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.

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.

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.

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.

Necrotizing fasciitis wound after debridement could be successfully treated with negative-pressure wound therapy with instillation and dwelling: A case report.

Background: Necrotizing fasciitis (NF) is associated with a high mortality rate. Adequate incision and drainage and repeated debridement are necessary for NF management. After drainage, daily local irrigation should be performed. Case presentation: A 72-year-old male patient complained of left lower quadrant pain. Computed tomography revealed a 7 cm mass in the descending colon, with retroperitoneal penetration. Hence, he underwent emergency surgery. The left abdomen was widely incised, and a transverse colostomy was performed for local wound control. Daily debridement of necrotic tissue and wound irrigation were continued. On postoperative day 48, the wound was extensive and complex and obtained a positive bacterial culture. Subsequently, we began a negative-pressure wound therapy with instillation and dwelling (NPWTi-d), which was very effective for extensive and complicated wounds with infection. Thereafter, a split-thickness skin was grafted, and the skin graft survived well. Ultimately, the wound successfully closed. Conclusions: NPWT is contraindicated for infected wounds, and an infection control period is required. However, NPWTi-d enables early initiation of wound care despite the presence of infection. Therefore, NPWTi-d is effective for extensive and complicated wounds with infection after NF debridement.

Diagnostic utility of EUS-FNA in distinguishing hepatocellular carcinoma from gastric submucosal tumor: A case report.

INTRODUCTION AND IMPORTANCE: Extrahepatically growing hepatocellular carcinoma (HCC) account for only 0.3 %-2.4 % of all hepatocellular carcinoma cases. We present the rare case of a patient in whom endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) was used to distinguish an extrahepatically growing HCC from a gastric submucosal tumor. CASE PRESENTATION: The patient was a 44-year-old man who underwent an esophagogastroduodenoscopy (EGD) and was found to have a submucosal tumor (SMT). A gastrointestinal stromal tumor was suspected. Computed tomography (CT) showed an unclear connecting between the tumor and the liver. On immunohistochemical analysis, the tumor cells were positive for CK7, PIVKA-II, and glypican-3, and negative for C-kit. Based on these findings, HCC was suspected, and ethoxybenzyl diethylenetriamine-enhanced magnetic resonance imaging (EOB-MRI) was performed. EOB-MRI revealed the connecting of the tumor and the liver. Thus, the patient was diagnosed as having an extrahepatically protruding HCC, and laparoscopic S2 partial hepatectomy was performed. Pathologically, the tumor was identified as a moderately differentiated HCC. According to the 8th edition of the UICC TNM Classification, the tumor was classified as T1bN0M0 and stage IB. CLINICAL DISCUSSION: Owing to its rarity, the diagnosis of an extrahepatically protruding HCC is often difficult when the differentiation of a gastric SMT and HCC is unclear on CT. As in this case, if an HCC is also differentiated on hematoxylin and eosin staining after EUS-FNA, immunohistochemistry findings can help in the diagnosis. CONCLUSION: The findings show that EUS-FNA could be helpful for diagnosis when an HCC needs to be differentiated from a gastric SMT.

Analogue signaling of somatodendritic synaptic activity to axon enhances GABA release in young cerebellar molecular layer interneurons.

Axons are equipped with the digital signaling capacity by which they generate and faithfully propagate action potentials (APs), and also with the analogue signaling capacity by which subthreshold activity in dendrites and soma is transmitted down the axon. Despite intense work, the extent and physiological role for subthreshold synaptic activity reaching the presynaptic boutons has remained elusive because of the technical limitation to record from them. To address this issue, we made simultaneous patch-clamp recordings from the presynaptic varicosities of cerebellar GABAergic interneurons together with their parent soma or postsynaptic target cells in young rat slices and/or primary cultures. Our tour-de-force direct functional dissection indicates that the somatodendritic spontaneous excitatory synaptic potentials are transmitted down the axon for significant distances, depolarizing presynaptic boutons. These analogously transmitted excitatory synaptic potentials augment presynaptic Ca++ influx upon arrival of an immediately following AP through a mechanism that involves a voltage-dependent priming of the Ca++ channels, leading to an increase in GABA release, without any modification in the presynaptic AP waveform or residual Ca++. Our work highlights the role of the axon in synaptic integration.

