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.

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.

Rab7 localized on zymogen granules is involved in maturation but not in autophagy or regulated exocytosis in pancreatic acinar cells.

Rab7 is known to function in the autophagy and endocytosis pathways in eukaryocytes and is related to various diseases. We recently reported that Rab7 plays a protective role against acute pancreatitis. However, its physiological function in exocytic cells remains unclear. Therefore, we investigated the role of Rab7 in pancreas-specific Rab7 knockout mice (Rab7Δpan). Immunofluorescence microscopy revealed that Rab7 colocalized with amylase in pancreatic acinar cells of wild-type mice, but not in Rab7Δpan mice. Western blotting confirmed Rab7 localization in the zymogen granule (ZG) membranes of wild-type mice. Cholecystokinin (CCK)-stimulated amylase secretion examined using isolated pancreatic acini was similar in Rab7Δpan and wild-type mice. In contrast, electron microscopy revealed that the diameters of ZGs were shorter and the number of ZGs was larger in the pancreatic acinar cells of Rab7Δpan mice than in those of wild-type mice. However, the number of ZGs decreased in both Rab7Δpan and wild-type mice after 24 h of starvation. In addition, the amount of amylase in the pancreas was decreased in both Rab7Δpan and wild-type mice. These data indicate that Rab7 localized on ZGs plays a crucial role in the maturation of ZGs but not in their autophagy or regulated exocytosis in pancreatic acinar cells.

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.

A case of needle tract seeding that seemed to be caused by endoscopic ultrasound-guided fine-needle aspiration.

A 66-year-old man underwent a single endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) session and distal pancreatectomy for the pancreatic body adenocarcinoma measuring 12 mm in diameter. At 3 years after surgery, we diagnosed needle tract seeding (NTS) and performed total gastrectomy. NTS can occur with small tumors or after a single session of EUS-FNA.

Gastric Extramural Tumor Caused by Mycobacteria Infection With Immunoreconstitution Inflammatory Syndrome.

Immunoreconstitution inflammatory syndrome (IRIS) was reported to occur in 7-13% of AIDS patients on anti-retroviral therapy (ART). IRIS due to Mycobacterium infection is one of the most difficult IRIS types to manage. A male patient in his early 70s was diagnosed with AIDS and treated with an ART. One year after starting ART, abdominal ultrasound was performed for screening and a 4 cm hypoechoic mass was found from the outside of the stomach to the surface of the hepatic lateral segment. Based on various imaging tests, including contrast CT, a malignant tumor, such as malignant lymphoma, was suspected. Then, a percutaneous tumor biopsy was performed. Pathologically, the tumor was recognized as mycobacterial granulomas. Disseminated mycobacterium avium complex can produce granulomas anywhere in the body. The patient was diagnosed with a mycobacterial infection associated with IRIS. When an intra-abdominal mass is found in a patient with HIV, both malignancy and mass formation due to opportunistic infections should be considered differential diseases.

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.

The Diagnosis of Small Gastrointestinal Subepithelial Lesions by Endoscopic Ultrasound-Guided Fine Needle Aspiration and Biopsy.

Endoscopic ultrasonography (EUS) has been widely accepted in the diagnosis of all types of tumors, especially pancreatic tumors, lymph nodes, and subepithelial lesions (SELs). One reason is that the examination can provide a detailed observation, with tissue samples being immediately obtained by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). Many SELs are detected incidentally during endoscopic examinations without symptoms. Most SELs are mesenchymal tumors originating from the fourth layer, such as gastrointestinal stromal tumors (GISTs), leiomyomas, and schwannomas. GISTs are potentially malignant. Surgical treatment is recommended for localized GISTs of ≥20 mm. However, the indications for the diagnosis and follow-up of GISTs of <20 mm in size are controversial. There are several reports on the rapid progression or metastasis of small GISTs. Therefore, it is important to determine whether a SEL is a GIST or not. The main diagnostic method is EUS-FNA. Recently, endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) using a new biopsy needle has been reported to obtain larger tissue samples. Additionally, various biopsy methods have been reported to have a high diagnostic rate for small GISTs. In local gastric SELs, regardless of the tumor size, EUS can be performed first; then, EUS-FNA/B or various biopsy methods can be used to obtain tissue samples for decision-making in relation to therapy and the follow-up period.

Effects of pemafibrate on primary biliary cholangitis with dyslipidemia.

AIM: The purpose of this study was to examine the effect of pemafibrate (PEM) in primary biliary cholangitis (PBC) patients with dyslipidemia. METHODS: Patients who were diagnosed with PBC between June 2018 and December 31, 2020 were included in the study if they also had dyslipidemia and their alkaline phosphatase (ALP) or gamma-glutamyl transferase (GGT) levels remained above the normal range despite taking 600 mg/day ursodeoxycholic acid (UDCA) for at least 6 months. Patients who were treated with UDCA alone were administered PEM as an add-on (PEM-add group), and patients who were treated with UDCA and bezafibrate (BEZ) for at least 6 months were given PEM instead of BEZ (PEM-switch group). Clinical parameters were compared in all patients, and the levels of ALP, GGT, the estimated glomerular filtration rate (eGFR), and creatinine (Cr) were compared between the PEM-add and PEM-switch groups. Improvement in cholangitis was also evaluated. RESULTS: In the PEM-add group, both ALP and GGT improved in 40 of 46 patients (87.0%). In the PEM-switch group, both ALP and GGT improved in 15 of 29 patients (51.7%). In the PEM-switch group, however, significant improvement was seen in eGFR and Cr. CONCLUSIONS: Administration of PEM is effective in PBC patients with dyslipidemia who are refractory to UDCA monotherapy. In patients using both UDCA and BEZ, there was an advantage in switching to PEM if they had renal damage; however, improvement of ALP and GGT occurred in about 50%.

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.

[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.

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.

Real-world efficacy and safety of 12-week sofosbuvir/velpatasvir treatment for patients with decompensated liver cirrhosis caused by hepatitis C virus infection.

AIM: This study aimed to evaluate the real-world efficacy and safety of 12-week sofosbuvir/velpatasvir (SOF/VEL) treatment for patients with decompensated liver cirrhosis caused by hepatitis C virus (HCV) infection. METHODS: A total 72 of patients with Child-Pugh (CP) class B or C were enrolled. We evaluated the sustained virologic response at 12 weeks after the end of treatment (SVR12), adverse events (AEs), and changes in the liver function. RESULTS: All participants had genotype 1 or 2 HCV infection. At baseline, the numbers of patients with CP class B and C were 59 and 13, respectively. The overall SVR12 rate was 95.8% (69/72); 94.9% (56/59) in CP class B and 100% (13/13) in CP class C. The serum albumin level, prothrombin time and ascites were significantly improved (P < 0.01); however, the serum bilirubin level and encephalopathy did not improve. Among patients who achieved SVR12, 75.0% showed an improvement in their CP score, while 5.9% showed a worsening. The presence of large portosystemic shunt (diameter ≥6 mm) and hyperbilirubinemia (≥2.0 mg/dL) were independent factors that interfered with the improvement in the CP score (P < 0.05). The most common AEs were encephalopathy (15.3%) and skin symptoms (7.9%). Two patients discontinued SOF/VEL due to AEs. CONCLUSIONS: Treatment with SOF/VEL for 12 weeks was relatively safe and effective for patients with decompensated cirrhosis. An SVR provided an improvement of the liver function in the majority of patients. However, large portosystemic shunt and hyperbilirubinemia were independent factors that interfered with the improvement in the CP score.

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.

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.

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.

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.