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Context: Mediastinal nodal staging is recommended for patients with resectable non-small cell lung cancer (NSCLC). Surgical staging has limitations, which results in the performance of unnecessary thoracotomies. Current guidelines acknowledge minimally invasive endosonography followed by surgical staging (if no nodal metastases are found by endosonography) as an alternative to immediate surgical staging.Objective: To compare the 2 recommended lung cancer staging strategies.Design, Setting, and Patients: Randomized controlled multicenter trial (Ghent, Leiden, Leuven, Papworth) conducted between February 2007 and April 2009 in 241 patients with resectable (suspected) NSCLC in whom mediastinal staging was indicated based on computed or positron emission tomography.Intervention: Either surgical staging or endosonography (combined transesophageal and endobronchial ultrasound [EUS-FNA and EBUS-TBNA]) followed by surgical staging in case no nodal metastases were found at endosonography. Thoracotomy with lymph node dissection was performed when there was no evidence of mediastinal tumor spread.Main Outcome Measures: The primary outcome was sensitivity for mediastinal nodal (N2/N3) metastases. The reference standard was surgical pathological staging. Secondary outcomes were rates of unnecessary thoracotomy and complications.Results: Two hundred forty-one patients were randomized, 118 to surgical staging and 123 to endosonography, of whom 65 also underwent surgical staging. Nodal metastases were found in 41 patients (35%; 95% confidence interval [CI], 27%-44%) by surgical staging vs 56 patients (46%; 95% CI, 37%-54%) by endosonography (P = .11) and in 62 patients (50%; 95% CI, 42%-59%) by endosonography followed by surgical staging (P = .02). This corresponded to sensitivities of 79% (41/52; 95% CI, 66%-88%) vs 85% (56/66; 95% CI, 74%-92%) (P = .47) and 94% (62/66; 95% CI, 85%-98%) (P = .02). Thoracotomy was unnecessary in 21 patients (18%; 95% CI, 12%-26%) in the mediastinoscopy group vs 9 (7%; 95% CI, 4%-13%) in the endosonography group (P = .02). The complication rate was similar in both groups.Conclusions: Among patients with (suspected) NSCLC, a staging strategy combining endosonography and surgical staging compared with surgical staging alone resulted in greater sensitivity for mediastinal nodal metastases and fewer unnecessary thoracotomies.Trial Registration: clinicaltrials.gov Identifier: NCT00432640. [ABSTRACT FROM AUTHOR]

