Added value of EUS-B-FNA to bronchoscopy and EBUS-TBNA in diagnosing and staging of lung cancer.

Background: Bronchoscopy and EBUS are standard procedures in lung cancer work-up but have low diagnostic yield in lesions outside the central airways and hilar/mediastinal lymph nodes. Growing evidence on introducing the EBUS endoscope into the oesophagus (EUS-B) in the same session as bronchoscopy/EBUS gives access to new anatomical areas that can be safely biopsied. Objective: To summarize the current evidence of the added value of EUS-B-FNA to bronchoscopy and EBUS-TBNA in lung cancer work-up. Methods: A narrative review. Results: Few randomized trials or prospective studies are available. Prospective studies show that add-on EUS-B-FNA increases diagnostic yield when sampling abnormal mediastinal lymph nodes, para-oesophageal lung and left adrenal gland. A large retrospective series on EUS-B-FNA from retroperitoneal lymph nodes suggests high diagnostic yield without safety concerns, as do casuistic reports on EUS-B-FNA from mediastinal pleural thickening, pancreatic lesions, ascites fluid and pericardial effusions. No study has systematically assessed both diagnostic yield, safety, patient reported outcomes, adverse events and costs. Conclusion: The diagnostic value of add-on EUS-B to standard bronchoscopy and EBUS in lung cancer work-up appears very promising without safety concerns, giving the pulmonologist access to a variety of sites out of reach with other minimally invasive techniques. Little is known on patient-reported outcomes and costs. Future and prospective research should focus on effectiveness aspects to clarify whether overall benefits of add-on EUS-B sufficiently exceed overall downsides.

Virtual Reality intervention to improve quality of care during Colonoscopy: A hybrid type 1 randomized controlled trial.

BACKGROUND AND AIMS: Effective management of patients' pain, anxiety, and discomfort during colonoscopy is crucial for successful completion of the procedure, patient adherence to follow-up examinations, and patient satisfaction. Virtual Reality (VR) interventions, as a nonpharmacological and innovative solution, have demonstrated promising results in managing these outcomes. Nevertheless, there is limited evidence on their effectiveness and implementation. This trial aimed to test clinical effectiveness and identify factors to facilitate the implementation of VR during colonoscopy. METHODS: A hybrid type 1 effectiveness-implementation, parallel randomized controlled, open-label trial was conducted. Fifty patients were randomized (1:1) to a VR or a control group. The effectiveness (pain, anxiety, discomfort, medication usage, and satisfaction) and implementation (reach, adoption, implementation, and maintenance) outcomes were assessed before, during, and after colonoscopy. RESULTS: Patients in the VR group reported significantly lower pain (p=0.043) and discomfort (p<0.0001) during colonoscopy, had a higher number of completed colonoscopy without sedation (p=0.003), and showed higher satisfaction (p=0.032). The major barrier to the implementation and maintenance of the VR intervention was inadequate VR content design. Staff were most worried about altered patient communications, unclear responsibilities, increasing workload, and patient safety. Patients expressed willingness to reuse VR glasses and to suggest them to other patients. CONCLUSION: VR can be used as a nonpharmacological method for pain management and for overcoming anxiety and discomfort during colonoscopy. VR can improve patients' satisfaction and diminish the need for sedative medications; accordingly, it has the potential to promote cooperation and compliance among patients and increase screening colonoscopy rates. CLINICALTRIALS: gov NCT05723861.

Endoscopic ultrasound-guided biopsies vs surgical specimens for establishing patient-derived pancreatic cancer organoids: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Patient-Derived Tumor Organoids (PDTOs) is a promising new disease model in pancreatic cancer for use in personalized medicine, but overall success rate (SR) of establishing these cultures from endoscopic ultrasound-guided biopsies is unknown. METHODS: We searched relevant databases publications reporting SR of PDTO establishment from pancreatic cancer. The primary outcome was SR stratified on tissue acquisition method (EUS-guided biopsies, percutaneous biopsies, and surgical specimens). RESULTS: We identified 24 studies including 1,053 attempts at establishing PDTOs. Overall SR was 63% (95% CI: 54%-72%). Pooled SR of PDTO establishment from EUS-guided biopsies, percutaneous biopsies, and surgical specimens were 60% (95% CI: 43-76%), 36% (95% CI: 14-61%) and 62% (95% CI: 48-75%), respectively and did not differ significantly (p = 0.1975). CONCLUSION: The SR of PDTO establishment from EUS-guided biopsies is comparable to surgical specimens. Both techniques are suitable for tissue acquisition for PDTOs in clinical and research settings.

