The additional value of the combined use of EUS and ERCP for the evaluation of unclear biliary strictures.

OBJECTIVE: Assessing unclear biliary strictures is challenging. We analyzed the diagnostic performance of radiology, EUS, and ERCP. METHODS: All patients referred for EUS and ERCP to assess an unclear biliary stricture were prospectively included. The data from radiology, EUS, ERCP, and tissue sampling were recorded. The diagnostic modalities were analyzed separately and in combination, with a focus on PSC. RESULTS: Between 2013 and 2020, 78 patients were included; 31% had PSC. A cholangioscopy was not performed in this study. The final diagnosis indicated that the biliary stricture was benign in 62% of the patients and malignant in 38%. The differences among the modalities were numerical, not significant. The modalities showed an accuracy between 78 and 83% in all the patients and between 75 and 83% in the patients with PSC. The combination of radiology and EUS showed the highest sensitivity of 94% in all the patients and a sensitivity of 100% in PSC. Tissue sampling showed the highest specificity of 93% in all patients and 89% in PSC. In 22 cases with combined EUS, ERCP, and tissue sampling, the accuracy, sensitivity, and specificity were 82%, 70%, and 92%, respectively. Minor differences were observed between the intention-to-diagnose analysis and the per-protocol analysis. Adverse events were recorded in 4% of cases. CONCLUSION: The combination of EUS and ERCP with tissue sampling seems to be useful and safe for excluding malignancy in unclear biliary strictures. In cases with a reduced suspicion of malignancy, radiology with an EUS may be sufficient.

Equivalent efficacy and safety of plastic stents and lumen-apposing metal stents in the treatment of peripancreatic fluid collections: a prospective cohort study.

Background: Endoscopic ultrasound (EUS)-guided transmural drainage using double pigtail plastic stents (DPPS) has been routine for the treatment of peripancreatic fluid collections (PFC). Lumen-apposing metal stents (LAMS) have since their introduction been the preferred choice; however, their superiority has not been proven. The aim of this study was to compare the efficacy and safety of DPPS and LAMS. Methods: This was a single-center, prospective study that included consecutive patients undergoing EUS-guided drainage between January 2010 and December 2020. The primary endpoints were technical success, clinical success and adverse event rate, while the secondary endpoints included symptomatic relief, length of hospital stay, and need for adjunct drainage. A subgroup analysis of walled-off necrosis (WON) was performed. Results: A total of 89 patients (median age 56 years) underwent EUS-guided transmural drainage (DPPS: n=53; LAMS: n=36) because of a pseudocyst (n=37) or a WON (n=52). Both DPPS and LAMS had a 100% technical success rate and a comparable adverse event rate (4% vs. 6%, P=0.24). An equivalent efficacy was recorded for the drainage of PFC comparing DPPS and LAMS, and no significant statistical difference was recorded in clinical success (DPPS 60% vs. LAMS 61%, P=0.94) or the need for reintervention (DPPS 11% vs. LAMS 13%, P=0.72). Conclusions: In this large, prospective study of EUS-guided drainage of peripancreatic fluid collections, LAMS and DPPS showed equivalent safety, technical success, clinical success and hospital stay. Both techniques were associated with a comparable need for complementary necrosectomy.

Curriculum for diagnostic endoscopic ultrasound training in Europe: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement.

