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.

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.

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.

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.

Utility of endoscopic ultrasonography-guided fine-needle biopsy (EUS-FNB) for diagnosing small subepithelial lesions (< 20 mm).

AIM: Subepithelial lesions (SELs) are defined as being located under the mucosa. Presently, endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is commonly performed to diagnose SELs. With the development of new puncture needles, endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB), which allows for the acquisition of large tissue samples, has been proposed. However, studies on EUS-FNB of SELs measuring < 20 mm have not yielded satisfactory results. Therefore, we aimed to assess the performance and usefulness of EUS-FNB of SELs measuring less than < 20 mm. METHODS: The present study included 62 patients who underwent EUS-FNA or EUS-FNB for SELs at our hospital between January 2015 and March 2019. EUS-FNA was performed using fine-needle aspiration needles, and EUS-FNB was performed using fine-needle biopsy needles. These needles, which come in different shapes and diameters, were compared in terms of their usefulness in performing procedures for SELs measuring ≥ 20 mm and those measuring < 20 mm. RESULTS: For SELs measuring ≥ 20 mm, the use of needles with a large diameter, such as 19 or 20 G, resulted in significantly improved diagnostic rates. For SELs measuring < 20 mm, the use of FNB needles showed significantly improved diagnostic rates, regardless of the size of the puncture needles. CONCLUSION: Even when SELs are less than 20 mm, they might have malignant potential, and histological diagnosis may be desirable in some cases. EUS-FNB has an advantage over EUS-FNA in the diagnosis of SELs measuring < 20 mm.

Pruritus is common in patients with chronic liver disease and is improved by nalfurafine hydrochloride.

Pruritus is known to be a common complication in hepatitis patients, but the exact frequency and degree are not fully elucidated. Thus, we evaluated pruritus of 450 patients with chronic liver disease at our hospital. Pruritus was observed in 240 (53%) of the patients. Pruritus was significantly associated with males (OR = 1.51, P = 0.038) and patients with alkaline phosphatase (ALP) ≥ 200 U/L (OR = 1.56, P = 0.0495) and was significantly less in HBsAg-positive patients (OR = 0.449, P = 0.004). Seasonally, there was no difference in the frequency of pruritus between summer and winter. Of the 24 refractory pruritus patients treated with nalfurafine, 17 (71%) indicated improvement of itch, which is defined as a decrease in the visual analog scale score ≥ 30 mm. Pruritus was improved by nalfurafine both during daytime and nighttime in the Kawashima's scores evaluation. All patients who received nalfurafine exhibited improved Kawashima's scores ≥ 1 point during the daytime or nighttime. In conclusion, pruritus occurred in > 50% of patients with chronic liver disease, and predictors of pruritus were males and ALP ≥ 200 U/L. Nalfurafine may be useful for pruritus, regardless of whether daytime or nighttime.

Clinical course of biliary-type sphincter of Oddi dysfunction: endoscopic sphincterotomy and functional dyspepsia as affecting factors.

BACKGROUND AND STUDY AIMS: The objective of this study was to clarify the effectiveness of treatment selection for biliary-type sphincter of Oddi dysfunction by severe pain frequency and the risk factors for recurrence including the history of functional gastrointestinal disorder. PATIENTS AND METHODS: Thirty-six sphincter of Oddi dysfunction patients who were confirmed endoscopic retrograde cholangiopancreatography enrolled in this study. Endoscopic sphincterotomy was performed for type I and manometry-confirmed type II sphincter of Oddi dysfunction patients with severe pain (⩾2 times/year; endoscopic sphincterotomy group). Others were treated medically (non-endoscopic sphincterotomy group). RESULTS: The short-term effectiveness rate of endoscopic sphincterotomy was 91%. The final remission rates of the endoscopic sphincterotomy and non-endoscopic sphincterotomy groups were 86% and 100%, respectively. Symptoms relapsed after endoscopic sphincterotomy in 32% of patients. Patients in the endoscopic sphincterotomy and non-endoscopic sphincterotomy groups had or developed functional dyspepsia in 41% and 14%, irritable bowel syndrome in 5% and 14%, and gastroesophageal reflux disorder in 14% and 0%, respectively. History or new onset of functional dyspepsia was related to recurrence on multivariate analysis. The frequency of occurrence of post-endoscopic retrograde cholangiopancreatography pancreatitis and post-endoscopic retrograde cholangiopancreatography cholangitis was high in both groups. Two new occurrences of bile duct stone cases were observed in each group. CONCLUSION: According to the treatment criteria, endoscopic and medical treatment for biliary-type sphincter of Oddi dysfunction has high effectiveness, but recurrences are common. Recurrences may be related to new onset or a history of functional dyspepsia.

