Natural History of Small Gastric Subepithelial Lesions Less than 20 mm: A Multicenter Retrospective Observational Study (NUTSHELL20 Study).

BACKGROUND AND AIM: Small gastric subepithelial lesions (SELs) are sometimes encountered in daily esophagogastroduodenoscopy (EGD) practice, but whether once-annual or twice-annual endoscopy can provide sufficient follow-up remains unclear. Because follow-up based on small-SEL characteristics is important, this study clarified the natural history of gastric SELs less than 20 mm. METHODS: This retrospective multicenter observation study conducted at 24 Japanese hospitals during April 2000 to March 2020 examined small gastric SELs of ≤20 mm diameter. The primary outcome was the rate of size increase of those SELs detected using EGD, with growth times assessed irrespective of SEL pathological diagnoses. RESULTS: We examined 824 cases with tumors of 1-5 mm diameter in 298 (36.2%) cases, 6-10 mm in 344 (41.7%) cases, 11-15 mm in 112 (13.6%) cases, and 16-20 mm in 70 (8.50%) cases. An increase of small gastric SELs was observed in 70/824 patients (8.5%). The SELs larger than 6 mm increased, even after 10 years. No-change and increasing groups had no significantly different malignant findings at diagnosis. In cases of gastrointestinal stromal tumors (GISTs), internal cystic change in endoscopic ultrasound (EUS) is a risk factor for an increased tumor size. The predictive tumor growth cutoff size at initial diagnosis was 13.5 mm. CONCLUSIONS: Small gastric SELs less than 20 mm have an approximately 8.5% chance of increase. Predictive markers for GIST growth are tumor size ≥13.5 mm and internal cystic change in EUS.

Making Hematochezia of Unknown Origin Known: A Retrospective Analysis.

INTRODUCTION: Hematochezia is observed frequently in daily practice. However, natural hemostasis often prevents identification of the bleeding source during observations. This study was conducted to clarify risk factors related to rebleeding in hematochezia patients without an identified cause of bleeding. METHODS: We analyzed patients who were admitted to Dokkyo Medical University Hospital during April 1, 2009, through March 31, 2015, with the chief complaint of hematochezia. Main outcome measures included the rebleeding rate and the period until rebleeding in hematochezia patients without an identified bleeding source. RESULTS: We selected 159 patients for analyses. Rebleeding was observed in 46 (28.9%) of 159 patients. The median period until first rebleeding was 166 days (2-3,046 days). Univariate analysis indicated that risk factors for rebleeding were male gender (p = 0.029), higher age (p = 0.023), antithrombotic medicines (p = 0.047), lower hemoglobin on admission (p = 0.024), and the presence of diverticula (p = 0.002). Multivariate analysis indicated the presence of diverticula (p = 0.023) and male gender (p = 0.043) as rebleeding risk factors. DISCUSSION/CONCLUSION: In patients with hematochezia of unknown origin, risk factors for rebleeding indicated in this study, especially the presence of diverticula and male gender, should be given particular attention by physicians.

A Case of Stevens-Johnson Syndrome Complicated with Multimatrix System Mesalamine in Ulcerative Colitis.

A 41-year-old man was treated with prednisolone (PSL) and multimatrix (MMX) mesalamine for remission induction therapy of ulcerative colitis. PSL was tapered due to successful remission induction treatment. During the treatment course, ocular foreign body sensation, eyelid swelling, ocular conjunctiva hyperemia, facial redness and swelling, watery nasal discharge, stomatitis, anal pain, and reddish puffiness on the bilateral dorsum of the hands appeared, and he was diagnosed with Stevens-Johnson syndrome (SJS). SJS was improved by PSL treatment and intravenous immunoglobulin. MMX mesalamine was the causative agent by drug-induced lymphocyte stimulation test. This is the first reported case of SJS with MMX mesalamine.

Risk Factor for Vital Signs Fluctuation during Colonoscopy under Conscious Sedation Consisting of Midazolam and Meperidine.

