GTS-21 Enhances Regulatory T Cell Development from T Cell Receptor-Activated Human CD4+ T Cells Exhibiting Varied Levels of CHRNA7 and CHRFAM7A Expression.

Immune cells such as T cells and macrophages express α7 nicotinic acetylcholine receptors (α7 nAChRs), which contribute to the regulation of immune and inflammatory responses. Earlier findings suggest α7 nAChR activation promotes the development of regulatory T cells (Tregs) in mice. Using human CD4+ T cells, we investigated the mRNA expression of the α7 subunit and the human-specific dupα7 nAChR subunit, which functions as a dominant-negative regulator of ion channel function, under resting conditions and T cell receptor (TCR)-activation. We then explored the effects of the selective α7 nAChR agonist GTS-21 on proliferation of TCR-activated T cells and Treg development. Varied levels of mRNA for both the α7 and dupα7 nAChR subunits were detected in resting human CD4+ T cells. mRNA expression of the α7 nAChR subunit was profoundly suppressed on days 4 and 7 of TCR-activation as compared to day 1, whereas mRNA expression of the dupα7 nAChR subunit remained nearly constant. GTS-21 did not alter CD4+ T cell proliferation but significantly promoted Treg development. These results suggest the potential ex vivo utility of GTS-21 for preparing Tregs for adoptive immunotherapy, even with high expression of the dupα7 subunit.

Can the location of the mural nodule indicate benign or malignant in branch duct-type intraductal papillary mucinous neoplasm of the pancreas?

BACKGROUND/OBJECTIVES: Intraductal papillary mucinous neoplasms (IPMNs) are classified into main duct (MD)-type IPMNs, branch duct (BD)-type IPMNs, and mixed type IPMNs. While MD-type IPMN has a high risk of malignancy and should therefore be considered for resection if the patient is fit, BD-type IPMN needs to be carefully judged for surgical indication. The decision to resect BD-type IPMN is often based on international consensus Fukuoka guidelines 2017, but further investigation is required. In this study, we focused on whether the location of the mural nodule (MN) could be an indicator of malignancy. METHODS: We enrolled 17 cases who had been diagnosed BD-type IPMNs which were surgically resected from January 2016 to December 2019. These cases were classified into benign and malignant group. Subsequently, a clinicopathological study was conducted based on the localization of MN (MN-central type or MN-peripheral type). RESULTS: Although MN was found in 57% (4/11) in the benign group, 88% (7/8) was noted in the malignant group, indicating the presence of MN to be more common in the malignant group. Those with MN consisted of 6 cases of MN-central type and 5 cases of MN-peripheral type. All cases of central type were malignant compared to only one case of the peripheral group being confirmed on histology as cancer. CONCLUSION: BD-IPMN with central mural nodule should be considered high risk for malignancy.

A case of pheochromocytoma with a marked decrease in catecholamine levels after rupture in which a good outcome was achieved by elective surgery.

Changes in imaging findings and hormone levels before and after pheochromocytoma rupture, as well as detailed histopathology of resected tumors, have rarely been reported. A 52-year-old woman developed hypertension and diabetes mellitus in 2014, but despite treatment with antihypertensive and hypoglycemic drugs, good control was not achieved. On April 2, 2016, the patient started to have headaches and palpitations, and on April 6, she visited our hospital. Plain computed tomography (CT) of the abdomen showed a 4-cm, isodense mass in the left adrenal gland, and the patient was hospitalized for further examination. Because the patient had hypertension, tachycardia, and hyperglycemia on admission, therapies for those were started. Catecholamine levels were markedly elevated. However, after the patient developed left flank pain on Day 4, antihypertensive and insulin therapies were no longer required. Plain CT then showed heterogeneous high density areas in the left adrenal mass. On Day 7, 3 meta-iodobenzylguanidine scintigraphy showed no abnormal uptake. On Day 8, contrast CT showed low density areas within the left adrenal tumor and contrast enhancement of the tumor margins, and catecholamine levels were markedly decreased. Elective left adrenal tumor resection was performed on Day 49. The capsule of the resected tumor was ruptured. Histopathology showed widespread hemorrhagic necrosis and viable cell components in the tumor margins. Positive chromogranin A staining of the tumor cells confirmed a diagnosis of pheochromocytoma. This patient displayed remarkable changes in imaging findings and hormone levels before and after pheochromocytoma rupture. Pheochromocytoma rupture and hemorrhagic necrosis were confirmed histopathologically.

Efficacy of a Novel Tapered Contrast Catheter for Endoscopic Ultrasound-Guided Hepaticogastrostomy: A Multicenter Study.

