Explore the vast range of titles available.

The use of ultrasound and microbubbles to enhance therapeutic efficacy (sonoporation) has shown great promise in cancer therapy from in vitro to ongoing clinical studies. The fastest bench-to-bedside translation involves the use of ultrasound contrast agents (microbubbles) and clinical diagnostic scanners. Despite substantial research in this field, it is currently not known which of these microbubbles result in the greatest enhancement of therapy within the applied conditions. Three microbubble formulations—SonoVue®, Sonazoid™, and Optison™—were physiochemically and acoustically characterized. The microbubble response to the ultrasound pulses used in vivo was simulated via a Rayleigh–Plesset type equation. The three formulations were compared in vitro for permeabilization efficacy in three different pancreatic cancer cell lines, and in vivo, using an orthotopic pancreatic cancer (PDAC) murine model. The mice were treated using one of the three formulations exposed to ultrasound from a GE Logiq E9 and C1-5 ultrasound transducer. Characterisation of the microbubbles showed a rapid degradation in concentration, shape, and/or size for both SonoVue® and Optison™ within 30 min of reconstitution/opening. Sonazoid™ showed no degradation after 1 h. Attenuation measurements indicated that SonoVue® was the softest bubble followed by Sonazoid™ then Optison™. Sonazoid™ emitted nonlinear ultrasound at the lowest MIs followed by Optison™, then SonoVue®. Simulations indicated that SonoVue® would be the most effective bubble using the evaluated ultrasound conditions. This was verified in the pre-clinical PDAC model demonstrated by improved survival and largest tumor growth inhibition. In vitro results indicated that the best microbubble formulation depends on the ultrasound parameters and concentration used, with SonoVue® being best at lower intensities and Sonazoid™ at higher intensities.

Quantitative determination of fecal fat still is the gold standard for measuring malabsorption. We evaluated the importance of standardized food intake before and under the collection of feces. In a project, evaluating patients with suspected chronic pancreatitis (CP) and healthy volunteers (HC), stools were collected for 72 hours coupled to registration of nutritional intake over five consecutive days. Patient groups were created by a modified Layer score, which includes imaging findings, clinical parameters and pancreas function testing. We found 12 patients with CP, 11 patients without CP and 13 healthy individuals in our database. Median fecal fat in CP patients was 12 g/day, in non-CP patients 5 g/day and in healthy controls 5 g/day. Median fat absorption coefficient was 81% in those with chronic pancreatitis, 92% in those without CP and 92% in healthy controls. Corresponding median fat intake was 65 g/day, 68 g/day and 81 g/day in the respective groups. Spearman Rank Order Correlation between fecal fat (g/d) and fat absorption coefficient in all study subjects (n = 36) was good (-0.88 (p<0.001)). When we stratified groups according to fat intake, correlation between fecal fat and fat absorption was also good (-0.86 to -0.95). In the diagnoses of fat malabsorption, calculating the ratio of fat absorption did not give additional information compared to fecal fat.

Fatty infiltration of the pancreas is a dominating feature in cystic fibrosis (CF). We evaluate the association between pancreatic fat content assessed by Dixon magnetic resonance imaging (MRI), pancreatic echogenicity at ultrasonography (US) and exocrine function in CF patients and healthy controls (HC). Transabdominal US, pancreatic Dixon-MRI and diffusion-weighted imaging (DWI) were performed in 21 CF patients and 15 HCs. Exocrine function was assessed by endoscopic secretin test and fecal elastase. CF patients were grouped according to exocrine pancreatic function as subjects with normal (CFS: n = 11) or reduced (CFI: n = 10) function. Among CFI 90% (9/10) had visual hyperechogenicity. CFI also had increased echo-level values (p<0.05 vs others). All CFI (10/10) had markedly increased pancreatic fat content estimated by MRI compared to sufficient groups, p<0.001). Among CFS patients and HC, 27% (3/11) and 33% (5/15), respectively, had hyperechoic pancreas. However, all these had low pancreatic fat-content at MRI compared to CFI. In CFI, pancreatic fat content was correlated to ADC (r = -0.93, p<0.001). Pancreas insufficient CF patients exhibit severe pancreatic fatty-infiltration at MRI and hyperechoic pancreas at US. Pancreas hyperechogenicity in pancreatic sufficient subjects does not co-exist with fatty infiltration at MRI. MRI evaluates pancreatic fatty infiltration more accurately than US and fat infiltration estimated by MRI outperforms sonographic hyper-echogenicity as a marker for exocrine pancreatic failure in CF.

