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PURPOSE: This study aimed to evaluate the effectiveness and safety of iodine-125 brachytherapy as a treatment for right lower paratracheal lymph node metastasis following unsuccessful prior therapies. METHODS: A retrospective review of patients who underwent iodine-125 brachytherapy for right lower paratracheal lymph node metastasis was conducted. The study included 24 patients who met the predefined criteria. Iodine-125 seeds were implanted under CT guidance, and treatment planning was performed using a treatment planning system. The primary endpoint was the objective response rate (ORR), while overall survival (OS) and complications were secondary endpoints. RESULTS: The ORR was 87.5%, with 4 patients achieving complete response (CR) and 17 patients achieving partial response (PR). The mean diameter of metastatic lymph nodes significantly reduced from 40.21 ± 6.66â¯mm before treatment to 12.25 ± 9.27â¯mm at the last follow-up (pâ¯<â¯0.001). The median OS was 14.70 months, with 1-year and 2-year survival rates of 78.9% and 20.9%, respectively. Clinical symptoms significantly improved, as indicated by increased Karnofsky Performance Score (KPS) scores. Complications were manageable, with no procedure-related deaths. CONCLUSION: Iodine-125 brachytherapy demonstrated promising efficacy and safety as an alternative treatment for right lower paratracheal lymph node metastasis after unsuccessful prior therapies.
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(1) Background: Respiratory virus infections, including Coronavirus disease 2019 (COVID-19), seasonal influenza (FLU), and respiratory syncytial virus (RSV) as prominent examples, can severely affect both children and adults. This study aimed to investigate the clinical characteristics of respiratory viral infections in pediatric and adult populations and to identify determinants influencing patient hospitalization. (2) Methods: This retrospective study analyzed the electronic medical records of patients admitted to a regional hospital's emergency department from 1 January 2015 to 31 December 2022, to investigate the clinical characteristics and hospitalization risk factors associated with these three viruses. (3) Results: Infants aged 1 to 11 months were most affected by COVID-19 and RSV, whereas FLU more commonly infected children aged 3 to 5 years. Key factors influencing hospitalization included age and abnormal chest X-ray findings, with higher risks observed in younger children and adults over 65. Notably, the presence of abnormal chest x-ray findings significantly increased the hospitalization risk by 1.9 times [1.5-2.4] in children and 21.4 times [2.4-189.0] in adults. (4) Conclusions: This analysis underscores the impact of COVID-19, FLU, and RSV on hospitalization risk, offering insights for managing these respiratory viral infections (RVIs). Age-related risk differences highlight the necessity for tailored strategies, improving understanding of and treatment development for RVIs.
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Purpose: This study investigated the anatomical and histological characteristics of the rat Eustachian tube (E-tube) and the feasibility of Eustachian tubography in a rat model. Materials and methods: Fifteen male Wistar rats were used in this study, and the bilateral E-tubes of each rat were examined. Ten E-tubes were used for anatomical studies, another ten for histological analysis, and the other ten for Eustachian tubography. Five rats were euthanized and decapitated, and ten E-tubes were dissected to describe the anatomy of the E-tube. Ten E-tube specimens obtained from five other rats were sectioned to investigate E-tube histology. Eustachian tubography was performed on the bilateral E-tubes of the other five rats using the trans-tympanic approach. Results: The rat E-tubes consisted of bony and membranous parts. Cartilage and bone tissue covered only the bony part. The E-tubes' mean diameter and overall length were 2.97 âmm and 4.96 âmm, respectively. The tympanic orifices' mean diameter was 1.21 âmm. The epithelium of E-tubes was mainly composed of pseudostratified ciliated and goblet cells. Eustachian tubography was successfully performed on both sides of the E-tube for each rat. The technical success rate was 100%, the average running time was 4.9 âmin, and no procedure-related complications occurred. On tubography images, the E-tube, tympanic cavity, and nasopharynx could be identified because of the visualization of bony landmarks. Conclusion: In this study, we described the anatomical and histological features of rat E-tubes. With the aid of these findings, E-tube angiography was successfully performed using a transtympanic approach. These results will facilitate further investigation of E-tube dysfunction.
