Role of advanced endoscopy in the management of inflammatory digestive diseases (pancreas and biliary tract).

The progress of endoscopic diagnosis and treatment for inflammatory diseases of the biliary tract and pancreas have been remarkable. Endoscopic ultrasonography (EUS) and EUS-elastography are used for the diagnosis of early chronic pancreatitis and evaluation of endocrine and exocrine function in chronic pancreatitis. Notably, extracorporeal shock wave lithotripsy and electrohydraulic shock wave lithotripsy have improved the endoscopic stone removal rate in patients for whom pancreatic stone removal is difficult. Studies have reported the use of self-expanding metal stents for stent placement for pancreatic duct stenosis and EUS-guided pancreatic drainage for refractory pancreatic duct strictures. Furthermore, EUS-guided drainage using a double-pigtailed plastic stent has been performed for the management of symptomatic pancreatic fluid collection after acute pancreatitis. Recently, lumen-apposing metal stents have led to advances in the treatment of walled-off necrosis after acute pancreatitis. EUS-guided biliary drainage is an alternative to refractory endoscopic biliary drainage and percutaneous transhepatic biliary drainage for the treatment of acute cholangitis. The placement of an inside stent followed by switching to uncovered self-expanding metal stents in difficult-to-treat cases has been proposed for acute cholangitis by malignant biliary obstruction. Endoscopic transpapillary gallbladder drainage is an alternative to percutaneous transhepatic gallbladder drainage for severe and some cases of moderate acute cholecystitis. EUS-guided gallbladder drainage has been reported as an alternative to percutaneous transhepatic gallbladder drainage and endoscopic transpapillary gallbladder drainage. However, it is important to understand the advantages and disadvantages of each drainage method and select the optimal drainage method for each case.

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.

Eosinophilic Duodenal Ulcer Exacerbation after Helicobacter pylori Eradication in a 14-Year-Old Boy.

Eosinophilic gastrointestinal disorders (EGIDs) cause various gastrointestinal symptoms due to infiltration of eosinophils into the gastrointestinal tract. Helicobacter pylori (H. pylori) is a microorganism that is associated with various diseases such as autoimmune diseases. In recent years, H. pylori is considered protective in inflammatory bowel diseases and gastrointestinal autoimmune disorders but is not known to be protective in EGIDs. A 14-year-old boy presented with epigastric pain and nausea, without diarrhea. His symptoms were not associated with meals. Blood examination showed an eosinophil count of 1,666 cells/µL (17.0%) and an interleukin-5 (IL-5) level of less than 3.9 pg/mL. Esophagogastroduodenoscopy showed chronic gastritis and duodenal ulcers. Capsule endoscopy and colonoscopy showed no abnormal findings. The patient was diagnosed with chronic gastritis due to H. pylori infection and eosinophilic duodenal ulcers. H. pylori eradication was performed. However, the abdominal pain worsened with elevated peripheral eosinophil count [2,314/µL (26%)] and serum IL-5 level (8.0 pg/mL). Montelukast administration improved the symptoms and laboratory findings [peripheral eosinophil count, 330/µL (5.9%); IL-5, < 3.9 pg/mL]. EGIDs should be considered as a cause of duodenal ulcers. H. pylori may be protective in EGIDs. Montelukast monotherapy may be considered as a first line treatment for eosinophilic duodenal lesions.

Proton Pump Inhibitor to Treat an Eosinophilic Duodenal Ulcer with Esophageal Involvement: A Pediatric Case.