The therapeutic possibilities of endoscopy have rapidly increased in the last decades and now allow organ-sparing treatment of early upper gastrointestinal malignancy as well as an increasing number of options for symptom palliation. This review contains an overview of the interventional endoscopic procedures in upper gastrointestinal malignancies. It describes endoscopic treatment of early oesophageal and gastric cancers, and the palliative options in managing dysphagia and gastric outlet obstruction. It also provides an overview of the therapeutic possibilities of biliary endoscopy, such as retrograde stenting and radiofrequency biliary ablation. Endoscopic ultrasound-guided therapeutic options are discussed, including biliary drainage, gastrojejunostomy and coeliac axis block. To aid in clinical decision making, the procedures are described in the context of their indication, efficacy, risks and limitations., (Copyright © 2023 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Background and Aims: International endoscopy societies vary in their approach for credentialing individuals in endoscopic ultrasound (EUS) to enable independent practice; however, there is no consensus in this or its implementation. In 2019, the Joint Advisory Group on GI Endoscopy (JAG) commissioned a working group to examine the evidence relating to this process for EUS. The aim of this was to develop evidence-based recommendations for EUS training and certification in the UK., Methods: Under the oversight of the JAG quality assurance team, a modified Delphi process was conducted which included major stakeholders from the UK and Ireland. A formal literature review was made, initial questions for study were proposed and recommendations for training and certification in EUS were formulated after a rigorous assessment using the Grading of Recommendation Assessment, Development and Evaluation tool and subjected to electronic voting to identify accepted statements. These were peer reviewed by JAG and relevant stakeholder societies before consensus on the final EUS certification pathway was achieved., Results: 39 initial questions were proposed of which 33 were deemed worthy of assessment and finally formed the key recommendations. The statements covered four key domains, such as: definition of competence (13 statements), acquisition of competence (10), assessment of competence (5) and postcertification mentorship (5). Key recommendations include: (1) minimum of 250 hands-on cases before an assessment for competency can be made, (2) attendance at the JAG basic EUS course, (3) completing a minimum of one formative direct observation of procedural skills (DOPS) every 10 cases to allow the learning curve in EUS training to be adequately studied, (4) competent performance in summative DOPS assessments and (5) a period of mentorship over a 12-month period is recommended as minimum to support and mentor new service providers., Conclusions: An evidence-based certification pathway has been commissioned by JAG to support and quality assure EUS training. This will form the basis to improve quality of training and safety standards in EUS in the UK and Ireland., Competing Interests: Competing interests: IP is British Society of Gastroenterology Vice President and chair of the Endoscopy Committee from 2019-2021.Dr Huggett has received paid honoraria from Boston Scientific, Cook Endoscopy and Olympus Keymed., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and study aims  Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has emerged as an important method for obtaining a preoperative tissue diagnosis for suspected cholangiocarcinoma. However, doubts remain about test sensitivity. This study assessed the value and limitations of EUS-FNA in clinical practice. Patients and methods  Patients undergoing EUS-FNA for biliary strictures/masses at a UK tertiary referral center from 2005 to 2014 were prospectively enrolled. Data on EUS-FNA findings, histology, and endoscopy and patient outcomes were collected to evaluate test performance and identify factors predictive of an inaccurate diagnostic result. Results  Ninety-seven patients underwent a total of 112 EUS-FNA procedures. Overall test sensitivity for an initial EUS-FNA for suspected cholangiocarcinoma was 75 % (95 % CI 64 %-84 %), with specificity 100 % (95 % CI 85 %-100 %) and negative predictive value 0.62 (95 % CI 0.47-0.75). Hilar lesions, the presence of a biliary stent, and a diagnosis of PSC were significantly independently associated with an inaccurate result. For the most difficult cases, repeat sampling and use of the Papanicolaou cytopathology grading scale led to an increase in test sensitivity from 17 % to 100 % ( P  = 0.015) with no loss of specificity. Conclusions  EUS-FNA was found to be a useful method for obtaining a preoperative tissue diagnosis for patients with suspected cholangiocarcinoma. This study identified markers that can reduce test accuracy and measures that can improve test performance of EUS-FNA., Competing Interests: Competing interests The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

We describe three-dimensionally preserved feathers in mid-Cretaceous Burmese amber that share macro-morphological similarities (e.g., proportionally wide rachis with a "medial stripe") with lithic, two-dimensionally preserved rachis-dominated feathers, first recognized in the Jehol Biota. These feathers in amber reveal a unique ventrally concave and dorsoventrally thin rachis, and a dorsal groove (sometimes pigmented) that we identify as the "medial stripe" visible in many rachis-dominated rectrices of Mesozoic birds. The distally pennaceous portion of these feathers shows differentiated proximal and distal barbules, the latter with hooklets forming interlocking barbs. Micro-CT scans and transverse sections demonstrate the absence of histodifferentiated cortex and medullary pith of the rachis and barb rami. The highly differentiated barbules combined with the lack of obvious histodifferentiation of the barb rami or rachis suggests that these feathers could have been formed without the full suite and developmental interplay of intermediate filament alpha keratins and corneous beta-proteins that is employed in the cornification process of modern feathers. This study thus highlights how the development of these feathers might have differed from that of their modern counterparts, namely in the morphogenesis of the ventral components of the rachis and barb rami. We suggest that the concave ventral surface of the rachis of these Cretaceous feathers is not homologous with the ventral groove of modern rachises. Our study of these Burmese feathers also confirms previous claims, based on two-dimensional fossils, that they correspond to an extinct morphotype and it cautions about the common practice of extrapolating developmental aspects (and mechanical attributes) of modern feathers to those of stem birds (and their dinosaurian outgroups) because the latter need not to have developed through identical pathways.

