Effect of sarcopenia on short-term outcomes of gastric endoscopic submucosal dissection.

BACKGROUND: Sarcopenia has been reported to be associated with short-term outcomes after gastric endoscopic submucosal dissection (ESD). The "strength, assistance with walking, rising from a chair, climbing stairs, and falls" (SARC-F) questionnaire has been widely used as a screening tool for sarcopenia; however, SARC-F combined with body mass index and age (SARC-F+EBM) has recently been reported to be more useful than SARC-F alone. This study aimed to investigate the association between sarcopenia, measured using SARC-F+EBM, and short-term outcomes after gastric ESD. METHODS: Patients who underwent gastric ESD at our institution between May 2020 and June 2023 were included, and their medical records were reviewed retrospectively. A SARC-F+EBM score ≥ 12 indicated sarcopenia. We evaluated the incidence of adverse events and the length of hospital stay in the sarcopenia and non-sarcopenia groups. RESULTS: Overall, 263 patients (64 and 199 in the sarcopenia and non-sarcopenia groups, respectively) were investigated. The incidence of adverse events with a Common Terminology Criteria for Adverse Events grade ≥ 3 was not significantly different between the sarcopenia and non-sarcopenia groups (6.2% vs. 8.5%, p = 0.791). The proportion of patients with an extended hospital stay (≥ 10 days) was significantly higher in the sarcopenia group than that in the non-sarcopenia group (12.5% [8/64] vs. 3.5% [7/199], p = 0.012). Multivariate analysis showed that sarcopenia and lesions that present technical difficulty in ESD were independent risk factors for extended hospital stays (≥ 10 days). Of the eight cases having extended hospital stays in the sarcopenia group, four were due to the management after gastric ESD, three were due to family circumstances, and one was due to decreased activities of daily living. CONCLUSIONS: Sarcopenia is not a predictor of adverse events associated with gastric ESD. However, patients with sarcopenia may be hospitalized for longer owing to non-ESD-related factors.

Widespread use of proton pump inhibitors or potassium-competitive acid blocker has changed the status of gastrointestinal bleeding in patients with ischemic heart disease: real-world data from high volume centers.

BACKGROUND: Although proton pump inhibitors (PPIs) or potassium-competitive acid blocker (PCAB) are useful in peptic ulcer prevention, their efficacy in preventing other gastrointestinal bleeding remains unclear. This study aimed to identify the status of gastrointestinal bleeding in the modern era when PPIs are widely used. METHODS: This study included patients who underwent percutaneous coronary intervention (PCI) between 2018 and 2019 at two high-volume centers. Patients were categorized based on whether they experienced gastrointestinal bleeding within 2 years of PCI into groups A (patients who experienced gastrointestinal bleeding within 2 years after PCI) and B (patients who did not experience gastrointestinal bleeding). RESULTS: Groups A and B included 21 (4.1%) and 494 (95.9%) patients, respectively (a total of 515 patients). Age at the initial PCI (77.8±2.4 and 72.0±0.5 years in groups A and B, respectively; p = 0.02), weight (53.8±3.2 and 61.8±0.7 kg in groups A and B, respectively; p = 0.01), and concomitant warfarin use (14.3% and 2.0% in groups A and B, respectively; p = 0.0005) were significantly different between the groups. The high bleeding risk rate (90.5% and 47.6% in groups A and B, respectively; p = 0.0001) was significantly different between the groups. A total of 95.9% of patients were taking PPIs or PCAB without significant differences between the groups. However, only one patient, who was taking steroids, had a gastric ulcer during PCAB treatment. CONCLUSIONS: Acid-related upper gastrointestinal bleeding is largely controlled by PPIs in post-PCI patients. Furthermore, the risk factors for non-acid-related bleeding include older age, lower weight, and concomitant warfarin use.

A Case of Refractory Gastroesophageal Reflux Disease Successfully Treated with Endoscopic Anti-gastroesophageal Reflux Mucosal Resection by the ESD-G Method (with video).