Background: Endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) is an alternative for failed endoscopic retrograde cholangiopancreatography (ERCP), with current success rates of 65-84% considered suboptimal. A novel ERCP catheter (SHOREN, Kaneka Corporation, Osaka, Japan) with a tapered 3.3-French tip may facilitate smoother insertion, potentially improving outcomes. Methods: This retrospective analysis encompassed EUS-HGS procedures conducted from January 2021 to August 2023 at four institutions. The aim of this study was to compare the performance of conventional and novel ERCP contrast catheters regarding the success rate of single-attempt catheter insertion, failure rates, technical success rates, and incidence of adverse events. Results: The study included 48 patients; 26 underwent EUS-HGS using conventional catheters and 22 with the novel catheter. The novel catheter achieved higher success rates in single-attempt insertions (96.5% vs. 80.8%) and lower failure rates (4.6% vs. 7.7%). The occurrence of bile peritonitis was comparable between the two groups. Conclusions: The novel ERCP contrast catheter with a tapered tip appears to contribute to successful catheter insertion and is useful for EUS-HGS.

Endoscopic ultrasound-guided tissue acquisition for focal liver lesions in the caudate lobe: a report of seven cases.

The caudate lobe of the liver is located deep within the body and surrounded by major blood vessels, such as inferior vena cava, portal vein, and hepatic veins. Thus, percutaneous biopsy is technically challenging. Herein, we report seven patients with focal liver lesions in the caudate lobe who underwent endoscopic ultrasound-guided tissue acquisition (EUS-TA). Their median age was 56 (25-79) years, consisting five males and two females, and the median lesion size was 44 (19-77) mm. Transgastric EUS-TA was performed in all patients. The needles used were 22G and 25G in six patients and one patient, and the median procedure time was 18 (13-30) min. In all patients, adequate specimens were collected, and pathological diagnosis was possible (three intrahepatic cholangiocarcinoma, two metastatic tumors from pancreatic cancer, one hepatocellular carcinoma, and one focal nodular hyperplasia). No adverse events associated with the procedure were observed. EUS-TA can be the first choice for tissue acquisition of the caudate lobe lesions.

A case of synchronous IgG4-associated pleuritis and type 1 autoimmune pancreatitis.

A 50-year-old man presented to the emergency department with left chest pain, epigastralgia, and low-grade fever for several days. A CT scan showed left pleural effusion, ground-glass opacities in the lower lobes of both lungs, and a capsule-like rim in the pancreas. ERCP showed narrowing of the main pancreatic duct. EUS-FNA was performed, but pathological findings showed no IgG4-positive cells. A thoracoscopic biopsy was performed, and pathological findings showed many IgG4-positive cells. A diagnosis of autoimmune pancreatitis and IgG4-associated pleurisy was made according to international diagnostic criteria. After that, oral steroid therapy was started, and left pleural effusion and pancreatic enlargement improved.

Long-term Follow-up of Small Nonfunctioning Pancreatic Neuroendocrine Tumors Diagnosed Using Endoscopic Ultrasound-guided Fine-needle Aspiration.

Objective Clinical practice guidelines in Japan recommend surgery for all nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs), regardless of their size or associated symptoms. Because pancreatic resection is highly invasive, follow-up for small NF-PNETs is often chosen in clinical practice. However, the natural history of NF-PNET remains poorly understood. We aimed to examine the natural history of pathologically confirmed NF-PNET. Methods This single-center retrospective case series investigated NF-PNETs that were pathologically diagnosed using endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) at our hospital between 2014 and 2018. Patients who were followed up without treatment due to their general condition or their wish were included in the study. Patients' background characteristics, imaging findings, pathological findings, and long-term prognoses were investigated using medical records. Results Overall, 26 patients were diagnosed with NF-PNET by EUS-FNA during the observation period. Of these, 9 patients (3 men and 6 women; median age: 64 years old) were followed up without treatment. All of these patients were asymptomatic, and localization was noticed in 3 cases in the head, body, and tail (1 each), with a median size of 12 (range: 4-18) mm. Neuroendocrine tumor (Grade 1 [G1]) was pathologically diagnosed in all patients with EUS-FNA. The median observation period was 63 (range: 26-90) months. Tumor growth and distant metastasis were not observed in any of the nine patients who remained asymptomatic. Conclusion Follow-up is a feasible option for asymptomatic NF-PNET ≤20 mm in size with a pathological grade of G1.

Anti programmed death-ligand 1 antibody-related cholangitis without bile duct dilation or stenosis.

Cholangitis has been reported as an immune-related adverse event, although it rarely occurs. Here we report a case of cholangitis due to atezolizumab in a 77-year-old woman who had been treated with atezolizumab and nab-paclitaxel for breast cancer and lung metastasis. On the seventh cycle, she presented with fever and epigastric pain, and computed tomography and endoscopic ultrasound showed slight wall thickening of the common bile duct, and transpapillary bile duct biopsy was performed. Pathologically, CD8+ T cells predominant infiltration was detected in the subepithelium of the bile duct, resulting in the diagnosis of atezolizumab-related cholangitis. The patient's symptoms were resolved immediately after discontinuing atezolizumab. Hepatobiliary enzymes returned to normal 21 days after onset, and bile duct wall thickening disappeared. Cholangitis should be included as the differential diagnosis of liver dysfunction in patients receiving immune checkpoint inhibitors.

