Clinical efficacy of first and second series of peptide receptor radionuclide therapy in patients with neuroendocrine neoplasm: a cohort study.

OBJECTIVES: Peptide receptor radionuclide therapy (PRRT) is an established treatment for metastatic neuroendocrine neoplasms (NEN). However, only limited data exists for the effect of multiple series of PRRT. The aim of this study was to investigate PFS and OS inNEN patients treated with multiple series of PRRT conforming to the ENETS treatment protocol. METHODS: We included all patients with gastrointestinal (GI), pancreatic and bronchopulmonary (BP) NEN treated with PRRT from 2008 to 2018. We used Kaplan-Meier estimation to evaluate PFS and OS with subgroup analysis of primary tumor, Ki67-index, type of radioisotope and number of PRRT series. RESULTS: 133 patients (female/male 61/72) were included, median age 70 (interquartile range 64-76) years. GI-NEN comprised 62%, pancreatic 23% and BP 11%. Median Ki67-index was 5%. After first PRRTG1- and G2-tumors had PFS of 25 and 22 months, compared to 11 months in G3-NENs (p < .05) and PFS was longer in G1/G2 GI-NENs than BP-NEN (30vs. 12 months, p < .05). After retreatment with a second series of PRRT, the overall PFS (G1-G3) was 19 months, with G1- and G2-tumors having the highest PFS of 19 and 22 months, respectively. Overall, the GI and BP tumors had an OS of 54 and 51 months. CONCLUSIONS: PRRT is an effective therapy with long-term PFS and OS, especially in G1 and G2 NENs, and with better prognosis in GI-NEN compared with BP-NENs. OS and PFS was shorter after the second series of PRRT compared with the first, however results were still encouraging.

Distension-evoked motility analysis in human esophagus.

BACKGROUND: The major function of the esophagus is to transport food from the mouth to the stomach by peristaltic muscle action. However, only few techniques exist for detailed evaluation of motor activity of the esophagus in vivo. The aim of this study is to use distension combined with manometry and impedance planimetry [pressure-cross-sectional area (P-CSA) recordings] to assess esophageal peristaltic motor function in terms of the mechanical energy output, and to examine the change in the motor activity of the esophagus in response to butylscopolamine, an anticholinergic drug known to impair the smooth muscle contraction in the gastrointestinal tract. METHODS: The probe with CSA measurements was positioned 7 cm above the lower esophageal sphincter in 16 healthy volunteers before and during butylscopolamine administration. Distension-evoked esophageal peristalsis was analyzed using P-CSA data during distension up to pressures of 5 kPa. The P-CSA, work output (area of the tension-CSA curves), and propulsive tension were analyzed. KEY RESULTS: The wave-like peristalsis resulted in P-CSA loops consisting of relaxation and contraction phases. The work increased with the distension pressure (from 1311 ± 198 to 16 330 ± 1845 µJ before butylscopolamine vs from 2615 ± 756 to 11 404 ± 1335 µJ during butylscopolamine administration), and propulsive tension increased from 18.7 ± 1.9 to 88.5 ± 5.5 N m(-1) before the drug and from 23.1 ± 3.9 to 79.5 ± 3.3 N m(-1) during butylscopolamine administration). Significantly, lower values were found during butylscopolamine administration compared with the distension before using the drug (P < 0.01). CONCLUSIONS & INFERENCES: Esophageal muscle properties during peristalsis can be assessed in vivo in terms of mechanical energy output parameters. Butylscopolamine impaired muscle contraction which could be detected as altered contraction parameters. The analysis can be further used as an adjunct tool of the combined manometry and impedance planimetry recordings to derive advanced esophageal motor function parameters for studying the physiological and pathophysiological mechanical consequences of esophageal contractions.

Clinical trial: vitamin D3 treatment in Crohn's disease - a randomized double-blind placebo-controlled study.