The European Society of Gastrointestinal Endoscopy (ESGE) has recognized the need to formalize and enhance training in diagnostic endoscopic ultrasound (EUS). This manuscript represents the outcome of a formal Delphi process resulting in an official Position Statement of the ESGE and provides a framework to develop and maintain skills in diagnostic EUS. This curriculum is set out in terms of the prerequisites prior to training; the recommended steps of training to a defined syllabus; the quality of training; and how competence should be defined and evidenced before independent practice. 1: Trainees should have achieved competence in upper gastrointestinal endoscopy before training in diagnostic EUS. 2: The development of diagnostic EUS skills by methods that do not involve patients is advisable, but not mandatory, prior to commencing formal training in diagnostic EUS. 3: A trainee's principal trainer should be performing adequate volumes of diagnostic EUSs to demonstrate maintenance of their own competence. 4: Training centers for diagnostic EUS should offer expertise, as well as a high volume of procedures per year, to ensure an optimal level of quality for training. Under these conditions, training centers should be able to provide trainees with a sufficient wealth of experience in diagnostic EUS for at least 12 months. 5: Trainees should engage in formal training and supplement this with a range of learning resources for diagnostic EUS, including EUS-guided fine-needle aspiration and biopsy (FNA/FNB). 6: EUS training should follow a structured syllabus to guide the learning program. 7: A minimum procedure volume should be offered to trainees during diagnostic EUS training to ensure that they have the opportunity to achieve competence in the technique. To evaluate competence in diagnostic EUS, trainees should have completed a minimum of 250 supervised EUS procedures: 80 for luminal tumors, 20 for subepithelial lesions, and 150 for pancreaticobiliary lesions. At least 75 EUS-FNA/FNBs should be performed, including mostly pancreaticobiliary lesions. 8: Competence assessment in diagnostic EUS should take into consideration not only technical skills, but also cognitive and integrative skills. A reliable valid assessment tool should be used regularly during diagnostic EUS training to track the acquisition of competence and to support trainee feedback. 9: A period of supervised practice should follow the start of independent activity. Supervision can be delivered either on site if other colleagues are already practicing EUS or by maintaining contacts with the training center and/or other EUS experts. 10: Key performance measures including the annual number of procedures, frequency of obtaining a diagnostic sample during EUS-FNA/FNB, and adverse events should be recorded within an electronic documentation system and evaluated.

Endoscopic ultrasound in the monitoring of the intestinal allograft.

OBJECTIVE: Chronic rejection (CR) of the small intestinal allograft includes mucosal fibrosis, bowel thickening and arteriopathy in the outer wall layers and the mesentery. CR lacks non-invasive markers and reliable diagnostic methods. We evaluated endoscopic ultrasound (EUS) as a novel approach for monitoring of the intestinal allograft with respect to CR. DESIGN: In intestinal graft recipients, EUS and enteroscopy with ileal mucosal biopsy were performed via the ileostomy. At EUS, the wall thickness of the intestinal graft was measured in standard mode, whereas the resistive index (RI) of the supplying artery was assessed in pulsed Doppler mode. At enteroscopy, the intestinal mucosa was assessed. Findings were compared with histopathology and clinical follow-up. RESULTS: EUS was successfully performed in all 11 patients (adequate clinical course (AC) n=9; CR n=2) after a median interval of 1537 days (range: 170-5204), post-transplantation. The total diameter of the wall (layer I-V) was comparable in all patients. Meanwhile, the diameter of the outermost part (layer IV-V; that is, muscularis propria-serosa) was among the two CR patients (range: 1.3-1.4 mm) in the upper end of measurements as compared with the nine AC patients (range: 0.5-1.4 mm). The RI was >0.9 in both CR patients, while the RI was ≤0.8 in all AC patients. Both CR patients had abnormal findings at enteroscopy and histopathology and deceased during follow-up. CONCLUSION: EUS is a promising tool providing detailed information on the intestinal graft morphology and rheology, which may be used for assessment of potential CR in long-term follow-up of intestinal allograft recipients.

Appendicitis: a rare adverse event in colonoscopy.

We present a case of a 41-year-old woman who visited the emergency department (ED) with acute abdomen. She was diagnosed with perforated appendicitis and abscess formation on CT. She was treated conservatively with antibiotics and discharged. On control CT 3 months later, the appendix had healed, but signs of thickening of the terminal ileum were noticed and colonoscopy was performed, which was uneventful and showed no signs of inflammation. Twelve hours later, she developed pain in the right lower quadrant, followed by fever, and visited the ED. Physical examination and blood work showed signs consistent with acute appendicitis, and appendectomy was performed laparoscopically 6 hours later. The patient recovered remarkably shortly afterwards. Whether colonoscopy resulted in de novo appendicitis or exacerbated an already existing inflammation remains unknown. However, endoscopists should be aware of this rare, yet serious complication and consider it in the workup of post-colonoscopy abdominal pain.

GAPS-EUS: a new and reliable tool for the assessment of basic skills and performance in EUS among endosonography trainees.

