parameters of prolonged static imbalance (PSI) among acute AUV, we compared several vestibular function test (VFT) results between control vestibulopathy (CV) and PSI patients. Materials and methods: Subjects were divided into two groups: PSI and CV. PSI was determined by the observation of spontaneous nystagmus at 1 month after discharge from the hospital. VFT results taken during the initial symptoms were compared. Results: Increased phase lead was observed in low-frequency stimulations (p < .05), while the other test results failed to reveal a significant difference. These results indicate that a larger phase lead, which is related to a decrease in the time constant, could be responsible for the delayed recovery of static imbalance. Conclusion and significance: The phase lead was higher in the PSI group compared to the CV group, suggesting the possible role of phase as a parameter to predict the delayed compensation of static imbalance.

Sustained Ca2+ mobilizations: A quantitative approach to predict their importance in cell-cell communication and wound healing.

Epithelial wound healing requires the coordination of cells to migrate as a unit over the basement membrane after injury. To understand the process of this coordinated movement, it is critical to study the dynamics of cell-cell communication. We developed a method to characterize the injury-induced sustained Ca2+ mobilizations that travel between cells for periods of time up to several hours. These events of communication are concentrated along the wound edge and are reduced in cells further away from the wound. Our goal was to delineate the role and contribution of these sustained mobilizations and using MATLAB analyses, we determined the probability of cell-cell communication events in both in vitro models and ex vivo organ culture models. We demonstrated that the injury response was complex and represented the activation of a number of receptors. In addition, we found that pannexin channels mediated the cell-cell communication and motility. Furthermore, the sustained Ca2+ mobilizations are associated with changes in cell morphology and motility during wound healing. The results demonstrate that both purinoreceptors and pannexins regulate the sustained Ca2+ mobilization necessary for cell-cell communication in wound healing.

Fluoroscopic self-expandable metallic stent placement for treating post-operative nonanastomotic strictures in the proximal small bowel: a 15-year single institution experience.

OBJECTIVE: To evaluate the efficacy and safety of fluoroscopic self-expandable metallic stent (SEMS) placement for treating postoperative nonanastomotic strictures in the proximal small bowel. METHODS: Data from 8 consecutive patients (mean age, 63.8 ± 6.9 years; 7 males and 1 female) who underwent 17 fluoroscopic SEMS placement procedures in total for treating postoperative nonanastomotic strictures in the proximal jejunum were retrospectively reviewed. The most recent surgery for all the patients was total gastrectomy with esophagojejunostomy. Strictures were located in the proximal jejunum in all patients. The mean length of the strictures was 5.8 ± 2.0 cm. Five patients with comorbidities were poor surgical candidates. Four patients underwent fluoroscopic balloon dilation, three of whom showed no resolution of obstructive symptoms and one demonstrated recurrence of symptoms. RESULTS: Technical and clinical success was achieved in 100% (17/17) SEMS procedures. Complete resolution of obstructive symptoms and improvement in oral intake status occurred within 3 days after all procedures, rendering a clinical success rate of 100% (17/17). No complication occurred during or after the procedures. The median follow-up duration was 167 [interquartile range (IQR), 48-576] days. Stent malfunction occurred after 58.8% (10/17) of the procedures, including six occurrences of stent migration and four of benign tissue hyperplasia. Surgical removal of the migrated stents was performed in two patients. Recurrence of symptoms occurred after 64.7% (11/17) of the procedures. The median stent dwell and recurrence-free times were 32 (IQR, 20-193) and 68 (IQR, 38-513) days, respectively. CONCLUSION: Fluoroscopic SEMS placement may be effective and safe for treating postoperative nonanastomotic strictures, but stent malfunction and recurrence are major drawbacks. ADVANCES IN KNOWLEDGE: SEMS placement is effective and relatively safe in patients with postoperative nonanastomotic strictures in the proximal small bowel. Patients section and counseling is highly encouraged.

In Vivo Fluorescence Microendoscopic Monitoring of Stent-Induced Fibroblast Cell Proliferation in an Esophageal Mouse Model.

