Metachronous recurrence frequently develops in patients with superficial esophageal squamous cell carcinomas (ESCCs) after curative endoscopic submucosal dissection (ESD), especially in those with multiple (>10) small Lugol-voiding lesions (LVLs) over the endoscopic background mucosa (ie, speckled pattern). We conducted a randomized controlled trial to investigate whether endoscopic radiofrequency ablation (RFA) for endoscopic background mucosal resurfacing (EBMR) can decrease the rate of metachronous neoplasia.

Patients who received curative ESD and whose Lugol staining showed a speckled pattern over the background mucosa were randomly assigned in a 1:1 ratio to receive either RFA (EBMR group) or endoscopic surveillance alone (control group). EBMR with RFA was performed with a balloon device for circumferential ablation of the total esophageal mucosa 2 to 3 months after ESD. The primary outcome was the metachronous recurrence of squamous neoplasia during a 5-year follow-up period. Secondary outcomes were major adverse events.

Of 112 patients screened, 30 were randomized to receive EBMR (n = 15) or surveillance (n = 15). The mean procedure time of EBMR was 30.7 minutes (range, 25-40). One patient developed post-RFA stenosis, which resolved after 3 sessions of endoscopic dilation. EBMR reduced the risk of metachronous recurrence (0% in the EBMR group vs 53% in the control group, P = .001), with a number needed to treat of 1.9. Reversal of the Lugol-staining speckled pattern to only a few LVLs occurred in all patients and persisted for at least 5 years in the ablation group.

In this randomized trial of patients with multiple small LVLs over the endoscopic background after curative ESD, EBMR with balloon-type RFA is a promising and safe procedure for preventing metachronous recurrence over 5 years of follow-up. (Clinical trial registration number: NCT03183115.).

Endoscopic submucosal dissection (ESD) is an effective technique for treating early esophageal cancer, and the prevention of postoperative esophageal stricture has emerged as a significant research topic. Zhou et al utilized an experimental minipig model to demonstrate that Kangfuxin (KFX) can improve postoperative esophageal stricture following ESD by inhibiting transforming growth factor-β1-driven fibrosis and the downstream fibrotic mediators Smad2/3. In this letter, we primarily discuss recent advancements in the treatment of esophageal stricture, the clinical applications of KFX, and the mechanisms involved in alleviating postoperative esophageal stricture, aiming to provide insights for advancing clinical practice and research in esophageal stricture after ESD.

Esophageal stricture is a prevalent condition affecting the digestive system, primarily marked by dysphagia and the obstruction of food passage through the esophagus. This narrowing of the esophageal lumen can significantly impact a person's ability to eat and drink comfortably, often leading to a decrease in nutritional intake and quality of life.

To explore the current research status and future trends of esophageal stricture through bibliometric analysis.

Literature on esophageal stricture from 2004 to 2023 was retrieved from the Web of Science Core Collection. Statistical analysis was performed using Excel, VOSviewer, CiteSpace, and RStudio. This study provides data on annual production trends, countries/regions, influential authors, institutions, journals, references, and keywords.

The study included 1485 publications written by 7469 authors from 1692 institutions across 66 countries/regions, published in 417 journals. The United States, China, and Japan are the major contributors to this field, with many quality papers. Song Ho-young, Diseases of the Esophagus, Gastrointestinal Endoscopy, and Mayo Clinic are the top authors, journals, co-cited journals, and institutions, respectively. The most frequent keywords are stent, endoscopy, management, etiology, and prevention; regenerative medicine, endoscopic injection, and autologous tissue transplantation are the latest research frontiers. These keywords reflect continuous advancements in technical innovation, treatment strategies, preventive measures in the esophageal stricture research field, and a sustained focus on improving patient prognosis. In contrast, the basic sciences were underrepresented.

This study provides an insightful analysis of the developments in the field of esophageal stricture over the past twenty years, with stent placement is currently a hot research topic.

Recent advances in endoscopic equipment have improved the diagnosis of gastrointestinal tumors. Image-enhanced endoscopy, including narrow-band imaging, blue light imaging, and linked color imaging, has unified magnifying observation classification methods and significantly improved the qualitative and quantitative diagnostic performance of gastrointestinal epithelial tumors. Endoscopic submucosal dissection (ESD), a minimally invasive treatment for early-stage gastrointestinal cancer, is widely used. The aging population in Japan has been gradually increasing. Despite this, ESD has shown good outcomes in older adults. However, long-term prognostic analyses should take into account the high mortality rate from other illnesses. Prognostic indicators such as the Charlson Comorbidity Index (CCI) and the Prognostic Nutrition Index (PNI) should be used to determine whether ESD should be performed. Even in cases of noncurative resection, follow-up without additional surgical resection is an option if there are other comorbidities that affect the prognosis.

In this editorial, we explored currently available strategies for reducing the occurrence of esophageal strictures following circumferential endoscopic submucosal dissection. This manuscript provided a comprehensive overview of the various strategies including recent insights from Wang et al. To this end, stenosis-related symptoms such as dysphagia and vomiting can severely affect a patient's quality of life. Therefore, we assess the efficacy of both reactive and proactive measures, ranging from traditional approaches like endoscopic balloon dilation and steroid administration to more advanced techniques, including tissue engineering and polyglycolic acid sheet placement. However, no single treatment has shown high efficacy, particularly for resections involving the entire circumference. Despite these shortcomings, the combination of different strategies may improve patient outcomes, although further large-scale studies are needed for validation.

