Assessment of sorafenib induced changes in tumor perfusion of uveal melanoma metastases with dynamic contrast-enhanced ultrasound (DCE-US).

PURPOSE: Dynamic contrast-enhanced ultrasound (DCE-US) was used to monitor early response to sorafenib therapy in patients with liver metastases from uveal melanoma. METHODS: In total, 21 patients with liver metastases were recruited within a prospective trial and underwent daily sorafenib therapy. DCE-US of a target lesion was performed before initiation of treatment, on day 15 and 56. Two independent blinded investigators performed software analysis for DCE-US parameters and inter-observer-correlation was calculated. Response to treatment was evaluated on day 56. DCE-US parameters were correlated with clinical response and RECIST1.1 criteria. RESULTS: Inter-observer-correlation (r) of DCE-US parameters [time-to-peak (TTP), mean-transit-time (MTT), peak intensity (PI), regional blood volume (RBV), regional blood flow (RBF)] at baseline, day 15, and day 56 was highly significant (r-range 0.73-0.97, all p < 0.001). Out of 17 evaluable patients, 12 patients survived day 56 (clinical responders, cRE), whereas, five patients died before day 56 and were classified as non-responders (cNR). TTP values significantly increased in the cRE group 15 days after initiation of treatment for investigator 1 (p = 0.034) and at day 56 for both investigators (p = 0.028/0.028). MTT had increased significantly in the cRE group on day 56 (p = 0.037/0.022). In the cNR group changes for TTP and MTT remained insignificant. Thus, increase of the DCE-US parameters TTP and MTT are associated with response to treatment and prognosis. CONCLUSION: An increase of TTP and MTT at frequent intervals could serve as a surrogate marker for early response evaluation to anti-angiogenic treatment of metastatic uveal melanoma.

ARFI cut-off values and significance of standard deviation for liver fibrosis staging in patients with chronic liver disease.

BACKGROUND: Acoustic radiation force impulse (ARFI) elastometry quantifies hepatic stiffness, and thus degree of fibrosis, non-invasively. Our aim was to analyse the diagnostic accuracy of ARFI cut-off values, and the significance of a defined limit of standard deviation (SD) as a potential quality parameter for liver fibrosis staging in patients with chronic liver diseases (CLD). MATERIAL AND METHODS: 153 patients with CLD (various aetiologies) undergoing liver biopsy, and an additional 25 patients with known liver cirrhosis, were investigated. ARFI measurements were performed in the right hepatic lobe, and correlated with the histopathological Ludwig fibrosis score (inclusion criteria: at least 6 portal tracts). The diagnostic accuracy of cut-off values was analysed with respect to an SD limit of 30% of the mean ARFI value. RESULTS: The mean ARFI elastometry showed 1.95 ± 0.87 m/s (range 0.79-4.40) in 178 patients (80 female, 98 male, mean age: 52 years). The cut-offs were 1.25 m/s for F ≥ 2, 1.72 m/s for F ≥ 3 and 1.75 m/s for F = 4, and the corresponding AUROC 80.7%, 86.2% and 88.7%, respectively. Exclusion of 31 patients (17.4%) with an SD higher than 30% of the mean ARFI improved the diagnostic accuracy: The AUROC for F ≥ 2, F ≥ 3 and F = 4 were 86.1%, 91.2% and 91.5%, respectively. CONCLUSION: The diagnostic accuracy of ARFI can be improved by applying a maximum SD of 30% of the mean ARFI as a quality parameter--which however leads to an exclusion of a relevant number of patients. ARFI results with a high SD should be interpreted with caution.

Near-infrared fiber optic spectroscopy as a novel diagnostic tool for the detection of pancreatic cancer.

We have investigated the application of near-infrared (NIR) fiber-optic spectroscopy for the diagnosis of pancreatic cancer. Cluster analysis of the Fourier transformed near-infrared (FTNIR) fiber-optic spectra of surgically resected pancreatic tumor tissues allowed discrimination of tumor from normal tissue with high sensitivity and specificity. The sensitivity of the method using spectral information of the CH stretching first overtone region (5951-5608 cm(-1)) was 83.3% with a specificity of 83.3%. Based on the CH stretching second overtone region (8605-7938 cm(-1)) we could achieve a sensitivity of 88.9% and specificity of 72.2%. These findings suggest that NIR spectroscopy offers the potential for minimally invasive in-vivo diagnosis of pancreatic cancer.