Eosinophilic gastrointestinal disorders are diseases that cause inflammation and dysfunction due to infiltration of eosinophils into various regions of the gastrointestinal tract. Symptoms and treatment vary depending on lesion severity. We describe the first pediatric case of an eosinophilic duodenal ulcer with esophageal involvement that was effectively treated using proton pump inhibitor monotherapy. A 12-year-old boy with no relevant family or medical history presented with a one-month history of epigastric pain. Laboratory test results were as follows: white blood cell count, 4,700/µL; eosinophil count, 150/µL (3.2%); and total IgE, 151.6 IU/L; and IgG antibodies for Helicobacter pylori were absent. Esophagogastroduodenoscopy revealed longitudinal linear furrows in the esophagus, indicating eosinophilic esophagitis with an A1 ulcer from the duodenal bulb to the descending duodenum. The patient was diagnosed with an eosinophilic duodenal ulcer with esophageal involvement based on pathological findings. Esomeprazole, a common proton pump inhibitor, was orally administered, after which the symptoms promptly improved. After two months, the esophagogastroduodenoscopy and pathological examination results showed improvement in both the esophagus and duodenum. There have been no previous reports of an eosinophilic duodenal ulcer with esophageal involvement without post-duodenal involvement at the time of diagnosis. The possibility of eosinophilic gastrointestinal disorders should be investigated in patients with duodenal ulcers by means of active biopsy, and patients should be investigated for other types of gastrointestinal lesions. Proton pump inhibitor monotherapy may be considered a first-line treatment for eosinophilic duodenal ulcers with esophageal involvement, depending on lesion severity.

Measuring optimal ultrasound speed using endoscopic ultrasound in patients with chronic pancreatitis, including early stage.

OBJECTIVES: Ultrasound speed (USS) correction improves image quality by estimating the optimal USS correcting the deviation from a predetermined USS. This study assessed USS differences between chronic pancreatitis (CP), early CP (ECP), and normal pancreas when using endoscopic ultrasound (EUS). The usefulness of measuring optimal USS was evaluated for patients with CP, including early stage patients. METHODS: This study enrolled 116 consecutive patients for whom USS was measured using an EUS system. The USS correction principle is generation of a B-mode image by changing the USS in all ranges while correcting the delay in the received data. Final diagnoses were made according to the Japanese diagnostic criteria for CP in 2019. They were classified as CP, ECP, or normal. We compared USS applied for these three groups. RESULTS: The medians and ranges of USS values for patients in the normal, ECP, and CP groups were 1506.0 (1407-1600) m/s, 1580.0 (1520-1630) m/s, and 1574.0 (1537-1610) m/s, respectively. The USS values of the ECP and CP groups were significantly higher than those of the normal group (P < 0.001). Analyses of the receiver operating characteristic curve in the normal pancreas, ECP, and CP revealed the area as 0.957, with specificity and sensitivity of 95.9% and 87.5%, respectively, using the USS of 1535 m/s as a cut-off. CONCLUSION: Measurement of USS might be particularly useful for distinguishing between normal and ECP imaging.

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.

Ulcerative colitis relapse after Helicobacter pylori eradication in a 12-year-old boy with duodenal ulcer.

BACKGROUND: Helicobacter pylori (H. pylori) prevalence is lower in patients with inflammatory bowel disease (IBD) than in those without IBD, suggesting that H. pylori plays a protective role in IBD. It has been reported that IBD may occur due to H. pylori eradication; however, it is unclear whether H. pylori eradication increases the incidence of IBD. Moreover, the effect of H. pylori eradication on IBD activity is unclear. CASE PRESENTATION: An 11-year-old boy diagnosed with ulcerative colitis (UC) was in clinical remission, with treatment involving 5-aminosalicylic acid. Fecal calprotectin (FC) level had decreased to 33.2 mg/kg, indicating mucosal healing. At age 12, he experienced epigastric pain on an empty stomach, which was relieved with dietary intake. His FC level was elevated without UC symptoms, such as diarrhea and bloody stools. He was diagnosed with H. pylori duodenal ulcer. H. pylori eradication (clarithromycin and amoxicillin for 7 days and a proton-pump inhibitor) led to symptom improvement the day after treatment initiation. However, he developed diarrhea and his FC level remained high despite improvement in duodenal ulcer symptoms and endoscopic findings of H. pylori eradication. Colonoscopy results indicated UC relapse. CONCLUSIONS: H. pylori eradication may worsen UC activity. However, further studies are required as this case report involved only one pediatric patient with increased UC activity after H. pylori eradication.

Does the Use of Low Osmolality Contrast Medium Reduce the Frequency of Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis: A Comparative Study between Use of Low and High Osmolality Contrast Media.

