Feasibility of Colorectal Endoscopic Submucosal Dissection in Elderly Patients: The Impact of Sarcopenia.

INTRODUCTION: Colorectal cancer is a public health concern associated with high incidence rates. Sarcopenia is a known risk factor for postoperative complications, although an association between increased complications after colorectal endoscopic submucosal dissection (ESD) and sarcopenia remains undocumented. Herein, we aimed to explore the feasibility of colorectal ESD in patients with sarcopenia. METHODS: This retrospective study included 499 patients (69 with and 430 without sarcopenia). We evaluated the short- and long-term outcomes of colorectal ESD. RESULTS: There were no significant differences between the two groups regarding en bloc, R0, or curative resection rates. However, poor bowel preparation was significantly more common in the sarcopenia group. Moreover, patients with sarcopenia exhibited a significant increase in complications (37.7% vs. 10.5%). Multivariate analysis revealed that sarcopenia (odds ratio [OR]: 3.78, 95% confidence interval [Cl]: 1.85-7.73, p < 0.001), anticoagulation therapy (OR: 3.59, 95% Cl: 1.86-6.92, p < 0.001), procedure time (OR: 1.28, 95% Cl: 1.11-1.47, p < 0.001), and resection size (OR: 1.25, 95% Cl: 1.03-1.52, p = 0.02) were significantly correlated with the Common Terminology Criteria for Adverse Events (CTCAE) ≥ grade 2. The correlation between sarcopenia and CTCAE ≥ grade 2 was maintained after matching, resulting in more extended hospital stays in patients with sarcopenia. However, we detected no association between sarcopenia and overall survival and ESD-related death. CONCLUSION: Sarcopenia is a risk factor for complications in colorectal ESD, suggesting that colorectal ESD could be performed for patients with sarcopenia, although much caution should be taken.

Transcriptome analysis reveals the essential role of NK2 homeobox 1/thyroid transcription factor 1 (NKX2-1/TTF-1) in gastric adenocarcinoma of fundic-gland type.

BACKGROUND: Gastric adenocarcinoma of fundic-gland type (GA-FG) is a gastric malignancy with little relation to Helicobacter pylori. Clinical characteristics of GA-FG have been established, but molecular mechanisms leading to tumorigenesis have not yet been elucidated. METHODS: We subjected three GA-FG tumors-normal mucosa pairs to microarray analysis. Network analysis was performed for the top 30 up-regulated gene transcripts, followed by immunohistochemical staining to confirm the gene expression analysis results. AGS and NUGC4 cells were transfected with the gene-encoding NK2 homeobox 1/thyroid transcription factor 1 (NKX2-1/TTF-1) to evaluate transcriptional changes in its target genes. RESULTS: Comprehensive gene expression analysis identified 1410 up-regulated and 1395 down-regulated gene probes with ≥ two-fold difference in expression. Among the top 30 up-regulated genes in GA-FG, we identified transcription factor NKX2-1/TTF-1, a master regulator of lung/thyroid differentiation, together with surfactant protein B (SFTPB), SFTPC, and secretoglobin family 3A member 2(SCGB3A2), which are regulated by NKX2-1/TTF-1. Immunohistochemical analysis of 16 GA-FG specimens demonstrated significantly higher NKX2-1/TTF-1 and SFTPB levels, as compared to that in adjacent normal mucosa (P < 0.05), while SCGB3A2 levels did not differ (P = 0.341). Transduction of NKX2-1/TTF-1 into AGS and NUGC4 cells induced transactivation of SFTPB and SFTPC, indicating that NKX2-1/TTF-1 can function as normally in gastric cells as it can in the lung cells. CONCLUSIONS: Our first transcriptome analysis of GA-FG indicates significant expression of NKX2-1/TTF1 in GA-FG. Immunohistochemistry and cell biology show ectopic expression and normal transactivation ability of NKX2-1/TTF-1, suggesting that it plays an essential role in GA-FG development.