Pump-assisted enteral nutrition can prevent aspiration in bedridden percutaneous endoscopic gastrostomy patients.

BACKGROUND: Vomiting, aspiration, and pneumonia are serious side effects in enteral feeding via percutaneous endoscopic gastrostomy (PEG), which often leads to hospitalization. To this day, it has not been proven whether pump-assisted (PA) or gravity-controlled application is the safer method for long-term feeding via PEG in bedridden patients. METHODS: This study was conducted as a prospective, randomized crossover study. Fifty bedridden PEG patients were fed using the pump-assisted method (G1) and 50 patients were fed using the gravity-controlled feeding method (G2). After 6 weeks of observation (O1), the feeding methods in both groups were switched, followed by another 6 weeks of observation (O2). Daily recording was done using a standardized questionnaire. The glucose levels during O1 and O2 were determined on days 1, 21, and 42. RESULTS: The patients in both groups were compatible in age, sex, and medical illness. By comparing G1 and G2, a significantly lower regurgitation rate (p < .0002), vomiting of feeding substrate (p < .009), aspiration (p < .01), and pneumonia (p < .02) was observed. The diarrhea rate in G2 was higher than in G1 (p < .007). The glucose profiles in G1 showed a significantly better development (p < .0007) than the ones in G2. After switching the application method in G2, the PA group (now G2) showed a significantly improved rate of regurgitation, vomiting, aspiration, and diarrhea and improved glucose profiles. CONCLUSION: Feeding via PA shows improved safety, which is documented in a lower rate of diarrhea, regurgitation, vomiting, and aspiration. PA also noted a more effective glucose metabolization, which results in better glucose levels. As a result of this prospective study, pump-assisted feeding is recommended for bedridden patients requiring long-term feeding via PEG.

Pump-assisted versus gravity-controlled enteral nutrition in long-term percutaneous endoscopic gastrostomy patients: a prospective controlled trial.

BACKGROUND: Vomiting, aspiration, flatulence, and diarrhea are well-known negative side effects of enteral nutrition through percutaneous endoscopic gastrostomy (PEG). However, it is not yet clarified if pump-assisted (PA) or gravity-controlled (GC) application is the more comfortable and safe choice for long-term nutrition through PEG. METHODS: This was a prospective, randomized, crossover study. Fifty long-term PEG patients were fed by PA nutrition (G1) and 50 patients were fed by GC nutrition (G2). Six weeks of observation (O1) was followed by a switch of method of nutritional application in both groups and an additional 6 weeks of observation (O2). Daily determination of comfort and safety was done with a standardized questionnaire. Evaluation of blood glucose levels on days 1, 21, and 42 during O1 and O2. RESULTS: The patients in both groups had the same medical conditions and were of the same age and sex. Far less flatulence (p < .0006) and epigastric fullness (p < .0003) was discovered in G1 during O1. Also, significantly less regurgitation (p < .0002) and vomiting of feeding diet (p < .0001) in G1 versus G2 could be observed. The rate of diarrhea (p < .0003) in G2 was higher than in G1. The daily profile of blood glucose was significantly better (p < .0008) in G1 than in G2. After the nutritional application was changed in O2, the PA group (G2) again showed a significantly better rate of flatulence, epigastric fullness, regurgitation, vomiting, diarrhea, and daily profile of blood glucose. Ninety-six percent of the patients in G2 preferred further nutrition by PA after finishing this study. All patients in G1 continued their accustomed nutrition by PA. CONCLUSION: Nutrition through PA showed not only a higher comfort rate but also increased safety, which was expressed through a low rate of regurgitation and vomiting. PA presented better glucose metabolization manifested in improved blood glucose levels. As a result of this prospective study, PA is preferable to GC and preferred by patients with long-term PEG nutrition.