OBJECTIVE: Endosonography (EUS) is a useful but complex diagnostic modality which requires advanced endoscopy training and guidance by a supervisor. Since learning curves vary among individuals, assessment of the actual competence among EUS trainees is important. DESIGN/METHODS: We designed a novel assessment tool entitled Global Assessment of Performance and Skills in EUS (GAPS-EUS) for assessing skills among EUS trainees. Five quality indicators were marked on a five-grade scale by the supervisor (Observer Score) and by the trainee (Trainee Score). Trainees were included in two high-volume centres (Gothenburg, Sweden, and Bologna, Italy). Outcomes were feasibility, patient safety, reliability, and validity of GAPS-EUS in trainee-performed EUS procedures. RESULTS: Twenty-two EUS-trainees were assessed in a total of 157 EUS procedures with a completion rate of 157/157 (100 %) and a patient adverse event rate of 2/157 (1.3 %; gastroenteritis n=1, fever n=1). GAPS-EUS showed a high measurement reliability (Cronbach's alpha coefficient=0.87) and a high inter-rater reliability comparing the supervisor and the trainee (r=0.83, r2=0.69, p<0.001). The construct of GAPS-EUS was verified by comparing low-level and high-level performance procedures and the content validity by recording that the EUS-FNA manoeuvre resulted in a lower score than other aspects of EUS 3.07 (95% CI 2.91 to 3.23) vs 3.51 (95% CI 3.37 to 3.65) (p<0.001). External validity was confirmed via similar findings in both centres. CONCLUSION: GAPS-EUS is an easy-to-use and reliable tool with a recorded high validity for the assessment of competence among trainees in EUS. It can be recommended to centres involved in the education of future endosonographers. TRIAL REGISTRATION NUMBER: NCT02455570.

High Sensitivity of Endoscopic Ultrasound-Guided Fine-Needle Aspiration and Endoscopic Ultrasound-Guided Fine-Needle Biopsy in Lymphadenopathy Caused by Metastatic Disease: A Prospective Comparative Study.

BACKGROUND/AIMS: The diagnostic work-up of lymphadenopathy is challenging but important to determine the correct therapy. Nevertheless, few studies have addressed the topic of endosonography (EUS)-guided tissue acquisition in lymphadenopathy. Therefore, we aimed to evaluate the accuracy and safety of EUS-guided fine-needle biopsy sampling (EUS-FNB) in intrathoracic and intraabdominal lymphadenopathy. METHODS: In a tertiary care center, patients with lymphadenopathy referred for EUS-guided sampling were included prospectively from 2014 to 2019 (NCT02360839). In all cases, EUS-FNB (22 gauge) and EUS-guided fine-needle aspiration (EUS-FNA) (25 gauge) were performed. The patients were randomized to the first needle pass with FNB or FNA. Study outcomes were the diagnostic accuracy and adverse event rate. RESULTS: Forty-eight patients were included (median age: 69 years [interquartile range, 59-76]; 24/48 females [50%]). The final diagnoses were metastasis (n=17), lymphoma (n=11), sarcoidosis (n=6), and inflammatory disease (n=14). The diagnostic performance of the two modalities was comparable, including a high sensitivity for metastatic nodes (EUS-FNB: 87% vs. EUSFNA: 100%, p=0.5). The sensitivity for lymphoma was borderline superior in favor of EUS-FNB (EUS-FNB: 55% vs. EUS-FNA: 9%, p=0.06). No adverse events were recorded. CONCLUSION: In lymphadenopathy, both EUS-FNB and EUS-FNA are safe and highly sensitive for metastatic lymph node detection. Lymphoma diagnosis is challenging regardless of the needle used.

EUS is accurate in characterizing pancreatic cystic lesions; a prospective comparison with cross-sectional imaging in resected cases.

