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The small intestine is the main organ for nutrient absorption, and its extensive resection leads to malabsorption and wasting conditions referred to as short bowel syndrome (SBS). Organoid technology enables an efficient expansion of intestinal epithelium tissue in vitro 1 , but reconstruction of the whole small intestine, including the complex lymphovascular system, has remained challenging 2 . Here we generate a functional small intestinalized colon (SIC) by replacing the native colonic epithelium with ileum-derived organoids. We first find that xenotransplanted human ileum organoids maintain their regional identity and form nascent villus structures in the mouse colon. In vitro culture of an organoid monolayer further reveals an essential role for luminal mechanistic flow in the formation of villi. We then develop a rat SIC model by repositioning the SIC at the ileocaecal junction, where the epithelium is exposed to a constant luminal stream of intestinal juice. This anatomical relocation provides the SIC with organ structures of the small intestine, including intact vasculature and innervation, villous structures, and the lacteal (a fat-absorbing lymphatic structure specific to the small intestine). The SIC has absorptive functions and markedly ameliorates intestinal failure in a rat model of SBS, whereas transplantation of colon organoids instead of ileum organoids invariably leads to mortality. These data provide a proof of principle for the use of intestinal organoids for regenerative purposes, and offer a feasible strategy for SBS treatment. In a rat model of short bowel syndrome, transplantation of small intestinal organoids into the colon partially restores intestinal function and improves survival—a proof of principle that organoid transplantation might have therapeutic benefit.

Background For almost 30 years, transanal endoscopic microsurgery (TEM) has been the mainstay treatment for large rectal lesions. With the advent of endoscopic submucosal dissection (ESD), flexible endoscopy has aimed at en bloc R0 resection of superficial lesions of the digestive tract. This systematic review and meta-analysis compared the safety and effectiveness of ESD and full-thickness rectal wall excision by TEM in the treatment of large nonpedunculated rectal lesions preoperatively assessed as noninvasive. Methods A systematic review of the literature published between 1984 and 2010 was conducted (Registration no. CRD42012001882). Data were integrated with those from the original databases requested from the study authors when needed. Pooled estimates of the proportions of patients with en bloc R0 resection, complications, recurrence, and need for further treatment in the ESD and TEM series were compared using random-effects single-arm meta-analysis. Results This review included 11 ESD and 10 TEM series (2,077 patients). The en bloc resection rate was 87.8 % (95 % confidence interval [CI] 84.3–90.6) for the ESD patients versus 98.7 % (95 % CI 97.4–99.3 %) for the TEM patients ( P  < 0.001). The R0 resection rate was 74.6 % (95 % CI 70.4–78.4 %) for the ESD patients versus 88.5 % (95 % CI 85.9–90.6 %) for the TEM patients ( P  < 0.001). The postoperative complications rate was 8.0 % (95 %, CI 5.4–11.8 %) for the ESD patients versus 8.4 % (95 % CI 5.2–13.4 %) for the TEM patients ( P  = 0.874). The recurrence rate was 2.6 % (95 % CI 1.3–5.2 %) for the ESD patients versus 5.2 % (95 % CI 4.0–6.9 %) for the TEM patients ( P  < 0.001). Nevertheless, the rate for the overall need of further abdominal treatment, defined as any type of surgery performed through an abdominal access, including both complications and pathology indications, was 8.4 % (95 % CI 4.9–13.9 %) for the ESD patients versus 1.8 % (95 % CI 0.8–3.7 %) for the TEM patients ( P  < 0.001). Conclusions The ESD procedure appears to be a safe technique, but TEM achieves a higher R0 resection rate when performed in full-thickness fashion, significantly reducing the need for further abdominal treatment.

BackgroundThe duodenum has become a metabolic treatment target through bariatric surgery learnings and the specific observation that bypassing, excluding or altering duodenal nutrient exposure elicits favourable metabolic changes. Duodenal mucosal resurfacing (DMR) is a novel endoscopic procedure that has been shown to improve glycaemic control in people with type 2 diabetes mellitus (T2D) irrespective of body mass index (BMI) changes. DMR involves catheter-based circumferential mucosal lifting followed by hydrothermal ablation of duodenal mucosa. This multicentre study evaluates safety and feasibility of DMR and its effect on glycaemia at 24 weeks and 12 months.MethodsInternational multicentre, open-label study. Patients (BMI 24–40) with T2D (HbA1c 59–86 mmol/mol (7.5%–10.0%)) on stable oral glucose-lowering medication underwent DMR. Glucose-lowering medication was kept stable for at least 24 weeks post DMR. During follow-up, HbA1c, fasting plasma glucose (FPG), weight, hepatic transaminases, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), adverse events (AEs) and treatment satisfaction were determined and analysed using repeated measures analysis of variance with Bonferroni correction.ResultsForty-six patients were included of whom 37 (80%) underwent complete DMR and 36 were finally analysed; in remaining patients, mainly technical issues were observed. Twenty-four patients had at least one AE (52%) related to DMR. Of these, 81% were mild. One SAE and no unanticipated AEs were reported. Twenty-four weeks post DMR (n=36), HbA1c (−10±2 mmol/mol (−0.9%±0.2%), p<0.001), FPG (−1.7±0.5 mmol/L, p<0.001) and HOMA-IR improved (−2.9±1.1, p<0.001), weight was modestly reduced (−2.5±0.6 kg, p<0.001) and hepatic transaminase levels decreased. Effects were sustained at 12 months. Change in HbA1c did not correlate with modest weight loss. Diabetes treatment satisfaction scores improved significantly.ConclusionsIn this multicentre study, DMR was found to be a feasible and safe endoscopic procedure that elicited durable glycaemic improvement in suboptimally controlled T2D patients using oral glucose-lowering medication irrespective of weight loss. Effects on the liver are examined further.Trial registration number NCT02413567

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.