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Secondary lymphedema is a severe complication of cancer treatment, but there is no effective curative method yet. Lymph node dissection and radiation therapy for cancer treatment may lead to secondary lymphedema, which is a chronic disease induced by malfunction of lymphatic flow. The lymphatic channel sheet (LCS) is an artificial micro-fluidic structure that was fabricated with polydimethylsiloxane to maintain lymphatic flow and induce lymphangiogenesis. The structure has two-dimensional multichannels that increase the probability of lymphangiogenesis and allow for relatively easy application. We verified the efficacy of the lymphatic channel sheet through macroscopic and microscopic observation in small animal models, which underwent brachial lymph node dissection and irradiation. The lymphatic channel sheet enabled the successful transport of lymphatic fluid from the distal to the proximal area in place of the removed brachial lymph nodes. It prevented swelling and abnormal lymphatic drainage during the follow-up period. Lymphangiogenesis was also identified inside the channel by histological analysis after 8 weeks. According to these experimental results, we attest to the roles of the lymphatic channel sheet as a lymphatic pathway and scaffold in the rat upper limb model of secondary lymphedema. The lymphatic channel sheet maintained lymphatic flow after lymph node dissection and irradiation in an environment where lymph flow is cut off. It also relieved symptoms of secondary lymphedema by providing a lymph-friendly space and inducing lymphangiogenesis.
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The self-expanding metal stent (SEMS) is a versatile, palliative treatment method for unresectable, malignant, non-vascular strictures. Colorectal cancer (CRC) is one of the candidates for the application of the SEMS, in combination with the photothermal ablation (PTA) technique that enhances its therapeutic efficacy. The objective of this study was to investigate the efficacy of stent-mediated PTA therapy in an endoscopy-guided, orthotopic rectal cancer model. A total of 30 of 40 mice with the tumor size of grade 4 were included and were divided into three groups of 10 mice each. Group A underwent a gold nanoparticle (AuNP)-coated SEMS but no near-infrared (NIR) irradiation, group B received an uncoated control SEMS with NIR irradiation, and group C received a AuNP-coated SEMS and NIR irradiation together. Colonoscopy and in vivo imaging, immunohistochemical analysis, and quantitative reverse-transcription polymerase chain reaction of major tumor markers were performed. Stent placement and PTA were technically successful using colonoscopy. The tumor grade reduction after PTA is significant in group C, compared with groups A or B (p < 0.001). Molecular analysis validated this observation with a significantly reduced Mapk1 proliferation marker or increased Jnk expression. Histological analysis confirmed the localized PTA therapy using AuNP-coated SEMS profoundly ablated tumor outgrowth through the stent. Our results indicate that this novel strategy of localized PTA therapy could be a promising option for palliative treatment of CRC and to support prolonged stent patency with a decreased tumor volume.
Subject(s)
Metal Nanoparticles , Rectal Neoplasms , Animals , Gold , Humans , Mice , Palliative Care , StentsABSTRACT
Human epidermal growth factor receptor 2 (HER2) is overexpressed in breast and gastric cancers and this causes poor clinical outcomes. Although both T-DM1 and Enhertu are approved as an HER2-targeting antibody-drug conjugate (ADC), the effects of these drugs are still not satisfactory to eradicate diverse tumors expressing HER2. To address this shortfall in HER2-targeted therapeutics, an elaborate cleavable linker is created and a novel HER2-targeting ADC composed with trastuzumab and monomethyl auristatin F, which is being investigated in a phase 1 clinical trial and is referred to as LegoChem Bisciences-ADC (LCB-ADC). LCB-ADC displays a higher cytotoxic potency than T-DM1 and it also has a higher G2/M arrest ratio. In animal studies, LCB-ADC produces noticeable tumor growth inhibition compared with trastuzumab or T-DM1 in an HER2 high-expressing N87 xenograft tumor. Especially, LCB-ADC shows good efficacy in terms of suppressing tumor growth in a patient-derived xenograft (PDX) model of HER2-positive gastric cancer as well as in T-DM1-resistant models such as HER2 low-expressing HER2 low expressing JIMT-1 xenograft tumor and PDX. Collectively, the results demonstrate that LCB-ADC with the elaborate linker has a higher efficacy and greater biostability than its ADC counterparts and may successfully treat cancers that are nonresponsive to previous therapeutics.