BACKGROUND: Imaging modalities for characterizing pancreatic cystic lesions (PCLs) is a known uncertainty. The aim of this prospective study was to compare the diagnostic performance of endoscopic ultrasound morphology, cytology and cyst fluid carcinoembryonic antigen (EUS-FNA-CEA) with cross-sectional imaging in resected PCLs. METHODS: The cross-sectional imaging and EUS-FNA-CEA results were collected in an academic tertiary referral centre using histology of the surgical specimen as the diagnostic standard. RESULTS: Of 289 patients undergoing evaluation for PCL with cross-sectional imaging and EUS-FNA between February 2007 and March 2017, 58 underwent surgical resection providing a final diagnosis of the PCLs: 45 mucinous, 5 serous, 1 pseudocyst, 2 endocrine, 2 solid pseudopapillary neoplasms and 3 other. EUS-FNA-CEA was more accurate than cross-sectional imaging in diagnosing mucinous PCLs (95% vs. 83%, p = 0.04). Ninety-two percent of the PCLs with high-grade dysplasia or adenocarcinoma were smaller than 3 cm in diameter. The sensitivity of EUS-FNA-CEA and cross-sectional imaging for detecting PCLs with high-grade dysplasia or adenocarcinoma were 33% and 5% (p = 0.03), respectively. However, there was no difference in accuracy between the modalities (62% vs. 66%, p = 0.79). The sensitivity for detecting pancreatic adenocarcinomas only was 64% for EUS-FNA-CEA and 9% for cross-sectional imaging (p = 0.03). Overall, EUS-FNA-CEA provided a correct diagnosis in more patients with PCLs than cross-sectional imaging (72% vs. 50%, p = 0.01). CONCLUSIONS: EUS-FNA-CEA is accurate and should be considered a complementary test in the diagnosis of PCLs. However, the detection of PCLs with high-grade dysplasia or adenocarcinoma needs to be improved. Cyst size does not seem to be a reliable predictor of high-grade dysplasia or adenocarcinoma.

Pretreatment Tumor DNA Sequencing of KIT and PDGFRA in Endosonography-Guided Biopsies Optimizes the Preoperative Management of Gastrointestinal Stromal Tumors.

BACKGROUND: Neoadjuvant tyrosine kinase inhibitor (TKI) therapy increases the chance of organ-preserving, radical resection in selected patients with gastrointestinal stromal tumors (GISTs). We aimed to evaluate systematic, immediate DNA sequencing of KIT and PDGFRA in pretreatment GIST tissue to guide neoadjuvant TKI therapy and optimize preoperative tumor response. METHODS: All patients who were candidates for neoadjuvant therapy of a suspected GIST [the study cohort (SC)] were prospectively included from January 2014 to March 2018. Patients were subjected to pretreatment endosonography-guided fine-needle biopsy (EUS-FNB) or transabdominal ultrasound-guided needle biopsy (TUS-NB), followed by immediate tumor DNA sequencing (< 2 weeks). A historic (2006-2013) reference cohort (RC) underwent work-up without sequencing before neoadjuvant imatinib (n = 42). The rate of optimal neoadjuvant therapy (TherapyOPTIMAL) was calculated, and the induced tumor size reduction (Tumor RegressionMAX, %) was evaluated by computed tomography (CT) scan. RESULTS: The success rate of pretreatment tumor DNA sequencing in the SC (n = 81) was 77/81 (95%) [EUS-FNB 71/74 (96%); TUS-NB 6/7 (86%)], with mutations localized in KIT (n = 58), PDGFRA (n = 18), or neither gene, wild type (n = 5). In patients with a final indication for neoadjuvant therapy, the TherapyOPTIMAL was higher in the SC compared with the RC [61/63 (97%) versus 33/42 (79%), p = 0.006], leading to a significantly higher Tumor RegressionMAX in patients treated with TKI (27% vs. 19%, p = 0.015). CONCLUSIONS: Pretreatment endosonography-guided biopsy sampling followed by immediate tumor DNA sequencing of KIT and PDGFRA is highly accurate and valuable in guiding neoadjuvant TKI therapy in GIST. This approach minimizes maltreatment with inappropriate regimens and leads to improved tumor size reduction before surgery.

Macroscopic appearance of the major duodenal papilla influences bile duct cannulation: a prospective multicenter study by the Scandinavian Association for Digestive Endoscopy Study Group for ERCP.