Comparison of Diagnostic Yield and Safety of Serial Pancreatic Juice Aspiration Cytologic Examination (SPACE) with Different Indications.

We assessed whether there are differences in the diagnostic yield and safety of serial pancreatic juice aspiration cytologic examination (SPACE) among different indications. We retrospectively analyzed 226 patients who underwent SPACE. They were classified into group A (patients with pancreatic masses, including advanced adenocarcinoma, sclerosing pancreatitis, or autoimmune pancreatitis), group B (suspicious pancreatic carcinoma patients without obvious pancreatic masses, including small pancreatic carcinoma, carcinoma in situ, or benign pancreatic duct stenosis), and group C (intraductal papillary mucinous neoplasm, IPMN). There were 41, 66, and 119 patients, with malignancy diagnosed in 29, 14, and 22 patients, in groups A, B, and C, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 69%, 100%, 100%, 57%, and 78% in group A; 79%, 98%, 92%, 94%, and 94% in group B; and 27%, 87%, 32%, 84%, and 76% in group C, respectively. PEP was observed in three (7.3%), three (4.5%), and fifteen (13%) patients in group A, B, and C, respectively (p = 0.20). SPACE is useful and safe in patients with suspicious small pancreatic carcinoma. However, it has limited efficacy and might not be recommended in patients with IPMN because of the high frequency of PEP.

Extracorporeal shock wave lithotripsy and endoscopic pancreatic stenting without pancreatic sphincterotomy for the treatment of pancreatolithiasis: a case series.

Endoscopic therapy and extracorporeal shock wave lithotripsy (ESWL) are recommended as the first choice in treating pancreatolithiasis. Endoscopic therapy is generally performed using endoscopic pancreatic sphincterotomy (EPST). Herein, we report our experience implementing a treatment protocol, combining endoscopic therapy and ESWL without EPST, for pancreatolithiasis. The inpatient treatment plan was performed every 3 months with a set number of sessions of ESWL with endoscopic pancreatic stenting (EPS) implanted or replaced. Finally, treatment was terminated when the stone was removed after implantation of a 10-Fr stent and crushed to approximately 3 mm or after spontaneous stone discharge. Eight patients were included in this study; the median time to stone disappearance was 208.5 days. The median number of inpatient treatment cycles, endoscopic retrograde cholangiopancreatography, and ESWL sessions was 2.5, 3, and 3, respectively. No serious adverse events were observed in all patients. Therefore, combining ESWL and EPS without EPST can safely treat pancreatolithiasis.

Suprapapillary placement of plastic versus metal stents for malignant biliary hilar obstructions: a multicenter, randomized trial.

BACKGROUND AND AIMS: The efficacy of the suprapapillary placement of inside plastic stents (iPSs) for unresectable malignant hilar biliary obstructions (MHOs) is unknown compared with that of uncovered inside metal stents (iMSs). This randomized controlled trial was designed to evaluate the outcomes of endoscopic placement of these stents for unresectable MHOs. METHODS: This open-label, randomized study was conducted at 12 Japanese institutions. The enrolled patients with unresectable MHOs were allocated to iPS and iMS groups. The primary outcome was defined as the time to recurrent biliary obstruction in patients for whom the intervention was both technically and clinically successful. RESULTS: Among 87 enrollments, 38 patients in the iPS group and 46 patients in the iMS group were analyzed. Technical success rates were 100% (38 of 38) and 96.6% (44 of 46), respectively (P = 1.00). After transferring 1 unsuccessful iMS-group patient to the iPS group (since iPSs were deployed), the clinical success rates were 90.0% (35 of 39) for the iPS group and 88.9% (40 of 45) for the iMS group from a per-protocol analysis (P = 1.00). Among the patients with clinical success, the median times to recurrent biliary obstruction were 250 (95% confidence interval, 85-415) and 361 (95% confidence interval, 107-615) days (log-rank test, P = .34). No differences were detected in rates of adverse events. CONCLUSIONS: This Phase II randomized trial did not show any statistically significant difference in stent patency between suprapapillary plastic versus metal stents. Considering the potential advantages of plastic stents for malignant hilar obstruction, these findings suggest that suprapapillary plastic stents could be a viable alternative to metal stents for this condition.

