CRB1-associated retinal degeneration is dependent on bacterial translocation from the gut.

The Crumbs homolog 1 (CRB1) gene is associated with retinal degeneration, most commonly Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP). Here, we demonstrate that murine retinas bearing the Rd8 mutation of Crb1 are characterized by the presence of intralesional bacteria. While normal CRB1 expression was enriched in the apical junctional complexes of retinal pigment epithelium and colonic enterocytes, Crb1 mutations dampened its expression at both sites. Consequent impairment of the outer blood retinal barrier and colonic intestinal epithelial barrier in Rd8 mice led to the translocation of intestinal bacteria from the lower gastrointestinal (GI) tract to the retina, resulting in secondary retinal degeneration. Either the depletion of bacteria systemically or the reintroduction of normal Crb1 expression colonically rescued Rd8-mutation-associated retinal degeneration without reversing the retinal barrier breach. Our data elucidate the pathogenesis of Crb1-mutation-associated retinal degenerations and suggest that antimicrobial agents have the potential to treat this devastating blinding disease.

Cost-efficient snare-assisted peroral endoscopic myotomy in comparison of conventional endoscopic knife for treatment of achalasia: results of a randomized controlled trial.

BACKGROUND: To date, the ideal endoscopic knife for peroral endoscopic myotomy (POEM) with good performance and cost-effectiveness is still under investigation. The present study was aimed to evaluate the efficacy, safety, and cost-effectiveness of snare-assisted POEM, compared with the conventional endoscopic knife approach. METHODS: From May 2017 to December 2018, patients with achalasia presenting for POEM without previous endoscopic or surgical therapy were prospectively recruited in this randomized controlled trial. Patients were randomly allocated to receive POEM using either the snare (snare group) or HookKnife (conventional group). The primary outcome was clinical success (Eckardt score ≤ 3) at 12-month follow-up, powered for noninferiority with a margin of -15%. The secondary outcomes included adverse events (AEs), procedure-related parameters, clinical outcomes, and cost-effectiveness. RESULTS: A total of 75 patients with similar baseline characteristics between the snare (N = 37) and conventional (N = 38) groups were included. Clinical success at 12-month follow-up was achieved in 94.6% of patients in the snare group and 92.1% of patients in the conventional group (difference, 2.5% [95% CI, -8.7% to 13.7%]; P < 0.001 for noninferiority). No severe AEs occurred in both groups. The use of snare is associated with comparable procedure time (40.6 minutes vs. 42.5 minutes, P = 0.337), a lower frequency of hemostatic forceps use (27.0% vs. 68.4%, P < 0.001), and lower hospital costs ($4271.1 vs. $5327.3, P < 0.001). The cost-effectiveness plane revealed that 96.9% of snare-assisted POEM procedures offered more cost-savings and health utility benefits. CONCLUSIONS: The snare-assisted POEM was noninferior to the conventional endoscopic knife approach in terms of clinical efficacy, with comparable safety outcomes and cost-effective benefits.

Peroral endoscopic myotomy for patients with achalasia with previous Heller myotomy: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Heller myotomy (HM) is considered the standard surgical treatment for patients with achalasia. However, approximately 10% to 20% of patients with achalasia have persistent or recurrent symptoms after HM that require further therapy. Several studies have reported the outcomes of peroral endoscopic myotomy (POEM) in these patients. We performed a systematic review and meta-analysis to evaluate the efficacy and safety of POEM in patients with achalasia with previous HM. METHODS: An electronic literature search of PubMed, Embase, and the Cochrane Library was conducted up to January 31, 2020. Studies evaluating the outcomes of POEM in patients with achalasia with previous HM were eligible for inclusion. The primary outcomes were the pooled rates of clinical success (defined as post-POEM Eckardt score ≤3), mean change in Eckardt score, lower esophageal sphincter pressure, and integrated relaxation pressure (IRP). The secondary outcomes were procedure-related adverse events (AEs) and incidence of postoperative GERD. RESULTS: A total of 9 studies involving 272 patients with achalasia were recruited in this review. POEM was successfully performed in 270 (99.3%) patients after previous HM. Clinical success was achieved in 90.0% (95% confidence interval [CI], 83.1%-96.8%) of patients. Eckardt score, lower esophageal sphincter pressure, and IRP were significantly lowered by 5.14 (95% CI, 4.19-6.09), 12.01 mm Hg (95% CI, 6.74-17.27), and 10.02 mm Hg (95% CI, 4.95-15.09), respectively. The pooled rates of postoperative symptomatic reflux, esophagitis, and abnormal pH monitoring were 36.9% (95% CI, 20.7%-53.1%), 33.0% (95% CI, 9.6%-56.4%), and 47.8% (95% CI, 33.4%-62.2%), respectively. Substantial heterogeneity was detected across all outcome measurements. Most of the AEs were self-limiting or managed conservatively. CONCLUSIONS: POEM is a safe and effective treatment for patients with achalasia with previous HM. Further data from prospective, controlled studies with long-term follow-up are needed to confirm these findings.

