Risk factors for biliary tract events during elective cholecystectomy waiting time after endoscopic retrograde cholangiopancreatography for choledocholithiasis.

Objectives: Endoscopic lithotripsy and elective cholecystectomy, followed by endoscopic retrograde cholangiopancreatography, are the first-line treatments for patients with common bile duct (CBD) stones (CBDS) and gallstones. However, this approach entails acute cholecystitis and recurrent cholangitis risk while patients await surgery. We aimed to identify acute cholecystitis and cholangitis risk factors during the waiting time for elective cholecystectomy. Methods: This study comprised 151 patients with CBDS combined with gallstones who underwent cholecystectomy within 90 days of the first endoscopic retrograde cholangiopancreatography at two tertiary care centers between January 2019 and October 2021. Results: The incidence of biliary tract events (acute cholecystitis, acute cholangitis, or any complications requiring unplanned cholangiopancreatography) was 28% (43 cases). In univariate and multivariate analyses, plastic stent placement as a bridge to surgery for the first treatment of CBDS was an independent risk factor for biliary tract events during the waiting time for surgery (odds ratio 4.25, p = 0.002). A subgroup analysis among those with plastic stent placement revealed a CBD diameter of ≤ 10 mm as an independent risk factor for acute cholecystitis (odds ratio 4.32; p = 0.027); a CBD diameter ≥ 11 mm was an independent risk factor for acute cholangitis and unplanned re-endoscopic retrograde cholangiopancreatography (odds ratio 5.66; p = 0.01). Conclusions: Plastic stent placement for CBDS before elective cholecystectomy increases the risk of acute cholecystitis or acute cholangitis during the waiting time for elective cholecystectomy.

Cl--dependent amplification of excitatory synaptic potentials at distal dendrites revealed by voltage imaging.

The processing of synaptic signals in somatodendritic compartments determines neuronal computation. Although the amplification of excitatory signals by local voltage-dependent cation channels has been extensively studied, their spatiotemporal dynamics in elaborate dendritic branches remain obscure owing to technical limitations. Using fluorescent voltage imaging throughout dendritic arborizations in hippocampal pyramidal neurons, we demonstrate a unique chloride ion (Cl-)-dependent remote computation mechanism in the distal branches. Excitatory postsynaptic potentials triggered by local laser photolysis of caged glutamate spread along dendrites, with gradual amplification toward the distal end while attenuation toward the soma. Tour de force subcellular patch-clamp recordings from thin branches complemented by biophysical model simulations revealed that the asymmetric augmentation of excitation relies on tetrodotoxin-resistant sodium ion (Na+) channels and Cl- conductance accompanied by a more hyperpolarized dendritic resting potential. Together, this study reveals the cooperative voltage-dependent actions of cation and anion conductance for dendritic supralinear computation, which can locally decode the spatiotemporal context of synaptic inputs.

Graded control of Purkinje cell outputs by cAMP through opposing actions on axonal action potential and transmitter release.

All-or-none signalling by action potentials (APs) in neuronal axons is pivotal for the precisely timed and identical size of outputs to multiple distant targets. However, technical limitations with respect to measuring the signalling in small intact axons have hindered the evaluation of high-fidelity signal propagation. Here, using direct recordings from axonal trunks and/or terminals of cerebellar Purkinje cells in slice and culture, we demonstrate that the timing and amplitude of axonal outputs are gradually modulated by cAMP depending on the length of axon. During the propagation in long axon, APs were attenuated and slowed in conduction by cAMP via specifically decreasing axonal Na+ currents. Consequently, the Ca2+ influx and transmitter release at distal boutons are reduced by cAMP, counteracting its direct facilitating effect on release machinery as observed at various CNS synapses. Together, our tour de force functional dissection has unveiled the axonal distance-dependent graded control of output timing and strength by intracellular signalling. KEY POINTS: The information processing in the nervous system has been classically thought to rely on the axonal faithful and high-speed conduction of action potentials (APs). We demonstrate that the strength and timing of axonal outputs are weakened and delayed, respectively, by cytoplasmic cAMP depending on the axonal length in cerebellar Purkinje cells (PCs). Direct axonal patch clamp recordings uncovered axon-specific attenuation of APs by cAMP through reduction of axonal Na+ currents. cAMP directly augments transmitter release at PC terminals without changing presynaptic Ca2+ influx or readily releasable pool of vesicles, although the extent is weaker compared to other CNS synapses. Two opposite actions of cAMP on PC axons, AP attenuation and release augmentation, together give rise to graded control of synaptic outputs in a manner dependent on the axonal length.