Intratumoral Air Bubbles and Hematemesis As Predictors of Pseudoaneurysm Rupture in Unresected Pancreatic Cancer.

Objective Pseudoaneurysm rupture associated with unresected pancreatic cancer can cause rare but fatal hemobilia and gastrointestinal bleeding. This study aimed to identify factors predicting pseudoaneurysm rupture. Methods We conducted a single-center case-control study of unresected pancreatic cancer patients treated at Shizuoka General Hospital between January 2011 and July 2020 using a retrospective cancer registry database. Included in the study were 611 consecutive patients with unresected pancreatic cancer, of whom 55 developed overt upper gastrointestinal bleeding or hemobilia. Twenty patients were excluded, as they had not undergone contrast-enhanced computed tomography (CT) or angiography. Patients were classified into pseudoaneurysm and non-pseudoaneurysm groups. One patient with arterial bleeding but without obvious pseudoaneurysm was included in the pseudoaneurysm group. Factors predicting pseudoaneurysm rupture at the onset of overt gastrointestinal bleeding were investigated using a logistic regression analysis. CT findings revealing air bubbles inside the tumor were described as intratumoral air bubbles. Results Thirty-five patients were included (15 in the pseudoaneurysm group, 20 in the non-pseudoaneurysm group). In the multivariate analysis, intratumoral air bubbles [odds ratio (OR), 12.9; 95% confidence interval (CI), 2.14-77.9; p=0.005] and hematemesis (OR, 6.30; 95% CI, 1.03-38.6; p=0.047) were independent predictors of pseudoaneurysm rupture. In addition, patients who experienced successful hemostasis and were re-administered chemotherapy survived more than six months. Conclusion This study reveals that intratumoral air bubbles and hematemesis may predict pseudoaneurysm rupture at the onset of overt gastrointestinal bleeding. For patients presenting these findings, an examination with conventional or CT angiography may lead to an early diagnosis and improve the patient prognosis.

Eosinophilic pancreatitis with serum IgG4-positivity, potentially associated with autoimmune pancreatitis.

A 70-year-old man presented with unprovoked weight loss and intermittent left upper quadrant tenderness for one-and-a-half month. Computed tomography revealed irregular cystic lesions in the pancreatic tail. Endoscopic ultrasonography (EUS) revealed pancreatic tail enlargement and giant, thick-walled cysts surrounding the pancreatic tail with no connection with the pancreatic duct. Endoscopic ultrasonography-guided fine-needle aspiration was performed on the enlarged pancreatic parenchyma and thickened cyst wall. Both biopsies showed hyper eosinophilia and few plasma cells. Endoscopic retrograde pancreatography revealed an irregular narrowing of the main pancreatic duct. Pancreatic juice cytology revealed substantial eosinophilia. Blood sampling showed an elevated eosinophil count and immunoglobulin G4 (IgG4) and immunoglobulin E (IgE) levels at the initial examination. We considered the patient to have eosinophilic pancreatitis (EP) with autoimmune pancreatitis, or alternately, EP with IgG4-related retroperitoneal fibrosis (RPF). Upon prednisolone administration, the abdominal pain improved, the peripheral blood eosinophil count decreased to zero, IgG4 and IgE levels decreased, pancreatic enlargement improved, and the cystic lesions disappeared. The condition did not recur within the following 3 years. Both EP and EP with IgG4-related RPF are rare etiologies of pancreatitis, and this case is very instructive.