Short-term outcomes of endoscopic resection for colorectal neuroendocrine tumors: Japanese multicenter prospective C-NET STUDY.

OBJECTIVES: The incidence of colorectal neuroendocrine tumors (NETs) has increased with colorectal cancer screening programs and increased colonoscopies. The management of colorectal NETs has recently shifted from radical surgery to endoscopic resection. We aimed to evaluate the short-term outcomes of various methods of endoscopic resection for colorectal NETs. METHODS: Among those registered in the C-NET STUDY, patients with colorectal NETs who underwent endoscopic treatment as the initial therapy were included. Short-term outcomes, such as the en bloc resection rate and R0 resection (en bloc resection with tumor-free margin) rate, were analyzed based on treatment modalities. RESULTS: A total of 472 patients with 477 colorectal NETs received endoscopic treatment. Of these, 418 patients with 421 lesions who met the eligibility criteria were included in the analysis. The median age of the patients was 55 years, and 56.9% of them were men. The lower rectum was the most commonly affected site (88.6%), and lesions <10 mm accounted for 87% of the cases. Endoscopic submucosal resection with a ligation device (ESMR-L, 56.5%) was the most common method, followed by endoscopic submucosal dissection (ESD, 31.4%) and endoscopic mucosal resection using a cap (EMR-C, 8.5%). R0 resection rates <10 mm were 95.5%, 94.8%, and 94.3% for ESMR-L, ESD, and EMR-C, respectively. All 16 (3.8%) patients who developed treatment-related complications could be treated conservatively. Overall, 23 (5.5%) patients had incomplete resection without independent clinicopathological risk factors. CONCLUSION: ESMR-L, ESD, and EMR-C were equally effective and safe for colorectal NETs with a diameter <10 mm.

Characteristics of colorectal neuroendocrine tumors in patients prospectively enrolled in a Japanese multicenter study: a first report from the C-NET STUDY.

BACKGROUND: This is the first report from a multicenter prospective cohort study of colorectal neuroendocrine tumor (NET), the C-NET STUDY, conducted to assess the long-term outcomes of the enrolled patients. This report aimed to elucidate the clinicopathological features of the enrolled patients and lesions. METHODS: Colorectal NET patients aged 20-74 years were consecutively enrolled and followed up at 50 institutions. The baseline characteristics and clinicopathological findings at enrollment and treatment were assessed. RESULTS: A total of 495 patients with 500 colorectal NETs were included. The median patient age was 54 years, and 85.3% were asymptomatic. The most frequent lesion location was the lower rectum (88.0%); 99.4% of the lesions were clinically diagnosed to be devoid of metastatic findings, and 95.4% were treated with endoscopic resection. Lesions < 10 mm comprised 87.0% of the total, 96.6% had not invaded the muscularis propria, and 92.6% were classified as WHO NET grade 1. Positive lymphovascular involvement was found in 29.2% of the lesions. Its prevalence was high even in small NETs with immunohistochemical/special staining for pathological assessment (26.4% and 40.9% in lesions sized < 5 mm and 5-9 mm, respectively). Among 70 patients who underwent radical surgery primarily or secondarily, 18 showed positive lymph node metastasis. CONCLUSIONS: The characteristics of real-world colorectal NET patients and lesions are elucidated. The high positivity of lymphovascular involvement in small NETs highlights the necessity of assessing the clinical significance of positive lymphovascular involvement based on long-term outcomes, which will be examined in later stages of the C-NET STUDY. TRIAL REGISTRATION NUMBER: UMIN000025215.

Impact of the Concomitant Use of Immunomodulator and a Lower Week 8 Partial Mayo Score on the Persistence of Adalimumab in Refractory Ulcerative Colitis.

