The current status of biodegradable stent to treat benign luminal disease

Therapeutic effect of decellularized extracellular matrix-based hydrogel for radiation esophagitis by 3D printed esophageal stent.

Esophageal cancer is a very deadly disease, killing more than 15,000 people in the United States annually. Almost 400,000 new cases happen in the worldwide every year. More than 50% esophageal cancer patients are diagnosed at an advanced stage when they need an esophageal stent to open the blocked esophagus for feeding and drinking. Esophageal stents have evolved in stages over the years. Current clinically used stents commonly include stainless steel or nitinol self-expandable metallic stent (SEMS) and self-expandable plastic stent (SEPS). There are many choices of different types of stents and sizes, with fierce competition among manufacturers. However, current stent technology, whether uncovered, partially covered, fully covered SEMS or SEPS, has their own advantages to solve the dysphagia, stricture, and fistula problems, but they also cause some clinical complications. The ideal stent remains elusive. New 3D printing technique may bring new promising potential to manufacturing personalized esophageal stents. Drug-eluting stents could be the new avenue to do more than just pry open a stricture or cover a defect in the esophageal lumen, a possibility of proving local anticancer therapy simultaneously. Additionally, the lack of esophageal cancer animal models also hinders the progress of stent development. This paper reviews these topics for a comprehensive understanding of this field. In a conclusion, the ultimate goal of the future esophageal stent would have multifunction to treat the underlying conditions and restore esophageal function to near normal.

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A Review of Self-Expanding Esophageal Stents for the Palliation Therapy of Inoperable Esophageal Malignancies.

Histone lysine-specific demethylase 1 (LSD1) expression has been shown to be significantly elevated in gastric cancer (GC) and may be associated with the proliferation and metastasis of GC. It has been reported that LSD1 repressed tumor immunity through programmed cell death 1 ligand 1 (PD-L1) in melanoma and breast cancer. The role of LSD1 in the immune microenvironment of GC is unknown.Expression LSD1 and PD-L1 in GC patients was analyzed by immunohistochemical (IHC) and Western blotting. Exosomes were isolated from the culture medium of GC cells using an ultracentrifugation method and characterized by transmission electronic microscopy (TEM), nanoparticle tracking analysis (NTA), sucrose gradient centrifugation, and Western blotting. The role of exosomal PD-L1 in T-cell dysfunction was assessed by flow cytometry, T-cell killing and enzyme-linked immunosorbent assay (ELISA).Through in vivo exploration, mouse forestomach carcinoma (MFC) cells with LSD1 knockout (KO) showed significantly slow growth in 615 mice than T-cell-deficient BALB/c nude mice. Meanwhile, in GC specimens, expression of LSD1 was negatively correlated with that of CD8 and positively correlated with that of PD-L1. Further study showed that LSD1 inhibited the response of T cells in the microenvironment of GC by inducing the accumulation of PD-L1 in exosomes, while the membrane PD-L1 stayed constant in GC cells. Using exosomes as vehicles, LSD1 also obstructed T-cell response of other cancer cells while LSD1 deletion rescued T-cell function. It was found that while relying on the existence of LSD1 in donor cells, exosomes can regulate MFC cells proliferation with distinct roles depending on exosomal PD-L1-mediated T-cell immunity in vivo.LSD1 deletion decreases exosomal PD-L1 and restores T-cell response in GC; this finding indicates a new mechanism with which LSD1 may regulate cancer immunity in GC and provides a new target for immunotherapy against GC. 

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LSD1 deletion decreases exosomal PD-L1 and restores T-cell response in gastric cancer

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Gastric cancer (GC) is a common tumour that affects humans worldwide, is highly malignant and has a poor prognosis. Small extracellular vesicles (sEVs), especially exosomes, are nanoscale vesicles released by various cells that deliver bioactive molecules to recipient cells, affecting their biological characteristics, changing the tumour microenvironment and producing long-distance effects. In recent years, many studies have clarified the mechanisms by which sEVs function with regard to the initiation, progression, angiogenesis, metastasis and chemoresistance of GC. These molecules can function as mediators of cell-cell communication in the tumour microenvironment and might affect the efficacy of immunotherapy. Due to their unique physiochemical characteristics, sEVs show potential as effective antitumour vaccines as well as drug carriers. In this review, we summarize the roles of sEVs in GC and highlight the clinical application prospects in the future.