BACKGROUND: Sedatives or analgesics are widely used to relieve a patient's discomfort during colonoscopy (CS). Although cardiopulmonary adverse events are sometimes experienced during the examination, the risk factors for vital signs fluctuation (VSF) have not been fully elucidated. This study thus aimed to identify the risk factors for VSF during the examination, as well as to evaluate the frequency and the degree of VSF. SUMMARY: A total of 755 consecutive subjects who received CS under endoscopist-administrated sedation using midazolam, meperidine, or combination of both were retrospectively analyzed. We assessed the distribution of vital signs during the procedure and frequency of VSF. To identify independent risk factors, we analyzed the association between VSF and subjects' characteristics and procedure information using the multivariate logistic regression model. Consequently, VSF was observed in 17% of all; hypotension and oxygen desaturation was observed in 13 and 5%, respectively. However, we could achieve the purpose of all procedure and, no one required hospitalization or extension of hospital stay. Multivariate analysis revealed that age (OR 1.05 [95% CI 1.04-1.07]), being female (OR 1.78 [95% CI 1.19-2.70]), and use of midazolam (OR 5.06 [95% CI 3.18-8.08]) were independent risk factors for VSF.

Usefulness of Mean Corpuscular Volume for Detection of Advanced Colorectal Cancer in Patients Older than 85 Years.

BACKGROUND/AIMS: The aim of this study was to elucidate clinical indicators for the detection of advanced colorectal cancer (ACRC). METHODS: This was a retrospective study conducted at a tertiary hospital. This study included 333 patients older than 85 years who underwent colonoscopy from April 2006 to May 2010. The detection rate of ACRC was assessed. Then, we analyzed the association between the detection of ACRC and various background factors including mean corpuscular volume (MCV). We also analyzed the cumulative overall survival of patients with detected ACRC. RESULTS: ACRC was found in 37 patients, resulting in a detection rate of 15%. Multivariate logistic regression analysis revealed that a decreased MCV was an independent predictor for the detection of ACRC (OR 0.88, 95% CI 0.84-0.94), whereas symptoms such as abdominal pain, hematochezia, or anemia were not independent predictors. MCV was an independent predictor irrespective of the location of the tumor. The cumulative survival rates at 3 and 5 years after diagnosis were 78 and 58%, respectively, during a median observational period of 30.3 months. CONCLUSION: This study demonstrated the usefulness of MCV as an indicator of the necessity of colonoscopy for older patients.

Initial Management of Colonic Diverticular Bleeding: Observational Study.

BACKGROUND/AIMS: Although colonic diverticular bleeding (CDB) often ceases spontaneously, re-bleeding occurs in about 30%. Bleeding diverticulum can be treated directly by endoscopic hemostasis; however, it is difficult to perform colonoscopy in all cases with limited medical resource and certain risks. The aim of this study was to clarify who should undergo colonoscopy as well as appropriate methods of initial management in CDB patients. METHODS: A total of 285 patients who were diagnosed as CDB and underwent colonoscopy from March 2004 to October 2015 were retrospectively analyzed. First, the association between re-bleeding and various factors including patients' background and initial management were analyzed. Second, the examination conditions that influenced bleeding point identification were analyzed. RESULTS: Of 285 patients, 187 were men and 98 were women. Median age was 75 years, and the median observation period was 17.5 months. Re-bleeding was observed in 79 patients (28%). A history of CDB (OR 2.1, p = 0.0090) and chronic kidney disease (CKD; OR 2.3, p = 0.035) were risk factors, and bleeding point identification (OR 0.20, p = 0.0037) was a preventive factor for re-bleeding. Bleeding point identification significantly reduced approximately 80% of re-bleeding. Furthermore, extravasation on CT (OR 3.7, p = 0.031) and urgent colonoscopy (OR 5.3, p < 0.001) were predictors for identification of bleeding point. Compared to bleeding point identification of 11% in all patients who underwent colonoscopy, identification rate in those who had extravasation on CT and underwent urgent colonoscopy was as high as 70%. CONCLUSIONS: Contrast-enhanced CT upon arrival is suggested, and patients with extravasation on CT would be good candidates for urgent colonoscopy, as well as patients who have a history of CDB and CKD.

[Diagnostic accuracy for alcoholic liver disease with controlled Attenuation Parameter (CAP) measured by transient elastography for the non-invasive assessment of liver steatosis].