The clinical role of remimazolam: Protocol for a scoping review.

BACKGROUND: Remimazolam, a novel benzodiazepine, shows promise as an alternative to traditional sedatives and hypnotic agents in procedural sedation and general anaesthesia. While preliminary research indicates potential advantages over conventional agents, such as faster onset, predictable duration, and improved safety profile, the extent and quality of existing evidence remain unclear. This scoping review aims to investigate the current clinical role of remimazolam and provide a broad and comprehensive overview. METHODS: The proposed review will adhere to the JBI methodology for scoping reviews and the Preferred Reporting Items for Systematic Review and Meta-Analysis for Scoping Reviews. A comprehensive search will be conducted across major peer-reviewed databases and grey literature will be sought. All studies involving individuals undergoing procedural sedation or general anaesthesia with remimazolam will be eligible. Data extraction will encompass trial and participant characteristics, intervention details, reported outcomes, comparative efficacy versus midazolam and propofol, patient and operator experience and economic costs. RESULTS: We will provide a descriptive summary supplemented by statistics, figures and tables where applicable. CONCLUSION: The outlined scoping review aims to assess the clinical use of remimazolam in procedural sedation and as the hypnotic component of general anaesthesia. The review will map the current body of evidence of remimazolam and identify knowledge gaps, contributing to understanding its clinical implications and guiding future research efforts in procedural sedation and general anaesthesia.

Using the Endoscope for Endobronchial Ultrasound in the Esophagus.

EUS-B is a procedure using the echoendobronchoscope in the esophagus and stomach. The procedure is a minimally invasive, safe, and feasible approach that pulmonologists can use to visualize and biopsy structures adjacent to the esophagus and stomach. EUS-B gives access to many structures of which some may also be reached by EBUS (mediastinal lymph nodes, lung or pleural tumors, pericardial fluid) while others cannot be reached such as retroperitoneal lymph nodes, ascites, and lesions in the liver, pancreas or left adrenal gland. The procedure is a pulmonologist- and patient- friendly version of the gastroenterologists' EUS using the thin EBUS endoscope that the pulmonologist already masters. Thus EUS-B training should be easy and a natural continuation of EBUS. With the patient under conscious sedation and in the supine position, the echoendoscope is introduced either through the nostril or mouth into the oropharynx. Then the patient is encouraged to swallow while the endoscope is slowly bent posteriorly and introduced into the esophagus and stomach. Using the ultrasonic image, the operator identifies the six landmarks by EUS-B and EUS: the left liver lobe, abdominal aorta (with the celiac trunk and superior mesenteric artery), left adrenal gland, and mediastinal lymph node stations 7, 4L, and 4R. Biopsies can be taken from suspected lesions under real-time ultrasonographic guidance- fine needle aspiration (EUS-B-FNA) using a technique similar to that used with EBUS-TBNA. The biopsy order is M1b-M1a-N3-N2-N1-T (M = metastasis, N = lymph node, T = tumor) to avoid iatrogenic upstaging. Pre- and post-procedural observation is similar to that of bronchoscopy. EUS-B is safe and feasible in the hands of experienced interventional pulmonologists and provides a significant expansion of the diagnostic possibilities in providing safe, fast, and thorough diagnosis and staging of lung cancer.

Virtual reality interventions to reduce psychological distress during colonoscopy: a rapid review.