Objective: In adults with hyperinsulinaemic hypoglycaemia (HH), in particular those with insulinoma, the optimal diagnostic and management strategies remain uncertain. Here, we sought to characterise the biochemical and radiological assessment, and clinical management of adults with HH at a tertiary centre over a thirteen-year period., Design: Clinical, biochemical, radiological and histological data were reviewed from all confirmed cases of adult-onset hyperinsulinaemic hypoglycaemia at our centre between 2003 and 2016. In a subset of patients with stage I insulinoma, whole-exome sequencing of tumour DNA was performed., Results: Twenty-nine patients were identified (27 insulinoma, including 6 subjects with metastatic disease; 1 pro-insulin/GLP-1 co-secreting tumour; 1 activating glucokinase mutation). In all cases, hypoglycaemia (glucose ≤2.2 mmol/L) was achieved within 48 h of a supervised fast. At fast termination, subjects with stage IV insulinoma had significantly higher insulin, C-peptide and pro-insulin compared to those with insulinoma staged I-IIIB. Preoperative localisation of insulinoma was most successfully achieved with EUS. In two patients with inoperable, metastatic insulinoma, peptide receptor radionuclide therapy (PRRT) with 177 Lu-DOTATATE rapidly restored euglycaemia and lowered fasting insulin. Finally, in a subset of stage I insulinoma, whole-exome sequencing of tumour DNA identified the pathogenic Ying Yang-1 ( YY1 ) somatic mutation (c.C1115G/p.T372R) in one tumour, with all tumours exhibiting a low somatic mutation burden., Conclusion: Our study highlights, in particular, the utility of the 48-h fast in the diagnosis of insulinoma, EUS for tumour localisation and the value of PRRT therapy in the treatment of metastatic disease., (© 2017 The authors.)

Linear endobronchial ultrasound was first described in 2003. Since then the technique has spread rapidly and has now become an established practice in many centres as the first-line mediastinal investigation for the diagnosis and staging of lung cancer. In combination with endoscopic ultrasound, the majority of the mediastinum can be assessed and this approach has been shown to have equivalent accuracy to surgical staging. This strategy is also cost-effective. New tissue processing techniques using liquid-based thin-layer cytology and cell blocks have increased diagnostic yield using immunohistochemical staining and molecular diagnostics. Several meta-analyses of case series and, more recently, randomised controlled trials have provided high-level evidence of efficacy leading to incorporation into national lung cancer staging guidelines. In addition, linear endobronchial ultrasound is increasingly used in the investigation of mediastinal lymphadenopathy for suspected sarcoidosis, tuberculosis and lymphoma. While undoubtedly endobronchial/endoscopic ultrasound has reduced the need for surgical staging in lung cancer, the latter still has an important role to play in certain scenarios. The challenge now facing clinicians is to learn to apply the appropriate test or sequence of tests in each patient while ensuring that operators are appropriately trained in order to ensure optimal outcomes., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: The location of positive lymph nodes has been abandoned in the seventh classification of the TNM staging system for esophageal adenocarcinoma. The present study evaluates whether distribution of involved nodes relative to the diaphragm in addition to TNM 7 further refines prediction., Methods: Pathology reports of patients who underwent esophagectomy between 2000 and 2008 for adenocarcinoma of the esophagus were reviewed and staging was performed according to the seventh UICC-AJCC staging system. In addition, lymph node involvement of nodal stations above and below the diaphragm was investigated by endoscopic ultrasonography (EUS) in a separate cohort of patients who were scheduled for esophagectomy between 2008 and 2009 at two institutions. Survival was calculated by the Kaplan-Meier method, and multivariate analysis was performed with a Cox regression model., Results: Some 327 patients who had undergone esophagectomy for cancer were included. Multivariate analysis revealed that patients with from three to six involved lymph nodes in the resection specimen on both sides of the diaphragm had a twofold higher chance of dying compared to patients with the same number of involved lymph nodes on one side of the diaphragm. EUS assessment of lymph node metastases relative to the diaphragm in 102 patients showed that nodal involvement on both sides of the diaphragm was associated with worse survival than when nodes on one side or no nodes are involved [HR (95 % CI) 2.38 (1.15-4.90)]., Conclusions: A combined staging system that incorporates distribution of lymph nodes relative to the diaphragm refines prognostication after esophagectomy as assessed in the resected specimen and pretreatment as assessed by EUS. This improved staging has the potential to have a great impact on clinical decision making as to whether to embark upon potentially curative or palliative treatments.

