Efficacy of GV1001 with gemcitabine/capecitabine in previously untreated patients with advanced pancreatic ductal adenocarcinoma having high serum eotaxin levels (KG4/2015): an open-label, randomised, Phase 3 trial.

BACKGROUND: The TeloVac study indicated GV1001 did not improve the survival of advanced pancreatic ductal adenocarcinoma (PDAC). However, the cytokine examinations suggested that high serum eotaxin levels may predict responses to GV1001. This Phase III trial assessed the efficacy of GV1001 with gemcitabine/capecitabine for eotaxin-high patients with untreated advanced PDAC. METHODS: Patients recruited from 16 hospitals received gemcitabine (1000 mg/m2, D 1, 8, and 15)/capecitabine (830 mg/m2 BID for 21 days) per month either with (GV1001 group) or without (control group) GV1001 (0.56 mg; D 1, 3, and 5, once on week 2-4, 6, then monthly thereafter) at random in a 1:1 ratio. The primary endpoint was overall survival (OS) and secondary end points included time to progression (TTP), objective response rate, and safety. RESULTS: Total 148 patients were randomly assigned to the GV1001 (n = 75) and control groups (n = 73). The GV1001 group showed improved median OS (11.3 vs. 7.5 months, P = 0.021) and TTP (7.3 vs. 4.5 months, P = 0.021) compared to the control group. Grade >3 adverse events were reported in 77.3% and 73.1% in the GV1001 and control groups (P = 0.562), respectively. CONCLUSIONS: GV1001 plus gemcitabine/capecitabine improved OS and TTP compared to gemcitabine/capecitabine alone in eotaxin-high patients with advanced PDAC. CLINICAL TRIAL REGISTRATION: NCT02854072.

Tailored hydration with lactated Ringer's solution for post-endoscopic retrograde cholangiopancreatography pancreatitis prevention: A randomized controlled trial.

OBJECTIVES: Aggressive hydration using lactated Ringer's solution (LRS) prevents post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). Concerns of this strategy are large volume and lengthy hydration. Our study aimed to evaluate the efficacy of tailored aggressive hydration (TAH) for PEP prevention. METHODS: In this prospective, multicenter, double-blinded, randomized trial conducted across three tertiary Korean hospitals, patients who underwent ERCP for the first-time were randomly assigned (1:1) to tailored standard hydration (TSH) and TAH groups. The TSH group received 1.5 mL/kg/h LRS during and after ERCP, whereas the TAH group was administered a 20 mL/kg bolus post-ERCP and 3 mL/kg/h during and after the procedure. Both groups were assessed for elevated serum amylase levels and pain 4-6 h after ERCP. If both were absent, hydration was discontinued. If either was present, hydration was continued at the original rate until 8 h. The primary endpoint was PEP development and was analyzed on an intention-to-treat analysis. RESULTS: A total of 344 patients were randomly assigned to treatment groups (171 to the TSH group and 172 to the TAH group). PEP was observed in 9.4% (16/171) in the TSH group and 3.5% (6/172) in the TAH group (relative risk 0.37, 95% confidence interval 0.15-0.93, p = 0.03). No difference was identified between the two groups in terms of PEP severity (p = 0.80) and complications related to volume overload (p = 0.32). CONCLUSIONS: TAH according to the presence of abdominal pain or elevated serum amylase levels at 4-6 h after ERCP is safe and prevents PEP development.

Dual role of deubiquitinating enzyme USP19 regulates mitotic progression and tumorigenesis by stabilizing survivin.