INTRODUCTION: A few reports stating that differences in the various types of contrast media injected into the pancreatic duct are related to the onset of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) have been published, and it was indicated that iodixanol which is a nonionic iodide radiographic contrast medium with a dimeric (2 dimers) structure may reduce the incidence of PEP. The aim of this retrospective study is to evaluate the usefulness of iodaxanol for prevention PEP in comparison with megulamine amidototrizoate. METHODS: Two hundred and ninety-one patients were enrolled and divided into the 2 groups according to the contrast medium used. One hundred and fifty-five patients underwent ERCP with meglumine amidotrizoate, and 136 patients underwent ERCP with iodaxanol. The primary outcome of this study was the incidence of PEP associated with the use of each contrast medium. RESULTS: In this study, comparison of the meglumine amidotrizoate treatment and iodaxanol treatment groups showed no significant difference with respect to the incidence of PEP. In addition, there was also no difference between the groups with respect to PEP severity. CONCLUSION: Our study suggested that iodaxanol does not necessarily contribute to the prevention of PEP in comparison with meglumine amidotrizoate.

Ustekinumab as the First Biological Agent for Crohn's Disease in a 10-Year-Old Girl.

Pediatric inflammatory bowel disease is associated with growth failure due to chronic inflammation, nutrient disorder, and the side effects of drugs, such as corticosteroids. Biological agents are therapeutic drugs that significantly improve the prognosis of patients with inflammatory bowel disease. The effectiveness of ustekinumab has been reported in the management of adult patients with inflammatory bowel disease. There are very few reports regarding the effectiveness and safety of ustekinumab in pediatric patients with inflammatory bowel disease, especially those who are biologically naive. A 10-year-old girl presented with chronic abdominal pain, diarrhea, and weight loss. Colonoscopy showed a longitudinal ulcer and cobblestone appearance in the ileum and discontinuous inflammation of the colon; therefore, she was diagnosed with Crohn's disease. She was prescribed a fat-restricted diet, elemental diet, 5-aminosalicylic acid, transient prednisolone, and ustekinumab. She achieved clinical and endoscopic remission based on the weighted Pediatric Crohn's Disease Activity Index, fecal calprotectin, and colonoscopy findings at week 75. This patient developed no adverse events, such as infusion reaction or susceptibility to infection over the 75 weeks. The use of ustekinumab as the first biological agent may be an effective and safe treatment for pediatric Crohn's disease.

A Case of Lung Abscess Caused by Double Immunosuppressive Therapy to Treat Ulcerative Colitis.

A 25-year-old man was admitted to our institution for remission induction therapy to treat a 12-year condition of ulcerative colitis (UC). Previously, he was treated with drugs, such as mesalamine, immunomodulators, prednisolone (PSL), and anti-TNFα anti-body, but remission was not maintained. Therefore, we started remission induction therapy with 20 mg/day of tofacitinib (TOF) to inhibit the action of Janus kinase. On the 29th day after TOF administration, he developed a lung abscess with high fever. A chronic bulla was already present in his lung; therefore, the lung abscess was likely formed due to a combination of the bulla being present and the pharmacological effects of TOF. Our report is significant as it highlights the compounding association between TOF and PSL therapy and bulla presence with the rare adverse effect of developing an abscess.

Safety and Efficacy of AJM300, an Oral Antagonist of α4 Integrin, in Induction Therapy for Patients With Active Ulcerative Colitis.