Repeated steroid injection and polyglycolic acid shielding for prevention of refractory esophageal stricture.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Verification of the increase in concomitant dysplasia and cancer with the size of sessile serrated lesions.

Background and study aims This study aimed to evaluate the relationship between sessile serrated lesion (SSL) size and the comorbidity rate of SSL with dysplasia (SSLD) and cancer in SSL (SSL-cancer). Patients and methods This retrospective, single-center analysis identified SSL cases that underwent endoscopic resection between January 2015 and December 2022. The prevalence of SSL, SSLD, and SSL-cancer and their annual trends were assessed. The tumor diameter was stratified as 0 to 5 mm, 6 to 9 mm, 10 to 19 mm, and ≥ 20 mm in size. Furthermore, the frequency of SSL-D/SSL-cancer was determined in each group. Results The prevalence of SSL was 2.9% (1328/45799). This prevalence was 1.8% (112/6192) in 2015 and 4.2% (230/5500) in 2022, indicating an increasing trend over time. A total of 1825 lesions were assessed: 1751 (96.0%), 55 (3.0%), 14 (0.8%), and 5 (0.3%) of lesions were SSL, SSL with low-grade dysplasia, SSL with high-grade dysplasia and SSL-cancer, respectively. Stratifying the SSLs by size: 0 to 5 mm, 5 to 9 mm, 10 to 19 mm, and ≥ 20 mm, SSLD and SSL-cancer rates were 2.3% (10/429), 2.4% (16/674), 5.3% (31/584), and 11.8% (16/136), respectively. SSLD and SSL-cancer were observed in 2.4% (26/1103) of small SSLs < 10 mm. Conclusions In cases of SSL, the rate of SSLD and SSL-cancer increased as the lesion diameter increased. A certain rate of SSLD and SSL-cancer was observed even in small SSLs less than 5mm.

Clinical meaning of sarcopenia in patients undergoing endoscopic treatment.

With increasing global life expectancy, the significance of geriatric assessment parameters has increased. Sarcopenia is a crucial assessment parameter and is defined as the age-related loss of muscle mass and strength. Sarcopenia is widely acknowledged as a risk factor for postoperative complications in diverse advanced malignancies and has a detrimental effect on the long-term prognosis. While most studies have primarily concentrated on the correlation between sarcopenia and advanced cancer, more recent investigations have focused on the relationship between sarcopenia and early-stage cancer. Endoscopic submucosal dissection (ESD), which is less invasive than surgical intervention, is extensively employed in the management of early-stage cancer, although it is associated with complications such as bleeding and perforation. In recent years, several reports have revealed the adverse consequences of sarcopenia in patients with early-stage cancer undergoing ESD. This literature review briefly summarizes the recent studies on the association between sarcopenia and ESD.

The impact of sarcopenia on short- and long-term outcomes of endoscopic submucosal dissection for early gastric cancer.

BACKGROUND: Sarcopenia prevalence has increased in proportion to the aging population in Japan. We aimed to investigate the association between sarcopenia and clinical outcomes and the prognostic factors of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). METHODS: This retrospective study involved patients aged ≥ 65 years who had undergone gastric ESD for EGC at our institution between January 2009 and December 2019. Patients were divided into two groups, namely, a sarcopenia group (109 patients) and a non-sarcopenia group (658 patients), based on the skeletal muscle index and intramuscular adipose tissue content (IMAC). Clinicopathological features, ESD-related adverse events, and outcomes were then compared. RESULTS: In the sarcopenia group, the mean age was higher, whereas performance and nutritional statuses were lower. There were no between-group differences in terms of treatment outcomes. Multivariate analyses (odds ratio [95% confidence interval (CI)]) indicated that a geriatric nutritional risk index score (GNRI) < 92 (2.12 [1.09-4.11], p = 0.03), anticoagulant therapy (1.76 [1.13-2.76], p = 0.01), tumor size ≥ 30 mm (2.09 [1.23-3.55], p = 0.01), and sarcopenia (1.90 [1.05-3.45], p = 0.03) were significantly associated with ESD-related adverse events. High Charlson comorbidity index, low prognostic nutritional index, low GNRI, and high IMAC were significantly associated with poor overall survival (OS). OS was significantly shorter in the sarcopenia group even after matching. CONCLUSIONS: Patients with sarcopenia had significantly more adverse events and shorter OS; therefore, evaluation of a patient's general condition, including sarcopenia, before ESD is important.