Increased intestinal hydration by activation of the epithelial enzyme linked receptor guanylate cyclase C (GC-C) is a pharmacological principle for treating constipation. Activating mutations in the GUCY2C gene encoding GC-C cause Familial GUCY2C diarrhea syndrome (FGDS) which has been diagnosed with severe dysmotility. To investigate gut motility and hormones before and after a meal in FGDS patients and compare with healthy controls (HC). Bristol stool chart and stool frequency was assessed. Before and after a meal occlusive and non-occlusive contractions were obtained using ultrasound. A wireless motility capsule (WMC) recorded gut transit time, pH, contractions and pressure. Plasma levels of selected gut hormones were measured at different time points. The FGDS patients had 4 (range 1-10) loose stools/day and prolonged total gut transit time compared to HC, 55.5 h vs 28.5 h, respectively,with significantly increased colon transit time. In FGDS patients, pH in duodenum, small bowel and colon was increased and the number of contractions and the intraluminal pressure were significantly decreased, measured by WMC. Ultrasound showed in small bowel increased number of non-occlusive contractions in the FGDS patients. Serotonin (5-HT) plasma levels in the HC peaked 30 min after the meal, while the FGDS patients had no response. Despite having diarrhea, the FGDS patients have prolonged transit time through the gut compared to HC, particularly in colon. The reduced number of intestinal contractions and lack of 5-HT release after a meal in FGDS patients surprisingly resemble colonic motility disturbances seen in patients with constipation.

Aim: To compare two- and three-dimensional (2D and 3D) ultrasound of the gallbladder in an adult cohort. Material and methods: In this observational, cross-sectional study, gallbladder volumes were measured using 2D and 3D ultrasound. Examinations were performed in the fasting state and at predefined time intervals after ingestion of a standardized nutritional drink. At each time point, measurements were performed twice using 2D and twice using 3D ultrasound. Volumes were calculated using the ellipsoid method for 2D ultrasound. For 3D, manual tracing was performed. Results: Sixty-two subjects were included, yielding 2,328 volume measurements. The mean age was 69 years (SD 6.6) and the median BMI was 24.3 kg/m2 (IQR 22.9–28.6). The mean difference between 2D measurements was significantly larger than the difference between 3D measurements (3.3 cm3 vs. 1.9 cm3, p <0.001). The intraclass correlation coefficient (ICC) between two sequential 2D measurements was 0.94 (p <0.001, 95% CI 0.94–0.95), and between two sequential 3D measurements 0.96 (p <0.001, 95% CI 0.96–0.97). The ICC between 2D and 3D measurements was 0.85 (95% CI 0.74–0.91, p <0.001). Conclusions: Our findings indicate that 3D ultrasound exhibits lower intra-observer variation when determining gallbladder volumes compared to 2D ultrasound. The discrepancy between the two methods increases with gallbladder volume.