INTRODUCTION: Colonoscopy can cause psychological distress in patients, consequently discouraging patients from undergoing an unpleasant procedure or reducing compliance with follow-up examinations. This rapid review aimed to assess the feasibility and efficacy of Virtual Reality (VR) interventions during colonoscopy on patients' perceived psychological distress and procedure satisfaction. AREAS COVERED: We searched PubMed, CINAHL, ProQuest/All Databases, and Cochrane Library databases on 1 December 2022, with a date limiter of 2002-2022 for articles that investigated the effect and feasibility of any type of immersive VR-based intervention on patients' pain, anxiety, discomfort, and procedure satisfaction immediately before, during, and/or post-procedure of colonoscopy. EXPERT OPINION: Initially, 118 articles were identified, of which seven were eligible and included in this rapid review. Our findings demonstrate that VR interventions during colonoscopy were feasible, significantly reduced participant pain and anxiety, and significantly increased participant satisfaction with the procedure. VR interventions appear to be an effective alternative for patients who prefer to avoid analgetic medications or as an adjunct to routine sedation during colonoscopy. Directions of research design should focus on an optimized blinding process, using the high-end technology of 3-dimensional devices, considering an audiovisual distracting intervention, and designing multicenter and high-quality Randomized Controlled Trials.

Performance of EUS-FNA and EUS-B-FNA for the diagnosis of left adrenal glands metastases in patients with lung cancer: A systematic review and meta-analysis.

OBJECTIVES: For diagnosing left adrenal gland metastasis in lung cancer, clinical guidelines recommend to perform EUS, but EUS-B (EUS using an EBUS-scope) is increasingly being used. We evaluated the diagnostic performance of both procedures. MATERIALS AND METHODS: We did a systematic review (PROSPERO, CRD42023416205) and searched MEDLINE and EMBASE on 04-July-2023 for studies evaluating EUS and/or EUS-B in diagnosing left adrenal gland metastases in adults with (suspected) lung cancer. Outcomes were: (1) ability to visualize the left adrenal gland, (2) ability to sample (in those with successful visualization and in whom sampling was attempted), (3) ability to obtain adequate material (in those with successful sampling), (4) malignancy detection rate (in those with successful sampling), and (5) remaining risk of malignancy (in those with a negative EUS(-B)-FNA and undergoing a reference standard). We performed random-effects meta-analyses. RESULTS: We included 19 studies (EUS: n = 11, EUS-B: n = 6, both: n = 2), covering 1712 patients. All studies had high (n = 18) or unclear (n = 1) risk of bias (QUADAS-2). Average ability to visualize the left adrenal gland was 0.94 (95 %CI 0.82-0.98; n = 7 studies). Average ability to sample was 1.00 (95 %CI 0.99-1.00; n = 9). Average ability to obtain adequate material was 0.96 (95 %CI 0.93-0.98; n = 18). Average malignancy detection rate was 0.42 (95 %CI 0.34-0.49; n = 18). Remaining risk of malignancy was 0.07 (95 %CI 0.04-0.12; n = 8). Ability to visualize was slightly higher for EUS (0.99; 95 %CI 0.90-1.00) than EUS-B (0.84; 95 %CI 0.70-0.92; p = 0.025), but the other performance characteristics were similar. No major complications were reported. CONCLUSION: Both EUS and EUS-B have good performance and are safe for left adrenal gland analysis in patients with lung cancer, but the number of high-quality studies is limited and further well-constructed prospective studies are needed.

Tissue amount and diagnostic yield of a novel franseen EUS-FNB and a standard EUS-FNA needle-A randomized controlled study in solid pancreatic lesions.