Along with the development of interferon and therapeutic medication, the incidence of viral hepatitis constituting the largest part of liver disease decreased, and the main target in the field of liver disease is now shifting from viral hepatitis to alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) as metabolic liver disease. Although these diseases tend.to. be gathered as non-viral liver disease because the similar specific liver tissue, the natural history and etiology are considerably different between them. We need to distinguish both of them to do appropriate treatment intervention. Questioning of amount of drinking is needed, but we experience some difficult cases to understand drinking history because of a too little declaration of amount of drinking. A new ultrasonic image analyses using propagation speed in the organization of the pulse vibration wave was developed as Fibroscan by Echosens company in recent years. Fibroscan is a non-invasive test to quantify liver fibrosis as Liver Stiffness Measurement (LSM). It also detects and quantifies steatosis simultaneously using the Controlled Attenuation Parameter (CAP). CAP is a measurement of the ultrasound attenuation. We measured liver steatosis of patients using Fibroscan, and other blood tests. 63 cases of ALD, 177 cases of NAFLD, 57 cases of Virus and 271 cases of Normal were enrolled. CAP value were significantly lower in the ALD group compared with NAFLD group. (P < 0.0053, ALD 268 dB/m : NAFLD 290 dB/m) We elucidate the diagnostic accuracy of CAP using Fibroscan for ALD patients, comparing the results of them to those of virus patients and NAFLD patients.

Hereditary Diffuse Gastric Cancer Treated by Prophylactic Total Gastrectomy.

We herein report a rare case of hereditary diffuse gastric cancer in a Japanese man. A 41-year-old man underwent esophagogastroduodenoscopy which revealed a small gastric erosion. Biopsy specimens showed signet ring cell carcinoma, and endoscopic submucosal dissection was performed. The patient's elder sister had died of gastric cancer at 38 years old. Considering the family history, a genetic test was conducted and revealed a CDH1 germline mutation. Although no carcinomatous lesion was detected endoscopically, prophylactic total gastrectomy was performed. The resection specimen showed seven microlesions of signet ring cell carcinoma confined to the lamina propria mucosae.

Superficial esophageal squamous cell carcinoma with melanocytosis that was endoscopically difficult to differentiate from malignant melanoma.

Esophageal squamous cell carcinoma (SCC) with dark spots caused by melanocytosis is very rare. A reddish and flat lesion, 4 cm in length and covering over two-thirds of the circumference, was found in the midthoracic esophagus of a 66-year-old male. Multiple brown and black spots are observed in the lesion. Superficial SCC with melanocytosis or malignant melanoma was also suspected. Endoscopic submucosal dissection was performed without biopsies of the spots. Histologically, a few melanocytes were observed in the black spots, and the lesion was diagnosed as SCC (T1a-lamina propria mucosae) with melanocytosis. We report a case of esophageal SCC with dark black spots that were difficult to differentiate endoscopically from malignant melanoma.

Comparison of early versus late addition of granulocyte and monocyte adsorption for incomplete remission induction in ulcerative colitis.

Background and aim: Ulcerative colitis (UC) is characterized by repeated relapse and remission. Because no fundamental therapeutic strategy has been established, the treatment goal is generally to maintain the remission phase for a long period after rapid remission induction. Granulocyte and monocyte adsorption (GMA) for UC is reportedly quite safe because it does not affect immunosuppression. Moreover, it is useful in combination with other remission induction therapy. The aim of this study was to evaluate the difference in efficacy by the timing of the addition of GMA with corticosteroids, calcineurin inhibitors, and anti-cytokine therapy for active UC. Methods: The study included 59 patients. Patients who started GMA of 5-11 days were in the early GMA combination group. Patients who started GMA 12 days or more were in the late GMA combination group. The primary endpoint was difference in the effect of additional GMA according to the timing of the intervention. The secondary endpoint was difference in the time to remission induction between the two groups. Results: Of the 32 early GMA group patients, 24 achieved remission induction. Of the 27 late group patients, 18 achieved remission induction. No significant difference in induction rates was found (P = 0.481). The early group had shorter mean time to remission induction (P < 0.001). Conclusions: In conclusion, results suggest that early addition of GMA might lead to earlier remission in patients who have had an inadequate response to remission induction therapy with corticosteroids, calcineurin inhibitors, and anti-cytokine therapy.

Risk Factors for Developing Metachronous Superficial Gastric Epithelial Neoplasms after Endoscopic Submucosal Dissection.