ObjectiveHydrothermal duodenal mucosal resurfacing (DMR) is a safe, outpatient endoscopic procedure. REVITA-2, a double-blind, superiority randomised controlled trial, investigates safety and efficacy of DMR using the single catheter Revita system (Revita DMR (catheter and system)), on glycaemic control and liver fat content in type 2 diabetes (T2D).DesignEligible patients (haemoglobin A1c (HbA1c) 59–86 mmol/mol, body mass index≥24 and ≤40 kg/m2, fasting insulin >48.6 pmol/L, ≥1 oral antidiabetic medication) enrolled in Europe and Brazil. Primary endpoints were safety, change from baseline in HbA1c at 24 weeks, and liver MRI proton-density fat fraction (MRI-PDFF) at 12 weeks.ResultsOverall mITT (DMR n=56; sham n=52), 24 weeks post DMR, median (IQR) HbA1c change was −10.4 (18.6) mmol/mol in DMR group versus −7.1 (16.4) mmol/mol in sham group (p=0.147). In patients with baseline liver MRI-PDFF >5% (DMR n=48; sham n=43), 12-week post-DMR liver-fat change was −5.4 (5.6)% in DMR group versus −2.9 (6.2)% in sham group (p=0.096). Results from prespecified interaction testing and clinical parameter assessment showed heterogeneity between European (DMR n=39; sham n=37) and Brazilian (DMR n=17; sham n=16) populations (p=0.063); therefore, results were stratified by region. In European mITT, 24 weeks post DMR, median (IQR) HbA1c change was –6.6 mmol/mol (17.5 mmol/mol) versus –3.3 mmol/mol (10.9 mmol/mol) post-sham (p=0.033); 12-week post-DMR liver-fat change was –5.4% (6.1%) versus –2.2% (4.3%) post-sham (p=0.035). Brazilian mITT results trended towards DMR benefit in HbA1c, but not liver fat, in context of a large sham effect. In overall PP, patients with high baseline fasting plasma glucose ((FPG)≥10 mmol/L) had significantly greater reductions in HbA1c post-DMR versus sham (p=0.002). Most adverse events were mild and transient.ConclusionsDMR is safe and exerts beneficial disease-modifying metabolic effects in T2D with or without non-alcoholic liver disease, particularly in patients with high FPG.Trial registration numberNCT02879383

Endoscopic submucosal dissection (ESD) allows for curative resection of superficial neoplasms of the gastrointestinal tract. Although ESD is the standard of care in Japan, its adoption in the West has been slow. Recent studies have shown the advantages of ESD over endoscopic mucosal resection, and as many of the barriers to ESD have been overcome, we are seeing an increasing interest in this technique. ESD can be used to treat superficial gastric, esophageal, and colorectal lesions. The most important pre-procedure step is estimating the depth of invasion of a lesion and by proxy the risk of lymph node metastasis. After a lesion has been resected, the histopathological analysis will determine whether the resection was curative or whether further surgery is needed. In conclusion, ESD is being more widely used in the West, and it is important to understand the indications, limitations, and techniques of ESD.

Objective Wide-field endoscopic mucosal resection (WF-EMR) is an alternative to surgery for treatment of advanced colonic mucosal neoplasia up to 120 mm in size, but has been criticised for its potentially high recurrence rates. We aimed to quantify recurrence at 4 months (early) and 16 months (late) following successful WF-EMR and identify its risk factors and clinical significance. Design Ongoing multicentre, prospective, intention-to-treat analysis of sessile or laterally spreading colonic lesions ≥20 mm in size referred for WF-EMR to seven academic endoscopy units. Surveillance colonoscopy (SC) was performed 4 months (SC1) and 16 months (SC2) after WF-EMR, with photographic documentation and biopsy of the scar. Results 1134 consecutive patients were enrolled when 1000 successful EMRs were achieved, of whom 799 have undergone SC1. 670 were normal. Early recurrent/residual adenoma was present in 128 (16.0%, 95% CI 13.6% to 18.7%). One case was unknown. The recurrent/residual adenoma was diminutive in 71.7% of cases. On multivariable analysis, risk factors were lesion size >40 mm, use of argon plasma coagulation and intraprocedural bleeding. Of 670 with normal SC1, 426 have undergone SC2, with late recurrence present in 17 cases (4.0%, 95% CI 2.4% to 6.2%). Overall, recurrent/residual adenoma was successfully treated endoscopically in 135 of 145 cases (93.1%, 95% CI 88.1% to 96.4%). If the initial EMR was deemed successful and did not contain submucosal invasion requiring surgery, 98.1% (95% CI 96.6% to 99.0%) were adenoma-free and had avoided surgery at 16 months following EMR. Conclusions Following colonic WF-EMR, early recurrent/residual adenoma occurs in 16%, and is usually unifocal and diminutive. Risk factors were identified. Late recurrence occurs in 4%. Overall, recurrence was managed endoscopically in 93% of cases. Recurrence is not a significant clinical problem following WF-EMR, as with strict colonoscopic surveillance, it can be managed endoscopically with high success rates. Trial registration number: NCT01368289.

