[A case of gastric hamartomatous inverted polyp (GHIP), preoperatively diagnosed based on EUS findings].

We report the case of a patient with a gastric hamartomatous inverted polyp (GHIP) and discuss the relevant literature. A 65-year-old woman was referred to our hospital because of a slow-growing pedunculated polyp measuring 30mm in diameter, present in the greater curvature of the fundic region of the stomach. It was covered with normal gastric mucosa, and the top was reddish. A biopsy specimen taken from the reddish area;it showed inflamed gastric mucosa with hyperplastic and mildly distorted foveolar glands. Abdominal contrast computed tomography showed a protruding tumor that was unevenly enhanced and contained multiple cystic lesions inside. Endoscopic ultrasonography (EUS, Olympus GIF-UCT260) showed a heterogeneous tumor with multiple anechoic or low-echoic cystic lesions, originating from the second or third layer of the stomach wall. The patient had no clinical symptoms, no family history, and no laboratory data abnormalities. Based on these findings, we diagnosed her with GHIP. As the polyp had shown an increase in size (5mm/5 years) and about 20% of GHIPs were reported to coexist with precancerous or cancerous lesions, we performed endoscopic polypectomy. The tumor was histologically characterized by submucosal growth of hypertrophic glands with cystic dilatation, accompanied by smooth muscle proliferation, branching from the bundles. Thus, the final diagnosis was GHIP. Though GHIP is a rare and basically benign polyp, the rate with gastric cancer was reported to be relatively high. EUS findings are important for the diagnosis and when GHIP is suspected, the lesion requires to be monitored closely. If there are some signs that suggest a malignancy (growth, changes in surface mucosa, etc.), endoscopic en bloc resection or surgical resection should be considered.

The role of calcium-binding protein S100g (CalbindinD-9K) and annexin A10 in acute pancreatitis.

BACKGROUND: We reported that the pancreas of the interferon-regulatory factor (IRF) 2 knock-out (KO) mouse represents an early phase of acute pancreatitis, including defective regulatory exocytosis, intracellular activation of trypsin, and disturbance of autophagy. The significantly upregulated and downregulated genes in the IRF2 KO pancreas have been reported. The catalogue of gene transcripts included two types of calcium-binding proteins (S100 calcium binding protein G [S100g] and Annexin A10 [Anxa10]), which were highly upregulated in the IRF2 KO pancreas. As the intracellular calcium signal plays a pivotal role in regulatory exocytosis and its disturbance is related to pancreatitis, we then evaluated the role of S100g and Anxa10 in acute pancreatitis. METHOD: We induced cerulein-pancreatitis in wild-type mice and examined the changes in the expression of these genes by qPCR and immunohistochemistry. We constructed S100g-overexpressing or Anxa10-overexpressing AR42J cells (AR42J-S100g, AR42J-Anxa10). We examined the changes in amylase secretion, intracellular calcium ([Ca2+]i), and cell viability in these cells, when incubated with cholecystokinin (CCK). RESULTS: The expression of S100g and Anxa10 was increased in cerulean-induced pancreatitis. The acini were patchily stained for S100g and the cytosol of acini was evenly but weakly stained for Anxa10. Stimulation with 100pM CCK-8, decreased amylase secretion and inhibited the [Ca2+]i increase in AR42J-S100g cells. These effects were weak in AR42J-Anxa10 cells. Cell viability was not changed by incubation with cerulein. CONCLUSION: In cerulean pancreatitis, the expression of S100g and Anxa10 was induced in the acini. S100g may work as a Ca2+ buffer in acute pancreatitis.

The efficacy of endoscopic submucosal dissection for colorectal tumors extending to the dentate line.