Rupture of Hepatic Pseudoaneurysm Formed Nine Years after Carbon Ion Radiotherapy for Hepatocellular Carcinoma.

An 83-year-old man with a history of carbon ion radiotherapy for hepatocellular carcinoma nine years ago presented to a primary care hospital with a fever and abdominal pain. He underwent computed tomography, which revealed the rupture of a hepatic pseudoaneurysm close to the fiducial marker for carbon ion radiotherapy and bleeding into the bile duct. He was successfully treated with transcatheter arterial embolization. Thereafter, re-rupture occurred from a site proximal to the first rupture, and this was treated similarly. It is necessary to be alert for not only tumor recurrence but also pseudoaneurysm occurrence after carbon ion radiotherapy.

Appropriate Timing of Discontinuation of Tacrolimus Therapy for Refractory Ulcerative Colitis.

BACKGROUND AND OBJECTIVES: Tacrolimus is very effective at inducing remission in patients with refractory ulcerative colitis. However, the optimal time-point for the discontinuation of tacrolimus is controversial because administration of tacrolimus for > 3 months is currently not approved for insurance reimbursement in Japan. We conducted this study to determine the optimal time of discontinuation of tacrolimus in patients with ulcerative colitis. METHODS: Of 38 patients who received tacrolimus as remission induction therapy for refractory active ulcerative colitis between 2009 and 2018, this study included 21 patients who received tacrolimus for ≥ 3 months before being switched to thiopurines. These patients were divided into two groups for analysis: the confirmed switch (CS) group (n = 13), in which tacrolimus was switched to azathioprine after endoscopic confirmation of mucosal improvement, and the mandatory switch (MS) group (n = 8), in which tacrolimus was switched to a thiopurine agent without endoscopic confirmation of improvement. RESULTS: The relapse rates after the switch to azathioprine were 23% and 88% in the CS and MS groups, respectively (p = 0.0075). No patient of the CS group underwent surgery, while 50% of patients of the MS group underwent surgery (p = 0.0117). The cumulative event-free rates at 6 months, 1 year, and 2 years were 92%, 92%, and 65%, respectively, in the CS group and 15%, 15%, and 0%, respectively, in the MS group (p < 0.0001). The incidence rate of adverse reactions was 31% in the CS group and 13% in the MS group, but there were no serious adverse reactions. CONCLUSIONS: It seems preferable to discontinue tacrolimus after endoscopic confirmation of mucosal healing. However, attention should be paid to the potential occurrence of adverse reactions associated with long-term tacrolimus therapy.

A Diagnostically Challenging Case of Autoimmune Pancreatitis Due to Contamination of the Pathological Specimen with Early Gastric Cancer.

A 73-year-old man with worsened diabetes underwent abdominal computed tomography and was diagnosed with localized enlargement of the pancreatic tail. Based on the suspicion of autoimmune pancreatitis, endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) was performed. A cytologic examination showed findings suggestive of adenocarcinoma. Due to discrepancies between the imaging and pathological findings, esophagogastroduodenoscopy was performed. An extensive early gastric cancer lesion was detected in the posterior wall of the gastric corpus. It was therefore likely that puncturing through the tumor resulted in the contamination with cancer tissue. The possibility of a concomitant malignancy should be considered in EUS-FNA, and thorough examinations should be conducted.

Crohn's Disease with Mesalazine Allergy that Was Difficult to Differentiate from Comorbid Ulcerative Colitis.

An 18-year-old man diagnosed with ileocolonic Crohn's disease with circumferential strictures of the ascending colon started treatment with mesalazine and subsequently underwent right hemicolectomy. After surgery, the patient was started on adalimumab, and the clinical course was favorable. Nine months postoperatively, colonoscopy revealed granular mucosa with circumferential and continuous involvement from the transverse colon down to the rectum, findings which resembled ulcerative colitis. Mesalazine allergy was suspected, and the inflammatory findings resolved after discontinuing mesalazine. In patients of inflammatory bowel disease receiving mesalazine with an atypical clinical course, the possibility of mesalazine allergy must be borne in mind.

A case of gossypiboma diagnosed with transanal double-balloon enteroscopy.