Survivin is a component of the chromosomal passenger complex, which includes Aurora B, INCENP, and Borealin, and is required for chromosome segregation and cytokinesis. We performed a genome-wide screen of deubiquitinating enzymes for survivin. For the first time, we report that USP19 has a dual role in the modulation of mitosis and tumorigenesis by regulating survivin expression. Our results found that USP19 stabilizes and interacts with survivin in HCT116 cells. USP19 deubiquitinates survivin protein and extends its half-life. We also found that USP19 functions as a mitotic regulator by controlling the downstream signaling of survivin protein. Targeted genome knockout verified that USP19 depletion leads to several mitotic defects, including cytokinesis failure. In addition, USP19 depletion results in significant enrichment of apoptosis and reduces the growth of tumors in the mouse xenograft. We envision that simultaneous targeting of USP19 and survivin in oncologic drug development would increase therapeutic value and minimize redundancy.

Malignant potential of small pancreatic neuroendocrine neoplasm and its risk factors: A multicenter nationwide study.

BACKGROUND: Pancreatic neuroendocrine neoplasms (PNENs) show heterogeneous biological behavior, and most small PNENs show indolent features. Consequently, selected cases can be considered for observation only, according to the National Comprehensive Cancer Network guideline, however, supporting clinical evidence is lacking. We investigated the clinical course of small PNENs and their risk factors for malignant potential. METHODS: A total of 158 patients with small pathologically confirmed PNENs ≤2 cm in initial imaging were retrospectively enrolled from 14 institutions. The primary outcome was any metastasis or recurrence event during follow-up. RESULTS: The median age was 57 years (range, 22-82 years), and 86 patients (54%) were female. The median tumor size at initial diagnosis was 13 mm (range, 7-20 mm). PNENs were pathologically confirmed by surgery in 137 patients and by EUS-guided fine needle aspiration biopsy (EUS-FNAB) in 21 patients. Eight patients underwent EUS-FNAB followed by surgical resection. The results of WHO grade were available in 150 patients, and revealed 123 grade 1, 25 grade 2, and 2 neuroendocrine carcinomas. A total of 145 patients (92%) underwent surgical resection, and three patients had regional lymph node metastasis. During the entire follow-up of median 45.6 months, 11 metastases or recurrences (7%) occurred. WHO grade 2 (HR 13.97, 95% CI 2.60-75.03, p = 0.002) was the only predictive factor for malignant potential in multivariable analysis. CONCLUSIONS: WHO grade is responsible for the malignant potential of small PNENs ≤2 cm. Thus, EUS-FNAB could be recommended in order to provide early treatment strategies of small PNENs.

Somatic Mutations in TSC1 and TSC2 Cause Focal Cortical Dysplasia.

Focal cortical dysplasia (FCD) is a major cause of the sporadic form of intractable focal epilepsies that require surgical treatment. It has recently been reported that brain somatic mutations in MTOR account for 15%-25% of FCD type II (FCDII), characterized by cortical dyslamination and dysmorphic neurons. However, the genetic etiologies of FCDII-affected individuals who lack the MTOR mutation remain unclear. Here, we performed deep hybrid capture and amplicon sequencing (read depth of 100×-20,012×) of five important mTOR pathway genes-PIK3CA, PIK3R2, AKT3, TSC1, and TSC2-by using paired brain and saliva samples from 40 FCDII individuals negative for MTOR mutations. We found that 5 of 40 individuals (12.5%) had brain somatic mutations in TSC1 (c.64C>T [p.Arg22Trp] and c.610C>T [p.Arg204Cys]) and TSC2 (c.4639G>A [p.Val1547Ile]), and these results were reproducible on two different sequencing platforms. All identified mutations induced hyperactivation of the mTOR pathway by disrupting the formation or function of the TSC1-TSC2 complex. Furthermore, in utero CRISPR-Cas9-mediated genome editing of Tsc1 or Tsc2 induced the development of spontaneous behavioral seizures, as well as cytomegalic neurons and cortical dyslamination. These results show that brain somatic mutations in TSC1 and TSC2 cause FCD and that in utero application of the CRISPR-Cas9 system is useful for generating neurodevelopmental disease models of somatic mutations in the brain.

Association between Charlson comorbidity index and complications of endoscopic resection of gastric neoplasms in elderly patients.