Subject(s)
Antineoplastic Agents, Immunological/therapeutic use , Immunoconjugates/therapeutic use , Oligopeptides/therapeutic use , Receptor, ErbB-2/genetics , Stomach Neoplasms/drug therapy , Trastuzumab/therapeutic use , Animals , Disease Models, Animal , Haplorhini , Heterografts , Humans , Mice , Mice, Nude , Rats , Stomach Neoplasms/genetics , Stomach Neoplasms/immunologyABSTRACT
Postoperative pancreatic fistula at the early stage can lead to auto-digestion, which may delay the recovery of the pancreaticojejunal (PJ) anastomosis. The efficacy and safety of an acetazolamide-eluting biodegradable tubular stent (AZ-BTS) for the prevention of self-digestion and intra-abdominal inflammatory diseases caused by pancreatic juice leakage after PJ anastomosis in a porcine model were investigated. The AZ-BTS was successfully fabricated using a multiple dip-coating process. Then, the drug amount and release profile were analyzed. The therapeutic effects of AZ were examined in vitro using two kinds of pancreatic cancer cell lines, AsPC-1 and PANC-1. The efficacy of AZ-BTS was assessed in a porcine PJ leakage model, with animals were each assigned to a leakage group, a BTS group and an AZ-BTS group. The overall mortality rates in these three groups were 44.4%, 16.6%, and 0%, respectively. Mean α-amylase concentrations were significantly higher in the leakage and BTS groups than in the AZ-BTS group on day 2-5 (p < 0.05 each all). The luminal diameters and areas of the pancreatic duct were significantly larger in the leakage group than in the BTS and AZ-BTS groups (p < 0.05 each all). These findings indicate that AZ-BTS can significantly suppress intra-abdominal inflammatory diseases caused by pancreatic juice leakage and also prevent late stricture formation at the PJ anastomotic site in a porcine model.
Subject(s)
Anastomotic Leak , Pharmaceutical Preparations , Acetazolamide , Animals , Humans , Pancreaticoduodenectomy , Stents , SwineABSTRACT
OBJECTIVE: To evaluate the efficacy and tolerability of a self-expandable covered metallic stent in patients with malignant prostatic obstruction secondary to prostate cancer (PC). METHODS: We reviewed 22 cases of insertion of self-expandable covered metallic stents with barbs. Data were collected about PC status. Uroflowmetry variables, residual urine volume, International Prostate Symptom Score (IPSS), quality of life (QOL), and duration from stent insertion to removal were surveyed. These clinical parameters were compared before and after stent insertion. RESULTS: The patients with PC showed a mean age of 75.5 ± 6.5 years and mean 5.1 ± 1.9 Charlson comorbidity index. The average flow rate (2.4 ± 1.9 vs 5.9 ± 2.4 mL/s, P = .005), peak flow rate (6.9 ± 6.2 vs 14.1 ± 5.5 mL/s, P = .003), flow time (54.6 ± 29.1 vs 23.6 ± 13.7 s, P = .002), residual urine volume (178.7 ± 195.5 vs 7.0 ± 7.1 mL, P = .004), IPSS (26.2 ± 8.1 vs 8.0 ± 6.5 points, P = .001), and QOL (4.7 ± 1.3 vs 2.4 ± 2.1 points, P = .030) improved between before and after stent insertion, respectively. Pain was the most common complication, but 60% of the patients were managed without any intervention. There were hematuria, urinary retention, urinary frequency, obstruction, and urinary incontinence. However, there was no urinary tract infection due to the stent. The median time to stent removal was 5.7 months. CONCLUSIONS: The stent was maintained for about 6 months with improved objective and subjective outcomes. The patients with PC, who had a poor comorbidity index and advanced PC status showed a tolerable maintenance period. Self-expandable covered metallic stents can be used for PC patients with a short life expectancy and unsuitability for general anesthesia.