Endoscopy is the gold standard for diagnosis of oesophageal cancer and its precursor lesions. Besides this, endoscopic treatment of these precursor lesions and early oesophageal cancer has been well evaluated and established. This includes dysplastic lesions associated with Barrett's oesophagus and early adenocarcinoma, as well as early squamous cell cancer of the oesophagus. The role of endoscopy for diagnosis and treatment of these lesions is summarised.

Esophageal stricture is one of the major complications after endoscopic submucosal dissection (ESD) of the esophagus. However, even with steroid prophylaxis, stenosis still occurs in up to 45% of patients. Accordingly, the aim of this study was to evaluate the efficacy and safety of steroid therapy in preventing esophageal strictures after ESD, as well as to assess the predictors of esophageal strictures after the application of steroids.

Between February 2018 and March 2023, 207 patients who underwent esophageal ESD at Southeast University Affiliated Zhongda Hospital were retrospectively enrolled. We evaluated stenosis rate, number of endoscopic dilations after ESD, the interval between the first endoscopic dilatation after ESD and explored risk factors for strictures after steroid prophylaxis.

In the control group, the oral steroids group, and the combined group, the stenosis rates were 83/87 (95.4%), 44/53 (83.0%), and 56/67 (83.6%), respectively; the number of endoscopic dilations were 3.43 (±2.22), 2.34 (±2.17), and 1.52 (±1.25), respectively; the time intervals between first endoscopic dilation and ESD procedure were 38.36 (±6.87), 68.18 (±9.49), and 96.82 (±8.41) days, respectively; all these indicators were significantly better in the oral and combined groups than in the control group (p < 0.05). Multivariate analysis identified lesion circumference ≥ 5/6th and submucosal injection of solution were two independent factors on esophageal stricture formation (p < 0.05).

Steroid prophylaxis is effective and safe in preventing esophageal stenosis. Moreover, lesion circumference and submucosal injection of sodium hyaluronate were two independent factors on esophageal stricture formation even with steroids administration.

This study aims to compare the effectiveness and safety of traditional endoscopic submucosal dissection (ESD), endoscopic submucosal tunneling dissection (ESTD), and endoscopic submucosal dissection with C-shaped incision (ESD-C) in the treatment of superficial esophageal cancer and precancerous lesions, providing reference and guidance for the treatment of esophageal cancer.

A retrospective analysis was conducted on the clinical data of patients who underwent ESD (n = 96), ESTD (n = 103), and ESD-C (n = 98) for superficial esophageal cancer or precancerous lesions between January 2017 and December 2022. Through comparative analysis, the effectiveness and safety of the three surgical methods were evaluated, and the risk factors for postoperative esophageal stricture were explored.

In terms of total operative time and dissection time, the ESD group > ESTD group > ESD-C group; in terms of dissection speed, the ESD group < ESTD group < ESD-C group; in terms of dissection area, the ESD group < ESTD group and ESD-C group; and in terms of wound treatment time, the ESD group > ESTD group and ESD-C group. In terms of surgical outcomes, the en bloc resection rate was 100% in all three groups, with complete resection rates of 86.84%, 90.79%, and 88.16% in the ESD, ESTD, and ESD-C groups, respectively. The risk factors for postoperative esophageal stricture included dissection area, circumferential proportion of the lesion, and injury to the muscularis propria.

Among the three surgical approaches, ESD-C demonstrated superior performance in operative time, resection speed, and procedural efficiency. Increased circumferential involvement of the lesion, larger resection area, and greater injury to the muscularis propria were associated with a heightened risk of postoperative esophageal stricture.

Adipose-derived mesenchymal stem cells (ADSCs) exhibit superior immunomodulatory properties and have broad therapeutic applications. They induce macrophage M2 polarization for anti-inflammatory responses. Exosomes derived from ADSCs (ADSC-EXOs) exhibit biological functions similar to those of ADSCs but can circumvent the limitations associated with cellular injection therapies. Potent anti-inflammatory substances contained in exosomes include the glycoprotein MFGE8, the cytokines such as prostaglandin E2, IL-6, and IGF, as well as non-coding nucleotides (miR-451a, miR-23, miR-30d-5p, let-7, lncRNA DLEU2, circRps5, Circ-Ptpn4, and mmu_ circ_0001359). The anti-inflammatory and immunomodulatory properties of these exosomes provide new perspectives for therapeutic approaches for graft inflammation, bone healing, acute lung injury, kidney stones, myocardial infarction, and diabetes-related diseases. This review summarizes the contents and functions of ADSC-EXOs, outlines their properties and the characteristics of macrophage phenotypes, and emphasizes their impact on macrophage polarization and their contribution to immune-related diseases.

Endoscopic submucosal dissection (ESD) is currently the standard therapy for superficial esophageal cancer (SEC). However, postoperative mucosal defects often lead to esophageal stricture. Although steroid application is effective prophylaxis, the efficacy and safety of various steroid administration modes remain unclear. Thus, this study aimed to evaluate the efficacy and safety of different steroid administrations for SEC patients after ESD.

A search for relevant studies was conducted on China National Knowledge Infrastructure, Wanfang Database, PubMed, Embase, and Web of Science up to March 25, 2024. Treatment strategies were categorized into 4 groups: no prevention as control (CON), steroid injection (SI), oral steroid (OS), and SI combined with OS (SI+OS). A comparative meta-analysis was conducted to assess outcomes, including postoperative esophageal stricture rate and the number of endoscopic balloon dilation (EBD) sessions required after stricture.