Gossypiboma is an iatrogenic granuloma caused by retained surgical gauze. A 48-year-old woman with a history of cesarean section was incidentally found to have a pelvic mass on preoperative computed tomography examination for pectus excavatum. Abdominal enhanced computed tomography showed a 40-mm mass containing air in the pelvis. The mass was suspected to be continuous with the ileum. Transanal double-balloon enteroscopy showed a small fistula that was likely caused by penetration of the ileum dozens of centimeters from the ileocecal valve. A yellow-brown, movable, and fibrous body was found in the fistula. A part of the fibrous body was extracted with forceps. Pathological examination revealed that it was gauze. This is the first reported case of an asymptomatic gossypiboma penetrating the ileum that was diagnosed with double-balloon enteroscopy. Our results suggest that double-balloon enteroscopy is useful for early diagnosis of pelvic mass penetrating intestine, including gossypiboma.

Post-ERCP biliary complications in patients with biliary type sphincter of Oddi dysfunction.

Sphincter of Oddi dysfunction (SOD) has a high risk of post-ERCP pancreatitis. Cholangitis, colicky pain, and jaundice from cholestasis also occur after ERCP. However, these post-ERCP biliary complications have not been sufficiently evaluated in SOD. Thus, the risk factors and post-ERCP biliary complications in biliary-type SOD were evaluated. From December 1996 to January 2017, 72 patients with suspected biliary-type SOD were selected, and 60 patients who underwent ERCP were included in this study. The incidence of biliary complications compared to control group and factors associated with post-ERCP cholangitis were investigated. More frequent biliary complications, including biliary pain and abnormal liver function, occurred in SOD group than in control group, especially in type I SOD patients. Post-ERCP cholangitis occurred significantly more often with bile duct diameter ≥12 mm (26%, 5/19) than with bile duct diameter <11 mm (2.4%, 1/41; p = 0.016). Age ≥75 years was also a risk factor for post-ERCP cholangitis (p = 0.013). Multivariate analysis confirmed that bile duct diameter ≥12 mm was a significant risk factor for post-ERCP cholangitis. Post-ERCP biliary complications occurred frequently in biliary-type SOD, especially type I. Biliary diameter ≥12 mm was an important risk factor for post-ERCP cholangitis.

Gangliocytic Paraganglioma with Carcinoma of the Ampulla of Vater.

The patient was a "73" -year-old woman who visited our hospital with the chief complaint of weight loss. Upper gastrointestinal endoscopy revealed an enlarged ampulla of Vater, and a biopsy led to a diagnosis of Group "4" gastric carcinoma; suspicious of adenocarcinoma. There were no findings suggesting invasion into the muscle layer of duodenum, despite tumor mass formation being observed in the sphincter of Oddi. We performed endoscopic papillectomy for both diagnostic and therapeutic purposes. Pathologically, a well-differentiated adenocarcinoma existed in the superficial layer of the mucous membrane of the papilla of Vater, and gangliocytic paraganglioma was present in the deep portion. The resected margins of both lesions were negative.

The role of Gαq/Gα11 signaling in intestinal epithelial cells.

Intestinal homeostasis and the coordinated actions of digestion, absorption and excretion are tightly regulated by a number of gastrointestinal hormones. Most of them exert their actions through G-protein-coupled receptors. Recently, we showed that the absence of Gαq/Gα11 signaling impaired the maturation of Paneth cells, induced their differentiation toward goblet cells, and affected the regeneration of the colonic mucosa in an experimental model of colitis. Although an immunohistochemical study showed that Gαq/Gα11 were highly expressed in enterocytes, it seemed that enterocytes were not affected in Int-Gq/G11 double knock-out intestine. Thus, we used an intestinal epithelial cell line to examine the role of signaling through Gαq/Gα11 in enterocytes and manipulated the expression level of Gαq and/or Gα11. The proliferation was inhibited in IEC-6 cells that overexpressed Gαq/Gα11 and enhanced in IEC-6 cells in which Gαq/Gα11 was downregulated. The expression of T-cell factor 1 was increased according to the overexpression of Gαq/Gα11. The expression of Notch1 intracellular cytoplasmic domain was decreased by the overexpression of Gαq/Gα11 and increased by the downregulation of Gαq/Gα11. The relative mRNA expression of Muc2, a goblet cell marker, was elevated in a Gαq/Gα11 knock-down experiment. Our findings suggest that Gαq/Gα11-mediated signaling inhibits proliferation and may support a physiological function, such as absorption or secretion, in terminally differentiated enterocytes.

Tacrolimus versus anti-tumor necrosis factor agents for steroid-refractory active ulcerative colitis based on the severity of endoscopic findings: a single-center, open-label cohort study.