Background: Although endoscopic submucosal dissection (ESD) provides a high rate of curative resection, the remaining gastric mucosa after ESD is at risk for metachronous superficial gastric epithelial neoplasms (MSGENs). It leaves room for risk factors for developing MSGENs after ESD. This study aimed to identify clinicopathological risk factors for the occurrence of MSGENs, and to evaluate the association of Helicobacter pylori (H. pylori) with the MSGENs. Methods: We conducted a retrospective cohort study including 369 patients with 382 lesions that underwent ESD for adenoma/early gastric cancer. Results: Twenty-seven MSGENs occurred. The subjects were divided into MSGEN and not-MSGEN groups. There was a significantly higher frequency of histological intestinal metaplasia (HIM) and initial neoplasm location in the upper or middle parts (INUM) in the MSGEN group. The HIM and INUM groups had a significantly higher cumulative incidence of MSGENs. We compared 27 patients from the MSGEN group and 27 patients from the not-MSGEN group that were matched to the MSGEN group for variables including HIM and INUM. There was a significantly higher frequency of the spontaneous disappearance of H. pylori in the MSGEN group. Conclusions: HIM, INUM, and the spontaneous disappearance of H. pylori may be clinicopathological risk factors for developing MSGENs after ESD.

Size reduction of gastric fundic gland polyposis by de-escalation of acid-suppressive therapy.

The patient, a 73-year-old woman, had been taking acid-suppressive therapy for refractory reflux esophagitis for 10 years. A potassium-competitive acid blocker was administered to strengthen acid-suppressive therapy for worsening symptoms of gastroesophageal reflux disease. Esophagogastroduodenoscopy showed an increase in the number and size of fundic gland polyposis (FGPs). When acid-suppressive therapy was changed from potassium-competitive acid blocker to proton pump inhibitor, the FGPs showed reduced size 1 year later. Furthermore, when acid-suppressive therapy was changed from proton pump inhibitor to histamine-2 receptor antagonist, FGPs were even smaller after 1 and 2 years. The patient, who had no flare-up of gastroesophageal reflux disease symptoms, continues to be treated medically with histamine-2 receptor antagonist. This case report describes changes in endoscopic findings of a patient with FGPs caused by acid-suppressive therapy for refractory gastroesophageal reflux disease.

Advanced Endoscopy for Benign Esophageal Disease: A Review Focused on Non-Erosive Reflux Disease and Eosinophilic Esophagitis.

Advanced endoscopy (AVE) techniques include image-enhanced endoscopy methods, such as narrow-band imaging (NBI), and types of microscopic endoscopy, such as endocytoscopy. In the esophagus, AVE first showed diagnostic utility in the diagnosis of superficial esophageal cancer and was then applied to inflammatory disease. This review focuses on non-erosive reflux disease (NERD) and eosinophilic esophagitis (EoE), which sometimes show no abnormal findings on standard white light endoscopy alone. Studies have demonstrated that advanced endoscopy, including NBI magnification endoscopy and endocytoscopy, improved the diagnostic performance of white-light endoscopy alone for NERD and EoE. In this review, we explain why advanced endoscopy is needed for the diagnosis of these esophageal inflammatory diseases, summarize the study results, and discuss future perspectives.

Salvage Endoscopic Submucosal Dissection for Local Recurrence of Superficial Esophageal Squamous Cell Cancer after Photodynamic Therapy.

Photodynamic therapy is useful as organ-preservation salvage therapy for residual recurrence of esophageal squamous cell carcinoma after chemoradiation therapy. However, the high residual recurrence rate of photodynamic therapy poses a problem. We herein report a patient who underwent photodynamic therapy for recurrence of superficial esophageal squamous cell carcinoma after chemoradiation therapy. The patient later exhibited another episode of recurrence of superficial esophageal squamous cell carcinoma, and R0 curative resection was obtained with endoscopic submucosal dissection. This suggests that endoscopic submucosal dissection may be an effective treatment option that can achieve R0 resection even for residual superficial cancer after salvage photodynamic therapy.

Curative resection with endoscopic submucosal dissection of early gastric cancer in Helicobacter pylori-negative Ménétrier's disease: A case report.