BACKGROUND AND AIMS: Certain appearances of the major duodenal papilla have been claimed to make cannulation more difficult during ERCP. This study uses a validated classification of the endoscopic appearance of the major duodenal papilla to determine if certain types of papilla predispose to difficult cannulation. METHODS: Patients with a naïve papilla scheduled for ERCP were included. The papilla was classified into 1 of 4 papilla types before cannulation started. Time to successful bile duct cannulation, attempts, and number of pancreatic duct passages were recorded. Difficult cannulation was defined as after 5 minutes, 5 attempts, or 2 pancreatic guidewire passages. RESULTS: A total of 1401 patients were included from 9 different centers in the Nordic countries. The overall frequency of difficult cannulation was 42% (95% confidence interval [CI], 39%-44%). Type 2 small papilla (52%; 95% CI, 45%-59%) and type 3 protruding or pendulous papilla (48%; 95% CI, 42%-53%) were more frequently difficult to cannulate compared with type 1 regular papilla (36%; 95% CI, 33%-40%; both P < .001). If an inexperienced endoscopist started cannulation, the frequency of failed cannulation increased from 1.9% to 6.3% (P < .0001), even though they were replaced by a senior endoscopist after 5 minutes. CONCLUSIONS: The endoscopic appearance of the major duodenal papilla influences bile duct cannulation. Small type 2 and protruding or pendulous type 3 papillae are more frequently difficult to cannulate. In addition, cannulation might even fail more frequently if a beginner starts cannulation. These findings should be taken into consideration when performing studies regarding bile duct cannulation and in training future generations of endoscopists.

The experiences of physical activity in irritable bowel syndrome-A qualitative study.

AIMS AND OBJECTIVES: To explore experiences of physical activity in patients with Irritable bowel syndrome. BACKGROUND: Irritable bowel syndrome is a common functional bowel disorder. The knowledge of physical activity in Irritable bowel syndrome is limited and has not been qualitatively studied before. METHODS: We adopted a qualitative approach and a hermeneutic analysis. Fifteen patients with Irritable bowel syndrome (10 women) with a median age of 52 (31-78) years were interviewed. The Consolidated criteria for reporting qualitative research was used. RESULTS: Two themes emerged from the data: requirements of physical activity and capability for physical activity. The first of these consisted of five subthemes: add additional value, enable transportation, maintain health, cultivate interests and give a feeling of belonging. These qualities were the patients' requirements of physical activity and comprised the patients' motives and reasons for being physically active. The second consisted of four subthemes: life situation, earlier experiences, self-image, and symptom variation and described the possibility and resources to be physically active in everyday life. The patients made active choices to adjust their physical activity in terms of type, intensity and amount. The two main themes affect each other reciprocally. CONCLUSIONS: The requirements of and capabilities for physical activity should be taken into account when giving advice to patients on physical activity. Physical activity for a person with Irritable bowel syndrome is about finding activities which meet the patient's individual requirements of and capability for physical activity. RELEVANCE TO CLINICAL PRACTICE: This qualitative study on the experience pf physical activity in Irritable bowel syndrome provides knowledge to facilitate promoting physical activity among patients suffering from Irritable bowel syndrome. This knowledge can be used in other diagnosis.

The assessment of endosonographers in training.

Endosonography (EUS) has an estimated long learning curve including the acquisition of both technical and cognitive skills. Trainees in EUS must learn to master intraprocedural steps such as echoendoscope handling and ultrasonographic imaging with the interpretation of normal anatomy and any pathology. In addition, there is a need to understand the periprocedural parts of the EUS-examination such as the indications and contraindications for EUS and potential adverse events that could occur post-EUS. However, the learning process and progress vary widely among endosonographers in training. Consequently, the performance of a certain number of supervised procedures during training does not automatically guarantee adequate competence in EUS. Instead, the assessment of EUS-competence should preferably be performed by the use of an assessment tool developed specifically for the evaluation of endosonographers in training. Such a tool, covering all the different steps of the EUS-procedure, would better depict the individual learning curve and better reflect the true competence of each trainee. This mini-review will address the issue of clinical education in EUS with respect to the evaluation of endosonographers in training. The aim of the article is to provide an informative overview of the topic. The relevant literature of the field will be reviewed and discussed. The current knowledge on how to assess the skills and competence of endosonographers in training is presented in detail.

Experiences of the effects of physical activity in persons with irritable bowel syndrome (IBS): a qualitative content analysis.