Pancreatic cancer risk in diabetic patients using the Japanese Regional Insurance Claims.

Pancreatic cancer presents a critical health issue characterized by low survival rates. Identifying risk factors in specific populations, such as those with diabetes, is crucial for early detection and improved outcomes. This study aimed to identify risk factors for pancreatic cancer in diabetic patients using a longitudinal cohort from the Shizuoka Kokuho database, spanning April 2012 to September 2021. Diabetic patients were identified and monitored for the onset of pancreatic cancer. Factors analyzed included age, sex, the Elixhauser comorbidity index, and specific comorbidities. Statistical analyses involved univariate and multivariate Cox proportional hazards regression. The study identified 212,775 as diabetic patients and 1755 developed pancreatic cancer during the period. The annual incidence rate of pancreatic cancer in this group was 166.7 cases per 100,000 person-years. The study identified older age, male sex, a history of liver disease, chronic pancreatitis, and pancreatic cystic lesions as significant risk factors for pancreatic cancer in diabetic patients. The study also highlighted the absence of a significant association between diabetes type or diabetic complications and the onset of pancreatic cancer. These findings may aid in the early diagnosis of pancreatic cancer in diabetic patients and may inform revisions in screening practices in diabetic patients.

Duodenal Papillary Metastasis of Lung Cancer with Bleeding Controlled by Endoscopic Treatment and Systemic Osimertinib Therapy: Case Report.

Introduction: Solid organ malignancies rarely metastasize to the duodenal papilla. We describe a case of primary lung cancer with duodenal papillary metastasis in a patient who presented with melena. To the best of our knowledge, this is only the second report of duodenal papillary metastasis from lung cancer. Case Presentation: A 65-year-old woman presented with complaints of anorexia, weight loss, and black stool. Imaging studies led to a clinical diagnosis of stage IVB lung cancer, and anticoagulants were initiated to treat pulmonary artery thrombosis. However, endoscopic hemostasis was challenging because of bleeding from a duodenal papillary tumor. Fortunately, the patient was positive for the plasma epidermal growth factor receptor (EGFR) gene mutation, and osimertinib, an EGFR tyrosine kinase inhibitor, was administered, successfully achieving hemostasis. Subsequently, endoscopic ultrasonography-guided transbronchial needle aspiration of an enlarged mediastinal lymph node and duodenal papillary tumor biopsy confirmed duodenal papillary metastasis of the primary lung adenocarcinoma. Conclusion: Although duodenal papillary metastasis is extremely rare, a good clinical outcome was achieved in this case by considering duodenal papillary metastasis from lung cancer as the differential diagnosis and administering systemic osimertinib therapy.

Safety and efficacy of atezolizumab plus bevacizumab combination therapy in patients with unresectable hepatocellular carcinoma undergoing dialysis: a case series.

Three patients aged 79, 75, and 81 years with unresectable hepatocellular carcinoma (HCC) and undergoing maintenance hemodialysis were treated with a combination of atezolizumab and bevacizumab. The patients, respectively, received their 22nd, 2nd, and 4th treatment cycles, and one achieved long-term stable disease. No serious adverse events, including immune-related adverse events, were observed in any patient. Remarkable progress has been made in chemotherapy for cancer; however, the efficacy and safety of chemotherapy in patients undergoing hemodialysis have not been adequately elucidated. This report provides novel insights into the feasibility and outcomes of atezolizumab and bevacizumab combination therapy in patients with HCC undergoing hemodialysis, highlighting its potential as a viable treatment option with manageable side effects.