A total of 25 studies, involving 1555 patients, were included. The surface under the cumulative rankings were as follows: SI+OS (98.9%) > OS (59.9%) > SI (41.2%) > CON (0.0%) in preventing postoperative esophageal stricture, and OS (76.9%) > SI+OS (62.1%) > SI (61.0%) > CON (0.0%) in the number of EBD sessions required. Forest plot results indicated that compared with the nonsteroid group, steroid interventions were associated with lower rates of postoperative stricture and fewer EBD sessions. Additionally, SI+OS was superior to SI or OS alone in preventing stricture, with no significant differences observed between different steroid administrations in terms of EBD sessions. The incidence of adverse reactions was <10% for all interventions, mostly mild and resolvable upon discontinuation.

This study suggests that combined administration appears preferable for preventing esophageal stricture in patients after ESD and that steroids could enhance stricture prognosis. However, owing to the lack of large-sample randomized controlled trials comparing different steroid administrations, more high-quality research is necessary to confirm these findings in the future.

Treatment of esophageal cancer in the remnant esophagus after esophagectomy is highly invasive, therefore, early detection and minimally invasive treatment are considered necessary. Consequently, we aimed to clarify the safety and efficacy of endoscopic submucosal dissection (ESD) for residual esophageal cancer compared to that for esophageal cancer in a normal cervical esophagus. This study involved 47 patients with 59 residual esophageal cancers and 92 patients with 107 cervical esophageal cancers in normal esophagus who underwent ESD between January 2008 and December 2023. Their clinicopathological findings and long-term outcomes were retrospectively collected and evaluated. The median tumor diameter was 13 mm, and the median procedure time was 31 minutes in remnant esophagus group, with no significant difference between the two groups. No serious complications such as perforation, massive intraoperative bleeding, and pneumonia were observed in the remnant group, except for one case of postoperative bleeding. The rates of complete resection and disease specific survival were not significantly different between two groups, with complete resection rate of 86.4% and 5-year disease-specific survival rate of 95.7% in the remnant esophagus group. No local recurrence was observed during the median observation period of 43 months in the remnant esophagus group. ESD for superficial cancer of the remnant esophagus showed a high complete resection rate without serious complications and good local-regional control with no evidence of local recurrence. This indicates that ESD is a safe and useful treatment for superficial cancer of the remnant esophagus.

Endoscopic submucosal dissection (ESD) has been widely used in the early neoplasia of the esophagus. However, postoperative esophageal stenosis is a big problem, particularly when a large circumferential proportion of esophageal mucosa is resected. Currently, there are several methods available to prevent esophageal stenosis after ESD, including steroid administration, esophageal stent implantation, and endoscopic balloon dilation (EBD). However, the therapeutic effects of these are not yet satisfactory. Stem cell-based therapies has shown promising potential in reconstructing tissue structure and restoring tissue function. In this study, we discussed the current strategies for preventing esophageal stenosis after ESD and perspectives of stem cell-based therapies for the prevention of esophageal stenosis.

Endoscopic submucosal dissection (ESD) is a reliable method to resect early esophageal cancer. Esophageal stricture is one of the major complications after ESD of the esophagus. Steroid prophylaxis for esophageal strictures, particularly local injection of triamcinolone acetonide (TA), is a relatively effective method to prevent esophageal strictures. However, even with steroid prophylaxis, stenosis still occurs in up to 45% of patients. Predicting the risk of stenosis formation after local TA injection would enable additional interventions in risky patients.

To identify the predictors of esophageal strictures after steroids application.

Patients who underwent esophageal ESD and steroid prophylaxis and who were comprehensively assessed for lesion- and ESD-related factors at Southeast University Affiliated Zhongda Hospital between February 2018 and March 2023 were included in the study. The univariate and multivariate regression analyses were conducted to identify the predictors of stricture among patients undergoing steroid prophylaxis.

A total of 120 patients were included in the analysis. In the oral prednisone and oral prednisone combined with local tretinoin injection groups, the stenosis rates were 44/53 (83.0%) and 56/67 (83.6%), respectively. Among them, univariate analysis showed that the lesion circumference (P = 0.01) and submucosal injection solution (P = 0.04) showed significant correlation with the risk of stenosis formation. Logistic regression analyses were then performed using predictors that were significant in the univariate analyses and combined with known predictors from previous reports, such as additional chemoradiotherapy and tumor location. We identified a lesion circumference < 5/6 (OR = 0.19; P = 0.02) and submucosal injection of sodium hyaluronate (OR = 0.15; P = 0.03) as independent predictors of on esophageal stricture formation.

Steroid prophylaxis effectively prevents stenosis. Moreover, the lesion circumference and submucosal injection of sodium hyaluronate were independent predictors of esophageal strictures. Additional interventions should be considered in high-risk patients.

Endoscopic submucosal dissection (ESD) is a widely utilized treatment for early esophageal cancer. However, the rising incidence of postoperative esophageal stricture poses a significant challenge, adversely affecting patients' quality of life and treatment outcomes. Developing precise predictive models is urgently required to enhance treatment outcomes.

This study retrospectively analyzed clinical data from 124 patients with early esophageal cancer who underwent ESD at Ningbo Medical Center Lihuili Hospital. Patients were followed up to assess esophageal stricture incidence. Binary logistic regression analysis was used to identify factors associated with post-ESD esophageal stricture. A novel nomogram prediction model based on Systemic Immune-inflammation Index (SII) was constructed and evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA).