Objective Real-world data of adalimumab (ADA) in the treatment of ulcerative colitis (UC) are scarce. We aimed to study the ADA response rates and predictors of response in UC treatment. Methods This observational, prospective and multi-center study assessed the clinical outcome of refractory UC patients treated with ADA who previously had an inadequate response to either conventional therapies or other anti-TNF antibodies or tacrolimus. The primary endpoint was the proportion of UC patients achieving a clinical response and remission at 8 and 52 weeks. We also evaluated the parameters which were associated with a clinical response at 8 and 52 weeks. Results A total of 35 patients were enrolled from 11 centers. The clinical responses at 8 and 52 weeks were 60.0% and 51.4%, respectively. The clinical remission rates at 8 and 52 weeks were 45.7% and 48.6%, respectively. Positive predictors for week 52 response were combination of ADA with immunomodulator (IM) (OR: 27.229; 95% CI; 1.897-390.76; p=0.015) and a week 8 lower partial Mayo score (OR: 0.406; 95% CI; 0.204-0.809; p=0.010). A receiver operation characteristic curve analysis revealed the optimal week 8 partial Mayo score to be 2.5, therefore a partial Mayo score of ≤2 was a positive predictor for the continuation of ADA. No malignancy or death occurred during this study. Conclusion ADA was effective for inducing and maintaining both a clinical response and remission in patients with refractory UC. It remains possible that the concomitant use of IM and a week 8 partial Mayo score of ≤2 may predict the long-term response of ADA.

Predicting a rapid response to adalimumab treatment and favorable short-term outcomes through the high platelet count in patients with ulcerative colitis: A multicenter retrospective cohort study.

This study aimed to investigate the short-term effectiveness of adalimumab therapy in patients with ulcerative colitis (UC), especially its rapid response.This retrospective, multicenter, cohort study involved 7 institutes in Japan, compiling data from patients with UC who had received at least 1 induction dose of 160 mg of adalimumab between June 2013 and May 2017. Patients should have a Lichtiger clinical activity index score of ≥5 at the initial adalimumab administration. Remission was defined as clinical activity index score of ≤4, whereas response was defined as a reduction of ≥50% from the baseline value. Rapid responders are defined as patients who achieved response at 2 weeks.A total of 91 patients were included in this study: 37.4% and 45.1% achieved clinical response at 2 and 8 weeks, respectively, whereas clinical remission rates 12 weeks were 45.1%. Among the rapid responders, 82.4% achieved clinical remission at 12 weeks. Multivariate logistic regression analysis identified a higher platelet count as an independent prognostic factor for a higher rate of rapid response. Receiver operating characteristic curve showed that a platelet counts cutoff value of ≥312 × 10/L was associated with a rapid response.Approximately 40% of patients with UC showed a rapid response to adalimumab therapy after 2 weeks. Up to 80% of the rapid responders also achieved remission at 12 weeks. A higher platelet count was identified as an independent prognostic factor for a higher rapid response rate.

Learning Effect of Diagnosing Depth of Invasion Using Non-Extension Sign in Early Gastric Cancer.

BACKGROUND: Determining the depth of invasion is important when considering therapeutic strategies for early gastric cancer (EGC). We determined the effects of learning the non-extension sign, that is, an index of T1b2 in EGC, on identifying its depth of invasion. METHODS: Endoscopic images of 40 EGC cases (20 showing positive non-extension sign on endoscopy as T1b2 and 20 showing negative non-extension sign on endoscopy as T1a-T1b1) were randomly displayed on PowerPoint. Participants read endoscopy findings (pretest) and attended a 60-min lecture on how to read the non-extension sign. Then, they read the same images using the non-extension sign as the marker (posttest). The primary endpoint was a change in accuracy rate for determining the depth of invasion before and after attending the lecture, for nonexperts (< 80%). RESULTS: Among 35 endoscopists, 12 were nonexperts; their test results were used for analyses. Accuracy rates for pretest and posttest among nonexperts were 75.2 and 82.5%, respectively, showing a significant increase in the accuracy rate after learning to read the non-extension sign (p = 0.003). CONCLUSION: Nonexperts' diagnostic ability to determine the depth of invasion of EGC improved by learning to read the non-extension sign. Thus, the non-extension sign is considered a simple and useful diagnostic marker.