Subject(s)
Prostatic Neoplasms , Urethral Obstruction , Aged , Aged, 80 and over , Device Removal , Humans , Male , Prostatic Neoplasms/complications , Prostatic Neoplasms/surgery , Quality of Life , Stents/adverse effectsABSTRACT
OBJECTIVES: To develop an ex- vivo perfusion flow model using a bovine kidney for future testing of embolic agents in an inexpensive and easy way. METHODS: Six bovine adult kidneys were used for this study. Kidneys were cannulated and perfused via a roller pump. Three embolic agents, coils, Gelfoam, and a glue mixture of Histoacryl + Lipiodol, were deployed by targeting three secondary segmental arteries per kidney via a 5Fr catheter under fluoroscopic guidance. Cannulation time, success rate of segmental artery selection and embolic agent deployment, total operational time, and fluoroscopy dose were recorded. RESULTS: Average kidney weight was 0.752 +/- 0.094 kg. All six bovine kidneys were successfully cannulated in 21.6 min +/- 3.0 min. Deployment of coils and glue was achieved in every case (12/12); however, Gelfoam injection was not successful in one instance (5/6, 83%). Coil deployment demonstrated no embolic effect while Gelfoam and glue injections demonstrated decreased distal contrast filling post-embolization. Mean dose area product was 12.9 ± 1.8 Gy·cm2, fluoroscopy time was 10 ± 4 min and operational time was 27 ± 8 min. CONCLUSIONS: We describe the creation of an ex vivo bovine kidney flow model for the preclinical evaluation of different embolic materials. The flow model can be modified to provide extensive bench testing and it is a promising tool for hands -on training in basic and advanced embolization techniques .
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BACKGROUND: An intragastric satiety-inducing device (ISD) (Full Sense Device; Baker, Foote, Kemmeter, Walburn, LLC, Grand Rapids, MI) is a novel weight-loss device, which may induce satiety by applying continuous pressure on the gastric cardia. This study investigated the effect of the ISD on food intake and body weight gain in a rodent model. METHODS: Thirty-two male Sprague-Dawley rats (weight, 250-300 g) were randomly divided into four groups of eight individuals. Single-disk (SD) and double-disk (DD) group animals underwent peroral placement of a single- or double-disk ISD, respectively, under fluoroscopic guidance. The ISD comprised a 4 mm × 1.5 cm nitinol stent placed in the lower esophagus and one (single-disk) or two (double-disk) 2.5-cm-diameter star-shaped nitinol disks placed in the gastric fundus. Esophageal stent (ES) and sham-operated (SO) group animals underwent peroral placement of the ES part of the ISD and a sham operation, respectively. RESULTS: Food intake was significantly different among the four groups over the 4-week study period (P < 0.001); food intake was significantly lower in the SD and DD groups than in the SO group (P = 0.016 and P = 0.002, respectively) but was not significantly different between the SD and DD groups (P > 0.999) and between the ES and SO groups (P = 0.677). Body weight was significantly different among the four groups by the end of the study period (P < 0.001); body weight was significantly lower in the DD group than in the SD, ES, and SO groups (P = 0.010, P < 0.001, and P < 0.001, respectively) and in the SD group than in the SO group (P = 0.001), but it was not significantly different between the ES and SO groups (P = 0.344). CONCLUSION: ISD reduced food intake and suppressed body weight gain in a rodent model.
