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Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are globally accepted minimally invasive treatments for superfcial gastrointestinal (GI) neoplasms. Especially, development of ESD has dramatically changed the way of management of superfcial GI cancers with negligible risk for lymph node metastasis. It achieves necessary and sufcient horizontal and vertical margins regardless of the size and the location of the lesion. Because of the great merit of this technique, it spread quickly throughout Japan and has become a standard practice. As a result, more than half of T1 (intramucosal or submucosal) gastric cancer is treated by endoscopic treatment alone in Japan, and target organs of ESD have been expanded to most of GI tract even for difcult location such as distal side of duodenum. As mentioned above, ESD has no boundary of the size for horizontal (lateral) direction, but there is a boundary of the depth for vertical direction and it is not suitable for cancers invading to deeper submucosal layer and muscularis propria (MP) or submucosal tumor (SMT) arising from MP. In this piece, we highlight several novel and emerging approaches for the treatment of gastric and duodenal neoplasms, including laparoscopy endoscopy cooperative surgery (LECS) and endoscopic closure techniques

BackgroundSmall bowel lesions of Crohn’s disease (CD) are known to be associated with a poor prognosis; however, endoscopic healing leads to favorable patients’ outcome. The aim of this study was to clarify the clinical impact of assessing deep small bowel lesions (DSB) using balloon-assisted enteroscopy (BAE) on CD patients in clinical remission.MethodsFrom January 2012 to July 2018, a total of 100 CD patients in clinical remission were enrolled to undergo trans-anal enteroscopy using single-balloon enteroscope. Endoscopic evaluations at the terminal ileum (TI) were performed using a partial Simple Endoscopic Score for CD (pSES-CD). Endoscopic evaluations at the DSB used a modified partial SES-CD (mpSES-CD). We evaluated the factors associated with relapse, and the correlation of endoscopic score between the TI and DSB. For this study, relapse was defined as hospitalization within a year from enteroscopy.Results30 patients (30.0%) relapsed within a year from enteroscopy. Multivariate logistic regression analysis revealed that the Harvey–Bradshaw Index (OR 1.77, 95% CI 1.18–2.65; p = 0.003) and an mpSES-CD at DSB (OR 3.10, 95% CI 1.86–5.15; p = 0.001) were independent predictors for relapse, whereas a SES-CD at the TI did not exhibit independence. There was a significant correlation trend between the relapse rate and greater than 5 points of an mpSES-CD at DSB; however, there was no correlation between the relapse rate and pSES-CD at the TI.ConclusionEven when Crohn's disease is in remission, it is important to evaluate DSB using BAE to assess endoscopic mucosal healing.

To compare the effectiveness of the novel hemostatic peptide, TDM-621, with that of conventional hemostatic methods in treating intraoperative blood oozing during endoscopic submucosal dissection (ESD). This multicenter, open-label, randomized controlled trial involved 227 patients with gastric and rectal epithelial tumors in whom ESD was indicated. Patients in whom the source of blood oozing was difficult to identify with waterjet washing during the procedure and required hemostasis with hemostatic forceps were randomly assigned to the TDM-621 and control groups. The TDM-621 group (in which hemostasis was achieved with TDM-621, followed by coagulation hemostasis with hemostatic forceps, as needed) was compared with the control group (in which hemostasis was achieved with hemostatic forceps). The primary end point was the mean number of coagulations with hemostatic forceps, determined by a blinded independent review committee. The secondary end points were the rate of achievement of hemostasis with only TDM-621, the dosage of TDM-621, and adverse events in the TDM-621 group. The mean number of coagulations with hemostatic forceps was significantly reduced in the TDM-621 group (1.0 ± 1.4) compared with that in the control group (4.9 ± 5.2) ( P < 0.001). The rate of hemostasis achievement with only TDM-621 was 62.2%; the mean dosage of TDM-621 was 1.75 ± 2.14 mL. The rates of grade ≥3 adverse events were 6.2% and 5.0% in the TDM-621 and control groups, respectively. TDM-621 is a useful, easily operable hemostatic peptide for treatment of blood oozing during gastric and rectal ESD, with no serious safety concerns.