PURPOSE: To evaluate the feasibility of self-expanding metal stent (SEMS) placement and fluorescence microendoscopic monitoring for determination of fibroblast cell proliferation after stent placement in an esophageal mouse model. MATERIALS AND METHODS: Twenty fibroblast-specific protein (FSP)-1 green fluorescent protein (GFP) transgenic mice were analyzed. Ten mice (Group A) underwent SEMS placement, and fluoroscopic and fluorescence microendoscopic images were obtained biweekly until 8 weeks thereafter. Ten healthy mice (Group B) were used for control esophageal values. RESULTS: SEMS placement was technically successful in all mice. The relative average number of fibroblast GFP cells and the intensities of GFP signals in Group A were significantly higher than in Group B after stent placement. The proliferative cellular response, including granulation tissue, epithelial layer, submucosal fibrosis, and connective tissue, was increased in Group A. FSP-1-positive cells were more prominent in Group A than in Group B. CONCLUSIONS: SEMS placement was feasible and safe in an esophageal mouse model, and proliferative cellular response caused by fibroblast cell proliferation after stent placement was longitudinally monitored using a noninvasive fluorescence microendoscopic technique. The results have implications for the understanding of proliferative cellular response after stent placement in real-life patients and provide initial insights into new clinical therapeutic strategies for restenosis.

EW-7197, an oral transforming growth factor ß type I receptor kinase inhibitor, for preventing peritoneal adhesion formation in a rat model.

BACKGROUND: EW-7197 is an oral transforming growth factor ß type I receptor kinase inhibitor currently undergoing phase I clinical trials for cancer treatment in the United States. This study evaluates whether EW-7197 prevents peritoneal adhesion formation in a rat model. METHODS: Forty-eight female Wistar rats underwent peritoneal adhesion induction by the creation of peritoneal ischemic buttons and were randomly divided into 4 groups of 12 each. The control group received 0.3 mL vehicle by oral gavage once daily for 7 days after adhesion induction. The 10 mg and 20 mg groups received 10 or 20 mg/kg EW-7197 phosphate dissolved in 0.3 mL vehicle by oral gavage once daily for 7 days after adhesion induction. The rebound group received 20 mg/kg EW-7197 phosphate dissolved in 0.3 mL vehicle by oral gavage once daily for 7 days after adhesion induction followed by 0.3 mL vehicle only by gavage once daily for an additional 21 days. After the respective treatments were completed, the animals were euthanized. RESULTS: All rats survived until the end of the study without complications. EW-7197 reduced the incidence, quality, and tenacity of peritoneal adhesions in a dose-dependent manner. Fibrosis and collagen production were reduced in EW-7197-treated peritoneal ischemic buttons. Transforming growth factor ß/Smad2/3 signaling and mesothelial-to-mesenchymal transition were inhibited in EW-7197-treated peritoneal ischemic buttons. Discontinuation of EW-7197 was not associated with rebound effects. CONCLUSION: EW-7197 prevented peritoneal adhesion formation potentially via inhibition of transforming growth factor ß1/Smad2/3-induced mesothelial-to-mesenchymal transition in a rat model.

Transnasal Placement of a Balloon-Expandable Metallic Stent: Human Cadaver Study of the Eustachian Tube.

PURPOSE: To investigate the technical feasibility of stent placement in the cartilaginous portion of the Eustachian tube (ET). MATERIALS AND METHODS: Twelve ETs of 6 cadavers were used. Two different-sized stents were placed on either the right (2.5 mm in diameter) or left (3.5 mm in diameter) side of the ET. The procedural feasibility was assessed by subtraction Eustachian tubography, computed tomography before and after the procedure, and fluoroscopic and endoscopic images. The stent location, inner luminal diameter of the stented ET, radiation dose, procedural time, and fluoroscopy time were analyzed. RESULTS: Stent placement was successful in 11 of 12 cadaveric specimens without procedure-related complications. In the 1 specimen, the balloon catheter with crimped stent was passed into the bony canal of the ET without any resistance. The distal end of the stent was located in the middle ear cavity. Stents were located within the cartilaginous portion of the ET (n = 1), the proximal tip bridging the nasopharyngeal orifice of the ET (n = 5), or the proximal end of the stent protruded from the tubal orifice (n = 5). The mean luminal diameter in the outer segment was significantly smaller than in the middle (P < .001) and inner (P < .001) segments. The mean procedure time was 128 ± 37 seconds. The mean radiation dose and fluoroscopy time of each cadaver were 3235.4 ± 864.8 cGy/cm2 and 139 ± 49 seconds, respectively. CONCLUSIONS: Stent placement of the ET under endoscopic and fluoroscopic guidance is technically feasible in a human cadaver model.