Independent and opposing associations of dietary phytosterols intake and PLCE1 rs2274223 polymorphisms on esophageal squamous cell carcinoma risk.

PURPOSE: This study was to evaluate the associations of dietary intake of total and specific phytosterols and risk of esophageal squamous cell carcinoma (ESCC) and to explore their joint effects with PLCE1 rs2274223 polymorphisms. METHODS: A population-based case-control study was conducted in a Chinese rural population and 856 eligible incident ESCC cases and 856 controls were included. A validated food frequency questionnaire was used to collect dietary consumption and PLCE1 rs2274223 polymorphisms were genotyped. Unadjusted and adjusted odds ratios (ORs) with 95% confidence interval (CI) were assessed via logistic regression model. RESULTS: When comparing the highest with lowest intake quartiles, ß-sitosterol, campesterol, stigmasterol, ß-sitostanol, campestanol, and total phytosterols were all associated with a decreased risk of ESCC, with adjusted ORs being 0.32 (95% CI 0.20-0.48), 0.18 (95% CI 0.11-0.27), 0.45 (95% CI 0.29-0.70), 0.13 (95% CI 0.08-0.20), 0.14 (95% CI 0.09-0.22) and 0.28 (95% CI 0.18-0.43), respectively. An exposure-response relationship was also observed for both total and five specific phytosterols (all P for trend < 0.001). In comparison to rs2274223 AA genotype, both GA genotype (OR: 1.47, 95% CI 1.16-1.85) and GG genotype (OR: 2.13, 95% CI 1.20-3.84) were associated with an increased risk of ESCC. However, no interaction was observed between total/specific phytosterols intake and rs2274223 polymorphisms. CONCLUSION: Higher dietary intake of total and five specific phytosterols was associated with a lower risk of ESCC, and the risk of ESCC increased with the increment of rs2274223 G allele. The negative association between phytosterols and ESCC risk was not modified by rs2274223 polymorphisms. Foods or supplements rich in phytosterols are a promising source for chemoprevention of ESCC, and still, clinical trials will be required in any specific case.

Antiperistaltic effect and safety of l-menthol oral solution on gastric mucosa for upper gastrointestinal endoscopy in Chinese patients: Phase III, multicenter, randomized, double-blind, placebo-controlled study.

OBJECTIVE: The topical antispasmodic agent l-menthol is commonly used for gastric peristalsis suppression during diagnostic upper gastrointestinal (GI) endoscopy. We evaluated the efficacy and safety of a single dose l-menthol solution in suppressing gastric peristalsis during upper GI endoscopy in Chinese patients. METHODS: In this phase III, multicenter, randomized, double-blind, placebo-controlled study (ClinicalTrials.gov: NCT03263910), 220 patients scheduled to undergo upper GI endoscopy at five Chinese referral centers received a single dose of either 160 mg of l-menthol (n = 109) or placebo (n = 111). Both treatments were sprayed endoscopically on the gastric mucosa. An independent committee evaluated the degree of gastric peristalsis (peristaltic score: grade 1-5). RESULTS: At baseline, the proportion of patients with grade 1 peristalsis (no peristalsis) did not differ between the groups. The proportion of patients with grade 1 peristalsis post-treatment was significantly higher in the l-menthol group (40.37%, 44/109) versus the placebo group (16.22%, 18/111; P < 0.001); the difference between the groups was 24.15% (95% confidence interval: 12.67%-35.63%; P < 0.001). In the l-menthol group, 61.47% of patients had grade 1 peristalsis after endoscopy versus 24.55% in the placebo group (P < 0.001). The ease of intragastric examination correlated significantly with the grade of peristalsis. The incidence of adverse events was comparable between the groups (P = 0.340). CONCLUSIONS: During upper GI endoscopy, a single dose of l-menthol solution (160 mg) sprayed on the gastric mucosa significantly attenuated gastric peristalsis versus placebo, thereby improving the visual stability without any safety concerns.