Investigating morphological changes in a simple mucinous cyst during the follow-up period: a case report.

A 64-year-old man was referred to our department after a small pancreatic cystic lesion was discovered on computed tomography performed to assess choledocholithiasis. Multiple standard imaging modalities, including endoscopic ultrasound (EUS), failed to reveal pancreatic masses, wall thickening, or mural nodules. Consequently, a benign pancreatic cystic lesion was suspected, and the patient underwent biannual imaging studies including rotating magnetic resonance imaging and EUS. Six years after the initial detection of the pancreatic cyst, wall thickening was observed, leading to a shortened observation period of once every 3 months. After 6.5 years, hypoechoic area surrounding the cyst, which could be interpreted as thickening of the cyst wall was observed, prompting distal pancreatectomy due to the suspicion of malignant disease. The histopathological examination revealed a unilocular mucinous cyst with a single layer of cuboidal cells and low-grade dysplasia. A fibrous proliferation of the polycystic stroma and no ovarian-type stroma was observed. Malignant cells were absent from the cystic epithelium and stroma. The final histopathological diagnosis was a simple mucinous cyst of the pancreatic tail.

Prospective study on planned biliary stent placement to treat small common bile duct stones.

Aims: Small common bile duct stones are known to occasionally clear spontaneously. This study aimed to prospectively assess the role of biliary stent placement in promoting the spontaneous clearance of small common bile duct stones. Methods and Results: We analyzed patients presenting with common bile duct stones of ≤5 mm diameter between June 2020 and May 2022. The exclusion criteria included asymptomatic patients, biliary pancreatitis, altered gastrointestinal anatomy, bile duct strictures (malignant or benign), and a history of EST. The biliary stents were inserted without stone removal. Stone clearance was assessed using endoscopic ultrasonography or endoscopic retrograde cholangiopancreatography after 3 months. Our primary endpoint was the clearance rate of common bile duct stones over 6 months, targeting a lower limit for the 95% confidence interval (CI) exceeding 25%. Of the 32 enrolled patients, 18 (56.3%; 95% CI: 37.7-73.6%) exhibited stone clearance. Early complications occurred in 11 patients (34.4%), totaling 12 incidents: acute cholecystitis in four, acute pancreatitis in three, biliary pain in three, and cholangitis in two patients. No severe complications occurred. Six (18.8%) patients experienced asymptomatic stent migration. Following stone clearance, four (12.5%) patients experienced stone recurrence, with an average duration of 256 ± 164 days. Conclusion: Biliary stenting appeared to effectively promote the clearance of small common bile duct stones in approximately half of the patients. However, the potential complications and risks of stone recurrence warrant close monitoring.This trial was registered in the Japan Registry of Clinical Trials (jRCT1042200020).

[Successful portal vein stent placement for chronic portal vein stenosis 5 years after pancreatoduodenectomy:a case report].

A 73-year-old man underwent pancreatoduodenectomy 5 years previously, and portal vein stenosis was observed immediately after surgery. A collateral vein with varices around the hepaticojejunostomy gradually developed. The patient experienced repeated episodes of melena that required transfusion. Enteroscopy confirmed varices around the hepaticojejunostomy, caused by portal vein stenosis, which was the source of intestinal bleeding. Varices were treated by placing an expandable metallic stent in the stenotic portal vein through a percutaneous transhepatic route. Although the portal vein stenosis was severe, the guidewire was successfully maneuvered into the superior mesenteric vein and stent placement was successful. Subsequently, the collateral vein disappeared and no further melena was observed.