Although superficial non‐ampullary duodenal epithelial tumor (SNADET) was previously considered a rare disease, in recent years, the opportunities to detect and treat SNADET are increasing. Considering the high morbidity of pancreatoduodenectomy, endoscopic resection can be a treatment option that preserves the organs and contributes maintain patients’ quality of life. Endoscopic mucosal resection (EMR) is a standard treatment for relatively small lesions in gastrointestinal tracts, however, it is difficult because submucosal fibrosis frequently occurs due to the previous biopsy. Recently, some modified EMR techniques including underwater EMR (UEMR) and cold polypectomy (CP) have been proposed. In UEMR, the duodenal lumen is filled with water or saline and resected the targe lesion with a snare without injection into the submucosa. It would be a treatment option that could reduce candidates for ESD especially SNADET less than 20 mm. CP was reported as a safe and convenient means for SNADET. It would also be one of the standard treatments for diminutive lesions, though there remain some concerns on its resectability. ESD for SNADET is technically challenging, especially with an extremely high risk of adverse event (AE) with a reported bleeding rate of more than 20% and perforation rate up to about 40%. However, modified treatment techniques including the water pressure method and pocket creation method have been reported to potentially contribute to improving outcomes of ESD. Moreover, accumulated evidence shows closing the mucosal defect significantly reduces delayed adverse events after duodenal endoscopic treatments. Further studies are warranted to elucidate curative criteria, long‐term outcomes, and appropriate surveillance strategy.

Background and AimsEndoscopic mucosal resection (EMR) and Underwater EMR have been reported as effective endoscopic treatment for superficial duodenal tumor (SDET). However, a notable problem of EMR for SDET is technical difficulty for the lesion with non-lifting sign, and it of UEMR is that en bloc resection rate is relatively low. Therefore, we performed partial submucosal injection combining UEMR (PI-UEMR). The aim of this study is to evaluate feasibility and safety of this technique for duodenal tumor.MethodsThis is a prospective observational study from tertiary care hospital. We performed PI-UEMR in patients with SDET that is 13–20 mm in diameter, or less than 13 mm with technical difficulty for EMR and UEMR from January 2019 to March 2020. Primary outcome was en bloc resection rate. Secondary outcomes were R0 resection rate, mean total procedure time, intra- and post-procedure complication.ResultsThirty patients were included in this study. Mean age was 62 ± 12 years old. Three fourths lesions were located at anal side from major papilla. Median lesion size was 12 mm [IQR 10–16 mm]. Twenty-four cases were taken endoscopic biopsy in prior hospital and observed biopsy scar. En bloc resection rate was 97%. Ro resection rate was 83%. Mean total procedure time was 17 ± 12 min. And there was an only one case of complication, intra-procedure bleeding that was controllable endoscopically.ConclusionsPI-UEMR might be very useful and safe technique of endoscopic resection for SDET including relatively large lesions.

Conventional endoscopic resection (CER) is a widely accepted treatment for early colorectal neoplasia; however, large colorectal neoplasias remain problematic, as they necessitate piecemeal resection, increasing the risk of local recurrence. Endoscopic submucosal dissection (ESD) can improve the en bloc resection rate. This study aimed to evaluate local recurrence and its associated risk factors after endoscopic resection (ER) for colorectal neoplasias ≥20 mm. A multicenter prospective study at 18 medium- and high-volume specialized institutions was conducted in Japan. Follow-up colonoscopy was performed after 12 months in cases of complete resection and after 3-6 months in cases of incomplete resection. Local recurrence was confirmed by endoscopic findings and/or pathological analysis. Follow-up colonoscopy was performed in 1,524 of 1,845 enrolled colorectal neoplasias (mean age, 65 years; 885 men; median tumor size, 32.8 mm). The local recurrence rates were 4.3% (65/1,524), 6.8% (55/808), and 1.4% (10/716) for the entire cohort, for CER, and for ESD, respectively. The relative risks of local recurrence were 0.21 (95% confidence interval, 0.11-0.39) with ESD compared with CER, 0.32 (95% confidence interval, 0.11-0.92) with en bloc ESD compared with en bloc CER, and 0.90 (95% confidence interval, 0.39-2.12) with piecemeal ESD compared with piecemeal CER. Significant factors associated with local recurrence were piecemeal resection, laterally spreading tumors of granular type, tumor size ≥40 mm, no pre-treatment magnification, and ≤10 years of experience in CER, and piecemeal resection only in ESD. En bloc ESD reduces the local recurrence rate for large colorectal neoplasias. Piecemeal resection is the most important risk factor for local recurrence regardless of the ER method used.