Gastric emptying measurements are mandatory in gastroparesis diagnostics, but the association between delayed emptying and symptoms is questionable. It is imperative to find biomarkers better correlated to symptom generation. Hence, we examined the association between symptom severity and gastrointestinal motility measured by wireless motility capsule. In this prospective single-centre study, patients with gastroparesis symptoms were simultaneously investigated with gastric emptying scintigraphy and wireless motility capsule, measuring regional transit times and contractility parameters. Symptom severity was assessed with the Patient Assessment of Upper Gastrointestinal Symptom Severity Index (PAGI-SYM), including the Gastroparesis Cardinal Symptom Index (GCSI). We included 107 patients (70% women). In the whole patient group, nausea correlated with the gastric ( = -0.31, = 0.007), small bowel ( = -0.41, < 0.001) and colonic ( = -0.33, = 0.012) motility indices. In patients with idiopathic etiology, nausea correlated with small bowel motility index ( = -0.81, < 0.001) and mean stomach pressure ( = -0.64, = 0.013). We also found negative correlations between total GCSI score and maximum pressure of the small bowel ( = -0.77, < 0.001) and colon ( = -0.74, = 0.002). In diabetes patients, total PAGI-SYM score correlated with colonic motility index ( = -0.34, = 0.012), and mean pressure of the colon correlated with upper abdominal pain ( = -0.37, = 0.007). We found no association between symptoms, gastric emptying nor any other transit times. In patients with gastroparesis symptoms, we found that symptom severity was associated with intestinal hypomotility. Based on these results, gastroparesis diagnostics should also include an evaluation of the small bowel and colon.

Purpose: Determining gastric emptying is mandatory in the diagnosis of diabetic gastroparesis. Several methods of investigation exist, but none has proven reliable, inexpensive and accessible. In this study, we aimed to compare gastric emptying of radiopaque markers (ROM) and 13carbon-labelled gastric emptying breath tests for solids (GEBT). We also aimed to determine any association between gastric emptying and patient-reported symptoms, glycemic control and the patients' age, diabetes duration and occurrence of other late complications. Patients and methods: Forty-five patients (30 women, 15 men) with diabetes mellitus types 1 or 2 (40, 5) and symptoms of gastroparesis were examined with ROM and GEBT. All were interviewed, filled out symptom questionnaires and had HbA1c levels measured. Results: Forty percent of patients had delayed gastric emptying of ROM, while 55% had delayed gastric emptying of GEBT. Correlation between ROM and GEBT was not significant. Compared to GEBT, sensitivity for a positive ROM test was 0.52, while specificity was 0.74. In women, we found a higher specificity of 0.92, sensitivity 0.47. Difference in HbA1c between patients with positive and negative results was of borderline significance for both tests. GEBT (r=0.41, P=0.008) correlated with HbA1c. Patients with any late complications of diabetes had higher gastric retention of ROM (P=0.028), while patients with polyneuropathy (P=0.014) and diabetic wounds (P=0.004) had slower emptying with GEBT. None of the methods identified significant associations between gastric emptying and symptom scores, age or diabetes duration. Conclusions: As a measure of gastric emptying, the ROM test has benefits of being affordable and available. Compared to GEBT, the method has low diagnostic reliability. Before continued use, we recommend additional studies validating the test in diabetes patients.Purpose: Determining gastric emptying is mandatory in the diagnosis of diabetic gastroparesis. Several methods of investigation exist, but none has proven reliable, inexpensive and accessible. In this study, we aimed to compare gastric emptying of radiopaque markers (ROM) and 13carbon-labelled gastric emptying breath tests for solids (GEBT). We also aimed to determine any association between gastric emptying and patient-reported symptoms, glycemic control and the patients' age, diabetes duration and occurrence of other late complications. Patients and methods: Forty-five patients (30 women, 15 men) with diabetes mellitus types 1 or 2 (40, 5) and symptoms of gastroparesis were examined with ROM and GEBT. All were interviewed, filled out symptom questionnaires and had HbA1c levels measured. Results: Forty percent of patients had delayed gastric emptying of ROM, while 55% had delayed gastric emptying of GEBT. Correlation between ROM and GEBT was not significant. Compared to GEBT, sensitivity for a positive ROM test was 0.52, while specificity was 0.74. In women, we found a higher specificity of 0.92, sensitivity 0.47. Difference in HbA1c between patients with positive and negative results was of borderline significance for both tests. GEBT (r=0.41, P=0.008) correlated with HbA1c. Patients with any late complications of diabetes had higher gastric retention of ROM (P=0.028), while patients with polyneuropathy (P=0.014) and diabetic wounds (P=0.004) had slower emptying with GEBT. None of the methods identified significant associations between gastric emptying and symptom scores, age or diabetes duration. Conclusions: As a measure of gastric emptying, the ROM test has benefits of being affordable and available. Compared to GEBT, the method has low diagnostic reliability. Before continued use, we recommend additional studies validating the test in diabetes patients.