Down-regulated expression of OPCML predicts an unfavorable prognosis and promotes disease progression in human gastric cancer.

BACKGROUND: OPCML belongs to the IgLON family of Ig domain-containing GPI-anchored cell adhesion molecules and was recently found to be involved in carcinogenesis, while its role in gastric cancer remains unclear. METHODS: We assessed expression and biological behavior of OPCML in gastric cancer. RESULTS: OPCML expression was markedly reduced in tumor tissues and cancer cell lines. Decreased OPCML expression had a significant association with unfavorable tumor stage (p = 0.007) and grading (p < 0.001). Furthermore, the results revealed that OPCML was an independent prognostic factor for overall survival in gastric cancer (p = 0.002). In addition, ectopic expression of OPCML in cancer cells significantly inhibited cell viability (p < 0.01) and colony formation (p < 0.001), arrest cell cycle in G0/G1 phase and induced apoptosis, and suppressed tumor formation in nude mice. The alterations of phosphorylation status of AKT and its substrate GSK3ß, up-regulation of pro-apoptotic regulators including caspase-3, caspase-9 and PARP, and up-regulation of cell cycle regulator p27, were implicated in the biological activity of OPCML in cancer cells. CONCLUSION: Down-regulated OPCML expression might serve as an independent predictor for unfavorable prognosis of patients, and the biological behavior supports its role as a tumor suppressor in gastric cancer.

Feasibility of endoscopic submucosal dissection for upper gastrointestinal submucosal tumors treatment and value of endoscopic ultrasonography in pre-operation assess and post-operation follow-up: a prospective study of 224 cases in a single medical center.

BACKGROUND AND AIMS: Diagram, diagnosis, and treatment with endoscopic submucosal dissection (ESD) for upper gastrointestinal submucosal tumors (SMTs) remain controversial, although endoscopic ultrasonography (EUS) and ESD have been established in diagnosis and treatment of SMTs in decades, respectively. In this study, we have investigated prospectively the profile of upper gastrointestinal SMTs, assessed the effect and feasibility of ESD in upper gastrointestinal SMTs treatment, as well as value of EUS in pre-ESD diagnosis and post-ESD follow-up for gastrointestinal SMTs. METHODS: The upper gastrointestinal SMTs patients detected with endoscopy were further checked by EUS, then received series ESD treatment, and fulfilled 3- and 12-month follow-up EUS detection between July 2011 and March 2015. The parameters of SMTs with EUS examination (size, original layer) and treatment with ESD (en bloc resection rate, procedure time, procedure-related complications) were investigated and analyzed. RESULTS: A total number of 224 patients with upper gastrointestinal SMTs were enrolled, and 108 (48.2 %) were men. The mean age was 50.4 ± 12.0 years (range 19-77 years). In total, 92 (41.1 %), 14 (6.3 %), 61 (27.2 %), 22 (9.8 %), 25 (11.2 %), and 10 (4.5 %) SMTs were located in esophagus, cardiac, fundus, body and antrum of stomach, duodenum, respectively. Two hundred and eight (92.9 %) patients were successfully treated with an en bloc ESD, while other 16 patients (7.1 %) suffered ESD failure (5.3 %, 12 case) or severe complications (1.8 %, 4 cases). The mean procedure time of ESD was 47.4 ± 27.3 min (range 10-180 min). The mean size of the SMTs measured with ESD samples was 13.6 ± 9.5 mm (range 4-113 mm). In total, 87 (38.8 %), 23 (10.3 %), and 114 (50.9 %) tumors originated from muscularis mucosa, submucosa, and muscularis propria, respectively. The majority of SMTs were leiomyoma (109, 48.7 %) and gastrointestinal stromal tumors (GIST) (77, 34.4 %), while other SMTs were confirmed as ectopic pancreas (21, 9.4 %), adenoid tumor (8, 3.6 %), lipoma (5, 2.2 %), neuroendocrine tumor (3, 1.3 %), and granulosa cell tumor (1, 0.4 %). The accuracy rate of EUS in pathological diagnosis or original layer was 82.6 % (185/224) or 74.6 % (167/224). Residual tumors were detected with EUS in 3 patients (1.3 %) in 3-month follow-up and no recurrence during 12-month follow-up period. CONCLUSIONS: The predominant SMTs in upper gastrointestinal tract were leiomyoma in esophageal tumors which originated from muscularis mucosae and GIST in stomach which originated from muscularis propria detected satisfactorily with EUS. This study showed that ESD was a safe and effective treatment for upper gastrointestinal SMTs.

