Aberrant oscillatory activity in neurofibromatosis type 1: an EEG study of resting state and working memory.

BACKGROUND: Neurofibromatosis type 1 (NF1) is a genetic neurodevelopmental disorder commonly associated with impaired cognitive function. Despite the well-explored functional roles of neural oscillations in neurotypical populations, only a limited number of studies have investigated oscillatory activity in the NF1 population. METHODS: We compared oscillatory spectral power and theta phase coherence in a paediatric sample with NF1 (N = 16; mean age: 13.03 years; female: n = 7) to an age/sex-matched typically developing control group (N = 16; mean age: 13.34 years; female: n = 7) using electroencephalography measured during rest and during working memory task performance. RESULTS: Relative to typically developing children, the NF1 group displayed higher resting state slow wave power and a lower peak alpha frequency. Moreover, higher theta power and frontoparietal theta phase coherence were observed in the NF1 group during working memory task performance, but these differences disappeared when controlling for baseline (resting state) activity. CONCLUSIONS: Overall, results suggest that NF1 is characterised by aberrant resting state oscillatory activity that may contribute towards the cognitive impairments experienced in this population. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03310996 (first posted: October 16, 2017).

Endoscopic Imaging of Pancreatic Cysts.

Pancreatic cystic lesions (PCLs) have been diagnosed with increasing frequency likely due to the widespread use of cross-sectional imaging. A precise diagnosis of the PCL is important because it helps identify patients in need of surgical resection and those who can undergo surveillance imaging. A combination of clinical and imaging findings as well as cyst fluid markers can help classify PCLs and guide management. This review focuses on endoscopic imaging of PCLs including endoscopic and endosonographic features and fine needle aspiration. We then review the role of adjunct techniques, such as microforceps, contrast-enhanced endoscopic ultrasound, pancreatoscopy, and confocal laser endomicroscopy.

Cognitive and Electrophysiological Correlates of Working Memory Impairments in Neurofibromatosis Type 1.

Neurofibromatosis 1 (NF1) is a single gene disorder associated with working Memory (WM) impairments. The aim of this study was to investigate P300 event-related potential (ERP) associated with WM in NF1. Sixteen adolescents with NF1 were compared with controls on measures of WM and EEG was recorded during a WM nback task. The NF1 group showed poorer performance on measures of WM as compared to the control group. No group differences were observed in P300 amplitude at Pz, but P300 latency was shorter in the NF1 group. Topographic analyses of P300 amplitude showed group differences indicating neural processing differences in the NF1 group relative to controls, which possibly contribute to the cognitive deficits seen in this population.

Morning and evening salivary cortisol levels in patients with chronic widespread pain and those at high risk.

BACKGROUND: Hypothalamic-Pituitary-Adrenal (HPA) axis dysregulation has been implicated in chronic widespread pain (CWP); the hallmark of fibromyalgia (FM). This is the first study to compare HPA axis changes in individuals with CWP and those at high risk of symptom development. METHODS: We sought to determine differences in morning and evening salivary cortisol levels in FM (n = 19), those at-risk (n = 20) and pain-free controls (n = 17). Risk factors included non-CWP pain, somatic symptoms, illness behaviour and sleep disturbance. We conducted the study in the absence of centrally acting medication, to address limitations of previous research. RESULTS: Repeated measures ANOVA revealed significant main effects of group (p = 0.003), and time of day (p = 0.002), with no significant interaction. Cortisol levels were higher in FM (p = 0.027) and at-risk (p = 0.003) groups, compared to controls, but there was no significant difference between FM and at-risk groups. The main effect of group remained significant with sleep problems (p = 0.021) and life events (p = 0.007), but was not significant with anxiety (p = 0.076) or depression (p = 0.098) scores as covariates. With sleep problems as a covariate, cortisol levels remained significantly higher only in the at-risk group (p = 0.017). CONCLUSIONS: This study indicates elevated salivary cortisol in FM and those at high risk, and identifies anxiety, depression and sleep problems as potential contributing factors. The results shed light on the dynamic relationship between stress, mood and sleep disorders and the brain's resilience to pain. SIGNIFICANCE: This study examines neurobiological changes in chronic widespread pain and high risk individuals. One strength of the study is the absence of centrally acting medication. We found high salivary cortisol common to Fibromyalgia and those at risk and identified contributing factors. Our results offer insight into the early mechanistic changes underlying Fibromyalgia development and open up possibilities for early diagnosis and prevention.