Fluoroscopic subtraction Eustachian tubography: initial feasibility test in a cadaver model.

OBJECTIVES: To evaluate the technical feasibility of direct Eustachian tube catheterisation and subtraction Eustachian tubography in a cadaver model. METHODS: A total of 12 separate sessions were performed on both sides of the Eustachian tube (ET) in six human cadavers. Cadavers were positioned for the submentovertical view on a fluoroscopy table. Endoscopy-guided ET selection was used in the first three cadavers, whereas fluoroscopy-guided ET selection was used in the remaining three. Eustachian tubography was performed by injecting 2 ml of contrast media through a 5-Fr catheter. We recorded the success of ET selection, number of attempts, procedure time, and tubography quality using native and subtraction images (range, 0-3). RESULTS: Both endoscopy- and fluoroscopy-guided selections were successfully performed in five of six sessions (83.3%). There were no statistically significant differences between the endoscopy- and fluoroscopy-guided procedures in terms of the number of attempts, procedure time, rate of immediate contrast leak to the middle ear cavity, and quality of tubography (p > 0.05). An excellent quality of tubography was obtained in 83.3% (10 of 12 sessions) of subtraction images and in 33.3% (4 of 12 sessions) of native images. The tubography quality score was significantly higher for the subtraction images than for the native images (p = 0.04). CONCLUSION: Subtraction Eustachian tubography using direct catheterisation seems to be technically feasible. The entire ET can be well visualised; thus, this technique can be used as a simple tool for assessment of ET function and anatomy. KEY POINTS: • Direct catheterisation of the Eustachian tube is technically feasible. • The entire Eustachian tube could be well visualised by direct Eustachian tubography. • Subtraction Eustachian tubography images have better image quality than native images. • Subtraction Eustachian tubography can provide objective assessment of ET function and anatomy.

Fluoroscopic Gastroduodenal Stent Placement in 55 Patients with Endoscopic Stent Placement Failure.

PURPOSE: To evaluate the technical feasibility and clinical effectiveness of fluoroscopic self-expandable metal stent (SEMS) placement in malignant gastroduodenal obstructions after failed endoscopic SEMS placement. MATERIALS AND METHODS: Between September 2010 and July 2017, 874 patients underwent endoscopic SEMS placement for dysphagia caused by malignant gastroduodenal obstructions. Endoscopic SEMS placement failed in 55 of 874 patients (6.3%). These patients were referred for fluoroscopic SEMS placement. In case of failed fluoroscopic SEMS placement, combined endoscopic and fluoroscopic SEMS placement was attempted at the same setting. RESULTS: Fluoroscopic SEMS placement was technically successful in 40 of 55 patients (72.7%). Combined endoscopic and fluoroscopic SEMS placement was technically successful in 6 of 15 patients with fluoroscopic SEMS placement failure. Failures in the nine patients were due to complete obstruction (n = 5) and acute angulation at the stricture site (n = 4). The overall technical success rate was 83.6% (46/55). Clinical success was achieved in 95.6% of patients (44/46). Complications occurred in 7 of 46 patients (15.2%), including tumor overgrowth (n = 3), SEMS migration (n = 3), and bleeding (n = 1). The median SEMS patency and patient survival periods were 515 (95% confidence interval (CI), 266.6-761.5) and 83 (95% CI 60.6-105.4) days, respectively. CONCLUSIONS: Fluoroscopic SEMS placement is technically feasible and clinically effective in cases of endoscopic SEMS placement failure. A combined endoscopic and fluoroscopic approach increases the technical success rate after failure of the endoscopic or fluoroscopic approach. LEVEL OF EVIDENCE: Level IV.

EW-7197 eluting nano-fiber covered self-expandable metallic stent to prevent granulation tissue formation in a canine urethral model.