Objective: Current practice to diagnose pancreatic cancer is accomplished by endoscopic ultrasound guided fine needle aspiration (EUS-FNA) using a cytological approach. This method is time consuming and often fails to provide suitable specimens for modern molecular analyses. Here, we compare the cytological approach with direct formalin fixation of pancreatic EUS-FNA micro-cores and evaluate the potential to perform molecular biomarker analysis on these specimen., Methods: 130 specimens obtained by EUS-FNA with a 22G needle were processed by the standard cytological approach and compared to a separate cohort of 130 specimens that were immediately formalin fixed to preserve micro-cores of tissue prior to routine histological processing., Results: We found that direct formalin fixation significantly shortened the time required for diagnosis from 3.6 days to 2.9 days (p<0.05) by reducing the average time (140 vs 33 min/case) and number of slides (9.65 vs 4.67 slides/case) for histopathological processing. Specificity and sensitivity yielded comparable results between the two approaches (82.3% vs 77% and 90.9% vs 100%). Importantly, EUS-FNA histology preserved the tumour tissue architecture with neoplastic glands embedded in stroma in 67.89% of diagnostic cases compared to 27.55% with the standard cytological approach (p < 0.001). Furthermore, micro-core samples were suitable for molecular studies including the immunohistochemical detection of intranuclear Hes1 in malignant cells, and the laser-capture microdissection-mediated measurement of Gli-1 mRNA in tumour stromal myofibroblasts., Conclusions: Direct formalin fixation of pancreatic EUS-FNA micro-cores demonstrates superiority regarding diagnostic delay, costs, and specimen suitability for molecular studies. We advocate this approach for future investigational trials in pancreatic cancer patients., (Copyright © 2012 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Objectives: To assess the sensitivity of double contrast barium enema (DCBE) for diagnosing colorectal cancer (CRC)., Design: Retrospective evaluation of DCBE performed in the 2 years prior to diagnosis of CRC., Setting: Teaching hospital in Cambridge, UK., Patients: 1310 consecutive cases of CRC identified from cancer registry data., Interventions: DCBE and colonoscopy., Main Outcome Measures: Sensitivity of DCBE for diagnosing CRC., Results: 215 patients had undergone a DCBE within the 2 years prior to diagnosis with CRC. After excluding those reported as inadequate, 37 of these were reported as normal, giving a sensitivity of 83% (81-85%)., Conclusions: The performance of DCBE is inadequate for the exclusion of CRC. Expansion of colonoscopy and CT colonography capacity is urgently required nationally so that DCBE can finally be abandoned as a firstline test in patients at risk of CRC., Competing Interests: Competing interests: None.