BACKGROUND: Vitamin D has immune-regulatory functions in experimental colitis, and low vitamin D levels are present in Crohn's disease. AIM: To assess the effectiveness of vitamin D3 treatment in Crohn's disease with regard to improved disease course. METHODS: We performed a randomized double-blind placebo-controlled trial to assess the benefits of oral vitamin D3 treatment in Crohn's disease. We included 108 patients with Crohn's disease in remission, of which fourteen were excluded later. Patients were randomized to receive either 1200 IU vitamin D3 (n = 46) or placebo (n = 48) once daily during 12 months. The primary endpoint was clinical relapse. RESULTS: Oral vitamin D3 treatment with 1200 IU daily increased serum 25OHD from mean 69 nmol/L [standard deviation (s.d.) 31 nmol/L] to mean 96 nmol/L (s.d. 27 nmol/L) after 3 months (P < 0.001). The relapse rate was lower among patients treated with vitamin D3 (6/46 or 13%) than among patients treated with placebo (14/48 or 29%), (P = 0.06). CONCLUSIONS: Oral supplementation with 1200 IE vitamin D3 significantly increased serum vitamin D levels and insignificantly reduced the risk of relapse from 29% to 13%, (P = 0.06). Given that vitamin D3 treatment might be effective in Crohn's disease, we suggest larger studies to elucidate this matter further. ClinicalTrial.gov(NCT00122184).

Oesophageal pressure-cross-sectional area distributions and secondary peristalsis in relation to subclassification of systemic sclerosis.

The aim of the present study was to correlate the severity of oesophageal motor dysfunction with the severity of cutaneous disease in systemic sclerosis (SS). Patients were divided into three groups based on the degree of skin involvement: type I, acrosclerosis distal to the wrist; type II, scleroderma extending above the wrist in proximal direction; type III, diffuse cutaneous systemic sclerosis. Impedance planimetry employing distensions with pressures up to 5 kPa with the concomitant measurement of oesophageal cross-sectional area (CSA) was used in combination with standard oesophageal manometry. Measurements were made at 7 and 15 cm above the lower oesophageal sphincter (LOS). Thirty patients (16 type I, six type II and eight type III patients) and 23 normal controls were included. LOS pressure was lower in SS patients than in normal patients, with the lowest values in type III. The CSAs were higher in SS patients than in controls at both sites (P < 0.001). The CSAs at the distal site were highest in type III, as compared to type I and II (P < 0.03). The CSA at the highest induced pressure (5.0 kPa) was 613 +/- 45, 719 +/- 79, and 808 +/- 115 mm2 in types I, II and III, respectively. No differences in CSA were found at the proximal site between the three types of SS. The distensibility did not differ between SS and normal patients at the distal site. The distensibility was lowest in SS patients (P < 0.001) at the proximal distension site. The distensibility did not vary with the type of SS at either site. Significant differences in contraction frequency of the secondary peristalsis as function of wall tension were demonstrated between the SS patients and controls at the distal site (P < 0.05). No differences were found at the proximal site. The contraction frequency and amplitude at the distal and proximal sites did not differ among the three types. In conclusion for most parameters studied, SS patients differed from normal patients. Among SS types, the most pronounced changes were found in type III.

Mechanical properties and collagen content differ between isolated guinea pig duodenum, jejunum, and distal ileum.

We compared the stress-strain distributions obtained from isolated segments of the guinea pig duodenum, jejunum, and distal ileum, and the relation between the elastic properties and the collagen content. The segments were immersed in Krebs-Ringer solution containing 10(-2) M MgCl2 to abolish contractile activity. Stepwise inflation of an intraluminal balloon in which the cross-sectional area (CSA) was measured provided the luminal pressure-loading stimulus. The wall thickness was measured by means of 20-MHz A-mode ultrasound. The stress-strain and the incremental elastic modulus-strain distributions were derived from the steady-state values of wall thickness, internal radius, and applied pressure. The CSA-pressure relations and the wall thickness-pressure relations were nonlinear and both differed between the segments (P < 0.01). The stress-strain distributions showed an exponential behavior that fitted well to the equation Y = a x Exp(b x X) (r2 = 0.97 +/- 0.01). The intercept with they axis (a) and the slope of the curves (b) differed between the segments (P < 0.01 and P < 0.05). The collagen contents were 3.99 +/- 0.18 microg/mg, 2.51 +/- 0.13 microg/mg, and 2.10 +/- 0.11 microg/mg in the duodenum, jejunum, and distal ileum, respectively. This difference was significant among all three locations (P > 0.05). An association was found between the collagen content and the incremental elastic modulus (stiffness) at a stress level of 70 kPa (P < 0.05).

Impedance planimetric characterization of esophagus in systemic sclerosis patients with severe involvement of esophagus.