PURPOSE: Although endoscopic submucosal dissection (ESD) is becoming the mainstay of the treatment strategies, rather than surgical treatment, for colorectal tumors extending to the dentate line, ESD is technically more difficult. This study was aimed at assessing the usefulness of ESD for the treatment of colorectal tumors extending to the dentate line. METHODS: This study included 531 patients with colorectal tumors who underwent colorectal ESD between 2008 and 2015. They were divided into three groups: rectal tumors extending to the dentate line (anorectal group), those not extending to the dentate line (proximal rectal group), and colonic tumors (colonic group), and a retrospective comparative analysis was carried out. RESULTS: Of the total patients, 18 (3.4%) had lesions extending to the dentate line area. The procedure times were 103.4 ± 84.0, 80.4 ± 64.3, and 71.8 ± 52.3 min, respectively (P = 0.0318). All the patients in the anorectal group were operated by operators who had performed at least 20 colorectal ESDs (P < 0.0001). No significant difference among the three groups was found in the en bloc resection rate, complete resection rate, or curative resection rate. Although no significant difference in the incidence of perforation was observed among the three groups, intraoperative bleeding was observed in 61% of the patients in the anorectal group (P < 0.0001). CONCLUSIONS: ESD is an effective treatment strategy for colorectal tumors extending to the dentate line. However, it seems that anorectal ESD, which is technically more difficult than colorectal ESD, should be performed by operators with ample experience in performing ESD.

Gradual improvement of hyperammonemic hepatic encephalopathy after the extirpation of a large uterine leiomyoma in a woman with constipation and liver cirrhosis resulting from autoimmune hepatitis.

There have been few reports regarding the improvement of hyperammonemic hepatic encephalopathy after the extirpation of a large uterine leiomyoma. We present a case of a 53-year-old postmenopausal woman who experienced a clouding of consciousness. She had been suffering from mild hepatitis and a large uterine leiomyoma. On admission, she had experienced constipation for seven days and exhibited a high serum ammonia level (251 µg/dL). She was diagnosed with liver cirrhosis as a result of autoimmune hepatitis, combined with Sjögren's syndrome. A total hysterectomy was performed 29 days after admission. Severe diarrhea lasted for three days after surgery. By the sixth postoperative day, the patient's consciousness level had normalized and her serum ammonia level had fallen to 47 µg/dL. Although the true mechanism of hyperammonemia in this case is unclear, we speculate that organic constipation following chronic obstruction of the colon might have played a role in the development of the condition.

Successful Response to Golimumab in a Case of Relapsing Polychondritis Overlapping with Ulcerative Colitis.

A 51-year-old Japanese man was diagnosed with left-sided ulcerative colitis (UC) at age 41. He was treated with mesalazine and azathioprine and maintained remission. At age 51, the patient developed bloody stools, abdominal pain, scleritis, arthritis, cough, bloody sputum, and pericardial effusion. Considering that pericardial effusion is an atypical extraintestinal complication of UC, and the patient met the diagnostic criteria for relapsing polychondritis (RP), a diagnosis of RP complicating a relapse of UC was made. Steroid therapy was administered, and both diseases improved. Golimumab, an anti-tumor necrosis factor-α inhibitor, was introduced as maintenance therapy for UC. All symptoms, including pericardial effusion, improved. Subsequently, no relapse of UC or RP was observed. As only a few cases of RP overlapping with UC have been reported and no treatment protocol has been established, we considered this case valuable and worthy of publication.

Successful Fistula Closure After Treatment with Colostomy and Infliximab in a Patient with Ulcerative Colitis Complicated by Rectovaginal Fistula.

The patient was a 50-year-old Japanese woman who was diagnosed with total-colitis-type ulcerative colitis (UC) at the age of 26 years. She was treated with mesalazine and azathioprine, and her disease activity was well controlled. At the age of 50 years, the patient was experiencing fever, abdominal pain, diarrhea, bloody stool, and anal pain, which led to a diagnosis of a relapse of UC. Although steroid therapy was administered and tended to improve her symptoms, fecaloid vaginal discharge occurred, and rectovaginal fistula (RVF) was confirmed. Colostomy was performed, and infliximab was initiated as maintenance therapy for UC. All symptoms improved, and RVF closure was confirmed 6 months after the initiation of infliximab. To date, she has been free from relapse of UC. There have been only a few reports of UC complicated by RVF, and this condition is often difficult to treat. To the best of our knowledge, no other case of UC complicated by RVF in which the fistula was closed after treatment with colostomy and infliximab has been previously reported; thus, our report of the present case is valuable to the literature.

Late-onset Wilson Disease in a Patient Followed-up for Nonalcoholic Fatty Liver Disease.