Endoscopic ultrasound (EUS) has become important in a variety of clinical settings. Echoendoscopes may be categorised into radial and linear configurations. Radial devices are used for diagnostic imaging, whereas linear echoendoscopes also facilitate image guided tissue sampling and intervention. EUS is an established primary diagnostic tool for a number of conditions including choledocholithiasis and biliary microlithiasis. It is therefore well suited to the investigation of the aetiology of pancreatitis where simpler measures fail to identify the aetiology. It can also be used to identify chronic non-calcific pancreatitis. EUS is important in the secondary evaluation of abnormalities detected by other imaging modalities-for example, cystic pancreatic lesions. The high resolution of EUS allows more detailed image based analysis than other imaging modalities. The ability to sample cyst fluid significantly increases the accuracy of lesion characterisation. Most importantly, EUS has become indispensable in the staging of a variety of upper gastrointestinal tract tumours. If resection is being considered, the high resolution images obtained via EUS are invaluable for local tumour staging. EUS guided tissue sampling permits accurate nodal staging without relying on lymph node size as proxy for malignant infiltration. In patients with contraindications to magnetic resonance imaging, EUS is an alternative for the staging of rectal carcinoma. It is used in the staging of lung cancer, often in combination with endobronchial ultrasound. Finally, EUS is used therapeutically in image guided drainage (such as gastrocystostomy in pancreatic pseudocyst) and coeliac plexus neurolysis in patients with abdominal pain caused by pancreatic cancer or pancreatitis.

Introduction: To determine the sensitivity and accuracy of endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) for clarification of the nature of fluorodeoxyglucose-positron emission tomography (FDG) positive hilar and/or mediastinal lymph nodes in patients with (suspected) lung cancer., Methods: All consecutive patients who had undergone EBUS-TBNA alone for assessment of abnormal FDG-uptake in hilar and/or mediastinal lymph nodes between January 2005 and August 2007 were reviewed., Results: One-hundred-nine patients underwent EBUS-TBNA of 127 positron emission tomography positive lymph nodes. Hilar (station 10 or 11) nodes (N1 or N3) were aspirated in 26 patients and mediastinal (stations 2, 4, 7) nodes (N2 or N3) in 90 patients. In 7 patients both hilar and mediastinal nodes were sampled. There were no procedure-related complications. Malignancy was detected in 77 (71%) cases. Thirty-two patients were tumor negative by EBUS-TBNA; subsequent surgical biopsy in 19 showed malignancy in 7. In four cases the false negative result was due to sampling error and in three cases due to detection error. In 13 cases surgical staging was not performed although long term follow-up in 3 showed no evidence of malignancy. The sensitivity and accuracy of EBUS-TBNA for malignancy in patients with reference pathology was 91% and 92%, respectively. The negative predictive value was 60%. If the 10 cases for which confirmatory surgical staging was not performed are assumed to be false negative results, overall sensitivity and accuracy were 82% and 84%, respectively., Conclusions: EBUS-TBNA offers an effective accurate, minimally invasive strategy for evaluating FDG avid hilar and mediastinal lymph nodes. However, negative findings should be confirmed by surgical staging.

Background: Obtaining a tissue diagnosis of malignancy is challenging in patients with suspected lung cancer presenting with centrally located intrapulmonary masses., Objective: (1) To evaluate the yield of endobronchial ultrasound with real-time guided transbronchial needle aspiration (EBUS-TBNA) for diagnosing centrally located lesions after a non-diagnostic conventional bronchoscopy. (2) To assess the impact of EBUS-TBNA on patient management for this indication., Study Design and Patients: A retrospective analysis of a series of patients with a central parenchymal lung lesion suspected to be lung cancer who had been referred to three university hospitals for EBUS-TBNA to obtain a tissue diagnosis was undertaken. If EBUS-TBNA did not result in a formal pathological diagnosis of malignancy, patients were subsequently referred for a transthoracic needle aspiration biopsy or a surgical diagnostic procedure., Results: Sixty patients were investigated with EBUS-TBNA. The majority (82%) had a prior (non-diagnostic) flexible bronchoscopy. EBUS-TBNA was performed in an out-patient setting in 97%. With ultrasound, the primary lung lesion was observed in all cases. EBUS-TBNA confirmed lung cancer in 46 (77%). A final reference pathology diagnosis was available in 59 (98%) cases. The sensitivity of EBUS-TBNA for diagnosing lung cancer was 82% (95% confidence intervals (CI) 69-91%) with a negative predictive value of 23% (95%CI 5-53%). Based on the EBUS-TBNA findings, transthoracic needle aspiration biopsy or a surgical diagnostic procedure was cancelled in 47% and 30% of patients, respectively. No serious procedure-related complications were reported., Conclusion: EBUS-TBNA is a sensitive tool for the diagnosis of centrally located primary lung cancer not visible at conventional bronchoscopy. Therefore, EBUS-TBNA can impact on patient management in this setting. However, the low negative predictive value indicates that a negative EBUS-TBNA result should be confirmed by other methods., Implication: EBUS-TBNA can be considered as a diagnostic test in patients with a centrally located lung lesion after a previous non-diagnostic conventional bronchoscopy.