A 70-year-old man who had undergone treatment for gastroesophageal reflux disease (GERD) by a family doctor presented to our hospital with severe heartburn and dysphagia despite taking vonoprazan (20 mg) for 3 months. A diagnosis of vonoprazan-refractory nonerosive reflux disease was made based on esophagogastroduodenoscopy and esophageal function examinations. The patient elected to undergo endoscopic treatment for GERD. Therefore, we performed endoscopic treatment using the endoscopic submucosal dissection (ESD-G) technique developed at our institution. After endoscopic treatment, his GERD symptoms disappeared and he no longer required GERD-related medications. An examination of his esophageal function revealed the improvement of items related to GERD.

Background factors of idiopathic peptic ulcers and optimal treatment methods: a multicenter retrospective Japanese study.

This study investigated the trends in idiopathic peptic ulcers, examined the characteristics of refractory idiopathic peptic ulcer, and identified the optimal treatment. The characteristics of 309 patients with idiopathic peptic ulcer were examined. We allocated idiopathic peptic ulcers that did not heal after 8 weeks' treatment (6 weeks for duodenal ulcers) to the refractory group and those that healed within this period to the healed group. The typical risk factors for idiopathic peptic ulcer (atherosclerosis-related underlying disease or liver cirrhosis complications) were absent in 46.6% of patients. Absence of gastric mucosal atrophy (refractory group: 51.4%, healed group: 28.4%; p = 0.016), and gastric fundic gland polyps (refractory group: 17.6%, healed group: 5.9%; p = 0.045) were significantly more common in the refractory group compared to the healed group. A history of H. pylori eradication (refractory group: 85.3%, healed group: 66.0%; p = 0.016), previous H. pylori infection (i.e., gastric mucosal atrophy or history of H. pylori eradication) (refractory group: 48.5%, healed group: 80.0%; p = 0.001), and potassium-competitive acid blocker treatment (refractory group: 28.6%, healed group, 64.1%; p = 0.001) were significantly more frequent in the healed group compared to the refractory group. Thus, acid hypersecretion may be a major factor underlying the refractoriness of idiopathic peptic ulcer.

Frontiers in Endoscopic Treatment for Gastroesophageal Reflux Disease.

BACKGROUND: The 3rd edition of the evidence-based clinical practice guidelines for gastroesophageal reflux disease (GERD) 2021 from the Japanese Society of Gastroenterology states that the treatment strategy for potassium-competitive acid blocker (PCAB)-refractory GERD remains unclear. Furthermore, even if GERD improves with the administration of an acid secretion inhibitor, it is feared that GERD may flare up after discontinuation of the drug, resulting in some cases in which patients are forced to take vonoprazan semipermanently (the so-called PCAB-dependent cases). From a global perspective, PCAB is not yet used in all countries and regions, and measures that can be taken now for cases in which a conventional proton pump inhibitor (PPI) is inadequately effective need to be devised. SUMMARY: Endoscopic treatment for GERD may be effective in cases where conventional proton pump inhibitors are ineffective; however, there are insufficient long-term studies to corroborate this, and its cost effectiveness is unknown. Other treatment options for PCAB or PPI-refractory GERD include surgical procedures (Nissen and Toupet operations), which have a longer history than endoscopic treatment for GERD. However, their long-term results are not as good as those of acid secretion inhibitors, and they are not cost effective. Endoscopic treatment for GERD may fill gaps in inadequate surgical treatment. In April 2022, endoscopic anti-reflux mucosal resections (ARMS [anti-reflux mucosectomy] and ESD-G [endoscopic submucosal dissection for GERD]) were approved for reimbursement, making endoscopic treatment of GERD possible throughout Japan. KEY MESSAGES: It is important to identify the background factors in cases in which endoscopic treatments are effective.

Red Dichromatic Imaging Improves the Recognition of Bleeding Points During Endoscopic Submucosal Dissection.