Background and Objectives: Several types of needles are available for EUS-guided tissue sampling of pancreatic lesions. Whereas fine-needle aspiration (FNA) needles typically provide cytological samples, fine-needle biopsy (FNB) needles are designed to obtain microcores with preserved tissue architecture. The aim of this study was to compare tissue amount and diagnostic yield between a modified Franseen-type FNB needle (TopGain; Medi-Globe GmbH, Grassau, Germany) and a standard FNA needle. Methods: We performed a prospective, multicenter randomized controlled study between June 2020 and September 2021, including patients with a solid pancreatic lesion referred for EUS-guided tissue sampling at 3 centers in Denmark. The patients were randomized 1:1 to either FNA needle or the novel FNB needle. Primary outcomes included the number of obtained tissue microcores and total and diagnostic tissue area. Results: Sixty-four patients were included. The median number of tissue microcores procured per pass was significantly higher in the FNB group compared with FNA (3 vs. 2, P < 0.001). Similarly, the mean total tissue area (2.74 vs. 0.44 mm2, P < 0.001) and mean diagnostic tissue area (1.74 vs. 0.28 mm2, P < 0.001) were more than 6-fold larger in the FNB samples compared with FNA. The median number of passes needed for a diagnostic sample was 1 for the FNB needle and 2 for FNA needle (P = 0.12). The novel FNB needle provided a higher percentage of samples of excellent quality (P = 0.002). Conclusions: The novel Franseen-type FNB needle seems to be significantly superior to a conventional FNA needle. The results of this study underline excellent performance of crown-cut needles.

Validation of a Novel EUS-FNB-Derived Organoid Co-Culture System for Drug Screening in Patients with Pancreatic Cancer.

Cancer-associated fibroblasts (CAFs) have been shown to impact the chemosensitivity of patient-derived tumor organoids (PDTOs). However, the published literature comparing PDTO response to clinical outcome does not include CAFs in the models. Here, a co-culture model was created using PDTOs and CAFs derived from endoscopic ultrasound-guided fine-needle biopsies (EUS-FNBs) for potential use in drug screening applications. Co-cultures were established, and growth was compared to monocultures using image metrics and a commercially available assay. We were able to establish and expand validated malignant PDTOs from 19.2% of adenocarcinomas from EUS-FNBs. CAFs could be established from 25% of the samples. The viability of PDTOs in the mixed cell co-culture could be isolated using image metrics. The addition of CAFs promoted PDTO growth in half of the established co-cultures. These results show that co-cultures can be established from tiny amounts of tissue provided by EUS-FNB. An increased growth of PDTOs was shown in co-cultures, suggesting that the present setup successfully models CAF-PDTO interaction. Furthermore, we demonstrated that standard validation techniques may be insufficient to detect contamination with normal cells in PDTO cultures established from primary tumor core biopsies.

Endoscopic Ultrasound-guided Radiofrequency Ablation Versus Surgical Resection for Treatment of Pancreatic Insulinoma.

BACKGROUND & AIMS: Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) is emerging as a safe and effective treatment for pancreatic neuroendocrine tumors. We aimed to compare EUS-RFA and surgical resection for the treatment of pancreatic insulinoma (PI). METHODS: Patients with sporadic PI who underwent EUS-RFA at 23 centers or surgical resection at 8 high-volume pancreatic surgery institutions between 2014 and 2022 were retrospectively identified and outcomes compared using a propensity-matching analysis. Primary outcome was safety. Secondary outcomes were clinical efficacy, hospital stay, and recurrence rate after EUS-RFA. RESULTS: Using propensity score matching, 89 patients were allocated in each group (1:1), and were evenly distributed in terms of age, sex, Charlson comorbidity index, American Society of Anesthesiologists score, body mass index, distance between lesion and main pancreatic duct, lesion site, size, and grade. Adverse event (AE) rate was 18.0% and 61.8% after EUS-RFA and surgery, respectively (P < .001). No severe AEs were observed in the EUS-RFA group compared with 15.7% after surgery (P < .0001). Clinical efficacy was 100% after surgery and 95.5% after EUS-RFA (P = .160). However, the mean duration of follow-up time was shorter in the EUS-RFA group (median, 23 months; interquartile range, 14-31 months vs 37 months; interquartile range, 17.5-67 months in the surgical group; P < .0001). Hospital stay was significantly longer in the surgical group (11.1 ± 9.7 vs 3.0 ± 2.5 days in the EUS-RFA group; P < .0001). Fifteen lesions (16.9%) recurred after EUS-RFA and underwent a successful repeat EUS-RFA (11 patients) or surgical resection (4 patients). CONCLUSION: EUS-RFA is safer than surgery and highly effective for the treatment of PI. If confirmed in a randomized study, EUS-RFA treatment can become first-line therapy for sporadic PI.