Endoscopic Treatment of Superficial Gastric Cancer: Present Status and Future.

Although the mortality rates of gastric cancer (GC) are gradually declining, gastric cancer is still the fourth leading cause of cancer-related death worldwide. This may be due to the high rate of patients who are diagnosed with GC at advanced stages. However, in countries such as Japan with endoscopic screening systems, more than half of GCs are discovered at an early stage, enabling endoscopic resection (ER). Especially after the introduction of endoscopic submucosal dissection (ESD) in Japan around 2000, a high en bloc resection rate allowing pathological assessment of margin and depth has become possible. While ER is a diagnostic method of treatment and may not always be curative, it is widely accepted as standard treatment because it is less invasive than surgery and can provide an accurate diagnosis for deciding whether additional surgery is necessary. The curability of ER is currently assessed by the completeness of primary tumor removal and the possibility of lymph node metastasis. This review introduces methods, indications, and curability criteria for ER of EGC. Despite recent advances, several problems remain unsolved. This review will also outline the latest evidence concerning future issues.

The feasibility of a novel injectable hydrogel for protecting artificial gastrointestinal ulcers after endoscopic resection: an animal pilot study.

Recently, covering materials for protecting post-endoscopic ulcers are being developed using hydrogels. Existing hydrogels are not ideal coating materials because it is difficult to control their physical properties. Therefore, we conducted an animal pilot study to investigate the protective effect of a novel ulcer coating material, whose physical properties can be easily controlled and designed. We applied the novel injectable hydrogel to artificial ulcers induced on the gastric mucosa of rats. Rats were assigned to the hydrogel or the control group. To measure the protective effect of hydrogel on ulcers, the perforation rate, ulcer diameter, and ulcer area were evaluated 48 h after gel application. As secondary endpoints, we assessed the residual rate of the hydrogel at the bottom of the ulcer, performed histological analysis, and analyzed adverse events associated with hydrogel. The perforation rate was significantly lower (16% vs. 75%) and the mean diameter of ulcers was significantly smaller (5.4 ± 1.8 mm vs. 7.8 ± 2.8 mm) in the hydrogel group. Histopathological findings revealed the inflammatory cell count was significantly higher in the control group. Our novel hydrogel showed a protective effect on artificial gastric ulcers in a rat model.

The natural history of sporadic non-ampullary duodenal epithelial tumors: Can we wait and see?

Objectives: The natural history of sporadic non-ampullary duodenal epithelial tumors (SNADETs) is poorly documented. The aim of this study was to evaluate the history of SNADETs in patients where immediate resection could not be performed. Methods: This is a single-center retrospective study of 86 consecutive cases of SNADETs who did not undergo immediate resection and were followed-up with upper gastrointestinal endoscopy for more than 6 months. Results: During a follow-up period of 36.8 (6.0-613.0) months, macroscopic progression was admitted in eight (9.3%). Of these, the final histology in four was adenocarcinoma, and three cases demonstrated submucosal invasion. Rates of macroscopic progression at 150 months after detection were 11.1%, 16.7%, and 30.0% for SNADETs <5 mm, <10 mm, and ≥10 mm, respectively. Conclusion: The overall risk of SNADETs progressing to invasive cancer is low. However, changes in macroscopic size or shape of SNADETs signify a high risk of progression to invasive cancer.