BACKGROUND: Previous studies have indicated that red dichromatic imaging (RDI) improved the visibility of gastrointestinal bleeding. AIMS: To investigate the recognition of bleeding points during endoscopic submucosal dissection (ESD) under RDI compared with that under white light imaging (WLI). METHODS: Consecutive patients scheduled to undergo esophageal or gastric ESD at a single center were enrolled. Paired videos of active bleeding during ESD under WLI and RDI were created. Six endoscopists identified the virtual hemostasis point on still images after random video viewing. The distance between virtual hemostasis and actual bleeding points was scored in four levels (0-3 points), and the association with the color value was analyzed in both WLI and RDI. RESULTS: We evaluated 116 videos for 58 bleeding points. The median visibility score and recognition rate were significantly higher for RDI than for WLI (2.17 vs. 1.42, p < 0.001 and 62.1% vs 27.6%, p < 0.001). Additionally, the recognition rate of trainees in RDI was higher than that of experts in WLI (60.3% vs. 43.1%, p = 0.067). The median color difference of RDI was significantly higher than that of WLI (8.97 vs. 3.69, p < 0.001). Furthermore, the correlation coefficient between the visibility score and color difference was 0.712 (strong correlation). CONCLUSION: RDI can provide better recognition of bleeding points than WLI during ESD. Therefore, further studies are warranted to investigate whether RDI improves ESD outcomes.

Biomarkers for Monitoring of Changes in Disease Activity in Ulcerative Colitis.

BACKGROUND: In recent years, various biomarkers of ulcerative colitis (UC) have emerged; however, few studies have simultaneously examined the utility of multiple biomarkers for monitoring disease activity. Additionally, serum leucine-rich alpha-2 glycoprotein (LRG), a new biomarker, may show a blunt response to anti-TNF antibody therapy. This prospective study explored effective biomarkers that could monitor disease activity changes in patients with UC. In addition, we examined the effect of anti-TNF antibody therapy on changes in LRG. METHODS: Blood and stool samples were collected twice from patients with UC: at baseline and at least 8 weeks later. Changes in serum LRG, interleukin (IL)-6, prealbumin (pre-Alb), high-sensitivity C-reactive protein (hs-CRP), CRP, and fecal calprotectin (FC) were measured and correlated with changes in disease activity. The relationship between anti-TNF antibody therapy and LRG levels was also examined in patients with the same disease activity. RESULTS: Forty-eight patients with UC (96 samples) were analyzed. ΔLRG and ΔIL-6 correlated strongly with the change in the partial Mayo (pMayo) score between the two time points (ΔpMayo) (r = 0.686, 0.635, respectively). In contrast, FC and IL-6 were particularly accurate predictors of clinical remission, and their area under the curves (AUCs) were significantly higher than that of CRP (AUC: 0.81, 0.76 vs. 0.50; p = 0.001, 0.005). No association was found between the administration of anti-TNF antibody preparations and the LRG values. CONCLUSIONS: Correlations were found between changes in UC disease activity and LRG, IL-6, pre-Alb, hs-CRP, CRP, and FC. LRG reflects disease activity during anti-TNF antibody therapy.

Efficacy of Switching to Adalimumab for Maintenance of Remission Following Induction Therapy with Tacrolimus in Patients with Ulcerative Colitis.