Endoluminal radiofrequency ablation of malignant biliary obstruction.

This case report describes the first Danish case of endoluminal radiofrequency ablation (RFA) of malignant biliary obstruction due to a Klatskin tumour in a 59-year-old male undergoing neoadjuvant therapy. The treatment was interrupted several times due to recurrent occlusions of the bile duct stents. The patient was offered endoluminal RFA of the central bile ducts in order to reduce his tumour burden and possibly achieve longer stent patency, so the palliative therapy could be resumed. The procedure was performed successfully without any adverse events achieving access to previously occluded left hepatic duct.

Targeted next-generation sequencing of EUS-guided through-the-needle-biopsy sampling from pancreatic cystic lesions.

BACKGROUND AND AIMS: Recent advances have introduced molecular subtyping of pancreatic cystic lesions (PCLs) as a possible amendment to the diagnostic algorithm. The study evaluated the feasibility and diagnostic accuracy of molecular analysis and subtyping of PCLs using the recently introduced EUS-guided through-the-needle-biopsy (TTNB) sampling. METHODS: We prospectively included 101 patients in the study who presented with PCLs >15 mm in the largest cross-section. EUS-guided TTNB samples were obtained by a micro-biopsy forceps introduced through a 19-gauge needle. The TTNB samples were analyzed by next-generation sequencing (NGS) for point mutations in tumor suppressors and oncogenes using a 51-gene customized hotspot panel. Sensitivity and specificity were calculated with the histologic diagnosis as reference. RESULTS: After initial microscopic evaluation of the samples, 91 patients had residual TTNB samples available for NGS. Of these, 49 harbored mutations, most frequently in KRAS and GNAS, reflecting an excess frequency of intraductal papillary mucinous neoplasms (IPMNs) in the study population. A sensitivity and specificity of 83.7% (95% confidence interval [CI], 70.3-92.7) and 81.8% (95% CI, 48.2-97.7), respectively, were demonstrated for the diagnosis of a mucinous cyst and 87.2% (95% CI, 74.2-95.2) and 84.6% (95% CI, 54.5-98.1) for the diagnosis of an IPMN. CONCLUSIONS: Thus, molecular analysis of TTNB samples by NGS has high sensitivity and specificity for diagnosing mucinous cysts and IPMNs. Although the procedure comes with a risk of adverse events of 9.9%, TTNB samples are a robust alternative to cyst fluid for a combined histologic and molecular diagnosis of PCLs. (Clinical trial registration number: NCT03578445.).

Historical perspective on needle development: From the past to the future.

With the introduction of EUS, endoscopy was no longer limited to luminal indications. However, the method was unable to distinguish malignant from benign lesions. Consequently, needles designed for tissue acquisition under EUS-guidance was designed. Initially, the needles were designed for fine needle aspiration (FNA); nevertheless, with increased requirement for the precured tissue in terms of quality and quantity, newly design needles aimed at obtaining tissue cores for histological assessment were developed. Recent studies demonstrate superiority of these fine needle biopsy needles (FNB) compared to FNA needles.

Radiofrequency ablation of pancreatic insulinomas.

Insulinomas are rare neoplasms which may cause significant symptoms and substantially reduce quality of life. In operable patients, the current treatment is primarily surgery with either enucleation or resection of all or parts of the gland. This treatment is associated with high morbidity and long convalescence. Endoscopic ultrasound-guided radiofrequency ablation is a new and minimally invasive treatment for patients with insulinomas. The purpose of this review is to draw attention to the method and to communicate our preliminary experience with this procedure in Denmark.

Assessing Putative Markers of Colorectal Cancer Stem Cells: From Colonoscopy to Gene Expression Profiling.