Akt Activation and Inhibition of Cytochrome C Release: Mechanistic Insights into Leptin-promoted Survival of Type II Alveolar Epithelial Cells.

Fetal growth restriction (FGR) increases the risk of perinatal death, partly due to defects in lung development. Leptin, a polypeptide hormone, is involved in fetal lung development. We previously demonstrated that treatment with exogenous leptin during gestation significantly promotes fetal lung maturity in the rat model of FGR. In this study, to delineate the molecular pathways through which leptin may enhance fetal lung development, we investigated the impact of leptin treatment on the survival of type II alveolar epithelial cells (AECs), essential leptin-responsive cells involved in lung development, in a rat model of FGR. The rat model of FGR was induced in pregnant Sprague-Dawley rats by partial uterine artery and vein ligation. In vivo and in vitro analyses of fetal lung tissues and freshly-isolated cultured AECs, respectively, showed that leptin protects type II AECs from hypoxia-induced apoptosis. Further molecular studies revealed the role of Akt activation in the leptin-mediated promotion of survival of type II AECs. The data also showed that the anti-apoptotic effects of leptin are dependent on phosphoinositol 3-kinase (PI3K) activation, and involve the down-regulation of caspases 3 and 9, upregulation of pro-survival proteins Bcl-2, and p-Bad, and inhibition of the release of cytochrome c from mitochondria. Taken together, our data suggested that leptin enhances the maturity of fetal lungs by mediating the regulation of caspase-3 and -9 during hypoxia-induced apoptosis of type II AECs and provide support for the potential of leptin as a therapeutic agent for promoting lung development in FGR.

Development and Validation of Serum Markers as Noninvasive Diagnostic Methods for Achalasia.

INTRODUCTION: Currently, the diagnosis of achalasia mainly relies on invasive or radioactive examinations. This study aimed to develop a noninvasive diagnostic method for achalasia based on specific serum markers. METHODS: Serum levels of profilin-1, galectin-10, immunoglobulin heavy variable 3-9, vasodilator-stimulated phosphoprotein, and transgelin-2 were measured in patients with achalasia and controls by enzyme-linked immunosorbent assay. The diagnostic values and thresholds were determined by the receiver operating characteristic curve analysis. Then, patients with dysphagia were prospectively enrolled to validate the ability of these molecules for achalasia diagnosing. RESULTS: A total of 142 patients with achalasia and 50 nonachalasia controls (healthy volunteers and patients with reflux esophagitis) were retrospectively included. The serum levels of profilin-1, galectin-10, and transgelin-2 in patients with achalasia were significantly higher than those in healthy volunteers and patients with reflux esophagitis ( P all < 0.001). Profilin-1, galectin-10, and transgelin-2 were of good performance in diagnosing achalasia, with optimal thresholds of 2,171.2, 33.9, and 1,630.6 pg/mL, respectively. Second, 40 patients with dysphagia were prospectively enrolled to the validation of achalasia. For profilin-1, the positive predictive value, negative predictive value, sensitivity, and specificity were 100.0%, 64.5%, 45.0%, and 100.0%, respectively. The figures for transgelin-2 were 65.5%, 90.9%, 95.0%, and 50.0%. When both increased, the positive predictive value reached to 100.0%. When both indexes were normal, the negative predictive value was 100.0%. DISCUSSION: Profilin-1 and transgelin-2 were promising biomarkers for achalasia diagnosis and performed better in combination. Further multicenter studies are necessary to verify their application as preliminary screening tools for achalasia.