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The role and application of small extracellular vesicles in gastric cancer

Biodegradable esophageal stents eliminate stent retrieval, but usually induce hyperplasia. This study investigated the properties of a novel biodegradable stent in vitro and in vivo. The degradation of the novel stent was observed in phosphate buffered saline (PBS) for 8 weeks. The radial forces, pH values, morphology, and retention rate of the intrinsic viscosity (R[η]) of the new biodegradable stent were all evaluated. In vitro, the pH values remained constant for 4 weeks and declined from weeks 4 to 8. The biodegradable threads degraded and ruptured at 6 weeks. Consequently, the radial force of the stent decreased to zero at that time. The curve of R[η] decreased with time linearly in PBS. To study the stents in vivo, we used a stricture model in which the middle esophagus of rabbits was damaged by alkali burn. Stents were inserted 2 weeks after injury and observed for 8 weeks. We assessed complications related to stent insertion, degradation of the stent, and survival of the rabbits. Two stents migrated, and one rabbit died. In the other rabbits, two stents degraded and moved into the stomach during the sixth week, five during the seventh week and one during the eighth week, respectively. One stent remained in position until the end of the study. In conclusion, our newly designed stent retained the strong radial force of self-expandable metal stents (SEMSs) and maintained the biodegradable properties of biodegradable (BD) stents.

A novel biodegradable esophageal stent: results from mechanical and animal experiments

AIM: To investigate a newly designed stent and its dilatation effect in a rabbit model of benign esophageal stricture.

METHODS: Thirty-four New Zealand white rabbits underwent a corrosive injury in the middle esophagus for esophageal stricture formation. Thirty rabbits with a successful formation of esophageal strictures were randomly allocated into two groups. The control group (n = 15) was implanted with a conventional stent, and the study group (n = 15) was implanted with a detachable “pieced” stent. The study stent (30 mm in length, 10 mm in diameter) was composed of three covered metallic pieces connected by surgical suture lines. The stent was collapsed by pulling the suture lines out of the mesh. Two weeks after stricture formation, endoscopic placement of a conventional stent or the new stent was performed. Endoscopic extraction was carried out four weeks later. The extraction rate, ease of extraction, migration, complications, and survival were evaluated.

RESULTS: Stent migration occurred in 3/15 (20%) animals in the control group and 2/15 (13%) animals in the study group; the difference between the two groups was not statistically significant. At the end of four weeks, the remaining stents were successfully extracted with the endoscope in 100% (11/11) of the animals in the study group, and 60% (6/10) of the animals in the control group; this difference was statistically significant (P < 0.05). There was no difference in the mean number of follow-up days between the control and study groups (25.33 vs 25.85). Minor bleeding was reported in five cases in the study group and four in the control group. There were no severe complications directly associated with stent implantation or extraction in either of the two groups.

CONCLUSION: In this experimental protocol of benign esophageal strictures, the novel “pieced” stent demonstrated a superior removal rate with a similar migration rate compared to a conventional stent.

Newly designed “pieced” stent in a rabbit model of benign esophageal stricture

Computed tomography (CT) has become an important technique for assessing skeletal muscle mass. Low skeletal muscle mass (LSMM) is considered an unfavorable factor for postoperative complications in...

CT assessment of preoperative nutritional status in gastric cancer: severe low skeletal muscle mass and obesity-related low skeletal muscle mass are unfavorable factors of postoperative complications

The radial force of esophageal stents may not completely change during extraction and therefore, the procedure of stent removal may cause tissue damage. The present study reports the manufacture of 2 novel detachable stents, which were designed to reduce tissue damage through their capacity to be taken or fall apart prior to removal and evaluated the supporting properties of these stents and the extent of local mucosal injury during their removal. The stents were manufactured by braiding, heat-setting, coating and connecting. The properties of the stents were evaluated by determining the following parameters: Expansion point, softening point, stent flexibility, radial compression ratio and radial force. A total of 18 rabbits with induced esophageal stricture were randomly assigned to 3 groups as follows: Detachable stent (DS) group, biodegradable stent (BS) group and control group. The stricture rate, complications, survival, degradation and stent removal were observed over 8 weeks. The stents of the DS and BS groups provided a similar supporting effect. The stricture rate, incidence of complications and survival were also similar between the 2 groups, while significant differences were noted between the DS and control groups and between the BS and control groups. In the BS group, the stents were degraded and moved to the stomach within 7 weeks (2 in 6 weeks and 3 in 7 weeks). The debris was extracted using biopsy forceps. In the DS group, all stents were easy to remove and 2 cases exhibited minor hemorrhage. In conclusion, the 2 types of novel detachable stent provided an equally efficient supporting effect in vitro and in vivo and may reduce the incidence of secondary injury during stent removal.

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Jin Liu

Papers

The role and application of small extracellular vesicles in gastric cancer

A novel biodegradable esophageal stent: results from mechanical and animal experiments

Newly designed “pieced” stent in a rabbit model of benign esophageal stricture

CT assessment of preoperative nutritional status in gastric cancer: severe low skeletal muscle mass and obesity-related low skeletal muscle mass are unfavorable factors of postoperative complications

Novel detachable stents for the treatment of benign esophageal strictures.