Subject(s)
Eating , Physiology/instrumentation , Satiation , Stomach/physiology , Weight Gain/physiology , Animals , Fasting/blood , Ghrelin/blood , Male , Models, Animal , Rats, Sprague-Dawley , RodentiaABSTRACT
PURPOSE: We aimed to develop a novel method for orthotopic colon cancer model, using tissue adhesive in place of conventional surgical method. MATERIALS AND METHODS: RFP HCT 116 cell line were used to establish the colon cancer model. Fresh tumor tissue harvested from a subcutaneous injection was grafted into twenty nude mice, divided into group A (suture method) and group B (tissue adhesive method). For the group A, we fixed the tissue on the serosa layer of proximal colon by 8-0 surgical suture. For the group B, tissue adhesive (10 µL) was used to fix the tumor. The mortality, tumor implantation success, tumor metastasis, primary tumor size, and operation time were compared between the two groups. Dissected tumor tissue was analyzed for the histology and immunohistochemistry. Also, we performed tumor marker analysis. RESULTS: We observed 30% increase in graft success and 20% decrease in mortality, by using tissue adhesive method, respectively. The median colon tumor size was significantly increased by 4 mm and operation time was shortened by 6.5 minutes. The H&E showed similar tumor structure between the two groups. The immunohistochemistry staining for cancer antigen 19-9, carcinoembryonic antigen, cytokeratin 20, and Ki-67 showed comparable intensities in both groups. Real-time quantitative reverse transcription analysis showed eight out of nine tumor markers are unchanged in the tissue adhesive group. Western blot indicated the tissue adhesive group expressed less p-JNK (apototic marker) and more p-MEK/p-p38 (proliferation marker) levels. CONCLUSION: We concluded the tissue adhesive method is a quick and safe way to generate orthotopic, colon cancer model.
Subject(s)
Colonic Neoplasms/pathology , Tissue Adhesives , Xenograft Model Antitumor Assays/instrumentation , Animals , Biomarkers, Tumor/analysis , Colonic Neoplasms/diagnosis , HCT116 Cells , Humans , Male , Mice , Mice, Nude , Sutures , Xenograft Model Antitumor Assays/methodsABSTRACT
c-Met, as a receptor expressed on the cell membrane, contributes to the growth and metastasis of tumors, as well as angiogenesis, mainly through the hepatocyte growth factor (HGF)/c-Met axis during tumor progression. Although several c-Met inhibitors, including small molecules and monoclonal antibody inhibitors, are currently being investigated, their clinical outcomes have not been promising. Development of an antibody-drug conjugate (ADC) against c-Met could be an attractive therapeutic strategy that would provide superior antitumor efficacy with broad-spectrum c-Met expression levels. In the present study, site-specific drug-conjugate technology was applied to develop an ADC using the human-mouse cross-reactive c-Met antibody and a prodrug pyrrolobenzodiazepine (PBD). The toxin payload was uniformly conjugated to the light-chain C-terminus of the native cIRCR201 antibody (drug-to-antibody ratio = 2), as confirmed using LC-MS. Using a high-throughput screening system, we found that cIRCR201-dPBD exhibited varying sensitivities depending on the expression levels of c-Met, and it induced receptor-mediated endocytosis and toxin-mediated apoptosis in 47 different cancer cell lines. cIRCR201-dPBD also showed significant antitumor activity on the MET-amplified cancer cells using in vivo xenograft models. Therefore, cIRCR201-dPBD could be a promising therapeutic strategy for tumors with c-Met expression.
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BACKGROUND AND AIMS: Minimally invasive therapies for obesity are a bridge between lifestyle interventions and bariatric surgery. We developed a novel device to reduce weight gain rate and evaluated its safety and efficacy in juvenile pigs. METHODS: The intragastric satiety-inducing device (ISD) comprises a self-expandable esophageal metal stent connected to a star-shaped disc placed in the stomach fundus. Eight juvenile pigs were randomized into ISD (n = 5) and control (n = 3) groups. Body weight and serum ghrelin hormone were monitored weekly for 6 weeks. One pig was followed up for 4 additional weeks (rebound pig) after ISD removal. Histological examination and immunohistochemistry for the interstitial cells of Cajal (ICCs) were performed. RESULTS: ISD placement was successful in all pigs. Two ISDs (40%) migrated at 4 and 5 weeks after placement. Weight gain rates were significantly lower in the ISD group than in the control group from week 1 to 6 but were higher in the rebound pig than in a control pig from week 7 to 10. Mean ghrelin hormone level was higher in the control group than in the ISD group from week 1 to 6. ISD induced reversible inflammatory changes in the esophagus and stomach fundus. The number of ICCs was lesser in ISD pigs than in control and rebound pigs. CONCLUSIONS: ISD placement is feasible and safe in juvenile pigs. It decreases weight gain rate but induces reversible inflammatory reaction and tissue hyperplasia. Its mechanism may be related to pressure exertion on the stomach fundus or gastric motility alteration.