Abdominal Actinomycosis Abscess Presenting as an Isolated Gastrointestinal Pseudotumor.

Actinomyces is a gram-positive anaerobic bacterium that is ubiquitous in nature. It typically presents as respiratory, cervicofacial, or abdominopelvic abscesses. We present a 66-year-old man with a progressive enlarging abdominal wall nodule concerning for malignancy. The patient had a negative workup, including an ultrasound-guided fine-needle aspiration and colonoscopy, with biopsy for a possible extension to the colonic wall. Diagnosis of an Actinomyces abscess was obtained through surgical resection with right hemicolectomy. He was successfully treated with a prolonged course of intravenous antibiotics. This is a rare case of an isolated abdominal wall Actinomyces abscess mimicking a gastrointestinal malignancy.

Advanced endoscopy fellowship training in the United States: recent trends in American Society for Gastrointestinal Endoscopy advanced endoscopy fellowship match, trainee experience, and postfellowship employment.

BACKGROUND AND AIMS: The American Society for Gastrointestinal Endoscopy (ASGE) advanced endoscopy fellowship (AEF) match offers a structured application process for AEF training in the United States. Our aim was to describe recent trends in AEF match, trainee experience, and postfellowship employment. METHODS: ASGE AEF match data from 2012 to 2020 were reviewed. Online surveys were sent to advanced endoscopy trainees in 2019 and 2020 to explore their perceptions about AEF training and postfellowship jobs. RESULTS: Data for 2020 showed 19% of matched applicants were women, 55% foreign medical graduates, and 17.5% U.S. visa holders. The number of AEF match applicants increased by 15.6% (90 in 2012 to 104 in 2020) and number of AEF programs increased by 23.5% (51 in 2012 to 63 in 2020). The average applicant match rate was 57% (range, 52.8%-60.6%) and position match rate 87.9% (range, 79.1%-94.6%). Ninety-one percent of trainees (n = 58) rated the quality of their training as very good/excellent; 75% of trainees participated in >300 ERCPs and 64.1% in >300 EUS cases. Seventy percent of trainees reported that advanced endoscopic procedures comprised ≤50% of their procedure volume in their first job, and 71.9% believed it was not easy to find a job after fellowship; however, 97% believed they would make the same decision to pursue AEF training again. CONCLUSIONS: There has been a steady increase in the number of advanced endoscopy applicants and training positions over recent years. Most graduating fellows reported 50% or less of their upcoming clinical practice would involve advanced endoscopic procedures. Future studies are needed to further clarify employment opportunities and personnel needs for advanced endoscopists.

An Unsuccessful Randomized Trial of Percutaneous vs Endoscopic Drainage of Suspected Malignant Hilar Obstruction.

Percutaneous transhepatic biliary drainage (PTBD) and endoscopic retrograde cholangiopancreatography (ERCP) are widely accepted but competing approaches for the management of malignant obstruction at the hilum of the liver. ERCP is favored in the United States on the basis of high success rates for non-hilar indications, the perceived safety and superior tissue sampling capability of ERCP relative to PTBD, and the avoidance of external drains that are undesirable to patients. A recent randomized controlled trial (RCT) comparing the 2 modalities in patients with resectable hilar cholangiocarcinoma was terminated prematurely because of higher mortality in the PTBD group.1 In contrast, most observational data suggest that PTBD is superior for achieving complete drainage.2-6 Because the preferred procedure remains uncertain, we aimed to compare PTBD and ERCP as the primary intervention in patients with cholestasis due to malignant hilar obstruction (MHO).

ACG Clinical Guideline: Chronic Pancreatitis.