Enteroenteric intussusception is a condition in which full-thickness bowel wall becomes telescoped into the lumen of distal bowel. In adults, there is usually an abnormality acting as a lead point, usually a Meckels' diverticulum, a hamartoma or a tumour. Duodeno-duodenal intussusception is exceptionally rare because the retroperitoneal situation fixes the duodenal wall. The aim of this report is to describe the first published case of this condition. A patient with duodeno-duodenal intussusception secondary to an ampullary lesion is reported. A 66 year-old lady presented with intermittent abdominal pain, weight loss and anaemia. Ultrasound scanning showed dilated bile and pancreatic ducts. CT scanning revealed intussusception involving the full-thickness duodenal wall. The lead point was an ampullary villous adenoma. Congenital partial (type II) malrotation was found at operation and this abnormality permitted excessive mobility of the duodenal wall such that intussusception was possible. This condition can be diagnosed using enhanced CT. Intussusception can be complicated by bowel obstruction, ischaemia or bleeding, and therefore the underlying cause should be treated as soon as possible.

Persistent infection with Pseudomonas aeruginosa and inflammatory mechanisms play an important role in cystic fibrosis (CF) lung disease. ANCA against BPI, a potent host defence protein with anti-bacterial and anti-endotoxin properties, have been described in CF. We have assessed the relationship of anti-BPI antibodies to pulmonary disease severity in 148 CF subjects. IgA and IgG anti-BPI antibodies were found in 55.4% and 70.3% of CF patients, respectively, and higher levels were strongly associated with colonization with P. aeruginosa (P = 0.001 and 0.039 for IgA and IgG antibodies, respectively). IgA and IgG anti-BPI antibodies were independently associated with more severe lung disease as assessed by chest radiograph score (P = 0.023) and a significantly lower forced expiratory volume in 1 s (FEV1)% (P = 0.01). The pathophysiological relevance of the autoantibodies was investigated further by determining their epitope specificity and their effect on bacterial phagocytosis in vitro. Both isotypes of anti-BPI antibodies were specific for the C-terminus of BPI shown recently to be important for BPI-mediated opsonization, and in vitro affinity-purified anti-BPI antibodies significantly reduced BPI-induced phagocytosis of Escherichia coli compared with controls. These data indicate that anti-BPI autoantibodies are associated with colonization with P. aeruginosa and worse lung disease in CF. The inhibition of bacterial phagocytosis suggests that these autoantibodies may contribute to the persistence of P. aeruginosa in the CF lung and so play a role in perpetuating CF lung damage.

Purpose: To develop a noninvasive method for demonstrating the main salivary gland duct systems., Materials and Methods: The authors developed a magnetic resonance (MR) imaging protocol that uses a heavily T2-weighted (echo time, 750 msec), fat-suppressed pulse sequence and rapid acquisition with relaxation enhancement. The technique was optimized to depict fluid within a two-dimensional thick slab. A preliminary evaluation was performed by examining the major salivary gland ducts in 10 asymptomatic volunteers and three symptomatic patients with known salivary duct abnormalities., Results: The main parotid gland ducts were clearly demonstrated in all volunteers. The submandibular ducts were visible in all cases, although not always on projection images. In the three patients, the MR technique clearly demonstrated bilateral sialectasis, a calculus obstructing the left submandibular duct, and a fluid-filled ranula, respectively., Conclusion: Preliminary work indicates that this MR technique can successfully demonstrate both normal and abnormal parotid and submandibular gland duct systems and has several advantages over conventional x-ray sialography.