A 73-year-old woman was referred to our hospital for persistent liver dysfunction. When the patient was 45 years old, her youngest sister had been diagnosed with Wilson disease (WD). The patient therefore underwent several family screening tests, all of which were unremarkable. She had an annual medical checkup and was diagnosed with liver dysfunction and fatty liver at 68 years old. A liver biopsy and genetic testing were performed, and she was diagnosed with WD; chelation therapy was then initiated. In patients with hepatic disorders and a family history of WD, multiple medical examinations should be conducted, as the development of WD is possible regardless of age.

Primary Bile Duct Diffuse Large B-cell Lymphoma Diagnosed by Repeated Endoscopic Ultrasound-guided Fine-needle Aspiration and Endoscopic Retrograde Cholangiopancreatography.

A 54-year-old man was admitted with obstructive jaundice. Computed tomography showed common bile duct stricture and a tumor around the celiac artery. Repeated endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and endoscopic retrograde cholangiopancreatography (ERCP) as well as a laparotomic biopsy around the celiac artery were diagnostically unsuccessful. Since the bile duct stricture progressed, EUS-FNA and ERCP were performed a third time, finally leading to the diagnosis of diffuse large B-cell lymphoma. The treatment plan and prognosis of obstructive jaundice differ greatly depending on the disease. It is important to conduct careful follow-up and repeated histological examinations with appropriate modifications until a diagnosis is made.

Ulcerative colitis: comparison between elderly and young adult patients and between elderly patients with late-onset and long-standing disease.

BACKGROUND AND AIM: We examined the pathologies, treatment characteristics, and clinical course of elderly ulcerative colitis (UC) patients. METHODS: Among 222 UC patients (127 men, 95 women; average age, 34 ± 16 years), we selected 109 with UC diagnosed between 20 and 39 years of age (young adult group) and 23 diagnosed at ≥ 60 years of age (elderly group). Moreover, 12 patients diagnosed between 60 and 64 years of age (late-onset group) and 6 patients aged ≥ 60 years diagnosed under 50 years old (long-standing group) were also extracted for sub-analysis. The clinical characteristics and course were compared among the groups. RESULTS: The average age at onset was 29 ± 6 years in the young adult group and 66 ± 5 years in the elderly group. The frequency of immunomodulator or steroid use did not differ between the two groups. The comorbidity rate was 14.7 % in the young adult group and 69.6 % in the elderly group (P < .0001). Seven patients (58.3 %) in the late-onset UC group and none of the patients in the long-standing UC group were on steroid treatment. None of the patients in the long-standing UC group required hospitalization/surgery for UC exacerbation, while 3 (25.0 %) and 2 patients (16.7 %) in the late-onset group required hospitalization and surgery, respectively. CONCLUSIONS: The comorbidity rate was significantly higher in the elderly group. Treatments did not differ significantly between the young adult and elderly groups. Therefore, it appears that the inflammation tends to subside with age in elderly patients with long-standing UC.

Reduction of gastric cancer mortality by endoscopic and radiographic screening in an isolated island: A retrospective cohort study.

OBJECTIVE: To evaluate the efficacy of endoscopic and radiographic screening for gastric cancer. DESIGN: A retrospective cohort study. SETTING: Community in an isolated island. PARTICIPANTS: The study involved 186 patients (131 men, 55 women) diagnosed with gastric cancer between 2000 and 2005. INTERVENTIONS: Endoscopic and radiographic screening. MAIN OUTCOME MEASUREMENTS: The odds ratio of death from gastric cancer in participants versus non-participants of screening, the cumulative survival rate of the gastric cancer patients. RESULTS: The odds ratio of death from gastric cancer in the participants versus non-participants of screening was 0.091 (95% confidence interval (CI) 0.027-0.308; P < 0.0001). The cumulative survival rate of the gastric cancer patients in the screening group was higher than that in the non-screening group (P < 0.0001). In the endoscopic screening district, the odds ratio of death from gastric cancer among the participants versus non-participants of endoscopic screening was 0.117 (95% CI 0.013-1.056; P = 0.0525), while in the radiographic screening district, it was 0.086 (95% CI 0.020-0.376; P < 0.0001). The cumulative survival rates were higher in both the screening groups as compared with the non-screening group (endoscopy, P = 0.0302; radiography, P = 0.0012). CONCLUSION: The results suggest that both radiographic and endoscopic screening may prevent gastric cancer deaths.