BACKGROUND: Adult-onset Ménétrier's disease is strongly associated with Helicobacter pylori (H. pylori) infection and an elevated risk of carcinogenesis. Cases of early-stage gastric cancer developed in H. pylori-negative Ménétrier's disease are extremely rare. We report a case of early gastric cancer in H. pylori-negative Ménétrier's disease that was curatively resected with endoscopic submucosal dissection (ESD). CASE SUMMARY: A 60-year-old woman was referred to our hospital after her medical examination detected anemia. Contrast-enhanced upper gastrointestinal (UGI) radiography revealed translucency of the nodule-aggregating surface with giant rugae. Blood tests showed hypoproteinemia and were negative for serum H. pylori immunoglobulin G antibodies. The 99mTc-DTPA-human serum albumin scintigraphy showed protein loss from the stomach. UGI endoscopy showed a 40-mm protruding erythematous lesion on giant rugae of the greater curvature of lower gastric body, suggesting early-stage gastric cancer due to Ménétrier's disease. En bloc resection with ESD was performed for diagnosis and treatment. Histology of ESD showed well-differentiated tubular adenocarcinoma. The cancer was confined to the mucosa, and complete curative resection was achieved. Foveolar hyperplasia and atrophy of the gastric glands were observed in non-tumor areas, histologically corresponding to Ménétrier's disease. Three years after ESD, gastric cancer had not recurred, and Ménétrier's disease remained in remission with spontaneous regression of giant gastric rugae. CONCLUSION: Complete curative resection was achieved through ESD in a patient with early-stage gastric cancer and H. pylori-negative Ménétrier's disease.

Analysis of Endoscopic Evaluation Reliability for Ulcerative Colitis in Histological Remission.

The Mayo endoscopic subscore (MES) is a major endoscopic scoring system used to assign a status of mucosal inflammation and disease activity to patients with ulcerative colitis (UC). Using interobserver reliability (IOR), this study clarified the difficulties for endoscopic observers imposed by MES parameters used for the endoscopic evaluation of UC in histological remission. First, 42 endoscopists of four observer groups examined each MES parameter, which were evaluated from endoscopically obtained images of 100 cases as Grade 0 or 1 of the Nancy histological index of histopathological inflammation. Then, IOR was assessed using multiple κ statistics for each finding of MES. The results showed that IOR among all the observers was slight or fair for all the parameters, indicating a low IOR. The experts of the UC practice group had "moderate" or higher IOR for seven of the nine parameters, whereas "slight" or "fair" results were found for all parameters by the trainee group. The IOR for each MES parameter was calculated separately for the observer groups. All the groups showed "slight" or "fair" for "Erythema" and "Decreased vascular pattern". Large differences between the endoscopists were found in the IOR for the MES parameters in UC in histological remission. Even among UC practice experts, the IOR was low for "Erythema" and "Decreased vascular pattern".

Whole circumferential endoscopic submucosal dissection of superficial adenocarcinoma in long-segment Barrett's esophagus: A case report.

BACKGROUND: Esophageal adenocarcinoma (EAC) derived from long-segment Barrett's esophagus (LSBE) is extremely rare in Asia. LSBE-related EAC is often difficult to diagnose in the horizontal extent. If the tumor has spread throughout the LSBE, whole circumferential endoscopic submucosal dissection (ESD) should be performed, which is difficult to complete safely. Additionally, whole circumferential ESD can bring refractory postoperative stenosis. We hereby report a case of EAC involving the whole circumference of the LSBE, achieving complete endoscopic removal without complications. CASE SUMMARY: An 85-year-old man with the chief complaint of dysphagia underwent esophagogastroduodenoscopy. We suspected a flat-type cancerous lesion that extended the whole circumference of the LSBE (C 3.5, M 4.0) using narrow-band imaging magnification endoscopy (NBI-M). We achieved circumferential en bloc resection of the lesion safely with special ESD techniques. Histology of the ESD specimens demonstrated that the superficial EAC extended the whole circumference of the LSBE, and papillary or well-differentiated tubular adenocarcinoma was confined in the lamina propria mucosa showing a vertical negative margin. To prevent post-ESD stenosis, we performed endoscopic local injection of steroids, followed by oral administration of steroids. There was no evidence of esophageal refractory stenosis or tumor recurrence 30 mo after ESD. In summary, we experienced a rare case of LSBE-related EAC. The horizontal tumor extent was accurately diagnosed by NBI-M. Additionally, we achieve whole circumferential ESD safely without postoperative refractory stenosis. CONCLUSION: NBI-M, ESD, and steroid therapy enabled the curative resection of superficial full circumferential LSBE-related EAC without refractory postoperative stenosis.