Subject(s)
Bariatric Surgery , Obesity, Morbid , Animals , Obesity, Morbid/surgery , Pilot Projects , Satiation , Stents , Swine , Weight GainABSTRACT
Recent therapeutic strategies to suppress restenosis after biliary stent placement are insufficient. Here, we demonstrate the usefulness of a self-expandable metal stent (SEMS), a stent mesh coated with silver nanoparticles (AgNPs), for suppression of both stent-induced tissue hyperplasia and biliary sludge formation in the rabbit bile duct. The AgNP-coated SEMSs were prepared using a simple bio-inspired surface modification process. Then, the prepared SEMSs were successfully placed in 22 of 24 rabbits. Sludge formation in the AgNP-coated SEMS groups was significantly decreased compared to the control group on gross findings. Cholangiographic and histologic examinations demonstrated significantly decreased tissue hyperplasia in the AgNP-coated SEMS groups compared with the control group (p < 0.05 for all). There were no differences between the AgNP-coated SEMS groups (p > 0.05 for all). However, in the group coated with the greatest concentration of AgNPs (Group D), submucosal fibrosis was thicker than in the other AgNP-coated groups (p < 0.05 for all). The AgNP-coated metallic stent mesh significantly suppressed stent-induced tissue hyperplasia and biliary sludge formation in the rabbit bile duct. Taken together, the AgNP coating strategy developed in this study could be widely utilized in non-vascular medical devices for anti-bacterial and anti-inflammatory responses.
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Background: Acquired lymphedema is a common consequence of cancer surgery. Fibrosis is one of the main causes of chronic lymphedema since it hinders lymphatic regeneration and this causes a significant decrease in lymphatic flow and accumulation of excessive protein-rich fluid. The transforming growth factor-ß1 (TGF-ß1) signaling pathway is known in a process of wound repair and fibrosis. In our study, the purpose was to evaluate the efficacy of EW-7197, a peroral TGF-ß type I receptor kinase inhibitor, in treating acquired lymphedema. Methods and Results: For lymphedema mouse tail model, we used 10- to 12-week-old female C57BL/6 mice. The skin was circumferentially excised, making a circular band followed by cauterization of lymphatic collecting vessels. Two groups were made in this study: control and treatment. The treatment group (n = 12) received a solution consisting of 0.1 mL of artificial gastric juice and 20 mg/kg EW-7197 by gavage once daily. For evaluation, tail diameter measurement, fluorescence lymphography, and immunofluorescence images were used. EW-7197 treatment ameliorates acquired lymphedema in a mouse tail model by increasing lymphangiogenesis and interstitial flow of the lymphatics by inhibition of the fibrosis. The differences in maximal tail thicknesses between the control and treatment groups were statistically significant from 2 to 4 weeks after surgery. The treatment group showed a greater number of lymphatic vessels at the surgery site than the control group. The treatment group also showed more FITC coverage area at the surgery site. Conclusion: EW-7197 treatment ameliorates acquired lymphedema in a mouse tail model by increasing lymphangiogenesis and interstitial flow.