ROC curve analysis showed that the optimal value of SII for predicting esophageal stricture was 312.67. Both univariate and multivariate analyses identified lesion infiltration depth (< M2 vs. ≥ M2, p = 0.002), lesion longitudinal length (< 4 cm vs. ≥ 4 cm, p = 0.008), circumferential resection range (< 0.5, 0.5-0.75, ≥ 0.75, p = 0.014), and SII (< 312.67 vs. ≥ 312.67, p = 0.040) as independent risk factors for post-ESD esophageal stricture. A novel nomogram prediction model incorporating these four risk factors was developed. Validation using ROC curve analysis demonstrated satisfactory model performance, while calibration curves indicated good agreement between model-predicted risk and observed outcomes.

We successfully constructed a novel nomogram prediction model based on SII, which can accurately and intuitively predict the occurrence of esophageal stricture after ESD, providing guidance for clinicians and improving treatment outcomes.

Background and study aims Endoscopic submucosal dissection (ESD) is sometimes challenging because of stenosis and scarring. We examined the use of an ultrathin endoscope for esophageal ESD, which is difficult using conventional endoscopes. Patients and methods A designated transparent hood and ESD knife for ultrathin endoscopes have been developed and clinically introduced. Esophageal ESD was performed on 303 lesions in 220 patients in our hospital from February 2021 to February 2023. Of them, an ultrathin endoscope was used on 26 lesions in 23 cases. The safety and utility of an ultrathin endoscope in esophageal ESD were retrospectively verified. Results All 26 lesions were resected en bloc, and serious complications such as perforation, massive bleeding, or pneumonia, were not observed. Lesions were found on the anal side of the stenosis and over the scarring in 38.6% (10/26) and 50% (13/26) of participants, respectively. Moreover, 46.2% of participants (12/26) had lesions on the cervical esophagus. The total procedure time was 64.1 ± 37.7 minutes, but the average time from oral incision to pocket creation was 121.2 ± 109.9 seconds. Conclusions Ultrathin endoscopes may be useful for difficult esophageal ESD.

This study aimed to investigate the utility of intensive triamcinolone acetonide (TA) injections after extensive esophageal endoscopic submucosal dissection (ESD).

This retrospective study included 27 lesions in 27 consecutive patients who underwent ESD (ulcers encompassing ≥3/4 of the esophageal circumference) and received TA injections without oral steroid administration. Groups A and B included patients undergoing ESD with and without complete circumferential resection, respectively. All patients received TA injections (100 mg/session) immediately after ESD. In Group A, weekly based TA injections were performed until near-complete ulcer epithelialization. In Group B, patients did not receive additional injections or received weekly or biweekly TA injections. The primary outcome was stricture rate, and the secondary outcomes were the proportion of patients requiring endoscopic balloon dilation (EBD) and the number of TA injections.

Group A included 7 lesions, and Group B included 20 lesions. The median (range) tumor lengths were 40 (30-90) and 45 (30-110) mm in Groups A and B, respectively. In Group A, the median circumferential resection diameter was 40 (20-80) mm. The stricture rate and the proportion of patients requiring EBD were 0 (0%) in Group A and 1 (5.0%) in Group B. The number of TA injection sessions was significantly higher in Group A than in Group B (8 [5-25] vs 1.5 [1-3]; p < 0.001).

Intensive weekly or biweekly based TA injections might aid in preventing post-ESD stricture and the need for EBD in patients undergoing extensive resection involving the entire esophageal circumference.

Endoscopic radiofrequency ablation (RFA) has shown good efficacy and safety in eradicating flat-type early esophageal squamous cell neoplasia (ESCN). However, post-RFA stricture is still a major concern, especially when treating ultralong-segment ESCNs. The aim of this study was to investigate the efficacy and safety of oral prednisolone to prevent post-RFA stricture.

We prospectively enrolled 48 patients treated with balloon-type RFA who had Lugol-unstained or mosaic-like flat-type ESCNs with an expected treatment area of >10 cm. Oral prednisolone was started at a dose of 30 mg/day on the third day after RFA and continued for 4 weeks. The results were compared with an historical control group of 25 patients who received RFA without oral steroids. The primary endpoint was the frequency of post-RFA stricture. Secondary endpoints were the number of balloon dilation sessions and adverse event rate.

No significant differences were found in the worst pathology grade at baseline and length of unstained lesions between the 2 groups. The complete response rates after 1 session of RFA were 73% and 72%, respectively. Compared with the control group, the oral prednisolone group had a significantly lower stricture rate (4% [2/48 patients] vs 44% [11/25 patients]; P < .0001) and a lower number of balloon dilation sessions (median, 0 [range, 0-4] vs 6 [range, 0-10]). Two cases of asymptomatic candida esophagitis occurred in the study group, but no severe adverse effects.

Oral prednisolone may offer a useful and safe preventive option for post-RFA stricture in ultralong ESCNs. (Clinical trial registration number: NCT05768282.).

Autologous oral mucosal epithelial cell sheet (AOMECS) transplantation has recently been applied in human patients to prevent postprocedural stenosis following endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma. However, the long-term safety of AOMECS transplantation remains unclear. We evaluated the long-term outcomes of 10 patients who participated in a clinical trial of AOMECS transplantation after esophageal ESD. Additionally, we assessed the local DNA damage response in the esophageal epithelium using p53 binding protein 1 (53BP1) immunofluorescence in post-AOMECS biopsy specimens. The median follow-up period was 118.5 months (range: 46-130 months). Two patients developed primary esophageal cancer near the AOMECS site and successfully underwent additional ESD. One patient developed lymph node metastasis and underwent chemotherapy. None of the patients died from the original disease, although one patient died from unrelated causes. The rate of abnormal 53BP1 nuclear foci, indicative of increased genome instability, increased with the progression of neoplasia in patients post AOMECS. Our case series suggests that AOMECS transplantation provides an acceptable long-term prognosis and 53BP1 foci may serve as a useful marker for assessing DNA instability in the post-AOMECS esophageal epithelium.