Pancreatic destruction affects the majority of patients with cystic fibrosis. We aimed to relate ultrasound findings to exocrine pancreatic function and cystic fibrosis genotype. Patients with cystic fibrosis and a matched group of healthy controls were included. We performed transabdominal ultrasound, and recorded echo intensities of the pancreas and parenchymal characteristics according to endoscopic ultrasound based Rosemont criteria. We included 39 patients and 29 healthy controls. The cystic fibrosis patients were grouped according to exocrine pancreatic function; Cystic fibrosis, insufficient (n = 20) and sufficient (n = 19). Echo intensity measures and visual score demonstrated hyper-echogenicity in the pancreas insufficient group compared to the pancreas sufficient groups (p<0.001). Ductal and parenchymal changes were not prevalent in any of the groups. The hyper-echoic pancreas was the most frequent ultrasonographic finding in exocrine pancreas insufficient cystic fibrosis patients. Pancreatic echo levels correlated to pancreatic phenotype.

Background Perfusion assessment of the pancreas is challenging and poorly evaluated. Pancreatic affection is a prevalent feature of cystic fibrosis (CF). Little is known about pancreatic perfusion in CF. We aimed to assess pancreatic perfusion by contrast-enhanced ultrasound (CEUS) analysed in the bolus-and-burst model and software. Methods We performed contrast enhanced ultrasound of the pancreas in 25 CF patients and 20 healthy controls. Perfusion data was analysed using a dedicated perfusion model providing the mean capillary transit-time (MTT), blood flow (BF) and blood-volume (BV). CF patients were divided according to exocrine function. Results The pancreas insufficient CF patients had longer MTT ( p  ≤ 0.002), lower BF ( p  < 0.001) and lower BV ( p  < 0.05) compared to the healthy controls and sufficient CF patients. Interrater analysis showed substantial agreement for the analysis of mean transit time. Conclusion The bolus-and-burst method used on pancreatic CEUS-examinations demonstrates reduced perfusion in CF patients with pancreas affection. The perfusion model and software requires further optimization and standardization to be clinical applicable for the assessment of pancreatic perfusion.

OBJECTIVE: To evaluate the brain's responses to painful visceral and somatic stimuli in diabetic patients with gastrointestinal symptoms. RESEARCH DESIGN AND METHODS: The sensitivity to electrical esophageal and median nerve stimulations was assessed in 15 healthy volunteers and 14 type 1 diabetic patients with autonomic neuropathy and gastrointestinal symptoms using a euglycemic-hyperinsulinemic clamp. Evoked brain potentials were recorded. RESULTS: Patients had reduced sensitivity to esophageal (48%; P < 0.001) and median nerve (80%; P < 0.001) stimulations. They also had increased (8.8%; P = 0.007) and nonreproducible (P = 0.006) latencies of evoked potentials in response to esophageal stimulations, with 26% reduction in amplitude (P = 0.011). No potential differences were seen to median nerve stimulations. In diabetic patients, the topographic location of the first peak in potentials was more central (P < 0.001) and gastrointestinal symptoms correlated with characteristics of brain potentials (P = 0.049). CONCLUSIONS: This study supports that diabetes induces changes in peripheral visceral nerves as well as in the central nervous system.