BackgroundDifferential diagnosis of superficial duodenal epithelial tumors (SDETs) and non-neoplastic lesions (NNLs) in duodenum by endoscopy is difficult. Here, we attempted to distinguish them by magnified endoscopic examination with image-enhanced endoscopy (IEE-ME).MethodsVarious IEE-ME findings of 95 SDETs who underwent endoscopic resection and 58 NNLs who underwent biopsy were retrospectively reviewed.ResultsWhen we compared the IEE-ME findings of SDETs and NNLs, the presence of demarcation line (DL) (97.9% vs. 79.3%, P = 0.0002), white opaque substance (WOS) (84.2% vs. 1.7%, P < 0.0001) and light blue crest (LBC) (93.7% vs. 32.8%, P < 0.0001) and the absence of enlarged marginal epithelium (EME) (98.9% vs. 62.1%, P < 0.0001) were significantly more frequent in SDETs than NNLs. When divided into each superficial structure, it was the most effective to evaluate the combination of WOS and LBC as SDET with open-loop structure (OLS), and the combination of DL and EME as SDET with closed-loop structure (CLS). However, LBC was excluded because of low inter- and intra-observer agreements. Finally, the sensitivity, specificity and accuracy for the diagnosis of SDETs were 88.4%, 98.3% and 92.2%, respectively, and we developed an algorithm for the differential diagnosis of duodenal lesions.ConclusionWe could distinguish SDET from NNL, diagnosed SDET as presence of WOS indicated OLS of superficial structure, and presence of DL and absence of EME indicated CLS of superficial structure.

Recent meta-analyses and a prospective multicenter trial of sentinel node (SN) mapping in early gastric cancer have demonstrated acceptable SN detection rates and accuracy of determination of lymph node status. SN mapping may play a key role in obtaining individual metastatic information. It also allows modification of surgical procedures, including function-preserving gastrectomy in patients with early gastric cancer. A dual-tracer method that uses radioactive colloids and blue dye is currently considered the most reliable method for the stable detection of SNs in patients with early gastric cancer. New technologies, such as indocyanine green infrared or fluorescence imaging, are also useful for accurate SN mapping in gastric cancer. Theoretically, laparoscopic function-preserving gastrectomy, including partial resection, proximal gastrectomy, segmental gastrectomy, and pylorus-preserving gastrectomy, is feasible in early gastric cancer when the SN(s) is/are nonmetastatic. Our study group conducted a multicenter prospective trial in Japan to evaluate function-preserving gastrectomy with SN mapping for long-term survival and patient quality of life. Non-exposed endoscopic wall-inversion surgery (NEWS) is a new technique for treating gastric cancer with partial resection involving full-thickness resection with endoscopy and laparoscopic surgery without transluminal access. The combination of NEWS and SN biopsy is expected to be a promising, minimally invasive, function-preserving surgery that is ideal for cases of cN0 early gastric cancer.

Tumor stromal remodeling is an obstacle for immune checkpoint inhibitors (ICI). A stroma modifying small interfering RNA (siRNA) to carbohydrate sulfotransferase 15 (CHST15) was recently shown to enhance tumor-infiltrating T cells, yet its impact on antitumor response of ICI remains unexplored. In mouse pancreatic cancer KPC and Pan02 subcutaneous syngeneic tumor models, mice were divided into 4 groups for treatment; (1) control, (2) CHST15 siRNA monotherapy, (3) anti-programmed death receptor 1 (PD-1) monotherapy, and (4) combination therapy with CHST15 siRNA and anti-PD-1 antibody. Mice were sacrificed after 2 week-treatments and anti-tumor effects were evaluated by immunohistochemistry for KPC and flow cytometry for Pan02 model, respectively. In the KPC model, combination treatment with intratumoral CHST15 siRNA (0.9–1.0 mg/kg) and systemic anti-PD-1 antibody (5 mg/kg) synergistically and robustly suppressed tumor growth with a significant increase of tumor-infiltrating CD4 + and CD8 + T cells compared to anti-PD-1 monotherapy. In the Pan02 model, combination treatment with CHST15 siRNA and anti-PD-1 showed anti-tumor effect with significant increases in % necrosis area of the tumor, and tumor-infiltrating T cells compared to the control. Notably, the combination therapy dramatically diminishes Ly6C + Ly6G + granulocytic myeloid-derived suppressor cells (MDSCs) compared to anti-PD-1 monotherapy. The present study demonstrated the robust synergy between systemic anti-PD-1 antibody and a single stroma modifying agent. Combination usage of intratumoral CHST15 siRNA would provide a novel therapeutic option to trigger the remarkable effect of ICI on this most hard-to-treat solid tumor.