Esophageal stricture caused by fibrosis is a serious complication after esophageal Endoscopic submucosal dissection (ESD). Myofibroblasts play a crucial role in esophageal fibrosis, so inhibiting activated myofibroblasts is a promising approach for treating esophageal fibrosis. β-Elemene, a natural product with anti-tumor and anti-fibrotic properties, has not been thoroughly examined in esophageal fibrosis. Additionally, fibroblast activation protein (FAP) and PTEN-PI3K/AKT signaling pathway are both notably linked to fibrotic diseases. Therefore, we investigated the potential mechanisms of β-elemene in esophageal fibrosis by treating primary human esophageal granulation fibroblasts (PHEGFs) with gradient concentrations of β-elemene. Our findings demonstrated that β-elemene inhibited the activity of PHEGFs in a dose-dependent manner, accompanied by downregulation of FAP, p-PI3K, and p-AKT protein expression, along with upregulation of p-PTEN protein expression. In addition, we substantiated the potential correlation between FAP and the PTEN-PI3K/AKT signaling pathway by establishing models of FAP overexpression and silencing. These results provide a new perspective on the potential mechanism of β-elemene in relieving esophageal fibrosis and offer novel therapeutic strategies for managing post-esophageal ESD stricture in clinical practice.

Self-expandable metallic stents (SEMSs) can be used to treat esophageal stricture after circumferential endoscopic submucosal dissection (ESD), but its efficacy and placement timing remain to be determined. In this study, the treatment time and number of dilatations were compared between the SEMS placement group and the balloon dilatation (BD) group to clarify the efficacy and placement time of SEMSs in the treatment of esophageal stricture after circumferential esophageal ESD.

This was a retrospective cohort study. Patients with esophageal stricture after circumferential ESD between January 2015 and January 2020 were included. Data on the patients' demographic characteristics, esophageal lesion-related factors, esophageal stricture occurrence, and measures taken to treat the stricture were collected. The primary outcome was the treatment time, and the secondary outcome was the number of dilatations.

The total number of dilatations was 30 in the SEMS group and 106 in the BD group. The average number of dilatations in the SEMS group (1.76 ± 1.64) was significantly lower than that in the BD group (4.42 ± 5.32) (P = 0.016). Among the patients who underwent SEMS placement first had a shorter treatment time (average 119 days) than those who underwent BD first (average 245 days) (P = 0.041), and the average number of dilatations inpatients who underwent SEMS placement first (0.71 ± 1.07) was significantly lower than that in the patients who underwent BD first (2.5 ± 1.54).

SEMSs were more efficient in the treatment of esophageal stricture in a cohort of patients after circumferential esophageal ESD.

Endoscopy is the gold standard for diagnosis of oesophageal cancer and its precursor lesions. Besides this, endoscopy treatment of these precursor lesions and early oesophageal cancer has been well evaluated and established. This includes dysplastic lesions associated with Barrett's oesophagus and early adenocarcinoma, as well as early squamous cell cancer of the oesophagus. The role of endoscopy for diagnosis and treatment of these lesions is summarised.

Early-stage esophageal cancer is primarily treated by endoscopic submucosal dissection (ESD). However, extensive mucosal dissection creates a significant risk of postoperative esophageal stricture. Clinically, postoperative stricture can be prevented by glucocorticoids; however, there are drawbacks to both systemic and local administration of glucocorticoids, and improving drug administration methods is crucial. In this study, we developed a chitosan-based thermosensitive hydrogel for triamcinolone (TA) delivery. Our results indicated that the hydrogel remains liquid at low temperatures and can be injected into the esophageal wound site through an endoscopic biopsy channel. Upon reaching body temperature, the hydrogel undergoes spontaneous gelation and firmly adheres to the wound surface. The liquid phase enables convenient and precise delivery, while the gel phase achieves remarkable adhesion, tensile strength, and resistance to degradation. Moreover, the hydrogel exhibited an extended release duration of >10 days when loaded with a 10 mg dose. In vitro studies revealed that the hydrogel suppresses the proliferation and fibrogenesis of human scar fibroblasts (HKF). In a rat skin dermal defect model, the hydrogel attenuated keloid formation during the healing process. Consequently, the chitosan-based thermosensitive hydrogel developed in this study for triamcinolone delivery may be an effective tool for preventing post-ESD esophageal stricture.

Endoscopic submucosal dissection (ESD) is carving out an increasing role in the treatment of esophageal neoplasia in the Western world. Contrary to Asia, most esophageal cancers in North America are associated with Barrett's esophagus. Patients with circumferential advanced neoplasia were previously managed by esophagectomy, but an increased experience with ESD has allowed for an endoscopic alternative. We present our experience with complete circumferential esophageal ESD at a North American referral center.

All patients undergoing 100% circumferential esophageal ESD between October 2016 and January 2023 at a single tertiary care center in Canada were included in the cohort. Demographics, procedural data, and lesion characteristics are presented in this series.

Eleven patients underwent 100% circumferential esophageal ESD during this period for Barrett's neoplasia. All patients had technically successful procedures with en-bloc resection. Nine patients (82%) had R0 resections, defined as clear lateral and deep margins on histologic examination. Two patients had positive deep margins on histologic examination and proceeded to esophagectomy. Seven patients (64%) had adenocarcinoma on the final pathology, of which 6 (86%) had upstaging from their initial biopsy sampling results. The median area of resected specimen was 48 cm2 (interquartile range [IQR], 26-80), and the median procedure time was 231 minutes (IQR, 180-246). Procedural efficiency was 4.0 min/cm2 (IQR, 2.7-5). Two patients (18%) developed refractory strictures after the procedure, which were endoscopically managed to resolution.