OBJECTIVE: Increased physical activity has been tested among patients with irritable bowel syndrome (IBS) in a randomized trial which demonstrated improvement in gastrointestinal (GI) symptoms. The patients' experiences of the effects of physical activity on IBS symptoms are unknown. This knowledge is necessary to enable suitable support from health care professionals. The aim of this study was therefore to explore patients' experiences of the effects of physical activity. MATERIALS AND METHODS: Deep interviews were conducted with 15 patients (10 women and 5 men) aged 31-78 years. Their IBS had lasted for 10-57 years. The transcribed interviews were analyzed through a qualitative content analysis. RESULTS: The analysis of the material revealed three themes; GI symptoms, extra-intestinal symptoms, and quality of life (QOL). In relation to GI symptoms, the patients discussed how physical activity affected these symptoms and how they used physical activity to normalize and control their GI symptoms. Extra-intestinal symptoms were also affected by physical activity, and the patients described how they experienced a general bodily wellbeing as well as improved mood and energy in relation to physical activity. In terms of QOL, the patients discussed their perspectives on physical activity as giving them achievements, being pleasurable, and being strengthening of the self. CONCLUSIONS: Our results emphasize the importance of taking into account the patient's experiences of the effects of physical activity when coaching patients with IBS to be physically active. Using a person-centred approach incorporating, the patient's own experiences and resources is the key to successfully promoting physical activity in the clinic.

EUS-guided reverse bevel fine-needle biopsy sampling and open tip fine-needle aspiration in solid pancreatic lesions - a prospective, comparative study.

OBJECTIVES: Different diagnostic entities can present as solid pancreatic lesions (SPL). This study aimed to explore the utility of endoscopic ultrasound-guided reverse bevel fine-needle biopsy sampling (EUS-FNB) in SPLs. MATERIAL AND METHODS: In 2012-2015, consecutive patients with SPLs were prospectively included in a tertiary center setting and subjected to dual needle sampling with a 22 gauge reverse bevel biopsy needle and a conventional 25 gauge open tip aspiration needle (EUS-FNA). The outcome measures were the diagnostic accuracy of sampling, calculated for each modality separately and for the modalities combined (EUS-FNA + FNB), and the adverse event rate related to sampling. RESULTS: In 68 unique study subjects, the most common diagnostic entities were pancreatic neuroendocrine tumor, PNET, (34%), pancreatic ductal adenocarcinoma, PDAC, (32%), pancreatitis (15%) and metastasis (6%). The overall diagnostic accuracy of EUS-FNB was not significantly different from that of EUS-FNA, (69% vs. 78%, p = .31). EUS-FNA + FNB, compared with EUS-FNA alone, had a higher sensitivity for tumors other than PDAC (89% vs. 69%, p = .02) but not for PDACs (95% vs. 85%, p = .5). No adverse event was recorded after the study dual-needle sampling procedures. CONCLUSIONS: Endoscopic ultrasound-guided tissue acquisition performed with a 22 gauge reverse bevel biopsy needle is safe but not superior to conventional fine-needle aspiration performed with a 25 gauge open tip needle in diagnosing solid pancreatic lesions. However, the performance of both these modalities may facilitate the diagnostic work-up in selected patients, such as cases suspicious for pancreatic neuroendocrine tumors and metastases. NCT02360839.

High clinical impact and diagnostic accuracy of EUS-guided biopsy sampling of subepithelial lesions: a prospective, comparative study.

BACKGROUND: In a tertiary center setting we aimed to study the diagnostic accuracy and clinical impact of EUS-guided biopsy sampling (EUS-FNB) with a reverse bevel needle compared with that of fine needle aspiration (EUS-FNA) in the work-up of subepithelial lesions (SEL). METHODS: All patients presenting with SELs referred for EUS-guided sampling were prospectively included in 2012-2015. After randomization of the first pass modality, dual sampling with both EUS-FNB and EUS-FNA was performed in each lesion. Outcome measures in an intention-to-diagnose analysis were the diagnostic accuracy, technical failures, and adverse events. The clinical impact was measured as the performance of additional diagnostic procedures post-EUS and the rate of unwarranted resections compared with a reference cohort of SELs sampled in the same institution 2006-2011. RESULTS: In 70 dual sampling procedures of unique lesions (size: 6-220 mm) the diagnostic sensitivity for malignancy and the overall accuracy of EUS-FNB was superior to EUS-FNA compared head-to-head (90 vs 52%, and 83 vs 49%, both p < 0.001). The adverse event rate of EUS-FNB was low (1.2%). EUS-FNB in 2012-2015 had a positive clinical impact in comparison with the reference cohort demonstrated by less cases referred for an additional diagnostic procedure, 12/83 (14%) vs 39/73 (53%), p < 0.001, and fewer unwarranted resections in cases subjected to surgery, 3/48 (6%) vs 12/35 (34%), p = 0.001. CONCLUSIONS: EUS-FNB with a reverse bevel needle is safe and superior to EUS-FNA in providing a conclusive diagnosis of subepithelial lesions. This biopsy sampling approach facilitates a rational clinical management and accurate treatment.