Subject(s)
Lymphatic Vessels , Lymphedema , Aniline Compounds , Animals , Disease Models, Animal , Female , Lymphangiogenesis , Mice , Mice, Inbred C57BL , Receptor, Transforming Growth Factor-beta Type I , Tail , Transforming Growth Factors , TriazolesABSTRACT
Stricture of pancreatic-enteric anastomoses is a major late complication of a pancreaticoduodenectomy for the treatment of a periampullary tumor and can lead to exocrine and endocrine insufficiency such as malnutrition and diabetes mellitus. We investigated the safety and efficacy of a biodegradable tubular stent (BTS) for preventing a pancreaticojejunostomy (PJ) anastomotic stricture in both a rat and porcine model. The BTS was manufactured using a terpolymer comprising poly p-dioxanone, trimethylene carbonate, and glycolide. A cohort of 42 rats was randomized into 7 groups of 6 animals each after BTS placement into the duodenum for the biodegradation assay. A total of 12 pigs were randomized equally into a control and BTS placement group. The effectiveness of the BTS was assessed by comparing radiologic images with histologic results. Surgical procedures and/or BTS placements were technically successful in all animals. The median mass losses of the removed BTS samples from the rat duodenum were 2.1, 6.8, 11.2, 19.4, 26.1, and 56.8% at 1, 2, 3, 4, 6, and 8 weeks, respectively. The BTS had completely degraded at 12 weeks in the rats. In the porcine PJ model, the mean luminal diameter and area of the pancreatic duct in the control group was significantly larger than in the BTS group (all p < 0.05). BTS placement thus appears to be safe and effective procedure for the prevention of PJ anastomotic stricture. These devices have the potential to be used as a temporary stent placement to treat pancreatic-enteric anastomoses, but further investigations are required for optimization in human.
Subject(s)
Absorbable Implants/veterinary , Anastomosis, Surgical/instrumentation , Anastomosis, Surgical/methods , Animals , Constriction, Pathologic/surgery , Disease Models, Animal , Male , Pancreas/surgery , Pancreatic Ducts/surgery , Pancreaticoduodenectomy/adverse effects , Pancreaticoduodenectomy/methods , Pancreaticojejunostomy , Postoperative Complications/surgery , Rats , Rats, Sprague-Dawley , Stents , SwineABSTRACT
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.
Subject(s)
Metal Nanoparticles , Stomach Neoplasms , Animals , Gold , Hot Temperature , Hyperplasia , Rats , Retrospective Studies , Stents , Treatment OutcomeABSTRACT
PURPOSE: To investigate the effect of prior chemotherapy on self-expanding metal stent (SEMS)-related complications in patients with locally advanced primary esophageal cancer. MATERIALS AND METHODS: Data from patients with locally advanced primary esophageal cancer who received SEMS placement with or without prior chemotherapy were retrospectively reviewed. Patients were grouped according to prior palliative therapy: group A (n = 41) had received SEMS only, and group B (n = 64) had received palliative chemotherapy prior to SEMS placement. Patients' age, stricture length, tumor location, and dysphagia score prior to SEMS placement were evaluated. The overall patient cohort had a median follow-up period of 129 days (range 11-463). Outcomes after SEMS placement, including technical and clinical success rates, the occurrence of complications, and overall survival, were compared. RESULTS: There were no significant differences between the two groups regarding patients' age, stricture length, tumor location, and dysphagia score prior to SEMS placement. SEMS placement was technically successful in all patients, with no procedure-related complications reported. Clinical success was achieved in 95.1% of patients in group A and 96.8% of patients in group B. The duration of stent patency was significantly shorter in group B [162 days; 95% confidence interval (CI) 126.6-198.4 vs. group A (339 days; 95% CI 258.8-419.3], p = 0.001. No significant differences were seen between the two groups regarding dysphagia score improvement [group A (3.15 ± 0.57 to 1.17 ± 0.83; p < 0.001) and group B (3.17 ± 0.80 to 1.14 ± 0.79; p < 0.001); p = 0.66], complications [group A (10/41), and group B (24/64); p = 0.094], or overall survival [the median and mean overall survival periods were 105 (95% CI 30-180) and 132 days (95% CI 97-167), respectively, in group A, and 126 (95% CI 88-164) and 156 days (95% CI 132-180), respectively, in group B; p = 0.592]. CONCLUSION: Prior chemotherapy did not increase the risk of complications following SEMS placement in patients with locally advanced esophageal cancer. SEMS patency was significantly longer in patients who did not receive chemotherapy prior to SEMS placement. LEVEL OF EVIDENCE: Level 4, Case Series.