Multifocal dysplastic Barrett's esophagus remains a challenging entity to treat. Circumferential ESD is a possible therapeutic option, with high procedural success and a low rate of adverse outcomes. This should be balanced against the risk of stricture development, as the optimal postprocedural prophylaxis regimen is investigated.

The primary treatment for early esophageal cancer and precancerous lesions is endoscopic submucosal dissection (ESD). However, this approach leads to a high incidence of postoperative esophageal stenosis, which can significantly impact a patient's quality of life. While various methods are available to prevent post-ESD esophageal stenosis, their effectiveness varies. Therefore, this study aims to provide an overview of the currently employed methods for preventing post-ESD esophageal stenosis in clinical practice in view of assisting clinical practitioners.

This study aimed to establish a rat model that simulates benign esophageal strictures induced by endoscopic submucosal dissection (ESD).

Sixteen male Sprague-Dawley rats were randomly divided into mucosal resection (n = 8) and sham-operated groups (n = 8). The rats in the mucosal resection group underwent a 5-mm three-fourths mucosal resection by way of a 3-mm incision in the distal esophagus under direct visualization via laparotomy. Rats in the sham-operated group underwent a 3-mm incision of the muscularis propria layer in the distal esophagus via laparotomy without mucosal resection. Dysphagia score, weight gain, mucosal constriction rate, and histology were evaluated 2 weeks after surgery.

Technical success was achieved in all the animals. One rat in the mucosal resection group died of infection, and no other complications were observed. Weight gain (P < 0.001) and luminal diameter derived from the esophagograms (P < 0.001) were significantly lower in the mucosal resection group than those in the sham-operated group. Dysphagia score (P < 0.001) and mucosal constriction rate (P < 0.001) were significantly higher in the mucosal resection group than those in the sham-operated group. The inflammation grade (P = 0.002), damage to the muscularis propria (P < 0.001), number of nascent microvessels (P = 0.006), and degree of α-SMA positive deposition (P = 0.006) were significantly higher in the mucosal resection group.

A rat model of benign esophageal stricture induced by ESD was successfully and safely established by mucosal resection.

Endoscopic treatment of early oesophageal squamous cell carcinoma is widely accepted. ESD (Endoscopic Submucosal Dissection), which allows en bloc resection regardless of size, provides resected specimens that facilitate histological evaluation of curability. In the histological investigation, the determination of tumor depth, lymphovascular involvement, and lateral and vertical margins play a great role in the assessment of curability. The diagnosis of lymphovascular invasion, in particular, is enhanced by the addition of immunostaining. The long-term outcome of ESD is comparable to that of oesophagectomy, and ESD may be the first-line treatment for early-stage oesophageal cancer due to its fewer complications. Surveillance after curative resection is also imperative because oesophageal cancer is often characterized by the concept of field cancerization, which results in metachronous multiple primary lesions.

Esophageal strictures significantly impair patient quality of life and present a therapeutic challenge, particularly due to the high recurrence post-ESD/EMR. Current treatments manage symptoms rather than addressing the disease's etiology. This review concentrates on the mechanisms of esophageal stricture formation and recurrence, seeking to highlight areas for potential therapeutic intervention.

A literature search was conducted through PUBMED using search terms: esophageal stricture, mucosal resection, submucosal dissection. Relevant articles were identified through manual review with reference lists reviewed for additional articles.

Preclinical studies and data from animal studies suggest that the mechanisms that may lead to esophageal stricture include overdifferentiation of fibroblasts, inflammatory response that is not healed in time, impaired epithelial barrier function, and multimethod factors leading to it. Dysfunction of the epithelial barrier may be the initiating mechanism for esophageal stricture. Achieving perfect in-epithelialization by tissue-engineered fabrication of cell patches has been shown to be effective in the treatment and prevention of esophageal strictures.

The development of esophageal stricture involves three stages: structural damage to the esophageal epithelial barrier (EEB), chronic inflammation, and severe fibrosis, in which dysfunction or damage to the EEB is the initiating mechanism leading to esophageal stricture. Re-epithelialization is essential for the treatment and prevention of esophageal stricture. This information will help clinicians or scientists to develop effective techniques to treat esophageal stricture in the future.

Methods to prevent esophageal stenosis (ES) after endoscopic submucosal dissection (ESD) for superficial esophageal squamous cell carcinoma (ESCC) have received increasing attention. Although steroid administration is a prophylactic treatment, the risk factors for ES during prophylactic steroid therapy remain unknown. Therefore, this study aimed to retrospectively evaluate the risk factors for refractory ES in patients administered prophylactic steroids after ESD for ESCC.

Among 795 patients with ESCC (854 lesions), 180 patients (211 lesions) administered local triamcinolone acetonide (TrA) and/or oral prednisolone were recruited for this study. We compared the total number of endoscopic balloon dilatation (EBD) procedures performed for post-ESD ES and clinical findings (tumor size, ESD history or chemoradiation therapy [CRT], entire circumferential resection, muscle layer damage, supplemental oral prednisolone administration, EBD with TrA injection, and additional CRT) between patients with refractory and non-refractory ES. EBD was continued until dysphagia resolved. We categorized cases requiring ≥ 8 EBD procedures as refractory postoperative stenosis and divided the lesions into two groups.