BACKGROUND & AIMS: AJM300 is an orally active small-molecule antagonist of the α4 integrin subunit. We performed a randomized trial to investigate the efficacy and safety of AJM300 in patients with active ulcerative colitis (UC). METHODS: In a double-blind, placebo-controlled, phase 2a study, 102 patients with moderately active UC (Mayo Clinic scores of 6-10, endoscopic subscores ≥2, and rectal bleeding subscores ≥1) who had inadequate response or intolerance to mesalamine or corticosteroids were randomly assigned to receive AJM300 (960 mg) or placebo 3 times daily for 8 weeks. The primary end point was a clinical response at week 8, defined as a decrease in Mayo Clinic score of at least 3 points and a decrease of at least 30% from baseline, with a decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of 0 or 1. RESULTS: Clinical response rates were 62.7% and 25.5% at week 8 in the AJM300 group and placebo group, respectively (odds ratio [OR] = 5.35; 95% confidence interval [CI]: 2.23-12.82; P = .0002). Rates of clinical remission (Mayo Clinic score ≤2 and no subscore >1) were 23.5% and 3.9% in the AJM300 group and placebo groups, respectively (OR = 7.81; 95% CI: 1.64-37.24; P = .0099), and rates of mucosal healing (endoscopic subscores of 0 or 1) were 58.8% and 29.4% (OR = 4.65; 95% CI: 1.81-11.90; P = .0014). No serious adverse event, including progressive multifocal leukoencephalopathy, was observed, although more investigations are needed to confirm the safety profile of this drug. CONCLUSIONS: AJM300 was well tolerated and more effective than placebo in inducing clinical response, clinical remission, and mucosal healing in patients with moderately active UC. ClinicalTrials.jp no: JapicCTI-132293.

Timing for dose-down of 5-ASA depends on mucosal status with ulcerative colitis.

OBJECTIVE: Although aminosalicylic acid (ASA) preparations have been used as first-line drugs for the treatment of ulcerative colitis (UC), no consistent view has been established regarding the ASA dose during the remission-maintenance phase of the disease. In this study, we examined whether the ASA dose should be reduced during the remission-maintenance phase. MATERIALS AND METHODS: This study included 203 patients in the remission-maintenance phase of UC. The Mayo endoscopic subscore (MES) was used to evaluate mucosa. Comparison and analysis were performed between patients whose ASA dose had been unchanged and whose dose had been reduced, between patients with endoscopic healing (EH) group and those without endoscopic healing (WEH) group, and between patients with an MES of 0 and 1. RESULTS: Comparison between the unchanged-ASA and reduced-ASA groups revealed that the remission-maintenance rate was higher in the unchanged-ASA group (p < 0.001). Next, the remission-maintenance rate was higher in the EH/unchanged-ASA group than in the EH/reduced-ASA group (p = 0.042). Comparison between the MES 0 and 1 groups revealed that the remission-maintenance rate was higher in the MES 0 group (p = 0.007). In addition, no significant difference in remission-maintenance rates was observed between the MES 0/unchanged-ASA group and the MES 0/reduced-ASA group (p = 0.108). CONCLUSION: When the same ASA dose is maintained regardless of the presence or absence of EH, remission is more likely to be maintained. If the ASA dose must be reduced, dose reduction is more advantageous after an MES of 0 is achieved.

Feasibility of detecting small intestinal disease by FDG-PET/CT.

Positron emission tomography (PET)/computed tomography with (18)F-fluorodeoxyglucose (FDG) is widely used for the diagnosis of malignant tumors. However, we occasionally encounter cases in which pathological accumulation is indistinguishable from physiological accumulation. We conducted a retrospective study of the maximum standardized uptake value (SUVmax) and the distribution pattern of FDG accumulation in 80 evaluable patients with records of accumulation in the small intestine identified from data acquired at Dokkyo Medical University PET Center from March 2005 to December 2010. Our aim was to distinguish pathological accumulation from physiological accumulation. Nineteen of the 80 patients had lesions that required some form of treatment. These lesions were categorized as pathological accumulation, while other 65 lesions in 61 patients were categorized as physiological accumulation. Cases with diffuse accumulation in the intestinal tract were assigned to Group L (linear), all others to Group F (focal), in our analysis. Lesions were focal in 22 patients and linear in 62. The pathological accumulation group had a mean SUVmax of 12.2, which was higher than that of 5.0 in the physiological accumulation group, and included more lesions that were categorized into Group F (16 of 19 lesions). The sensitivity and specificity for detecting focal accumulation regarded as being pathological accumulation were 84% and 91%, respectively, and accuracy was 89%. The sensitivity and specificity with a cut-off SUVmax of 5.87 obtained in the ROC analysis were 84% and 78%, respectively, and accuracy was 80%. Evaluation of SUVmax in the small intestine and the distribution pattern of FDG accumulation may be useful for diagnosing lesions in the small intestine.