PURPOSE: To evaluate an EW-7197-eluting nanofiber-covered stent (NFCS) for suppressing granulation tissue formation after stent placement in a canine urethral model. MATERIALS AND METHODS: All experiments were approved by the committee of animal research. A total of 12 NFCSs were placed in the proximal and distal urethras of six dogs. Dogs were divided into two groups with 3 dogs each. The control stent (CS) group received NFCSs and the drug stent (DS) group received EW-7197 (1000 µg)-eluting NFCSs. All dogs were sacrificed 8 weeks after stent placement Histologic findings of the stented urethra were compared using the Mann-Whitney U test. RESULTS: Stent placement was technically successful in all dogs without procedure-related complications. On urethrographic analysis, the mean luminal diameter was significantly larger in the DS group than in the CS group at 4 and 8 weeks after stent placement (all p < 0.001). On histological examination, mean thicknesses of the papillary projection, thickness of submucosal fibrosis, number of epithelial layers, and degree of collagen deposition were significantly lower in the DS group than in the CS group (all p < 0.001), whereas the mean degree of inflammatory cell infiltration was not significantly different (p > 0.05). CONCLUSION: The EW-7197-eluting NFCS is effective and safe for suppressing granulation tissue formation after stent placement in a canine urethral model.

Self-Expandable Metal Stent Use to Palliate Malignant Esophagorespiratory Fistulas in 88 Patients.

PURPOSE: To identify predictors associated with clinical outcomes (initial clinical failure, stent patency, and survival) after self-expandable metal stent (SEMS) placement for malignant esophagorespiratory fistulas (ERFs). MATERIALS AND METHODS: Using logistic and Cox regression analyses, this study reviewed 88 patients (mean age 59.4 y ± 8.4; 84 men [95.5%] and 4 women [4.5%]) who underwent fluoroscopic SEMS placement for palliating malignant ERF from January 2000 to December 2016. RESULTS: Technical success was achieved in all patients. Initial clinical success was achieved in 78.4% (69/88; 95% confidence interval [CI], 68.7%-85.7%). Among the 69 patients in whom initial clinical success was achieved, aspiration symptoms recurred in 37.7% (26/69; 95% CI, 27.2%-49.5%). Overall major complication rate was 25.0% (22/88; 95% CI, 17.1%-35.0%). Cumulative stent patency and cumulative survival rates at 1, 3, 6, and 12 months were 72.8%, 38.9%, 32.4%, and 21.6% and 81.4%, 51.9%, 30.5%, and 13.3%, respectively. Stricture of the upper esophagus was an independent predictor of initial clinical failure (odds ratio, 3.760; 95% CI, 1.207-11.811) and shorter stent patency (hazard ratio [HR], 2.036; 95% CI, 1.170-3.544). Initial clinical failure was an independent predictor of shorter survival (HR, 2.902; 95% CI, 1.587-5.305). CONCLUSIONS: SEMS placement offers sufficient short-term relief despite considerable major complications. Stricture of the upper esophagus is an independent predictor of initial clinical failure and shorter stent patency. Initial clinical failure is an independent predictor of shorter survival.

Sirolimus-eluting Biodegradable Poly-l-Lactic Acid Stent to Suppress Granulation Tissue Formation in the Rat Urethra.

Purpose To investigate the use of sirolimus-eluting biodegradable stents (SEBSs) to suppress granulation tissue formation after stent placement in a rat urethral model. Materials and Methods All experiments were approved by the animal research committee. A total of 36 male Sprague-Dawley rats were randomized into three equal groups after biodegradable stent placement. Group A received control biodegradable stents. Groups B and C received stents coated with 90 µg/cm2 and 450 µg/cm2 sirolimus, respectively. Six rats in each group were sacrificed after 4 weeks; the remaining rats were sacrificed after 12 weeks. The therapeutic effectiveness of SEBSs was assessed by comparing the results of retrograde urethrography and histologic examination. Analysis of variance with post hoc comparisons was used to evaluate statistical differences. Results SEBS placement was technically successful in all rats. Urethrographic and histologic examinations revealed significantly less granulation tissue formation at both time points in the rats receiving SEBSs (groups B and C) compared with those that received control stents (group A) (P < .05 for all). There were no significant differences in urethrographic and histologic findings between groups B and C (P > .05 for all). However, the mean number of epithelial layers in group B was higher than that in group C at 4 weeks after stent placement (P < .001). Apoptosis increased in group C compared with groups A and B (P < .05 for all). Conclusion The use of SEBSs suppressed granulation tissue formation secondary to stent placement in a rat urethral model; local therapy with SEBSs may be used to decrease stent-related granulation tissue formation. © RSNA, 2017.