A case of hemobilia caused by pancreatic metastasis of renal cell carcinoma treated with a covered metallic stent.

We present the case of an 86-year-old man who had undergone left nephrectomy for renal cell carcinoma (clear cell carcinoma) 22 years ago. He visited the emergency department complaining of right hypochondrial pain and fever. He was eventually diagnosed with acute cholangitis. Abdominal contrast-enhanced computed tomography showed multiple tumors in the pancreas. The tumor in the pancreatic head obstructed the distal bile duct. Endoscopic retrograde cholangiopancreatography detected bloody bile juice flowing from the papilla of Vater. Therefore, he was diagnosed with hemobilia. Cholangiography showed extrinsic compression of the distal bile duct; a 6 Fr endoscopic nasobiliary drainage tube was placed. Endoscopic ultrasound showed that the pancreas contained multiple well-defined hypoechoic masses. Endoscopic ultrasound-guided fine-needle aspiration was performed using a 22 G needle. Pathological examination revealed clear cell carcinoma, and the final diagnosis was pancreatic metastasis of renal cell carcinoma (RCC) causing hemobilia. A partially covered metallic stent was placed in the distal bile duct. Consequently, hemobilia and cholangitis were resolved.

Permanent endoscopic transpapillary gallbladder drainage using a novel spiral stent (IYO-stent).

Background and aim: Endoscopic transpapillary gallbladder drainage (ETGBD) is widely performed. However, there is no consensus on the appropriate diameter, length, and shape of the stent that should be used in this procedure. In addition, there are limited data on the outcomes of permanent ETGBD. In our facility, a stent with a novel spiral structure (IYO-stent) is permanently placed in patients with acute cholecystitis who are not indicated for surgery. This study examined the efficacy and safety of the IYO-stent in cases of permanent ETGBD. Methods: We retrospectively examined patients who underwent permanent ETGBD using the IYO-stent from April 2018 to December 2020. Results: Eleven patients were included in this study. The technical success and the clinical success rate were 91%. One patient had a post-procedure adverse event (post-endoscopic sphincterotomy bleeding). Within the median observation period of 312 days (range: 109-742), late adverse events, including cholangitis (n = 1) and incomplete stent migration (n = 1), were observed. However, none of the patients experienced cholecystitis relapse. Conclusion: Permanent ETGBD with IYO-stent is an effective treatment for the patients with acute cholecystitis who are not indicated for surgery.

Usefulness of endoscopic ultrasound-guided fine needle aspiration for splenic parenchyma in patients suspected of having primary splenic malignant lymphoma.

Background and study aims The diagnosis of malignant lymphoma (ML) is sometimes difficult, especially in patients with primary splenic malignant lymphomas (psML) which have no lymph nodes capable of acting as the biopsy target. We carried out endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for "splenic parenchyma" in patients suspected of having a psML, even without any obvious neoplastic lesions in the spleen. Patients and methods A retrospective study using medical records was conducted of eight patients suspected of having a psML that received EUS-FNA for the splenic parenchyma between January 2016 and January 2019. Data analyzed included clinical background, EUS-FNA procedure (puncture needle/route), diagnostic ability (pathological/flow cytometry [FCM]), and complications. Results EUS-FNA was performed from the stomach in all eight cases, and no patients had complications. As a result of splenic parenchymal biopsy found on EUS-FNA, 75 % of patients (6/8) were histologically diagnosed with MLs, monoclonality of B-cells was identified in all cases (8/8) with FCM, and all patients (8/8) were definitively diagnosed with psMLs. Conclusion EUS-FNA for "splenic parenchyma" is useful for patients with spML, even if they have no obvious neoplastic lesions in the spleen.

A case of bile duct diverticulum with repeated acute cholangitis due to diverticular stone fall.

A 34-year-old man presented to the emergency department with a chief complaint of epigastric pain. Endoscopic ultrasound detected a 5 mm stone in the common bile duct. After endoscopic sphincterotomy, the black stones and debris were removed with balloon catheter. Abdominal ultrasonography detected no gallbladder stones; hence, the patient was followed up. However, 3 months later, the patient again developed acute cholangitis caused by common bile duct stones and underwent endoscopic stone removal. Cholangiography under balloon occlusion revealed a left hepatic duct diverticulum with an internal defect. Intraductal ultrasonography showed a hyperechoic lesion with acoustic shadow in the diverticulum, suggesting a stone or debris. Therefore, the patient was considered to have had repeated acute cholangitis because of the presence of falling diverticular stones. The patient underwent left hemihepatectomy plus segmentectomy 1 and cholecystectomy. Histopathologically, it was a true diverticulum without internal epithelial atypia. Many debris were seen in the diverticulum. Gallbladder stones were not observed. Eventually, the patient was discharged from the hospital with no postoperative complications and no recurrence of cholangitis after 20 months.