Chronic pancreatitis (CP) is historically defined as an irreversible inflammatory condition of the pancreas leading to varying degrees of exocrine and endocrine dysfunction. Recently however, the paradigm for the diagnosis has changed in that it breaks with the traditional clinicopathologic-based definition of disease, focusing instead on diagnosing the underlying pathologic process early in the disease course and managing the syndrome more holistically to change the natural course of disease and minimize adverse disease effects. Currently, the most accepted mechanistically derived definition of CP is a pathologic fibroinflammatory syndrome of the pancreas in individuals with genetic, environmental, and/or other risk factors who develop persistent pathologic responses to parenchymal injury or stress. The most common symptom of CP is abdominal pain, with other symptoms such as exocrine pancreatic insufficiency and diabetes developing at highly variable rates. CP is most commonly caused by toxins such as alcohol or tobacco use, genetic polymorphisms, and recurrent attacks of acute pancreatitis, although no history of acute pancreatitis is seen in many patients. Diagnosis is made usually on cross-sectional imaging, with modalities such as endoscopic ultrasonography and pancreatic function tests playing a secondary role. Total pancreatectomy represents the only known cure for CP, although difficulty in patient selection and the complications inherent to this intervention make it usually an unattractive option. This guideline will provide an evidence-based practical approach to the diagnosis and management of CP for the general gastroenterologist.

Pancreatic Adenocarcinoma.

Pancreatic cancer is a common gastrointestinal malignancy, and is often associated with a poor prognosis. Challenges to effective screening for pancreatic cancer include low disease prevalence and high cost of screening modalities such as endoscopic ultrasound and cross-sectional imaging. Further, most patients are asymptomatic during the early course of disease, which often leads to delay in diagnosis. Treatment options include surgery, chemotherapy, and palliative care.

Percutaneous transhepatic vs. endoscopic retrograde biliary drainage for suspected malignant hilar obstruction: study protocol for a randomized controlled trial.

BACKGROUND: The optimal approach to the drainage of malignant obstruction at the liver hilum remains uncertain. We aim to compare percutaneous transhepatic biliary drainage (PTBD) to endoscopic retrograde cholangiography (ERC) as the first intervention in patients with cholestasis due to suspected malignant hilar obstruction (MHO). METHODS: The INTERCPT trial is a multi-center, comparative effectiveness, randomized, superiority trial of PTBD vs. ERC for decompression of suspected MHO. One hundred and eighty-four eligible patients across medical centers in the United States, who provide informed consent, will be randomly assigned in 1:1 fashion via a web-based electronic randomization system to either ERC or PTBD as the initial drainage and, if indicated, diagnostic procedure. All subsequent clinical interventions, including crossover to the alternative procedure, will be dictated by treating physicians per usual clinical care. Enrolled subjects will be assessed for successful biliary drainage (primary outcome measure), adequate tissue diagnosis, adverse events, the need for additional procedures, hospitalizations, and oncological outcomes over a 6-month follow-up period. Subjects, treating clinicians and outcome assessors will not be blinded. DISCUSSION: The INTERCPT trial is designed to determine whether PTBD or ERC is the better initial approach when managing a patient with suspected MHO, a common clinical dilemma that has never been investigated in a randomized trial. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT03172832 . Registered on 1 June 2017.

Gastrointestinal Pyogenic Granuloma (Lobular Capillary Hemangioma): An Underrecognized Entity Causing Iron Deficiency Anemia.

Pyogenic granuloma (PG), more accurately known as lobular capillary hemangioma, is a benign vascular tumor that usually occurs in the skin or oral mucosa. This lesion is rarely reported in the gastrointestinal tract but is known to bleed if not resected. We herein describe a case series with the clinical, endoscopic, and histologic findings of four cases of gastrointestinal PG at our institution. In addition, we provide a review of the literature and summation of all reported cases of PG specific to the gastrointestinal tract. Based on our experience, we suggest that the actual incidence of gastrointestinal PG may in fact be higher than reported because PG can be unrecognized or improperly diagnosed. It is important for the clinician to properly recognize this lesion as a source of anemia and its propensity to bleed during biopsy or resection.