ObjectiveTo compare the cost-effectiveness of endoscopic submucosal dissection (ESD) and wide-field endoscopic mucosal resection (WF-EMR) for removing large sessile and laterally spreading colorectal lesions (LSLs) >20 mm.DesignAn incremental cost-effectiveness analysis using a decision tree model was performed over an 18-month time horizon. The following strategies were compared: WF-EMR, universal ESD (U-ESD) and selective ESD (S-ESD) for lesions highly suspicious for containing submucosal invasive cancer (SMIC), with WF-EMR used for the remainder. Data from a large Western cohort and the literature were used to inform the model. Effectiveness was defined as the number of surgeries avoided per 1000 cases. Incremental costs per surgery avoided are presented. Sensitivity and scenario analyses were performed.Results1723 lesions among 1765 patients were analysed. The prevalence of SMIC and low-risk-SMIC was 8.2% and 3.1%, respectively. Endoscopic lesion assessment for SMIC had a sensitivity and specificity of 34.9% and 98.4%, respectively. S-ESD was the least expensive strategy and was also more effective than WF-EMR by preventing 19 additional surgeries per 1000 cases. 43 ESD procedures would be required in an S-ESD strategy. U-ESD would prevent another 13 surgeries compared with S-ESD, at an incremental cost per surgery avoided of US$210 112. U-ESD was only cost-effective among higher risk rectal lesions.ConclusionS-ESD is the preferred treatment strategy. However, only 43 ESDs are required per 1000 LSLs. U-ESD cannot be justified beyond high-risk rectal lesions. WF-EMR remains an effective and safe treatment option for most LSLs.Trial registration numberNCT02000141.

INTRODUCTION:Underwater endoscopic mucosal resection (UEMR) and cold snare polypectomy (CSP) are novel endoscopic procedures for superficial nonampullary duodenal epithelial tumors (SNADET). However, consensus on how to use both procedures appropriately has not been established. In this study, we evaluated treatment outcomes of both procedures, including resectability.METHODS:In this single-center randomized controlled study conducted between January 2020 and June 2022, patients with SNADET ≤12 mm were randomly allocated to UEMR and CSP groups. The primary end point was sufficient vertical R0 resection (SVR0), which was defined as R0 resection including a sufficient submucosal layer. We compared treatment outcomes including SVR0 rate between groups.RESULTS:The SVR0 rate was significantly higher in the UEMR group than in the CSP group (65.6% vs 41.5%, P = 0.01). By contrast, the R0 resection rate was not significantly different between study groups (70.3% vs 61.5%, P = 0.29). The submucosal layer thickness was significantly greater in the UEMR group than in the CSP group (median 546 [range, 309-833] μm vs 69 [0-295] μm, P < 0.01). CSP had a shorter total procedure time (median 12 [range, 8-16] min vs 1 [1-3] min, P < 0.01) and fewer total bleeding events (9.4% vs 1.5%, P = 0.06).DISCUSSION:UEMR has superior vertical resectability compared with CSP, but CSP has a shorter procedure time and fewer bleeding events. Although CSP is preferable for most small SNADET, UEMR should be selected for lesions that cannot be definitively diagnosed as mucosal low-grade neoplasias.

Colorectal cancer is a major cause of death in Japan, where it accounts for the largest number of deaths from malignant neoplasms among women and the third largest number among men. Many new methods of treatment have been developed during recent decades. The Japanese Society for Cancer of the Colon and Rectum Guidelines 2014 for treatment of colorectal cancer (JSCCR Guidelines 2014) have been prepared as standard treatment strategies for colorectal cancer, to eliminate treatment disparities among institutions, to eliminate unnecessary treatment and insufficient treatment, and to deepen mutual understanding among health-care professionals and patients by making these guidelines available to the general public. These guidelines have been prepared as a result of consensuses reached by the JSCCR Guideline Committee on the basis of careful review of evidence retrieved by literature searches and taking into consideration the medical health insurance system and actual clinical practice in Japan. They can, therefore, be used as a guide for treating colorectal cancer in clinical practice. More specifically, they can be used as a guide to obtaining informed consent from patients and choosing the method of treatment for each patient. As a result of the discussions of the Guideline Committee, controversial issues were selected as clinical questions, and recommendations were made. Each recommendation is accompanied by a classification of the evidence and a classification of recommendation categories, on the basis of consensus reached by Guideline Committee members. Here we present the English version of the JSCCR Guidelines 2014.