This study was designed to evaluate the distensibility and secondary peristalsis of the esophagus in patients suffering from systemic sclerosis with severe esophageal involvement. Balloon distension with impedance planimetric measurement of luminal cross-sectional area was done 7 and 15 cm above the lower esophageal sphincter in 13 patients and nine healthy controls. The controls were studied both with and without receiving the anticholinergic drug butylscopolamine. The cross-sectional area--pressure relations were nonlinear with the largest cross-sectional area in patients at both measuring sites when compared to controls (P < 0.001). The anticholinergic drug butylscopolamine increased the cross-sectional area in controls (P < 0.001). The cross-sectional area distensibility, defined as CSA0(-1) delta CSA delta P-1 did not differ between patients and controls. Balloon distensions elicited contractions proximal to the distension site. The amplitude and frequency of contractions at the distal distension site were significantly reduced in the patients when compared to the controls (P < 0.05). In conclusion, the distal esophagus is most severely affected in patients with systemic sclerosis with increased cross-sectional area and impaired peristalsis.

Dimensions and mechanical properties of porcine aortic segments determined by combined impedance planimetry and high-frequency ultrasound.

The aim of the study is to devise a method for direct measurements of pressure, cross-sectional area (CSA) and wall thickness of a vessel when pressurised. Segments of porcine descending thoracic aorta from 22 and 35 kg pigs (in groups 1 and 2, respectively) and of abdominal aorta from 35 kg pigs are studied in vitro. Impedance planimetry provides measurements of the luminal pressure and CSA of the aorta. The wall thickness is measured simultaneously by means of 20 MHz A-mode ultrasound. The pressure, CSA and wall thickness are registered at different pressure at steady state. At maximum pressure, the CSAs are 107 +/- 10, 215 +/- 19 and 257 +/- 17 mm2 in the abdominal, group 1 and 2 segments, respectively. There is a difference between the abdominal group and groups 1 and 2 (p < 0.05), but not between group 1 and 2 segments (p > 0.2). At maximum pressure, the wall thickness is 0.52 +/- 0.04, 0.79 +/- 0.07 and 1.07 +/- 0.02 mm, in the abdominal group 1 and 2 segments, respectively (p < 0.05). The circumferential stress-strain relationship accorded well with stress = a x exp(b x strain). The stress-strain curve of the abdominal aortas is shifted to the left, indicating an increase (p < 0.05).

Passive elastic wall properties in isolated guinea pig small intestine.

The aim was to study and compare the passive biomechanical wall properties in the isolated duodenum and distal ileum of the guinea pig in vitro. The organ bath contained a Krebs-Ringer solution with 10(-2) M MgCl2 to abolish smooth muscle contractile activity. Stepwise inflation of an intraluminal balloon, in which the cross-sectional area (CSA) was measured, provided the distension stimulus. The circumferential wall tension-strain distributions and wall stiffness-strain relations were computed from steady-state values of these measurements in order to evaluate the passive elastic properties. The CSA always reached equilibrium within the 2-min distension period. The CSAs obtained in the distal ileum were higher than those in the duodenum (P < 0.001). The basal CSA was 17.31 +/- 1.14 mm2 and 12.96 +/- 0.42 mm2 for the distal ileum and the duodenum, respectively (P < 0.01). At a maximum pressure of 6 kPa, the CSA of the ileum was 56.63 +/- 1.81 mm2 and 36.86 +/- 1.76 mm2 for the duodenum (P < 0.01). The circumferential wall tension-strain distributions showed an exponential behavior that accorded well with the equation Y = exp(a+bX) with determination coefficients of 0.96 +/- 0.01 and 0.99 +/- 0.00 in the duodenal segments in the distal ileal segments, respectively. The values of a (intercept with the y-axis) were 0.54 +/- 0.11 and -0.35 +/- 0.19 for the duodenal and ileal segments, respectively (P < 0.001). The slope of the curves (b values) were 4.34 +/- 0.35 in the duodenal and 5.23 +/- 0.37 in the ileal segments (0.1 > P > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Prediction of light-for-gestational age at delivery in twin pregnancies: an evaluation of fetal weight deviation and growth discordance measured by ultrasound.

The purpose of this retrospective study was to evaluate and discuss different ultrasound methods widely used, among other things, as predictors for light-for-gestational age (LGA) in twin pregnancies. The methods evaluated and compared as predictors for LGA at birth were: (1) Difference between twins in biparietal diameter; (2) difference in abdominal diameter; (3) the percentage difference in estimated fetal weight between twins; and (4) estimation of the weight deviation from the expected weight during pregnancy. The study comprised 66 twin pregnancies, examined by ultrasound scanning less than 15 days before delivery. Using Relative Operating Characteristic curves (ROC curves) estimated fetal weight deviation was the most sensitive and specific of the methods. It is stressed that fetal discordance is not the appropriate predictor of LGA at birth in twin pregnancies.