BACKGROUND: Although endoscopic resection is safe and effective for gastric epithelial neoplasms, information is limited on its efficacy and safety in extremely elderly patients who have various comorbidities. Further, the relationship between comorbidities and complications of endoscopic resection is not well established. Therefore, we aimed to evaluate the efficacy and safety of endoscopic resection of gastric epithelial neoplasms in extremely elderly patients. METHODS: From October 2008 to December 2017, 4475 consecutive patients underwent endoscopic resection of gastric epithelial neoplasms. Among them, 242 were 75 years or older. We assessed Charlson comorbidity index (CCI) scores, procedural outcomes, and procedure- and sedation-related complications related to endoscopic resection. RESULTS: Mean patient age was 78.7 ± 3.2 years. Of the 242 patients, 124 (51.2%) had low-grade dysplasia and 112 (46.3%) had adenocarcinoma. The most common comorbidity was hypertension (55.4%), followed by diabetes (23.1%). The mean CCI score was 1.67 ± 1.43. Sixty patients (24.8%) had a CCI score ≥ 3. During the procedure, 10 (4.1%) patients had desaturation that recovered by flumazenil use with mask (n = 2) or Ambu bag (n = 3) ventilation. During subsequent admission, atelectasis or pneumonia occurred in 45 (18.6%) patients, post-procedural bleeding in 12 (5.0%), and perforation in 3 (1.2%). Respiratory complications were more common in patients with a CCI score ≥ 3 (20/60, 33.3%) than in those with a CCI score < 3 (25/182, 13.7%, P = 0.002). CONCLUSIONS: CCI score is related to respiratory complications of endoscopic resection in extremely elderly patients. Endoscopic resection must be performed cautiously, particularly in elderly patients with a high CCI score, to prevent respiratory complications.

Correction to: A rare case of pericarditis and pleural empyema secondary to transdiaphragmatic extension of pyogenic liver abscess.

An amendment to this paper has been published and can be accessed via the original article.

A prospective, randomized, multicenter clinical trial comparing 25-gauge and 20-gauge biopsy needles for endoscopic ultrasound-guided sampling of solid pancreatic lesions.

BACKGROUND: Various core biopsy needles have previously been developed for endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB). However, the properties of needle gauge in the diagnostic outcomes of solid pancreatic lesions remain unknown. This trial compared the procurement rates of histologic cores from solid pancreatic lesions with EUS-FNB using 20- and 25-gauge (G) FNB needles. METHODS: In a prospective randomized multicenter clinical trial, patients with solid pancreatic lesions underwent EUS-FNB with either a 20-gauge or a 25-gauge FNB needle. The rates of histologic core procurement, overall diagnostic accuracy, and adverse events were compared between the two groups (20-gauge or 25-gauge FNB needle). RESULTS: In total, 88 patients (48 men, 40 women, mean age 65.7 years) were enrolled. No significant differences were found in the demographic characteristics between the two groups (20-gauge or 25-gauge FNB needle). The procurement rate of histologic cores in the 20-guage FNB needle group (41/45, 91.1%) was significantly higher than that in the 25-guage FNB needle group (32/43, 74.4%, P = 0.037). However, no significant differences were found in the overall diagnostic accuracy between 20-guage FNB needle (40/45, 88.9%) and 25-guage FNB needle (34/43, 79.1%, P = 0.208). No procedure-related adverse events were observed in either group. CONCLUSIONS: Although both FNB needles provided high overall diagnostic accuracy, the reliability of the 20-guage FNB needle is better than the 25-guage FNB needle when retrieving samples for histological analysis.

Main duct and mixed type intraductal papillary mucinous neoplasms without enhancing mural nodules: Duct diameter of less than 10 mm and segmental dilatation of main pancreatic duct are findings support surveillance rather than immediate surgery.