Cancer stem cells (CSCs) are proposed to be involved in colorectal cancer (CRC) initiation, growth, and metastasis. The aim of our pilot study was to assess possible correlations between the clinicopathological characteristics of CRC patients and CSCs gene expression patterns, in order to provide insight into new methods for patient stratification and targeted therapeutic strategies. Our study involved 60 CRC patients, and the following three specific CSC genes were targeted: PROM1/CD133, ALCAM/CD166 and HCAM /CD44. Data are presented as relative mRNA expression of target genes to GAPDH. The expression of total CD133 and CD166 was assessed in paired samples of CRC tumors and adjacent tissue, while CD44 was assessed in similar samples. The qRT-PCR analysis detected all three targeted genes to different extents, in both normal and tumor tissue. In nine cases (15.69%), total CD133 had a higher expression in tumor tissue, whilst in 28 cases (47.06%) the expression was higher in non-malignant peritumor tissue. The total CD166 expression was increased in tumor tissue compared with paired non-invaded peritumor samples in eight cases (13.73%), whilst in eight cases (13.73%) the expression was higher in non-malignant peritumor tissue. Total CD44 expression was higher in tumor tissue compared with paired non-invaded peritumor samples in 47 cases (78.95%). In the remaining cases the difference between paired samples was biologically insignificant. In conclusion, our study suggests that qRT-PCR is feasible in assessing the gene expression profiles of CSCs from CRC, and a promising pathway to be followed for determining how often a person needs screening by colonoscopy and at which age to start. This could improve CRC diagnosis and early patient stratification, and open the way for new oncologic treatment development.

COLAR: open-label clinical study of IL-6 blockade with tocilizumab for the treatment of immune checkpoint inhibitor-induced colitis and arthritis.

BACKGROUND: Immune-related adverse events due to immune checkpoint inhibitors (ICIs) are not always effectively treated using glucocorticoids and it may negatively affect the antitumor efficacy of ICIs. Interventional studies of alternatives to glucocorticoids are lacking. We examined whether interleukin-6 blockade by tocilizumab reduced ICI-induced colitis and arthritis. PATIENTS AND METHODS: Patients with solid cancer experiencing Common Terminology Criteria for Adverse Events (CTCAE v5.0) grade >1 ICI-induced colitis/diarrhea (n=9), arthritis (n=9), or both (n=2) were recruited and treated with tocilizumab (8 mg/kg) every 4 weeks until worsening or unacceptable toxicity. Patients were not allowed to receive systemic glucocorticoids and other immunosuppressive drugs within the 14-day screening period. The primary endpoint was clinical improvement of colitis and arthritis, defined as ≥1 grade CTCAE reduction within 8 weeks. Secondary endpoints were improvements and glucocorticoid-free remission at week 24; safety; radiologic, endoscopic, and histological changes; and changes in plasma concentrations of C reactive protein, cytokines (IL-6, IL-8, and IL-17), and YKL-40. RESULTS: Nineteen patients were available for efficacy analysis; one patient was excluded due to pancreatic insufficiency-induced diarrhea. Patients received treatment with pembrolizumab (n=10) or nivolumab (n=4) as monotherapy or ipilimumab and nivolumab (n=5) combined. Seven patients had been initially treated with glucocorticoids, and two of them also received infliximab. Ten patients continued ICI therapy during tocilizumab treatment. The primary endpoint was achieved in 15 of 19 (79%) patients. Additional one patient had ≥1 grade reduction at week 10, and another patient had stabilized symptoms. At week 24, ongoing improvement without glucocorticoids (n=12), including complete remission (n=10), was noted. Five patients had grades 3-4 treatment-related adverse events, which were manageable and reversible. CONCLUSIONS: Tocilizumab showed promising clinical efficacy and a manageable safety profile in the treatment of ICI-induced colitis and arthritis. Our findings support the feasibility of randomized trials of immune-related adverse events. TRIAL REGISTRATION NUMBER: NCT03601611.

National clinical practice guidelines for the treatment of symptomatic gallstone disease: 2021 recommendations from the Danish Surgical Society.