BACKGROUND AND AIMS: At Saitama Medical Center, for remission induction in active ulcerative colitis (UC) patients with endoscopic evidence of severe disease, we tend to preferentially use tacrolimus (TAC) over anti-tumor necrosis factor (TNF)-α agents. We conducted this study to evaluate the validity of our therapeutic strategies. PATIENTS AND METHODS: This retrospective study was conducted in 52 steroid-refractory active UC patients with a Clinical Activity Index (CAI) score of ≥7 who were receiving remission induction therapy with TAC or anti-TNF-α agents. The patients were divided into a TAC treatment group (TAC group, n = 29) and an anti-TNF-α agent treatment group (anti-TNF group, n = 23). The CAI, Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and incidence of events (relapse, hospitalization and surgery) were retrospectively analyzed. RESULTS: At treatment initiation, the CAI score was 12.6 in the TAC group and 11.5 in the anti-TNF group (P = 0.09), while the corresponding values of the UCEIS were 6.5 and 5.1, respectively (P = 0.0035). The clinical remission rate at 12 weeks was 55% (65% when only the subgroup that received rapid induction therapy was included in the analysis) in the TAC group and 57% in the anti-TNF group, with no significant difference. The cumulative event-free rates at 1, 6 and 12 months were 65.5%, 39.4%, and 39.4%, respectively, in the TAC group and 95.7%, 77.2% and 71.7%, respectively, in the anti-TNF group (P = 0.0037). CONCLUSION: Rapid induction therapy with TAC tended to be selected for active UC patients with endoscopic evidence of severe disease, and the present study supported the validity of this therapeutic approach. However, transition to the remission-maintenance phase was more favorable in the anti-TNF group.

Should Emergency Endoscopy be Performed in All Patients With Suspected Colonic Diverticular Hemorrhage?

OBJECTIVE: We attempted to develop a scoring system for facilitating decision making regarding the performance of emergency endoscopy in patients with colonic diverticular hemorrhage. METHODS: This study involved analysis of the data of 178 patients who presented with hematochezia and were diagnosed as having colonic diverticular hemorrhage by colonoscopy. The patients were divided into 2 groups depending on whether the bleeding source was identified or not at the initial endoscopy (source-identified and source-not-identified groups), and on the basis of the results obtained, we established a scoring system for predicting successful identification of the bleeding source. RESULTS: The percentages of patients on oral anticoagulant therapy or with a Charlson comorbidity index of ≥6, serum C-reactive protein level of ≥1 mg/dL, or extravasation of contrast medium visualized on contrast-enhanced computed tomographic (CT) images were all significantly higher in the identified than in the nonidentified group. Multivariate analysis identified extravasation of contrast medium on contrast-enhanced CT images (odds ratio [OR]: 10.6; 95% confidence interval [CI]: 2.7-42.2) and use of anticoagulants (OR: 4.5; 95% CI: 1.5-13.5) as independent predictors of successful identification of the bleeding source at the initial endoscopy in patients with colonic diverticular hemorrhage. On the basis of these results, we established a scoring system, which showed a sensitivity of 80% and specificity of 81% for successful identification of the bleeding source at the initial endoscopy. CONCLUSIONS: Herein, we propose a scoring system as a useful tool for determining whether emergency endoscopy is indicated in individual patients with suspected colonic diverticular hemorrhage.

Risk factors of post- endoscopic retrograde cholangiopancreatography pancreatitis in biliary type sphincter of Oddi dysfunction in Japanese patients.

OBJECTIVE: Suspected sphincter of Oddi dysfunction (SOD) is a well-known risk factor for post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). The indication of ERCP for suspected SOD patients was very low in Japan compared to other countries. Therefore, the risk of PEP may be different in Japanese SOD patients. The objective of this study was to evaluate the risk of PEP in suspected biliary type SOD in Japan. METHODS: From December 1996 to January 2017, 72 patients were suspected as having biliary type SOD, by questionnaire, liver function tests, hepatobiliary scintigraphy, abdominal ultrasonography, upper gastrointestinal endoscopy, endoscopic ultrasonography and magnetic resonance cholangiopancreatography. Finally, 60 patients who underwent ERCP were included in this study, and the factors associated with PEP were evaluated. RESULTS: The overall PEP rate was 23.3% (n = 14). Diagnostic ERCP alone for SOD did not increase the risk of PEP. The correlation of PEP incidence with pancreatic duct guidewire (PGW) technique and endoscopic sphincterotomy (EST) was indicated in univariate and multivariate analysis. Pancreatic stent placement was a risk in univariate analysis but not in multivariate analysis. CONCLUSIONS: PGW technique and EST for biliary type SOD were important risk factors for PEP. Pancreatic stenting was ineffective for prevention of PEP.