OBJECTIVE: The guidelines for pancreatic intraductal papillary mucinous neoplasms (IPMNs) recommend surgical resection of all main-duct (MD) and mixed-type IPMNs in surgically fit patients. We conducted this study to identify the rates of high-grade dysplasia (HGD) and invasive carcinoma according to the morphological features of the main pancreatic duct (MPD) in patients with MD and mixed IPMN. METHODS: We performed a retrospective study of 259 patients with histologically proven MD and mixed-type IPMNs who underwent surgery at six academic institutions. RESULTS: The rate of HGD and invasive carcinoma was 11.1% (24/216) in patients without enhancing mural nodules (MNs) and 69.8% (30/43) in patients with MNs. Multivariate analysis showed that MPD diameter of ≥10 mm [odds ratio (OR), 2.5; 95% confidence interval (CI), 1.155-5.505; P = 0.02], diffuse MPD dilatation (OR, 3.2; 95% CI, 1.152-8.998; P = 0.02), and presence of enhancing MNs in MPD (OR, 9.6; 95% CI, 3.928-23.833, P < 0.0001) were significant predictors of HGD and invasive carcinoma. Of the 216 patients without enhancing MNs, 79 patients (36.6%) having both segmental MPD dilatation and MPD diameter of <10 mm showed significantly lower rates of HGD and invasive carcinoma (3/79, 3.8%) than patients having both diffuse MPD dilatation and MPD diameter ≥10 mm (9/36, 25%, P = 0.001). CONCLUSIONS: MD and mixed-type IPMNs having segmental MPD dilatation with MPD dilation <10 mm and no enhancing MNs on imaging showed a significantly lower rate of HGD and invasive carcinoma, and watchful follow-up instead of immediate surgical resection might be possible in these patients.

Preparation and Characterization of the Sputtered TiAlN Coatings Using a Ti-Al Alloy Metal Target.

Titanium aluminium nitride (TiAlN) ternary coatings were deposited on glass substrates by means of reactive magnetron sputtering technique, using a Ti-Al alloy metal target (Ti0.5Al0.5). The depositions were performed at various N2 and Ar flux ratios of N2/(Ar + N2) ═ 33, 50, 67, 83%. The structure, morphology, chemical composition and mechanical properties were investigated by X-ray diffraction (XRD), field emission scanning electron microscope (FE-SEM), energy dispersive X-ray spectroscopy (EDS), and nano indenter (MTS System), respectively. The orientation of coatings depends on the flux ratios of N2/(Ar + N2) and substrate temperature. The coatings deposited with N2/(Ar + N2) ratios of 33, 50 at.% consists of pyramid-like column grains separated by porous and voids, which can be attributed to cubic-TiN (220) preferred orientation. The coatings deposited with N2/(Ar + N2) greater than 67% exhibits the phase of hexagonal-AlN and cubic-TiN. The surface of coatings becomes more compact and smoother with the N2/(Ar + N2) ratios increase. The coatings deposited with N2/(Ar+N2) ratio of 83% shows the largest hardness of 21.5 GPa, which is attributed to the preferred (200) orientation. However, this hardness increases significantly with increasing substrate temperature. The coatings deposited at more than 100 °C exhibited the (111) and/or (200) orientation. The amounts of grains grown along the (111) and (200) orientations play a significant role on the mechanical performance of TiAlN coatings. Four independent mechanisms, such as TiAlN stoichiometry and lattice parameter, the (111) preferred growth orientation, and the density increases (elimination of void), were found to contribute to the enhancement of TiAlN mechanical performance.

Aggressive intravenous hydration with lactated Ringer's solution for prevention of post-ERCP pancreatitis: a prospective randomized multicenter clinical trial.