Usefulness of Serum Leucine-rich Alpha 2 Glycoprotein in Crohn's Disease: Is There Any Difference between Small Intestine and Colonic Lesions?

Background: The usefulness of leucine-rich alpha 2 glycoprotein (LRG) to evaluate Crohn's disease (CD) activity differs among various intestinal lesions. We aimed to evaluate the association between endoscopic disease activity based on the Simple Endoscopic Score for Crohn's disease (SES-CD) and LRG level separately for small intestinal and colonic lesions. Methods: We examined the correlation between LRG level and SES-CD and performed receiver operating characteristic (ROC) analysis to determine the LRG cutoff value in 141 patients who underwent endoscopy (total 235 measurements). Furthermore, the LRG cutoff value was analyzed by comparing small intestinal and colonic lesions. Results: LRG levels were significantly higher in patients without mucosal healing than in those with mucosal healing (15.9 µg/mL vs 10.5 µg/mL, P < .0001). The LRG cutoff value for mucosal healing was 14.3 µg/mL (area under the ROC curve [AUC]: 0.80; sensitivity: 0.89; specificity: 0.63). The LRG cutoff value for patients with type L1 was 14.3 µg/mL (sensitivity: 0.91; specificity: 0.53), and that for patients with type L2 was 14.0 µg/mL (sensitivity: 0.95; specificity: 0.73). The diagnostic performance (AUC) of LRG and C-reactive protein (CRP) for mucosal healing was, respectively, 0.75 and 0.60 (P = 0.01) in patients with type L1 and 0.80 and 0.85 (P = 0.90) in patients with type L2. Conclusions: The optimal LRG cutoff value for evaluating mucosal healing in CD is 14.3 µg/mL. LRG is more useful than CRP for predicting mucosal healing in patients with type L1. The superiority of LRG to CRP differs between small intestinal and colonic lesions.

Relationship between human herpesvirus 6 infection and inflammatory bowel disease using novel biomarker.

Objective: Inflammatory bowel disease (IBD) is closely related to stress and fatigue. Human herpesvirus 6B (HHV-6B) is reactivated by stress and fatigue and is associated with IBD. This study aimed to clarify the relationship between IBD and HHV-6B. Methods: Antibody titers to SITH-1, a protein specific to HHV-6B latent infection, were measured in 163 patients with IBD (107 with ulcerative colitis [UC] and 56 with Crohn's disease [CD]); clinical and endoscopic scores and depression scores of UC and CD were analyzed to examine the relationship between SITH-1 and IBD. The SITH-1 cut-off value was set as 1.96, according to known reports. Results: In patients with UC, C-reactive protein (CRP) level was significantly higher (1.5 vs 0.6 mg/L, P = 0.006) and disease exacerbation within 6 months after entry was significantly more common in the SITH-1 (+) group (20% vs 0%, P < 0.001). In the subanalysis comparing with and without UC exacerbation, the optimal cut-off value for SITH-1 to detect UC exacerbation was 3.44 (area under the curve: 0.81; 95% confidence interval: 0.72-0.90). CRP levels, SITH-1 levels, and disease activity scores by the clinical or endoscopic index were significantly higher in the exacerbation group than in the non-exacerbation group (2.6 vs 0.9 mg/L, P = 0.03; 4.90 vs 1.71, P < 0.001; 4 vs 3, P = 0.03; 5 vs 3, P = 0.02; respectively). Conclusion: Patients with UC with high titers of SITH-1 have high disease activity and frequent disease exacerbation. SITH-1 can be associated with UC disease activity.

Evaluation of the Jichi Medical University diverticular hemorrhage score in the clinical management of acute diverticular bleeding with emergency or elective endoscopy: A pilot study.