Frequency and Significance of Abnormal Pancreatic Imaging in Patients with BRCA1 and BRCA2 Genetic Mutations.

Objective. Pancreatic adenocarcinoma is typically diagnosed in advanced stages resulting in a significant reduction in the number of patients who are candidates for surgical resection. Although the majority of cases are believed to occur sporadically, about 10% show familial clustering and studies have identified an increased frequency of BRCA germline mutations. The role of screening for pancreatic adenocarcinoma in these populations is unclear. Our study aims to identify the abnormal pancreatic imaging findings in BRCA1 and BRCA2 mutation carriers. Methods. A retrospective review of patient medical records with known BRCA1 and BRCA2 mutations was conducted. Data was collected and all available abdominal imaging studies were reviewed. Results. A total of 66 patients were identified, 36 with BRCA1 and 30 with BRCA2 mutations. Only 20/66 (30%) had abdominal imaging (14 BRCA1 and 6 BRCA2 patients). Of those patients with abdominal imaging, abnormal pancreatic imaging findings were detected in 7/20 (35%) cases. Conclusion. Our study shows a high incidence of abnormal pancreatic imaging findings in patients with BRCA genetic mutations (35%). Larger studies are needed to further define the role of pancreatic cancer screening and the significance of abnormal imaging findings in BRCA1 and BRCA2 mutation carriers.

A unique case of a patient with rectal cancer who developed benign esophageal stenosis after localized rectal radiation and systemic chemotherapy.

Acute esophagitis and esophageal strictures typically occur after local radiation therapy to the thoracic field. Toxicity is usually limited to the field of radiation and potentially augmented by concomitant use of chemotherapy, however esophageal stricturing due to chemotherapy alone is exceedingly rare. Gastrointestinal toxicity has been previously reported in the setting of 5-fluorouracil (5-FU)-based chemotherapy with abnormal thymidylate synthase or dihydropyrimidine dehydrogenase activities. We present a unique case of isolated chemotherapy-induced esophageal stricture in the setting of stage IIIa rectal adenocarcinoma which presented shortly after initiation of treatment with 5-FU-based chemotherapy in a patient with normal thymidylate synthase and dihydropyrimidine dehydrogenase assays. These findings prompt further investigation of pathways and potential risk factors leading to esophageal toxicity in patients treated with 5-FU-based chemotherapy.

Transpapillary Gallbladder Stents Can Stabilize or Improve Decompensated Cirrhosis in Patients Awaiting Liver Transplantation.

GOALS: To describe the short-term and long-term outcomes in 34 consecutive decompensated cirrhotic patients with symptomatic gallbladder disease undergoing transpapillary gallbladder stent (TGS) placement. BACKGROUND: Endoscopic TGS placement is a minimally invasive means of treating symptomatic gallbladder disease in poor surgical candidates. STUDY: Between June 2005 and June 2011, 34 patients with cirrhosis and symptomatic gallbladder disease underwent attempted TGS placement. RESULTS: Median patient age was 52 years, 56% were hospitalized, and 48% were listed for liver transplantation. The median model for end-stage liver disease (MELD) score was 15 (range, 6 to 40) and 88% were Child-Turcotte-Pugh class B/C. A double pigtailed stent was successfully placed in 94% of the patients. At 1-month follow-up, clinical improvement was noted in 82% of the treated subjects and the MELD scores in 14 of 22 (64%) evaluable subjects improved or stabilized. Actuarial transplant-free survival was 53% in the liver transplant candidates with a mean follow-up of 352 days, whereas survival was 44% in the 18 nontransplant candidates with a mean follow-up of 1.5 years. Periprocedural complications included pancreatitis in 5 patients, cholangitis in 3, and 1 patient with cystic duct perforation. In addition, 2 subjects had symptomatic bleeding from traumatic duodenal ulcerations 2 years after TGS placement that necessitated stent removal. CONCLUSIONS: Endoscopic TGS placement was technically feasible in 94% of decompensated cirrhotics and was associated with a relatively low rate of periprocedural (26%) and long-term complications (6%). Stabilization or improvement in clinical status and MELD scores was seen in the majority of treated patients.