Clinical manifestation, lifestyle, and treatment patterns of chronic erosive gastritis: A multicenter real-world study in China.

BACKGROUND: Although chronic erosive gastritis (CEG) is common, its clinical characteristics have not been fully elucidated. The lack of consensus regarding its treatment has resulted in varied treatment regimens. AIM: To explore the clinical characteristics, treatment patterns, and short-term outcomes in CEG patients in China. METHODS: We recruited patients with chronic non-atrophic or mild-to-moderate atrophic gastritis with erosion based on endoscopy and pathology. Patients and treating physicians completed a questionnaire regarding history, endoscopic findings, and treatment plans as well as a follow-up questionnaire to investigate changes in symptoms after 4 wk of treatment. RESULTS: Three thousand five hundred sixty-three patients from 42 centers across 24 cities in China were included. Epigastric pain (68.0%), abdominal distension (62.6%), and postprandial fullness (47.5%) were the most common presenting symptoms. Gastritis was classified as chronic non-atrophic in 69.9% of patients. Among those with erosive lesions, 72.1% of patients had lesions in the antrum, 51.0% had multiple lesions, and 67.3% had superficial flat lesions. In patients with epigastric pain, the combination of a mucosal protective agent (MPA) and proton pump inhibitor was more effective. For those with postprandial fullness, acid regurgitation, early satiety, or nausea, a MPA appeared more promising. CONCLUSION: CEG is a multifactorial disease which is common in Asian patients and has non-specific symptoms. Gastroscopy may play a major role in its detection and diagnosis. Treatment should be individualized based on symptom profile.

The prognostic value of E-cadherin in gastric cancer: a meta-analysis.

The prognostic impact of E-cadherin downregulation in gastric cancer has been assessed for years while the results are controversial and heterogeneous. We thus comprehensively reviewed the evidence for evaluation of E-cadherin expression in gastric cancer to determine this effect. We searched PubMed and Embase to identify eligible studies, and 26 studies comprising 4,383 gastric cancer patients were included to assess the association between E-cadherin immunohistochemical expression and overall survival (OS) and clinicopathological characteristics. Summary hazard ratios (HRs) or odds ratios (ORs) with 95% confidence interval (95% CI) were calculated to estimate the effect. We also performed meta-regression and subgroup analysis according to study location, publication year, number of patients, quality score of studies and cut-off value. Reduced E-cadherin expression was significantly correlated with poor OS of gastric cancer patients (HR 1.62, 95% CI 1.34-1.96). Subgroup analysis indicated that E-cadherin low-expression had an unfavorable impact on OS in Asian patients (HR 1.87, 95% CI 1.45-2.41). Moreover, downregulation of E-cadherin was significantly associated with TNM stage (OR 2.52, 95% CI 1.85-3.43), the depth of invasion (OR 2.01, 95% CI 1.39-2.90), lymph node metastasis (OR 2.39, 95% CI 1.68-3.40), distant metastasis (OR 2.23, 95% CI 1.21-4.11), grade of differentiation (OR 2.26, 95% CI 1.60-3.21), vascular invasion (OR 1.86, 95% CI 1.10-3.13) and histological type of gastric cancer (OR 4.22, 95% CI 2.96-6.02). This meta-analysis revealed that E-cadherin expression might be a predicative factor of poor prognosis for gastric cancer particularly in Asia.

The molecular pathogenesis of achalasia: a paired lower esophageal sphincter muscle and serum 4D label-free proteomic study.