BACKGROUND: Tacrolimus (TAC) effectively induces remission in refractory ulcerative colitis (UC). However, TAC therapy usually lasts for 3 months. Although azathioprine (AZA) is often used in maintenance therapy, the relapse rate remains high. Herein, we evaluated the efficacy of adalimumab (ADA) for remission maintenance in patients with UC after induction therapy with TAC. METHODS: We prospectively enrolled patients with moderate-to-severe UC who achieved clinical remission after 3 months of TAC therapy with endoscopic non-mucosal healing (Cohort A). After TAC discontinuation, the remission maintenance rate up to 1 year after starting ADA therapy was examined. We retrospectively enrolled patients with UC treated with TAC (Cohort B). Among patients in clinical remission after TAC treatment for 3 months, those who received AZA as remission maintenance therapy after TAC discontinuation constituted the AZA group. Patients in Cohort A who received ADA and AZA as remission maintenance therapy after TAC discontinuation constituted the ADA + AZA group. We compared the remission maintenance rates in the AZA and ADA + AZA groups for up to 5 years after TAC discontinuation. RESULTS: In Cohort A, of the 46 patients with UC treated with TAC, 17 were eligible for analysis after receiving ADA as remission maintenance therapy. A notable 88.2% (15/17) were still in remission 1 year after starting ADA. The ADA + AZA group (n = 16) exhibited a significantly higher relapse-free rate than the AZA group (n = 26) (p < 0.05; log-rank test). CONCLUSION: switching to ADA for remission maintenance in patients with refractory UC who achieved clinical remission with TAC is clinically useful.

Relationship between Chemotherapy-Induced Diarrhea and Intestinal Microbiome Composition.

BACKGROUND AND AIM: Fluoropyrimidines (FPs) are key drugs in many chemotherapy regimens; however, recipients are often prone to diarrhea due to gastrointestinal toxicity. Disruption of the intestinal epithelial barrier function by FPs leads to dysbiosis, which may exacerbate intestinal epithelial cell damage as a secondary effect and trigger diarrhea. However, despite studies on chemotherapy-induced changes in the intestinal microbiome of humans, the relationship between dysbiosis and diarrhea is unclear. In this study, we aimed to investigate the relationship between chemotherapy-induced diarrhea and the intestinal microbiome. METHODS: We conducted a single-center prospective observational study. Twenty-three patients who received chemotherapy, including FPs as first-line chemotherapy for colorectal cancer, were included. Stool samples were collected before the start of chemotherapy and after one cycle of treatment to analyze intestinal microbiome composition and perform PICRUSt predictive metagenomic analysis. RESULTS: Gastrointestinal toxicity was observed in 7 of 23 patients (30.4%), diarrhea was observed in 4 (17.4%), and nausea and anorexia were observed in 3 (13.0%). In 19 patients treated with oral FPs, the α diversity of the microbial community decreased significantly following chemotherapy only in the diarrheal group. At the phylum level, the diarrheal group showed a significant decrease in the abundance of Firmicutes and a significant increase in the abundance of Bacteroidetes with chemotherapy (p = 0.013 and 0.011, respectively). In the same groups, at the genus level, Bifidobacterium abundance was significantly decreased (p = 0.019). In contrast, in the non-diarrheal group, Actinobacteria abundance increased significantly with chemotherapy at the phylum level (p = 0.011). Further, Bifidobacterium, Fusicatenibacter, and Dorea abundance significantly increased at the genus level (p = 0.006, 0.019, and 0.011, respectively). The PICRUSt predictive metagenomic analysis revealed that chemotherapy caused significant differences in membrane transport in KEGG pathway level 2 and in 8 KEGG pathway level 3, including transporters and oxidative phosphorylation in the diarrhea group. CONCLUSION: Organic-acid-producing bacteria seem to be involved in diarrhea associated with chemotherapy, including FPs.

Examination on Factors Affecting Symptom Change after Drug Withdrawal in Patients with Mild Erosive Gastroesophageal Reflux Disease Undergoing Symptom-Controlled Maintenance Therapy with Acid-Secretion Inhibition Drugs.