BACKGROUND AND AIMS: Emergency endoscopic hemostasis for colonic diverticular bleeding is effective in preventing serious consequences. However, the low identification rate of the bleeding source makes the procedure burdensome for both patients and providers. We aimed to establish an efficient and safe emergency endoscopy system. METHODS: We prospectively evaluated the usefulness of a scoring system (Jichi Medical University diverticular hemorrhage score: JD score) based on our experiences with past cases. The JD score was determined using four criteria: CT evidence of contrast agent extravasation, 3 points; oral anticoagulant (any type) use, 2 points; C-reactive protein ≥1 mg/dL, 1 point; and comorbidity index ≥3, 1 point. Based on the JD score, patients with acute diverticular bleeding who underwent emergency or elective endoscopy were grouped into JD ≥3 or JD <3 groups, respectively. The primary and secondary endpoints were the bleeding source identification rate and clinical outcomes. RESULTS: The JD ≥3 and JD <3 groups included 35 and 47 patients, respectively. The rate of bleeding source identification, followed by the hemostatic procedure, was significantly higher in the JD ≥3 group than in the JD <3 group (77% vs. 23%, p <0.001), with a higher JD score associated with a higher bleeding source identification rate. No significant difference was observed between the groups in terms of clinical outcomes, except for a higher incidence of rebleeding at one-month post-discharge and a higher number of patients requiring interventional radiology in the JD ≥3 group than in the JD <3 group. Subgroup analysis showed that successful identification of the bleeding source and hemostasis contributed to a shorter hospital stay. CONCLUSION: We established a safe and efficient endoscopic scoring system for treating colonic diverticular bleeding. The higher the JD score, the higher the bleeding source identification, leading to a successful hemostatic procedure. Elective endoscopy was possible in the JD <3 group when vital signs were stable.

Adult-onset Still's Disease Diagnosed during Puerperium with Liver Dysfunction in Pregnancy and Liver Failure of the Infant.

Most cases of liver dysfunction in pregnancy are pregnancy-related, but the onset of systemic autoimmune diseases is also differentiated. A 24-year-old woman presented with liver dysfunction at 28 weeks' gestation with suspected autoimmune hepatitis and started taking ursodeoxycholic acid. She gave birth prematurely at 35 weeks' gestation, and the infant presented with pancytopenia and liver failure but survived because of liver transplantation. Since the patient had major symptoms during the puerperium, she was diagnosed with adult-onset Still's disease. When encountering a patient with liver dysfunction during pregnancy, we should also consider the onset of autoimmune diseases.

[Successful endoscopic transpapillary pancreaticobiliary drainage for omental panniculitis by hepatocellular carcinoma complicated by biliary fistula and pancreatic fistula].

A 78-year-old man with hepatocellular carcinoma treated by chemoembolization and percutaneous ethanol injection was admitted to our hospital because of acute abdomen. The CT scan showed biliary fistula caused by hepatocellular carcinoma protruding from S3. Endoscopic retrograde cholangiopancreatography showed disruption of an intrahepatic duct and the main pancreatic duct, and contrast agent leaked into the peritoneal cavity from each duct. Omental panniculitis with biliary fistula and pancreatic fistula was diagnosed. The symptoms improved by endoscopic nasobiliary drainage and endoscopic pancreatic stenting. On the 13th day after admission, we added endoscopic nasopancreatic drainage because his abdominal pain had been exacerbated by pancreatic juice leakage. Omental panniculitis by hepatocellular carcinoma complicated by biliary fistula and pancreatic fistula is extremely rare. Endoscopic transpapillary pancreaticobiliary drainage was effective for omental panniculitis in this case.

Usefulness of the Optimal Cutoff Value and Delta Value of Leucine-Rich Alpha 2 Glycoprotein in Ulcerative Colitis.