BACKGROUND AND STUDY AIMS : The present study aimed to determine the type of intravenous hydration that is best suited to reducing the incidence of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. PATIENTS AND METHODS: In a prospective randomized multicenter trial, average-to-high risk patients who underwent first-time ERCP were randomly assigned to three groups (1:1:1) who received: aggressive intravenous hydration (3 mL/kg/h during ERCP, a 20-mL/kg bolus and 3 mL/kg/h for 8 hours after ERCP) with either lactated Ringer's solution (LRS) or normal saline solution (NSS), or standard intravenous hydration with LRS (1.5 mL/kg/h during and for 8 hours after ERCP). The primary end point was post-ERCP pancreatitis (PEP). RESULTS: 395 patients were enrolled, and 385 completed the protocols. The three groups showed no significant differences in demographic characteristics. There was a significant difference in the intention-to-treat (ITT) PEP rate between the aggressive LRS group (3.0 %, 95 % confidence interval [CI] 0.1 % - 5.9 %; 4 /132), the aggressive NSS group (6.7 %, 95 %CI 2.5 % - 10.9 %; 9 /134) and the standard LRS group (11.6 %, 95 %CI 6.1 % - 17.2 %; 15 /129; P = 0.03). In the two-group comparisons, the ITT PEP rate was significantly lower for the aggressive LRS group than for the standard LRS group (relative risk [RR] 0.26, 95 %CI 0.08 - 0.76; P = 0.008). There was no significant difference in the ITT PEP rate between the aggressive NSS group and the standard LRS group (RR 0.57, 95 %CI 0.26 - 1.27; P = 0.17). CONCLUSION: Aggressive hydration with LRS is the best approach to intravenous hydration for the prevention of PEP in average-to-high risk patients.

Feasibility of a 20-gauge ProCore needle in EUS-guided subepithelial tumor sampling: a prospective multicenter study.

BACKGROUND: Endoscopic ultrasonography-guided fine-needle biopsy (EUS-FNB) may facilitate tissue acquisition for a definitive diagnosis of gastrointestinal subepithelial tumors (SETs). This study aimed to determine the diagnostic yield of EUS-FNB using a novel 20-gauge ProCore needle with a coiled sheath in tissue sampling of gastrointestinal SETs. METHODS: Between July 2016 and February 2017, 39 patients with gastrointestinal SETs were prospectively recruited from six university hospitals in Korea. Hypoechoic SETs ≥2 cm in size and originating from the submucosal and/or muscularis propria layer under EUS were eligible. This study was registered on ClinicalTrials.gov (NCT02884154). RESULTS: A total of 36 patients were included in the final analyses. EUS-FNB was diagnostic in 88.9% of SETs. Tissue adequacy was judged as optimal in 97.2% of FNB specimens according to on-site visual evaluation by endosonographers, and in 88.9% of specimens according to pathologists. A macroscopically optimal core sample was obtained with two needle passes in 94.4% of cases. Technical failure rate was encountered in two cases (5.6%) after two needle passes. There were two cases (5.6%) of bleeding, which was managed endoscopically. CONCLUSIONS: EUS-FNB using a 20-gauge ProCore needle is a technically feasible and effective modality for histopathologic diagnosis of gastrointestinal SETs, providing adequate core samples with fewer needle passes; ClinicalTrials.gov number, NCT02884154.

Lower expression of endogenous intestinal alkaline phosphatase may predict worse prognosis in patients with Crohn's disease.