Multivariate logistic regression analysis revealed that factors such as ESD history, CRT history, tumor size, and entire circumferential resection were independently associated with the development of refractory ES. The withdrawal rates of EBD at 3 years were 96.1% (52/53) and 58.5% (39/59) in the non-refractory and refractory groups, respectively.

Our data suggest that entire circumferential resection and CRT history are risk factors for refractory post-ESD ES in ESCC, even with prophylactic steroid administration.

Esophageal stricture is a major complication after esophageal endoscopic submucosal dissection (ESD) and when the mucosal defect exceeds 3/4 of the circumference. Various preventive methods have been reported to prevent stenosis. However, in the case of circumferential ESD, there is no way to prevent luminal stenosis effectively. This retrospective study aimed to evaluate the efficacy of 20-French nasogastric tubes (NGT) combined with oral steroids for the prevention of esophageal stricture after endoscopic submucosal dissection.

Between January 2012 and December 2021, we enrolled 57 patients with post-ESD mucosal defects exceeding 3/4 of the esophageal circumference. Of them, the initial seven patients received oral steroid therapy and the subsequent 50 patients received 20-French NGT placements combined with oral steroid therapy. We retrospectively evaluated the rates of strictures and refractory strictures and explored risk factors for strictures with 20-French NGT.

The overall esophageal stricture rate was 42.1% (24/57). In the noncircumferential group, the esophageal stricture rate in patients with only oral steroid to prevent esophageal stricture was 85.7% (6/7), while the esophageal stricture rate was only 4.3% (1/23) in those with 20-French NGT placements and oral steroid. All 27 patients with whole-circumferential resection received 20-French NGT placements. The stricture rate was 63.0% (17/27), and the refractory stricture rate was 17.6% (3/27).

Using a 20-French NGT placement combined with oral steroid administration is an easy and safe alternative to prevent esophageal stricture after ESD, especially for patients with noncircumferential mucosal defects. Further studies are needed to develop an effective stricture prevention method for post-ESD whole-circumferential mucosal defects of the esophagus.

Esophageal stricture caused by complete circumferential endoscopic submucosal dissection (ESD) of extensive esophageal squamous cell carcinoma (ESCC) is a major concern and can result in a low quality of life. Normal mucosa may remain within a complete circumferential lesion of ESCC in some cases. We herein report a case of ESCC in which a complete circumferential lesion was treated with ESD while leaving an island of normal mucosa within it. This case demonstrates that preserving areas of normal mucosa within lesions during complete circumferential ESD is not technically difficult and may be an effective measure for preventing esophageal stricture.

Local triamcinolone (TA) injection is widely used to prevent stricture formation after endoscopic submucosal dissection (ESD). However, stricture develops in up to 45% of patients despite this prophylactic measure. We therefore conducted a single-center prospective study to identify predictors of stricture after esophageal ESD and local TA injection.

Patients who underwent esophageal ESD and local TA injection and who were comprehensively assessed for lesion- and ESD-related factors were included in the study. Multivariate analyses were conducted to identify the predictors of stricture.

A total of 203 patients were included in the analysis. Multivariate analysis identified residual mucosal width ≤5 mm (odds ratio [OR], 29.0; P < .0001) or 6 to 10 mm (OR, 3.7; P = .04), history of chemoradiotherapy (OR, 5.1; P = .045), and tumor in the cervical or upper thoracic esophagus (OR, 3.8; P = .018) as independent predictors of stricture. Based on the ORs of the predictors, patients were stratified into 2 groups according to stricture risk: patients in the high-risk group (residual mucosal width ≤5 mm or 6-10 mm with another predictor) had a stricture rate of 52.5% (31 of 59 cases), and patients in the low-risk group (residual mucosal width ≥11 mm or 6-10 mm without other predictors) had a stricture rate of 6.3% (9 of 144 cases).

We identified predictors of stricture after ESD and local TA injection. Local TA injection prevented stricture formation after ESD in low-risk patients but was not sufficient to prevent stricture in high-risk patients. Additional interventions should thus be considered in high-risk patients. (University Hospital Medical Network Clinical Trials Registry number: UMIN 000028894.).

Postoperative stricture and refractory stricture are severe adverse events which occur after expansive esophageal endoscopic submucosal dissection (ESD). The aim of this study was to assess the efficacy of steroid injection, polyglycolic acid (PGA) shielding, and of additional steroid injection thereafter for the prevention of refractory esophageal stricture.

This is a retrospective cohort study of 816 consecutive cases of esophageal ESD performed between 2002 and 2021 at the University of Tokyo Hospital. After 2013, all patients with a diagnosis of superficial esophageal carcinoma covering over 1/2 the esophageal circumference underwent preventive treatment immediately after ESD with either "PGA shielding", "steroid injection", or "steroid injection + PGA shielding". Additional steroid injection was performed for high-risk patients after 2019.

The risk of refractory stricture was especially high in the cervical esophagus (OR 24.77, p = 0.002) and after total circumferential resection (OR 894.04, p < 0.001). "Steroid injection + PGA shielding" was the only method significantly effective in preventing stricture occurrence (OR 0.36; 95% CI 0.15-0.83, p = 0.012). This method also decreased the risk of refractory stricture (OR 0.38; 95% CI 0.10-1.28, p = 0.096), but additional steroid injection was the only significantly effective method for prevention of refractory stricture (OR 0.42; 95% CI 0.14-0.98, p = 0.029).

Combining steroid injection and PGA shielding is effective for preventing post-ESD stricture and refractory stricture. Additional steroid injection is a viable option for patients at high-risk for refractory stricture.