Background: Leucine-rich alpha 2 glycoprotein (LRG) is a novel serum biomarker used to determine disease activity in inflammatory bowel disease. We investigated the association between endoscopic scores based on the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and LRG in ulcerative colitis (UC). Methods: A total of 1019 LRG measurements were obtained from 358 patients with UC. This study included 190 patients (199 measurements) who underwent colonoscopy within 3 months before and after LRG measurement with unchanged disease status or treatment during the same period. The patients were divided into those with and without UC relapse. We evaluated the correlation between LRG levels and UCEIS scores and performed a receiver operating characteristic curve analysis to determine the optimal LRG cutoff value. Delta values of LRG were then analyzed. Results: LRG levels were positively correlated with UCEIS scores (correlation coefficient: 0.638; 95% CI: 0.548-0.714; P < .0001) in all disease types. The LRG cutoff value for mucosal healing was 12.6 µg mL-1 (area under the curve: 0.736; 95% CI: 0.651-0.821); this value had a sensitivity of 0.72 and a specificity of 0.66. In patients with UC relapse, the median delta value of LRG before and after relapse was 5 µg mL-1. Conclusions: LRG levels were positively correlated with the UCEIS scores. The optimal LRG cutoff value for determining mucosal healing was 12.6 µg mL-1. The median delta value of LRG before and after relapse was 5 µg mL-1.

Long-term clinical and real-world experience with Crohn's disease treated with anti-tumor necrosis factor-α antibodies.

BACKGROUND/AIMS: Although anti-tumor necrosis factor (TNF)-α agents are important therapeutic drugs for Crohn's disease (CD), data regarding their long-term sustained effects are limited. Herein, we evaluated the long-term loss of response (LOR) to anti-TNF-α agents in patients with CD. METHODS: This retrospective study included patients with CD who started treatment with infliximab or adalimumab as a first-line therapeutic approach. The cumulative event-free, retention, and surgery-free rates after the start of biological therapy were analyzed. Secondary LOR was analyzed in patients who achieved corticosteroid-free clinical remission after the start of biological therapy. Cox proportional hazards models were used to analyze the predictive factors of secondary LOR. RESULTS: The cumulative event-free rates at 1, 2, 5, and 10 years were 83.3%, 75.1%, 37.4%, and 23.3%, respectively. The incidence of LOR was 10.6% per patient-year of follow-up. At 12-14 weeks after the start of biological therapy, the proportion of patients with a C-reactive protein to albumin (CRP/ALB) ratio ≥0.18 was significantly higher in patients with LOR (P<0.001). Multivariate analysis indicates that a CRP/ALB ratio ≥0.18 (hazard ratio [HR], 5.86; 95% confidence interval [CI], 1.56-22.0; P=0.009) and upper gastrointestinal tract inflammation (HR, 3.00; 95% CI, 1.26-7.13; P=0.013) were predictive factors of secondary LOR. CONCLUSIONS: Although anti-TNF-α agents contributed to long-term clinical remission of CD, the annual incidence of secondary LOR was 10.6%. The CRP/ALB ratio at 3 months after the start of biological therapy and upper gastrointestinal tract inflammation were identified as predictive factors of secondary LOR.

Endoscopic Mucosal Incision to Remove a Fish Bone Completely Embedded Under the Esophageal Mucosa: A Case Report and Literature Review.

BACKGROUND Esophageal foreign bodies are known to cause esophageal perforation, penetration, and mediastinitis if left untreated. Therefore, it is desirable to remove them immediately upon being diagnosed. While endoscopic removal is the first choice for removing esophageal foreign bodies, surgical procedures are required when endoscopic removal is not possible due to the shape of the foreign bodies, or if they are completely embedded within or outside the esophageal wall. CASE REPORT An 83-year-old woman experienced pain in her throat after eating grilled fish. She visited our hospital the following day. Computed tomography (CT) confirmed a linear foreign body had likely become completely embedded inside the cervical esophageal wall. Upper gastrointestinal endoscopy was performed under general anesthesia, but the foreign body was not visible. Thereafter, endoscopic mucosal incision was performed and the malpositioned fish bone was finally found. We were able to remove it with gripping forceps. The procedure was completed with the mucosal incision site left open, as there was no obvious damage to the muscle layer. Postoperative CT also confirmed the full removal of the fish bone as well as the lack of any perforation. Following surgery, she underwent 2 days of fasting before re-starting meals. She was discharged uneventfully from the hospital on the seventh hospital day. CONCLUSIONS Even when the foreign body is not visible via endoscopy, it can still be removed by endoscopic mucosal incision based on the CT and endoscopic findings. We summarized 10 similar cases and discussed the efficacy of endoscopic removal of foreign bodies buried under the esophageal mucosa.