Subject(s)
Esophageal Neoplasms/drug therapy , Palliative Care , Self Expandable Metallic Stents , Aged , Female , Fluoroscopy , Humans , Male , Middle Aged , Retrospective StudiesABSTRACT
Background: Radiation therapy has been applied to prolong the duration of lymphedema. This study aimed to evaluate the effect of radiation on the development of lymphedema in a mouse hindlimb model. Methods and Results: A total of 24 Balb/c mice underwent the right popliteal lymph node excision and the afferent and efferent lymphatics blockage. The radiation group (n = 12) received a single 20 Gy radiation 1 day before surgery in the right hindlimb of each mouse, whereas the control group (n = 12) only received surgery without radiation. The right hindpaw thickness of each mouse was measured twice a week for 4 weeks. Fluorescence microscopy images using fluorescein isothiocyanate-dextran tracer were obtained once weekly. Immunohistochemical (IHC) staining images using anti-lymphatic vessel endothelial hyaluronan receptor-1 (anti-LYVE-1) were obtained at 4 weeks after surgery. The radiation group showed significant increase in the thickness of the right hind paws from 0.5 to 2 weeks compared with the control group. As for fluorescence lymphography, the radiation group showed a lower number of regenerated lymphatics and more congestion of tracers in the operated limb at the surgery sites at 1, 2, 3, and 4 weeks after surgery. For the IHC analysis, the radiation group showed a lower number of regenerated lymphatics per high-power field at the surgery site than the control group. Conclusion: Radiation therapy transiently aggravated the extent of lymphedema by inhibiting regenerated lymphatics in a mouse hindlimb model. However, it did not prolong the duration of lymphedema because the cutaneous interstitial flow contributes to the lymphatic fluid clearance.
Subject(s)
Gamma Rays/adverse effects , Hindlimb/pathology , Lymphatic Vessels/pathology , Lymphedema/pathology , Animals , Biomarkers/metabolism , Dextrans/analysis , Dextrans/pharmacokinetics , Disease Models, Animal , Female , Fluorescein-5-isothiocyanate/analogs & derivatives , Fluorescein-5-isothiocyanate/analysis , Fluorescein-5-isothiocyanate/pharmacokinetics , Fluorescent Dyes/analysis , Fluorescent Dyes/pharmacokinetics , Gene Expression , Hindlimb/diagnostic imaging , Hindlimb/metabolism , Humans , Lymph Node Excision/methods , Lymph Nodes/surgery , Lymphatic Vessels/diagnostic imaging , Lymphatic Vessels/metabolism , Lymphedema/diagnostic imaging , Lymphedema/radiotherapy , Lymphography , Membrane Transport Proteins/genetics , Membrane Transport Proteins/metabolism , Mice , Mice, Inbred BALB CABSTRACT
PURPOSE: To prospectively evaluate the midterm outcomes of fluoroscopic eustachian tube (E-tube) balloon dilation by using a flexible guide wire in patients with obstructive E-tube dysfunction. MATERIALS AND METHODS: From October 2016 to September 2017, adult outpatients with persistent otitis media who were unable to perform the Valsalva maneuver were prospectively enrolled. The analysis included 32 E-tubes from 31 patients (18 women, 13 men; mean age, 47 years old, range 25-72 years). Participants underwent fluoroscopic E-tube balloon dilation with a 0.035-inch flexible guide wire and a 6- × 20-mm balloon catheter. Clinical examinations to check for the ability to perform the Valsalva maneuver and otomicroscopy were conducted at 1 week and then at 1, 3, 12, and 18 months after the procedure. RESULTS: Balloon dilation was technically successful in all E-tubes. The mean time required for the procedure was 6.9 minutes (range, 5.8-10.3 minutes). The Valsalva maneuver was successful in opening 25 of 32 E-tubes (78.1%) at 3 months after balloon dilation. During the median follow-up of 15.9 months, failure of the Valsalva maneuver occurred in 4 of 25 improved E-tubes (16%), yielding a 2-year patency rate of 84%. CONCLUSIONS: The fluoroscopic balloon dilation results were encouraging, and using a flexible guide wire for E-tube balloon dilation did not cause a false passage.