Endoscopic-assisted transoral surgery (TOS) for superficial cancer of the pharyngo-esophageal junction (PEJ) is risk of stricture, and therapeutic outcomes are unclear. This study aimed to evaluate clinical outcomes of endoscopic-assisted TOS for superficial PEJ cancers.

We retrospectively compared clinical outcomes of endoscopic-assisted TOS for superficial PEJ cancers (group A) and of other sites in the hypopharynx (group B).

The group A comprised 12 lesions in 12 patients, and group B comprised 198 lesions in 146 patients. Group A and group B exhibited en bloc resection rates of 100% and 99%. Median operative times were 82 and 37 min (p < 0.001). The frequency of stricture and local recurrence in group A was significantly higher in group B (42% vs. 1%, p < 0.001; 25% vs. 6%, p = 0.036). All adverse events could be managed with conservative treatments.

Endoscopic-assisted TOS is not ideal for treating superficial PEJ cancers compared to other sites.

Radiotherapy (RT) or chemoradiotherapy (CRT) are frequently selected as treatments for esophageal squamous cell carcinoma (ESCC). However, salvage treatment remains challenging when endoscopic resection is not indicated for residual or recurrent ESCC following RT or CRT. Recently, owing to the emergence of second-generation photodynamic therapy (PDT) using talaporfin sodium, PDT can be performed with less phototoxicity and therefore has regained popularity in the treatment of ESCC. In this study, the effectiveness and safety of second-generation PDT in patients with residual or recurrent ESCC following RT or CRT were examined. Local complete response (L-CR) rates, procedure-related adverse events, and prognosis were evaluated. In 12 patients with 20 ESCC lesions, the L-CR rates were 95.0%. Perforation, postoperative bleeding, and photosensitivity were not observed. Esophageal stricture following PDT developed in one patient, but this could be addressed using balloon dilation. During a median follow-up period of 12 (range, 3-42) months, the 3-year cause-specific survival rate was 85.7%. Even in patients with a Charlson comorbidity index score ≥ 3, the 2-year overall survival rates were 100%. In conclusion, PDT was an efficacious and a safe salvage treatment in patients with local residual or recurrent ESCC following RT or CRT.

Recent improvements in endoscopists' skills and technological advances have allowed endoscopic submucosal dissection (ESD) to become a standard treatment in general hospitals. As this treatment entails a high risk of accidental perforation or hemorrhage, therapeutic procedures and training methods that enable ESD to be conducted more safely and efficiently are constantly being developed. This article reviews the therapeutic procedures and training methods used to improve the safety and efficiency of ESD and describes the ESD training system used in a Japanese university hospital at which the number of ESD procedures has gradually increased in a newly established Department of Digestive Endoscopy. During the establishment of this department, the ESD perforation rate was zero among all procedures, including those conducted by trainees.

Nonthermal irreversible electroporation (NTIRE) is emerging as a promising tissue ablation technique. However, maintaining irreversible electroporation (IRE) electrodes against displacement during strong esophageal spasms remains an obstacle. The present study aimed to evaluate the efficacy and safety of newly designed balloon-type endoscopic IRE catheters. Six pigs were randomly allocated to each catheter group, and each pig was subjected to four ablations at alternating voltages of 1500 V and 2000 V. Esophagogastroscopy was performed during the IRE. The ability of balloon-type catheters to execute complete IRE with 40 pulses was assessed. The success rate was higher for the balloon-type catheter than that for the basket-type (12/12 [100%] vs. 2/12 [16.7%], p < 0.001). Following gross inspection and histologic analysis of the 1500-V vs. 2000-V balloon-type catheter revealed a larger mucosal damage area (105.3 mm2 vs. 140.8 mm2, p = 0.004) and greater damage depth (476 μm vs. 900 μm, p = 0.02). Histopathology of the ablated tissue revealed separated epithelium, inflamed lamina propria, congested muscularis mucosa, necrotized submucosa, and disorganized muscularis propria. Balloon-type catheters demonstrated efficacy, achieving full electrical pulse sequences under NTIRE conditions, and a safe histological profile below 2000 V (1274 V/cm). Optimal electrical conditions and electrode arrays pose ongoing challenges.

Subclinical stricture after esophageal endoscopic submucosal dissection (ESD) makes the detection and re-ESD of metachronous lesions difficult. This study aimed to investigate the effectiveness of prophylactic steroid use after esophageal ESD for mucosal defects with a circumference less than 75% for the prevention of symptomatic and asymptomatic stricture.

In 80 retrospectively enrolled patients, we collected paired endoscopic images of a mucosal defects immediately after resection and a scar thereafter. After calculating circumference by image analysis software, all patients were classified into three groups in reference to mucosal defect circumference (MDC; ≤ 50%, 50-75%, ≥ 75%). Frequency of steroid use and symptomatic stricture were compared, and in < 75% MDC patients, a degree of asymptomatic stricture with or without steroid was compared by calculating a scar contraction rate (SCR).

In the ≤ 50% (43 patients), 50-75% (27 patients) and ≥ 75% (10 patients) MDC groups, steroids were used in 12%, 59% and 100%, respectively, and symptomatic stricture occurred in 0%, 7% and 40%, respectively. In < 75% MDC patients, SCR in the steroid cohort was significantly lower than that in the nonsteroid cohort (42% vs. 65%, p = 0.002). No steroid-related adverse events occurred.

Steroid use even for mucosal defects with < 75% circumference appears effective for the reduction of the risk on both symptomatic and asymptomatic stricture after esophageal ESD.