A second-look endoscopy may not reduce the bleeding after endoscopic submucosal dissection for gastric epithelial neoplasm.

BACKGROUND: Gastric endoscopic submucosal dissection (ESD) has gradually come to be recommended as the optimal treatment for early gastric cancer; however, one of the primary issues is postoperative bleeding. Although second-look endoscopy is conventionally performed to reduce the risk of postoperative bleeding, its benefit has not yet been clearly elucidated. The objective of this study was to elucidate the benefit of second-look endoscopy. METHODS: A total of 459 lesions in patients were underwent gastric ESD from May 2004 to April 2013 at our hospital were included in the analysis. The patients were divided into those who had bleeding within 24 hours after ESD (immediate bleeding) and those in whom bleeding occurred 24 hours or more after the procedure (delayed bleeding); the underlying disease, age, lesion site, diameter of the resected specimen, and lesion diameter were analyzed to identify the risk factors for postoperative bleeding after ESD. RESULTS: Post-ESD immediate or delayed bleeding occurred in 23 of the 459 cases (5.0%). Second-look endoscopy was performed in 210 of 447 cases (47.0%) excluding 12 cases with immediate bleeding; in the remaining 237 of the 447 cases (53.0%), it was not performed. Post-ESD delayed bleeding occurred in 6 of the 210 cases (2.9%) and 5 of the 237 cases (2.1%), with no statistically significant difference between the two groups. Overall, the following factors were identified as the risk factors for postoperative bleeding: young age (P = 0.005), lesions in the L segment (P = 0.042), and large size of the resected specimen (P = 0.005). The risk factors identified in the immediate bleeding group were lesions in the L segment (P = 0.032), large size of the resected specimen (P < 0.001), and large tumor size (P = 0.011), and those in the delayed bleeding group were young age (P = 0.013) and concomitant renal disease (P = 0.011). CONCLUSIONS: The results of this study suggest that second-look endoscopy after gastric ESD may not be useful for preventing postoperative bleeding.

Acute Pancreatitis Leading to the Diagnosis of Presymptomatic Crohn's Disease: A Pediatric Case Report.

A 14-year-old boy presented with fever and abdominal pain and was diagnosed with acute pancreatitis based on computed tomography findings. The patient had neither diarrhea nor bloody stool but was diagnosed with microcytic anemia. Endoscopic examination revealed a cobblestone pattern and longitudinal ulcer scars in the jejunum. However, no abnormal findings were observed in the ileum or colon. Endoscopic ultrasound-guided fine-needle aspiration was performed from pancreatic body-tail. Pathological examination revealed no evidence of autoimmune pancreatitis (AIP). It was unclear from pathological examination whether idiopathic pancreatitis had self-limitedly improved or whether it was AIP localized to the pancreatic head. The patient was diagnosed with asymptomatic small-bowel Crohn's disease (CD), which may have been two unrelated events of acute pancreatitis. Acute pancreatitis may precede a diagnosis of inflammatory bowel disease. CD with only jejunal involvement (Montreal classification L4) is extremely rare, and we were able to diagnose it early.

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.

Symptomatic duodenal intramural hematoma caused by weight training: a report of two cases.

Symptoms of traumatic duodenal intramural hematoma, a rare disease caused by trauma, blood disease, or antithrombotic therapy, can include abdominal pain. Case 1 is that of a 35-year-old man at a gym who dropped a 100 kg barbell on his abdomen. It was diagnosed as a duodenal obstruction caused by a traumatic intestinal wall hematoma. In Case 2, a 16-year-old male adolescent performing deadlift training at a gym had subsequent abdominal pain. It was diagnosed as intestinal wall hematoma. Both patients improved with conservative treatment. Malignancy is sometimes suspected from imaging findings. Detailed patient history and imaging studies can avoid unnecessary surgery.