INTRODUCTION: In patients with gastroesophageal reflux disease (GERD) on maintenance therapy with acid-suppressive drugs, it is not clear what background factors allow patients to discontinue the drugs. The aims of this study were to examine the relationship of the changes in the frequency and severity of gastrointestinal symptoms after discontinuation of acid-secretion inhibitors for erosive GERD (eGERD) with possible patient background factors and to identify factors that influence these changes. METHODS: This is a multicenter, open-label, interventional, exploratory study. eGERD patients with mild mucosal injury whose symptoms were under control and who were on maintenance therapy with acid-suppressive drugs were withdrawn from the drug treatment for 4 weeks. We examined the relationship of patient backgrounds (sex, age, body mass index, alcohol consumption, smoking habits), esophageal hiatal hernia, Helicobacter pylori infection, pepsinogen I and II concentrations and I/II ratios, blood gastrin levels before and after drug discontinuation with total score change in Frequency Scale for the Symptoms of GERD (FSSG). RESULTS: Of the 92 patients whose symptoms could be assessed before and after drug withdrawal, 66 patients (71.7% of the total) had FSSG <8 and no symptom relapse after the withdrawal. Furthermore, patient background factors that may be related to symptom relapse/non-relapse were examined, but no related factors were detected. The maintenance medications before discontinuation in the above 92 patients were a proton pump inhibitor (PPI) and vonoprazan (VPZ, a potassium ion competitive acid blocker). Since PPI and VPZ were administered to about the same number of patients, though incidentally, we additionally examined the relationship between patient background factors and symptom relapse/non-relapse by treatment group. As a result, no relevant background factors were detected in both groups. Although there were no significant differences between the two groups, the severity and frequency of symptom recurrence in the VPZ group tended to be higher than in the PPI group. CONCLUSIONS: Consideration of background factors is unlikely to be required in the discontinuation of maintenance therapy for eGERD. There was no significant difference in the extent of disease or frequency of recurrence during the discontinuation period, regardless of whether the drug before discontinuation was a PPI or VPZ.

A case of recurrent massive thickening of the gastric wall caused by pancreatitis of the gastric ectopic pancreas: Detailed pathogenesis based on imaging.

A 40-year-old Japanese male presented with epigastric pain and loss of appetite at a general hospital three years ago. Computed tomography revealed massive thickening of the gastric wall, and gastroscopy revealed diffuse erythema and edematous thickening of the gastric mucosa. Thereafter, epigastric pain and gastric wall thickening recurred frequently, causing an inability to intake food. Conservative treatment was marginally effective; therefore, a distal gastrectomy was performed. Postoperatively, the patient resumed food intake without complications. Histopathological examination of the surgical specimen revealed Heinrich type 1 gastric ectopic pancreas (EP) with pancreatitis. In this case, the gastric wall's massive thickening was caused by gastric EP's pancreatitis. Although there are some reports of pancreatitis of gastric EP, there are no detailed reports of endoscopic findings, including endoscopic ultrasonography and the disease progression. Recurrent pancreatitis of EP leads to forming a septum within the gastric wall, resulting in a hematoma. Eventually, irreversible narrowing of the gastric lumen may occur, as observed in the present case. We consider this an important case report presenting detailed pathogenesis supported by endoscopic and pathohistological findings of surgical specimens. Our study will help in the early diagnosis and better management of the condition.

Very Delayed Perforation after Esophageal Endoscopic Submucosal Dissection and Intralesional Triamcinolone Injection.

We report a case of delayed perforation following esophageal endoscopic submucosal dissection (ESD). A patient with Parkinson's disease presented with two superficial carcinomatous lesions in the middle third of the esophagus. ESD was performed, and 4/5 of the esophageal circumference was resected, including the adjacent lesion area. Immediately post-ESD, triamcinolone acetonide was injected into the submucosa underlying the ulcer to prevent scarring and stenosis. Histopathological examination of the resected specimen revealed squamous cell carcinoma limited to the lamina propria with negative margins. Seventeen days post-ESD, the patient experienced sudden-onset chest pain during a meal. Computed tomography showed pneumomediastinum, which indicated a delayed perforation. We immediately performed subtotal esophagectomy. A sharply torn longitudinal perforation was present in the post-ESD ulcer. Delayed perforation after esophageal ESD is extremely rare. In this case, the perforation might have been caused by food impaction and delayed ulcer healing due to triamcinolone injection.

Therapeutic Drug Monitoring of Golimumab for the Prediction of Long-Term Clinical Remission in Patients with Ulcerative Colitis.