Highly Accurate Identification of Cystic Precursor Lesions of Pancreatic Cancer Through Targeted Mass Spectrometry: A Phase IIc Diagnostic Study.

Purpose Pancreatic cystic lesions are common incidental findings on imaging, but up to half may be forerunners of pancreatic cancer. Therefore, accurate differential diagnosis is crucial for correct patient management. Unfortunately, currently available diagnostic methods cannot robustly identify premalignant and malignant pancreatic cystic lesions. Methods Cyst fluid samples obtained by routine endoscopic ultrasound-guided aspiration were used for the analyses. In a cohort of 24 patients, eight biomarker candidates for malignant potential and high-grade dysplasia/cancer were identified by an explorative proteomic approach. Subsequently, a quantitative analysis, using 30 heavy-labeled peptides from the biomarkers and parallel reaction monitoring mass spectrometry, was devised, tested in a training cohort of 80, and prospectively evaluated in a validation cohort of 68 patients. End points were surgical pathology diagnosis/clinical follow-up. Diagnostic assessments were blinded to mass spectrometry results. Results The optimal set of markers for detecting malignant potential was a panel of peptides from mucin-5AC and mucin-2, which could discriminate premalignant/malignant lesions from benign with an accuracy of 97% (95% CI, 89% to 99%) in the validation cohort. This result compared favorably with the accuracy of standard analyses: cyst fluid carcinoembryonic antigen (61%; 95% CI, 46% to 74%; P < .001) and cytology (84%; 95% CI, 71% to 92%; P = .02). A combination of proteins mucin-5AC and prostate stem-cell antigen could identify high-grade dysplasia/cancer with an accuracy of 96% (95% CI, 90% to 99%), and detected 95% of malignant/severely dysplastic lesions, compared with 35% and 50% for carcinoembryonic antigen and cytology ( P < .001 and P = .003, respectively). Conclusion Targeted mass spectrometry analysis of just three cyst fluid biomarkers provides highly accurate identification and assessment of cystic precursors to pancreatic adenocarcinoma. Additional studies should determine whether the method can facilitate timely cancer diagnosis, successful intervention, and prevention.

Characterizing gastrointestinal stromal tumors and evaluating neoadjuvant imatinib by sequencing of endoscopic ultrasound-biopsies.

AIM: To evaluate endoscopic ultrasound (EUS)-guided biopsies for the pretreatment characterization of gastrointestinal stromal tumors (GIST) to personalize the management of patients. METHODS: All patients with lesions suspected to be GIST who were referred for EUS-sampling at a tertiary Swedish center were eligible for inclusion 2006-2015. During the observational study phase (2006-2011), routine fine-needle-aspiration (EUS-FNA) was performed. In 2012-2015, we converted to an interventional, randomized protocol with dual sampling EUS-FNA and fine-needle-biopsy-sampling (EUS-FNB) for all lesions. c-KIT- and DOG-1-immunostaining was attempted in all samples and a manual count of the Ki-67-index was performed. FNB-sampled tissue and the resected specimens were subjected to Sanger sequencing of the KIT and platelet-derived growth factor alpha (PDGFRA) genes. RESULTS: In all, 64 unique patients with GIST were included, and of these, 38 were subjected to pretreatment dual sampling. EUS-FNB had a higher diagnostic sensitivity when compared head-to-head with EUS-FNA (98% vs 58%, P < 0.001) and was more adequate for Ki-67-indexing (Ki-67EUS) (92% vs 40%, P < 0.001). Sequencing of EUS-biopsies was successful in 43/44 (98%) patients, and the mutation profiles (KIT-mutation 73%, PDGFRA-mutation 18%, wild-type 7%) were fully congruent with those detected in the corresponding resected specimens. In imatinib-naïve patients, the Ki-67EUS was comparable with the Ki-67-index in the corresponding surgical specimens (Ki-67SURG) (2.7% vs 2.9%, P = 0.68). In patients treated with neoadjuvant imatinib who also carried mutations indicating sensitivity, the Ki-67EUS was higher than the Ki-67SURG (2.5% vs 0.2%, P = 0.005), with a significant reduction in the Ki-67-index of -91.5% (95%CI: -82.4 to -96.0, P = 0.005). CONCLUSION: EUS-guided biopsy sampling is accurate for the pretreatment diagnosis and characterization of GISTs and allows the prediction and evaluation of tumor response to neoadjuvant imatinib therapy.