BACKGROUNDS: Intestinal alkaline phosphatase (IAP) plays important role in gut homeostasis. We aimed to evaluate the expression of endogenous IAP and to assess the clinical course according to the expression of endogenous IAP in patients with Crohn's disease (CD). METHODS: A total of 32 consecutive patients (14 males) with CD were included in the study. We measured the level of endogenous iAP in inflamed and noninflamed colonic mucosa. To verify the inflammation status, we measured the level of mRNA for IL-6, TNF-α, and TLR-4. We monitored the clinical courses of patients during follow-up after acquisition of biopsy specimens. RESULTS: Median age of patients was 22.5 years (range, 15-49). Median CD activity index (CDAI, range) was 93.7 (22.8~ 154.9). There were colonic involvements in all patients and perianal involvement in 43.8% patients. The mRNA levels of IL-6 (p = 0.005) and TLR-4 (p = 0.013) in inflamed mucosa were significantly higher than those in non-inflamed mucosa. However, there was no difference of expression of TNF-α mRNA (p = 0.345). During a 14-month follow-up (range, 9 months-54 months), there were 19 patients with clinical recurrences. There were 9 patients (9/19, 47.4%) with IAP expression ratio (inflamed to non-inflamed) ≤ 1.0 in patients with clinical recurrence while there was one patient (1/13, 7.7%) with IAP ratio ≤ 1.0 in patients without clinical recurrence (p = 0.024). CONCLUSION: Lower expression of IAP in inflamed mucosa compared to non-inflamed mucosa may be associated with clinical recurrence in patients with CD.

A rare case of pericarditis and pleural empyema secondary to transdiaphragmatic extension of pyogenic liver abscess.

BACKGROUND: Transdiaphragmatic extension of pyogenic liver abscess is the rarest cause of pericarditis and pleural empyema. It is a rapidly progressive and highly lethal infection with mortality rates reaching 100% if left untreated. However, the transmission route, treatment methods and prognosis have not been well studied. CASE PRESENTATION: A 65-year-old male patient presented with a fever, dyspnea, and right upper quadrant abdominal pain. Computed tomography of the chest and abdomen showed huge liver abscess without full liquefaction in the left lobe, large amount of left pleural effusion, and mild pericardial effusion, and the patient was treated with parenteral antibiotics and pigtail insertion at the left pleura. However, four days later, cardiac tamponade was developed and surgical drainage of the abscess and pericardium was performed. Klebsiella pneumonia was isolated from pleural empyema. Twenty-five days after surgery, the patient was discharged without any complications. CONCLUSIONS: Herein, we report a rare case of pleural empyema and pericarditis in that resulted from the extension of huge pyogenic liver abscess. Early surgical treatment may have prevented progression of the pericarditis to the more dismal purulent pericarditis. We also review pertinent English literature on pericarditis as a complication of PLA.

Self-expandable metal stents for the extraction of common bile duct stones in patients receiving dual antiplatelet agents: a pilot study.

BACKGROUND: Endoscopic sphincterotomy or endoscopic papillary balloon dilatation during endoscopic retrograde cholangiopancreatography (ERCP) are associated with a high risk of bleeding in patients receiving dual antiplatelet agents (APAs). However, the discontinuation of antiplatelet agents increases the risk of thromboembolic events in these patients. To date, the placement of self-expandable metal stents (SEMSs) in patients receiving dual APAs has not been well investigated. The aim of this study was to evaluate the feasibility and safety of SEMS placement for the removal of common bile duct (CBD) stones in patients in whom APAs were not discontinued. METHODS: Ten consecutive patients who were suspected of having CBD stones and who were receiving dual APAs were prospectively enrolled and underwent temporary SEMS placement, followed by stone extraction and SEMS removal. The patients continued taking dual APAs at the time of undergoing the procedure. RESULTS: SEMS placement was successful in all ten patients. Complete duct clearance with the SEMSs was achieved in a single session in all patients with CBD stones (9/9, 100%). One patient had cholangitis, but ERCP did not reveal biliary stones. There were no cases of bleeding during or after the procedure, even though all patients continued to take dual APAs. There were no new thromboembolic events. CONCLUSIONS: SEMSs can be used for the extraction of CBD stones in patients on dual APAs, and does not lead to hemorrhagic or thromboembolic events.

Efficient Generation of Dopamine Neurons by Synthetic Transcription Factor mRNAs.