Refractory Immune Checkpoint Inhibitor-Induced Colitis Improved by Tacrolimus: A Case Report.

Immune checkpoint inhibitors (ICIs) increase T-cell activity and antitumor immune response. However, they also have immune-related adverse effects that can affect the gastrointestinal (GI) tract. A 62-year-old male patient who had undergone right lung upper lobectomy for adenocarcinoma of the lung received chemotherapy with pemetrexed sodium hydrate, carboplatin, and pembrolizumab to prevent postoperative recurrence of liver metastasis. However, the patient experienced severe diarrhea four months after the start of chemotherapy. Although a corticosteroid and two biological preparations were administered to alleviate the diarrhea, no improvement was observed. Eventually, remission was achieved when tacrolimus was administered. Treatment with corticosteroids is recommended for patients with GI adverse effects of ICIs. Rapid introduction of infliximab is necessary for refractory patients. Nevertheless, for refractory cases such as that of our patient, for whom even this regimen is inefficacious, tacrolimus might be recommended to induce remission as with cases of ulcerative colitis.

A Case of Crohn's Disease with Cardiac Tamponade Caused by Tuberculous Pericarditis: Assessment of a Rare Phenomenon.

A 28-year-old woman was hospitalized for cardiac tamponade caused by tuberculous pericarditis. She was taking ustekinumab (UST) for Crohn's disease. UST is not considered to significantly increase the risk of developing serious infections, including tuberculosis. However, there is still a risk of Mycobacterium tuberculosis reactivation. Therefore, for patients on concurrent UST and antituberculosis medication, a close collaboration among specialists in infectious diseases, cardiology, and gastroenterology is necessary.

Continuous warfarin administration versus heparin bridging therapy in post colorectal polypectomy haemorrhage: a study protocol for a multicentre randomised controlled trial (WHICH study).

BACKGROUND: Endoscopic removal of colorectal adenoma is considered an effective treatment for reducing the mortality rates associated with colorectal cancer. Warfarin, a type of anticoagulant, is widely used for the treatment and prevention of thromboembolism; however, bleeding may increase with its administration after polypectomy. In recent times, a high incidence of bleeding after endoscopic polypectomy has been reported in patients receiving heparin bridge therapy. However, previous studies have not compared the bleeding rate after endoscopic colorectal polypectomy between patients who continued with anticoagulant therapy and those who received heparin bridge therapy. We hypothesised that endoscopic colorectal polypectomy under the novel treatment with continuous warfarin is not inferior to endoscopic colorectal polypectomy under standard treatment with heparin bridge therapy with respect to the rate of postoperative bleeding. This study aims to compare the efficacy of endoscopic colorectal polypectomy with continuous warfarin administration and endoscopic colorectal polypectomy with heparin bridge therapy with respect to the rate of postoperative bleeding. METHODS: We will conduct a prospective multicentre randomised controlled non-inferiority trial of two parallel groups. We will compare patients scheduled to undergo colorectal polypectomy under anticoagulant therapy with warfarin. There will be 2 groups, namely, a standard treatment group (heparin bridge therapy) and the experimental treatment group (continued anticoagulant therapy). The primary outcome measure is the rate of postoperative bleeding. On the contrary, the secondary outcomes include the rate of cumulative bleeding, rate of overt haemorrhage (that does not qualify for the definition of haemorrhage after endoscopic polypectomy), incidence of haemorrhage requiring haemostasis during endoscopic polypectomy, intraoperative bleeding during endoscopic colorectal polypectomy requiring angiography, abdominal surgery and/or blood transfusion, total rate of bleeding, risk factors for postoperative bleeding, length of hospital stay, incidence of thromboembolism, prothrombin time-international ratio (PT-INR) 28 days after the surgery, and incidence of serious adverse events. DISCUSSION: The results of this randomised controlled trial will provide valuable information for the standardisation of management of anticoagulants in patients scheduled to undergo colorectal polypectomy. TRIAL REGISTRATION: UMIN-CTR UMIN000023720 . Registered on 22 August 2016.