Are the definitions for chronic diarrhoea adequate? Evaluation of two different definitions in patients with chronic diarrhoea.

BACKGROUND: The classical definition of chronic diarrhoea is ≥3 defecations/day, with a stool weight of more than 200 g and duration of ≥4 weeks. However, with this definition many patients with substantial symptoms and pathology will be excluded from further investigations. As a consequence other definitions have been proposed, mainly based on evaluation of the stool form. OBJECTIVE: To evaluate the accuracy of the classic criteria for diarrhoea in comparison with a definition based on stool consistency, using the Bristol Stool Form Scale. METHODS: All patients were investigated with laboratory tests, upper and lower gastrointestinal endoscopy with biopsies, and SeHCAT test. They were asked to complete a diary recording stool frequency and consistency during a week, as well as other gastrointestinal symptoms (pain, bloating and gas). RESULTS: One hundred and thirty-nine subjects were eligible for analysis. Ninety-one had an organic cause of diarrhoea. Fifty-three patients had ≥3 loose stools/day, whereas 86 reported <3 stools/day. Ninety had a median stool consistency that was mushy or loose and 49 had harder stools. A higher proportion of subjects with an organic cause of their diarrhoea compared with subjects with a functional bowel disorder had ≥3 loose stools/day, 43/91 (47%) vs. 10/48 (21%) (p < 0.01). Similarly, more subjects with an organic cause of their diarrhoea versus patients with a functional bowel disorder had a median stool consistency that was mushy or watery, 73/91 (80%) vs. 17/48 (35%), p < 0.0001. When diarrhoea was defined according to stool form, more patients were classified correctly as having a functional disorder or organic disorder, compared with the classical definition (p < 0.05). CONCLUSION: Loose stools defined according to the Bristol Stool Form scale seem to be the best predictor of having an organic cause of the diarrhoea.

Intervention to increase physical activity in irritable bowel syndrome shows long-term positive effects.

AIM: To assess the long-term effects of physical activity on irritable bowel syndrome (IBS) symptoms and on quality of life, fatigue, depression and anxiety. METHODS: Seventy-six patients from a previous randomized controlled interventional study on increased physical activity in IBS were asked to participate in this long-term follow-up study. The included patients attended one visit in which they filled out questionnaires and they underwent a submaximal cycle ergometer test. The primary end point was the change in the IBS Severity Scoring System (IBS-SSS) at baseline, i.e., before the intervention and at follow-up. The secondary endpoints were changes in quality of life, fatigue, depression and anxiety. RESULTS: A total of 39 [32 women, median age 45 (28-61) years] patients were included in this follow-up. Median follow-up time was 5.2 (range: 3.8-6.2) years. The IBS symptoms were improved compared with baseline [IBS-SSS: 276 (169-360) vs 218 (82-328), P = 0.001]. This was also true for the majority of the dimensions of psychological symptoms such as disease specific quality of life, fatigue, depression and anxiety. The reported time of physical activity during the week before the visit had increased from 3.2 (0.0-10.0) h at baseline to 5.2 (0.0-15.0) h at follow-up, P = 0.019. The most common activities reported were walking, aerobics and cycling. There was no significant difference in the oxygen uptake 31.8 (19.7-45.8) mL per min per kg at baseline vs 34.6 (19.0-54.6) mL/min per kg at follow-up. CONCLUSION: An intervention to increase physical activity has positive long-term effects on IBS symptoms and psychological symptoms.