Background: Achalasia is a primary esophageal motility disorder with potential molecular pathogenesis remaining uncertain. This study aimed to identify the differentially expressed proteins and potential pathways among achalasia subtypes and controls to further reveal the molecular pathogenesis of achalasia. Methods: Paired lower esophageal sphincter (LES) muscle and serum samples from 24 achalasia patients were collected. We also collected 10 normal serum samples from healthy controls and 10 normal LES muscle samples from esophageal cancer patients. The 4D label-free proteomic analysis was performed to identify the potential proteins and pathways involved in achalasia. Results: Analysis of Similarities showed distinct proteomic patterns of serum and muscle samples between achalasia patients and controls (both P < 0.05). Functional enrichment analysis suggested that these differentially expressed proteins were immunity-, infection-, inflammation-, and neurodegeneration-associated. The mfuzz analysis in LES specimens showed that proteins involved in the extracellular matrix-receptor interaction increased sequentially between the control group, type III, type II, and type I achalasia. Only 26 proteins altered in the same directions in serum and muscle samples. Conclusions: This first 4D label-free proteomic study of achalasia indicated that there were specific protein alterations in both the serum and muscle of achalasia, involving immunity, inflammation, infection, and neurodegeneration pathways. Distinct protein clusters between types I, II, and III revealed the potential molecular pathways associated with different disease stages. Analysis of proteins changed in both muscle and serum samples highlighted the importance of further studies on LES muscle and revealed potential autoantibodies.

Use of the Scissor-Type Knife During the Peroral Endoscopy Myotomy Procedure for the Treatment of Achalasia.

Peroral endoscopic myotomy (POEM) is one of the first-line treatment modalities along with pneumatic dilation and Heller myotomy for patients with achalasia. Endoscopists, especially trainees during the learning phase, commonly face difficulty in tissue plane dissection and selective myotomy while working near the esophagogastric junction, with increased risks of inadvertent injury, unexpected bleeding, and inadequate myotomy. To minimize the technical difficulty and improve the safety of POEM, we describe a protocol for using a scissor-type knife for the main steps of POEM, including mucosal incision, submucosal tunneling, myotomy, and hemostasis. The standard techniques used with the scissor-type knife involve grasping the target tissue, and then dissection or coagulation. The confirmation of the cutting line after grasping improves the accuracy and reliability of dissection, which is particularly useful for the selective myotomy of the internal circular muscle. Meanwhile, the scissor-type knife provides enhanced hemostatic capability and enables hemostasis and pre-coagulation without the device exchange for hemostatic forceps. Evaluation of the clinical outcomes in three patients who successfully received POEM using the scissor-type knife revealed no perioperative adverse events. At the 3-month follow-up, all patients achieved clinical success with postoperative Eckardt scores ranging from 0 to 1. In conclusion, the use of a scissor-type knife could minimize the technical difficulty and improve the safety of the POEM procedures, which may be suitable for trainees during the learning phase.

Achalasia: The Current Clinical Dilemma and Possible Pathogenesis.

Achalasia is a primary esophageal motility disorder manifested by dysphagia and chest pain that impair patients' quality of life, and it also leads to chronic esophageal inflammation by food retention and increases the risk of esophageal cancer. Although achalasia has long been reported, the epidemiology, diagnosis and treatment of achalasia are not fully understood. The current clinical dilemma of achalasia is mainly due to its unclear pathogenesis. In this paper, epidemiology, diagnosis treatment, as well as possible pathogenesis of achalasia will be reviewed and summarized. The proposed hypothesis on the pathogenesis of achalasia is that genetically susceptible populations potentially have a higher risk of infection with viruses, triggering autoimmune and inflammation responses to inhibitory neurons in lower esophageal sphincter.

Farnesoid X receptor protects human and murine gastric epithelial cells against inflammation-induced damage.

Bile acids from duodenogastric reflux promote inflammation and increase the risk for gastro-oesophageal cancers. FXR (farnesoid X receptor/NR1H4) is a transcription factor regulated by bile acids such as CDCA (chenodeoxycholic acid). FXR protects the liver and the intestinal tract against bile acid overload; however, a functional role for FXR in the stomach has not been described. We detected FXR expression in the normal human stomach and in GC (gastric cancer). FXR mRNA and protein were also present in the human GC cell lines MKN45 and SNU5, but not in the AGS cell line. Transfection of FXR into AGS cells protected against TNFα (tumour necrosis factor α)-induced cell damage. We identified K13 (keratin 13), an anti-apoptotic protein of desmosomes, as a novel CDCA-regulated FXR-target gene. FXR bound to a conserved regulatory element in the proximal human K13 promoter. Gastric expression of K13 mRNA was increased in an FXR-dependent manner by a chow diet enriched with 1% (w/w) CDCA and by indomethacin (35 mg/kg of body weight intraperitoneal) in C57BL/6 mice. FXR-deficient mice were more susceptible to indomethacin-induced gastric ulceration than their WT (wild-type) littermates. These results suggest that FXR increases the resistance of human and murine gastric epithelial cells to inflammation-mediated damage and may thus participate in the development of GC.