[Tracheobronchitis as an extraintestinal manifestation of Crohn's disease].

A 27-year-old woman with Crohn's disease, who had sustained clinical remission for two years following treatment with mesalazine and nutrition therapy, was admitted to our hospital complaining of dry cough, mild dysphagia, and slight fever. A computed tomography of the chest demonstrated an increase in the thickness of the tracheal wall. Bronchoscopy showed a diffusely erythematous and edematous mucosa with whitish granular lesions in the trachea and main carina. Bronchial biopsy specimens showed epithelioid cell granuloma. We diagnosed tracheobronchitis as an extraintestinal manifestation of Crohn's disease. She was treated with 40mg/day prednisolone. Her symptoms improved immediately. However, dry cough recurred two months after prednisolone treatment, and further treatment with inhaled steroids was prescribed. Tracheobronchial involvement in Crohn's disease is rare, with only 13 cases having been reported. Tracheal involvement should be considered in Crohn's disease patients with respiratory symptoms.

Endoscopic submucosal dissection of squamous cell carcinoma in the upper stomach 5 years after chemoradiotherapy for adenocarcinoma.

Primary squamous cell carcinoma is rarely observed, with a reported incidence of 0.04-0.07 % of all gastric cancers. An 81-year-old male underwent chemoradiotherapy for type 1 gastric cancer of the posterior wall of the cardiac region in 2005. The tumor disappeared after 1 year of therapy, following which an area of white epithelium, approximately 30 mm in diameter and continuous with the esophageal mucosa, became visible. Biopsy of the white epithelium indicated normal squamous epithelium. An elevated lesion was subsequently detected in the area of white epithelium on upper gastrointestinal endoscopy during a follow-up examination 5 years after therapy. As a biopsy of the same site indicated squamous cell carcinoma, we performed endoscopic submucosal dissection. Histopathological examination indicated high-grade fibrosis due to radiotherapy and showed a moderately differentiated squamous cell carcinoma invading the scarred portion. We describe a case where the developmental process of a squamous cell carcinoma was observed using endoscopy, including narrow band imaging with magnification. This carcinoma likely originated from squamous metaplasia that developed after chemoradiotherapy was administered for a gastric cancer.

[A case of IgG4-related sclerosing disorders involving the mesentery and the pancreas].

A 78-year-old man presented with upper abdominal pain. He underwent an abdominal computed tomography scan which revealed irregularly shaped mass lesions in the mesentery and in the pancreatic head and body. The mass lesions were suspected to be pancreatic cancer with peritoneal dissemination and a surgical biopsy was performed. Histologic studies revealed lymphoplasmacytic sclerosing pancreatitis with significant infiltration of IgG4-positive plasma cells. His serum IgG4 level was 223 mg/dl. Findings from histologic and serum studies were compatible with IgG4-related sclerosing disorders. The mass lesions responded to steroid therapy and disappeared. The difficulty in making a definitive diagnosis is discussed.

A case of postirradiation angiosarcoma of the greater omentum with hemorrhage.

Angiosarcoma, one of the least common sarcomas, occurs most commonly in the skin and soft tissues, and postirradiation angiosarcoma of the greater omentum is extremely rare. Only one reported case of postirradiation angiosarcoma involved the greater omentum. We describe the case of 74-year-old female with a history of cervical cancer treated with abdominal irradiation 5 years before. On admission, she had nausea, vomiting anorexia, and fatigue. She underwent an abdominal computed tomography scan that revealed an irregularly shaped tumor bounded by transverse colon. The patient died on the 34th hospital day. Autopsy revealed that the tumor was composed of anastomosing irregular vascular channels of variable calibers, involving the adipose tissue of the omentum. Histological studies suggested angiosarcoma. The definitive diagnosis was postirradiation angiosarcoma of the greater omentum, which is an extremely rare condition with an overall dismal prognosis.