Generation of functional dopamine (DA) neurons is an essential step for the development of effective cell therapy for Parkinson's disease (PD). The generation of DA neurons can be accomplished by overexpression of DA-inducible genes using virus- or DNA-based gene delivery methods. However, these gene delivery methods often cause chromosomal anomalies. In contrast, mRNA-based gene delivery avoids this problem and therefore is considered safe to use in the development of cell-based therapy. Thus, we used mRNA-based gene delivery method to generate safe DA neurons. In this study, we generated transformation-free DA neurons by transfection of mRNA encoding DA-inducible genes Nurr1 and FoxA2. The delivery of mRNA encoding dopaminergic fate inducing genes proved sufficient to induce naive rat forebrain precursor cells to differentiate into neurons exhibiting the biochemical, electrophysiological, and functional properties of DA neurons in vitro. Additionally, the generation efficiency of DA neurons was improved by the addition of small molecules, db-cAMP, and the adjustment of transfection timing. The successful generation of DA neurons using an mRNA-based method offers the possibility of developing clinical-grade cell sources for neuronal cell replacement treatment for PD.

Nuclear receptor Nurr1 agonists enhance its dual functions and improve behavioral deficits in an animal model of Parkinson's disease.

Parkinson's disease (PD), primarily caused by selective degeneration of midbrain dopamine (mDA) neurons, is the most prevalent movement disorder, affecting 1-2% of the global population over the age of 65. Currently available pharmacological treatments are largely symptomatic and lose their efficacy over time with accompanying severe side effects such as dyskinesia. Thus, there is an unmet clinical need to develop mechanism-based and/or disease-modifying treatments. Based on the unique dual role of the nuclear orphan receptor Nurr1 for development and maintenance of mDA neurons and their protection from inflammation-induced death, we hypothesize that Nurr1 can be a molecular target for neuroprotective therapeutic development for PD. Here we show successful identification of Nurr1 agonists sharing an identical chemical scaffold, 4-amino-7-chloroquinoline, suggesting a critical structure-activity relationship. In particular, we found that two antimalarial drugs, amodiaquine and chloroquine stimulate the transcriptional function of Nurr1 through physical interaction with its ligand binding domain (LBD). Remarkably, these compounds were able to enhance the contrasting dual functions of Nurr1 by further increasing transcriptional activation of mDA-specific genes and further enhancing transrepression of neurotoxic proinflammatory gene expression in microglia. Importantly, these compounds significantly improved behavioral deficits in 6-hydroxydopamine lesioned rat model of PD without any detectable signs of dyskinesia-like behavior. These findings offer proof of principle that small molecules targeting the Nurr1 LBD can be used as a mechanism-based and neuroprotective strategy for PD.

Self-expandable metal stents for choledocholithiasis in Billroth II gastrectomy patients.

BACKGROUND: Efficient ampullary intervention is essential for endoscopic retrograde cholangiopancreatography (ERCP) in patients with a prior Billroth II gastrectomy. We retrospectively evaluated the safety and effectiveness of ampullary intervention using fully covered self-expandable metal stents (FCSEMSs) for the management of common bile duct (CBD) stones in a subset of patients with a history of Billroth II gastrectomy. METHODS: This retrospective analysis involved patients with a prior Billroth II gastrectomy who underwent ampullary intervention with FCSEMSs for the management of CBD stones. The factors associated with FCSEMSs placement, treatment success, and procedural complications were analyzed. RESULTS: A group of 15 patients (10 males; median age, 78 years) underwent biliary metal stent placement for high degree of CBD angulation (6), small or flat papilla with unclear margin (5), current use of double antiplatelet agents or an anticoagulant (2), unwanted instrumentation of the cystic duct (1), and insecure position of the scope (1). Ampullary intervention with FCSEMSs was successful in all patients. After dilating the ampulla of Vater and building a durable conduit with FCSEMSs immediately, CBD stones were removed successfully from all patients in a single session. A mild post-ERCP pancreatitis occurred in one patient, who recovered without complications. CONCLUSION: Ampullary intervention with FCSEMSs is safe and effective for the management of CBD stones in a subset of patients with a history of Billroth II gastrectomy.