Clinical outcomes of asymptomatic low-grade esophagitis: results from a multicenter Chinese cohort.

Background: Asymptomatic low-grade (Los Angeles Classification Grades A and B) esophagitis is common in clinical practice with unclear clinical outcomes. This study aimed to explore the clinical outcomes of asymptomatic low-grade esophagitis. Methods: This was a multicenter cohort study conducted by three academic hospitals in China. Asymptomatic low-grade esophagitis patients between January 2015 and December 2019 were included. Mucosal healing condition 1 year after initial diagnosis, symptom outcomes, and proton-pump inhibitor (PPI) use within 1 year after initial diagnosis were studied and compared. Results: A total of 248 asymptomatic low-grade esophagitis patients were included. Esophagitis disappeared in 76.2% of patients 1 year after initial diagnosis. In terms of symptom outcomes, 89.9% of patients did not present gastroesophageal reflux disease (GERD) symptoms within 1 year after initial diagnosis. No significant difference was found in the proportion of patients who presented GERD symptoms and in the proportion of patients with persistent esophagitis between the PPI group and the non-PPI group (all P > 0.05). Patients with initial Grade B esophagitis were more likely to present follow-up GERD symptoms (16.0% vs 7.5%, P = 0.041) and had more severe follow-up esophagitis than those with Grade A (P < 0.001). Patients with follow-up GERD symptoms were more likely to have persistent esophagitis than those without. Conclusions: This study demonstrated that asymptomatic low-grade esophagitis had relatively benign clinical outcomes. Patients with initial Grade B esophagitis and patients with follow-up GERD symptoms were more likely to be those who are in genuine need of further follow-up and treatments.

Neoadjuvant programmed cell death 1 blockade combined with chemotherapy for resectable esophageal squamous cell carcinoma.

BACKGROUND: Programmed cell death 1 (PD-1) blockade induces tumor regression in patients with advanced esophageal squamous cell carcinoma (ESCC); however, little is known about the efficacy of PD-1 blockade as neoadjuvant therapy in resectable ESCC. We aim to assess the safety and feasibility of using the combination of neoadjuvant PD-1 blockade with chemotherapy in patients with ESCC. METHODS: Patients with previously untreated, resectable (stage II or III) ESCC were enrolled. Each patient received two 21-day cycles of neoadjuvant treatment with camrelizumab, nab-paclitaxel, and carboplatin before undergoing surgical resection approximately 6-9 weeks after the first cycle. RESULTS: Between January 2020 and September 2020, 37 patients were screened, of whom 23 were enrolled. The neoadjuvant therapeutic regimen had an acceptable side effect profile, and no delays in surgery were observed. Severe (grade 3-4) treatment-related adverse events included neutropenia (9 of 23, 39.1%) and leukopenia (2 of 23, 8.7%). The objective response and disease control rates were 90.5% and 100%, respectively. Twenty patients received surgery, and R0 resection was achieved in all cases. Five (25%) patients had a pathological complete response (PCR) and 10 (50%) patients had a major pathological response. The proportion of patients with a high tumor mutation burden and a high expression of programmed death-ligand 1 (PD-L1) in primary tumor was significantly higher in the PCR group than in the non-PCR group (p=0.044). The number of infiltrating PD-L1+ CD163+ cells was significantly lower in the PCR group than in the non-PCR group after treatment (p=0.017). CONCLUSIONS: Neoadjuvant camrelizumab plus carboplatin and nab-paclitaxel had manageable treatment-related adverse effects and induced an objective response in 90.5% of patients, demonstrating its antitumor efficacy in resectable ESCC. TRIAL REGISTRATION NUMBER: ChiCTR2000028900.