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.

Benefits of endoscopic gallbladder stenting following percutaneous transhepatic gallbladder drainage.

BACKGROUND: Endoscopic transpapillary gallbladder drainage is challenging because of the complexity of the procedure and high incidence of adverse events (AEs). To overcome these problems, endoscopic gallbladder stenting (EGBS) after percutaneous transhepatic gallbladder drainage (PTGBD) can be effective, as it mitigates inflammation and adhesion. AIM: To examine the benefits of EGBS after PTGBD to assess its efficacy and impact on AEs. METHODS: We retrospectively analyzed data from 35 patients who underwent EGBS after PTGBD at a single center between January 2016 and December 2023. The primary outcomes were technical success and AEs, and the rate of recurrent cholecystitis was evaluated. In addition, the reasons for the failure of the procedure were identified. RESULTS: Among the 35 patients, the technical success rate was 77.1% and the final contrast of the cystic duct was successful in 97.1% of patients. The incidence of early AEs was relatively low (11.4%), with no instances of cystic duct perforation. The rate of recurrent cholecystitis was 3.7%, and no other biliary events were observed. CONCLUSION: EGBS after PTGBD may be significantly beneficial, with a substantial success rate and minimal AEs in both short- and long-term follow-ups.

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.

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.

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.

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.