BACKGROUND AND AIMS: A considerable number of patients with ulcerative colitis (UC) who initially respond to golimumab (GLM), an anti-TNF-α antibody, gradually lose clinical response. Therapeutic drug monitoring has been proposed to optimize serum anti-TNF-α antibody concentrations before the loss of response; however, little is known about ideal serum GLM concentrations. We aimed to evaluate whether the serum GLM trough levels (TLs) early after the initiation of induction therapy affect the long-term outcomes in UC and to identify the early GLM TLs that should be targeted for better long-term outcomes. METHODS: Thirty-one patients were prospectively evaluated. The primary outcome was clinical remission at 54 weeks, and we measured the serum GLM TLs at weeks 6, 10, and 14. Receiver operating characteristic (ROC) curves were constructed to identify optimal GLM TL thresholds early after induction therapy that were associated with clinical remission at week 54. RESULTS: The GLM TL at week 14, but not at weeks 6 or 10, was significantly associated with clinical remission at week 54 (median [IQR] 1.6 [1.3-1.6] µg/mL vs. 0.9 [0.6-1.3] µg/mL; p = 0.04). The area under the ROC curve for GLM TLs at week 14 was 0.78. We identified a week-14 GLM TL of 1.1 µg/mL as the target threshold for achieving clinical remission at week 54. CONCLUSION: Our results demonstrate the value of early serum GLM TLs in predicting the long-term outcomes of GLM for patients with UC.

Risk Factors for Nephrotoxicity due to Tacrolimus Therapy for Ulcerative Colitis.

BACKGROUND AND AIMS: The calcineurin inhibitor tacrolimus is reportedly effective for moderate/severe ulcerative colitis (UC); however, it is also reportedly associated with nephrotoxicity. We investigated the risk factors for tacrolimus-induced nephrotoxicity and whether renal impairment adversely affected the outcomes of tacrolimus treatment in patients with UC. METHODS: We conducted a retrospective study of 93 patients with UC who were administered tacrolimus leading to high trough levels (10-15 ng/mL) for 2 weeks and low trough levels (5-10 ng/mL) for 3 months. RESULTS: Acute kidney injury (AKI) occurred in 44 patients (47.3%) during tacrolimus treatment. Of these patients, 34 (36.6%) developed AKI during the high trough phase and 17 (18.3%) developed AKI when the trough value exceeded the original target value of 15 ng/mL. Multivariate logistic regression analysis revealed that the male sex was significantly associated with AKI (p = 0.002, AOR = 4.38, 95% CI [1.69-11.3]). Clinical remission rate after 4, 8, 12, and 24 weeks of tacrolimus treatment in patients with AKI was lower than that in patients without AKI. Six patients (6.5%) had chronic kidney disease (CKD) after tacrolimus treatment completion, and all patients with CKD developed AKI during treatment. The median duration of treatment with no improvement in AKI was significantly longer in patients with CKD than in those without CKD (p = 0.016). CONCLUSION: We revealed the risk factors for tacrolimus-induced nephrotoxicity. Renal impairment occurrence adversely affected the tacrolimus treatment outcome; therefore, it is important to carefully administer tacrolimus to prevent renal impairment.

Treating an Intractable Jejunocutaneous Fistula by Endoscopic Metallic Stent Placement: A Case Report of Successful Palliative Endoscopic Treatment in a Case Demonstrating Peritoneal Dissemination with Terminal Stage Gastric Cancer.

A 74-year-old woman with recurrent gastric cancer underwent laparotomy for peritoneal dissemination, and the damaged jejunum formed a jejunocutaneous fistula. Because conservative treatment alone could not cure the fistula, we performed an endoscopic placement of a partially covered self-expandable metallic stent (SEMS) to cover the fistula. After the procedure, the contrast medium no longer leaked from the intestinal lumen. One month after stent placement, the cutaneous opening had closed. This case report demonstrates the potential for using partially covered SEMS to treat intractable jejunocutaneous fistula in patients with terminal-stage malignant tumors.