BACKGROUND AND OBJECTIVE: Gallstones are highly prevalent, and more than 9000 cholecystectomies are performed annually in Denmark. The aim of this guideline was to improve the clinical course of patients with gallstone disease including a subgroup of high-risk patients. Outcomes included reduction of complications, readmissions, and need for additional interventions in patients with uncomplicated gallstone disease, acute cholecystitis, and common bile duct stones (CBDS). METHODS: An interdisciplinary group of clinicians developed the guideline according to the GRADE methodology. Randomized controlled trials (RCTs) were primarily included. Non-RCTs were included if RCTs could not answer the clinical questions. Recommendations were strong or weak depending on effect estimates, quality of evidence, and patient preferences. RESULTS: For patients with acute cholecystitis, acute laparoscopic cholecystectomy is recommended (16 RCTs, strong recommendation). Gallbladder drainage may be used as an interval procedure before a delayed laparoscopic cholecystectomy in patients with temporary contraindications to surgery and severe acute cholecystitis (1 RCT and 1 non-RCT, weak recommendation). High-risk patients are suggested to undergo acute laparoscopic cholecystectomy instead of drainage (1 RCT and 1 non-RCT, weak recommendation). For patients with CBDS, a one-step procedure with simultaneous laparoscopic cholecystectomy and CBDS removal by laparoscopy or endoscopy is recommended (22 RCTs, strong recommendation). In high-risk patients with CBDS, laparoscopic cholecystectomy is suggested to be included in the treatment (6 RCTs, weak recommendation). For diagnosis of CBDS, the use of magnetic resonance imaging or endoscopic ultrasound prior to surgical treatment is recommended (8 RCTs, strong recommendation). For patients with uncomplicated symptomatic gallstone disease, observation is suggested as an alternative to laparoscopic cholecystectomy (2 RCTs, weak recommendation). CONCLUSIONS: Seven recommendations, four weak and three strong, for treating patients with symptomatic gallstone disease were developed. Studies for treatment of high-risk patients are few and more are needed. ENDORSEMENT: The Danish Surgical Society.

History of Ultrasound in Medicine from its birth to date (2022), on occasion of the 50 Years Anniversary of EFSUMB. A publication of the European Federation of Societies for Ultrasound In Medicine and Biology (EFSUMB), designed to record the historical development of medical ultrasound.

The history of the European Federation of Societies in Ultrasound in Medicine and Biology (EFSUMB) is closely related to the general history of ultrasound. In the presented paper the physical background and history of technologies including A-mode, Time motion or M-mode, 2D Imaging (B-mode) are summarized. In addition, ultrasound tissue characterization, Doppler ultrasound, 3D and 4D ultrasound, intracavitary and endoscopic ultrasound, interventional ultrasound, ultrasonic therapy, contrast enhanced ultrasound (CEUS) and key developments in echocardiography are discussed.

Physico-chemical characterization of aspirated and simulated human gastric fluids to study their influence on the intrinsic dissolution rate of cinnarizine.

To elucidate the critical parameters affecting drug dissolution in the human stomach, the intrinsic dissolution rate (IDR) of cinnarizine was determined in aspirated and simulated human gastric fluids (HGF). Fasted aspirated HGF (aspHGF) was collected from 23 healthy volunteers during a gastroscopic examination. Hydrochloric acid (HCl) pH 1.2, fasted state simulated gastric fluid (FaSSGF), and simulated human gastric fluid (simHGF) developed to have rheological, and physico-chemical properties similar to aspHGF, were used as simulated HGFs. The IDR of cinnarizine was significantly higher in HCl pH 1.2 (952 ± 27 µg/(cm2·min)) than in FaSSGF pH 1.6 (444 ± 7 µg/(cm2·min)), and simHGF pH 2.5 (49 ± 5 µg/(cm2·min)) due to the pH dependent drug solubility and viscosity differences of the three simulated HGFs. The shear thinning behavior of aspHGF had a significant impact on the IDR of cinnarizine, indicating that the use of FaSSGF, with viscosity similar to water, to evaluate gastric drug dissolution, might overestimate the IDR by a factor of 100-10.000, compared to the non-Newtonian, more viscous, fluids in the human stomach. The developed simHGF simulated the viscosity of the gastric fluids, as well as the IDR of the model drug, making it a very promising medium to study gastric drug dissolution in vitro.