Purpose
To assess the effect of a shrinking rectal balloon implant (RBI) on the anorectal dose and complication risk during the course of moderately hypofractionated prostate radiotherapy.
Methods
In ...15 patients with localized prostate cancer, an RBI was implanted. A weekly kilovolt cone-beam computed tomography (CBCT) scan was acquired to measure the dynamics of RBI volume and prostate–rectum separation. The absolute anorectal volume encompassed by the 2 Gy equieffective 75 Gy isodose (V
75Gy
) was recalculated as well as the mean anorectal dose. The increase in estimated risk of grade 2–3 late rectal bleeding (LRB) between the start and end of treatment was predicted using nomograms. The observed acute and late toxicities were evaluated.
Results
A significant shrinkage of RBI volumes was observed, with an average volume of 70.4% of baseline at the end of the treatment. Although the prostate–rectum separation significantly decreased over time, it remained at least 1 cm. No significant increase in V
75Gy
of the anorectum was observed, except in one patient whose RBI had completely deflated in the third week of treatment. No correlation between mean anorectal dose and balloon deflation was found. The increase in predicted LRB risk was not significant, except in the one patient whose RBI completely deflated. The observed toxicities confirmed these findings.
Conclusions
Despite significant decrease in RBI volume the high-dose rectal volume and the predicted LRB risk were unaffected due to a persistent spacing between the prostate and the anterior rectal wall.
Background
Achalasia is a rare motility disorder characterized by myenteric neuron and interstitial cells of Cajal (ICC) abnormalities leading to deranged/absent peristalsis and lack of relaxation of ...the lower esophageal sphincter. The mechanisms contributing to neuronal and ICC changes in achalasia are only partially understood. Our goal was to identify novel molecular features occurring in patients with primary achalasia.
Methods
Esophageal full‐thickness biopsies from 42 (22 females; age range: 16‐82 years) clinically, radiologically, and manometrically characterized patients with primary achalasia were examined and compared to those obtained from 10 subjects (controls) undergoing surgery for uncomplicated esophageal cancer (or upper stomach disorders). Tissue RNA extracted from biopsies of cases and controls was used for library preparation and sequencing. Data analysis was performed with the “edgeR” option of R‐Bioconductor. Data were validated by real‐time RT‐PCR, western blotting and immunohistochemistry.
Key Results
Quantitative transcriptome evaluation and cluster analysis revealed 111 differentially expressed genes, with a P ≤ 10−3. Nine genes with a P ≤ 10−4 were further validated. CYR61, CTGF, c‐KIT, DUSP5, EGR1 were downregulated, whereas AKAP6 and INPP4B were upregulated in patients vs controls. Compared to controls, immunohistochemical analysis revealed a clear increase in INPP4B, whereas c‐KIT immunolabeling resulted downregulated. As INPP4B regulates Akt pathway, we used western blot to show that phospho‐Akt was significantly reduced in achalasia patients vs controls.
Conclusions & Inferences
The identification of altered gene expression, including INPP4B, a regulator of the Akt pathway, highlights novel signaling pathways involved in the neuronal and ICC changes underlying primary achalasia.
Primary achalasia is a disorder due to neuronal defects supplying the esophagus leading to altered peristalsis and lack of sphincter relaxation. Nonetheless, the molecular mechanisms involved in this condition are poorly understood.
Transcriptomic analysis of achalasic tissues identified a dysregulated expression of different genes, in particular c‐KIT (downregulated) and INPP4B (upregulated), the latter being linked to Akt pathway regulation.
Our results unravel novel signaling pathways involved in the neuronal and interstitial cells of Cajal abnormalities in primary achalasia.
We present a case of a male kidney transplant patient harbouring two kidney grafts of which one is functional. In the failed graft, he developed urothelial cell carcinoma with cells containing ...XX-chromosome, and female tumour cells were also found in the bladder. The patient underwent donor nephrectomy, was treated with epirubicin bladder instillations, and immunosuppression was tapered. Less than a year before re-transplantation a CT scan showed no abnormalities of the first graft. Transplantectomy before a second kidney transplantation is debated.
Abstract
Background
Strictures develop in over half of Crohn’s Disease (CD) patients and can lead to complaints of bowel obstruction, requiring treatment. A study showed that strictures and ...pre-stricture small bowel (SB) have lower motility measured with cine-MRI, compared to normal bowel in CD. However, stricture motility has not been correlated with disease duration or Harvey Bradshaw Index (HBI). Investigating this correlation can provide insight in the physiologic behavior of a stricture in relation to the extent of bowel damage (disease duration) and clinical complaints (HBI). This could possibly support the clinician in treatment decisions. Our aim is to investigate correlations between stricture motility measured with cine-MRI and disease duration and HBI, respectively.
Methods
At a tertiary center CD patients (≥18yrs) with SB strictures were included. Patients fasted 4 hours, after which they drank 1600 mL (2.5%-mannitol-solution) in 60 minutes prior to 3T MRI. All underwent coronal dynamic 2D bFFE scans of the most stenotic SB and the pre-stenotic dilation if present, during a 20-second expiration breath-hold. Bowel motility was assessed with a validated displacement mapping technique (GIQuant, Entrolytics, Motilent, UK). Strictures (wall thickening >3mm and ≥50% luminal reduction) and pre-stenotic dilations (luminal diameter >3cm) were delineated on a reference image and motility was quantified on a motility map within these regions of interest (ROI), producing a single, numerical motility score (Arbitrary Units=AU). Stricture and pre-stenotic dilation motility scores are presented in medians IQR. Correlation was tested between stricture motility, disease duration and HBI by means of spearman’s rank correlation test.
Results
Twenty-two patients (55% male, age 37yrs IQR 25-55, disease duration 7yrsIQR 4-12) were included. SB stricture motility was 57AUIQR 48-71. Pre-stenotic dilation motility (n=6) was 131AUIQR 88-340. Disease duration and stricture motility showed no correlation(r=0.2, p=0.4). HBI and stricture motility were inversely correlated(r=-0.6, p<0.01).
Conclusion
We found an inverse correlation between SB stricture motility and HBI. No correlation was found between SB stricture motility and disease duration. The inverse correlation between HBI and stricture motility suggests that lower motility is associated with poorer clinical condition. This finding can possibly lead to earlier endoscopic or surgical intervention, since it indicates lower motility is associated with poorer clinical condition. Interestingly, we also measured higher pre-stenotic dilation motility compared to stricture motility, presumably a physiological response of the pre-stenotic dilation to the distal stricture and ongoing proximal peristalsis.
Abstract
Background
In 30%-50% of patients with Crohn’s disease (CD) stenotic complications occur1. There is currently no imaging modality to identify stricture composition, which would allow early ...targeted (anti-inflammatory vs surgical) treatment. Intestinal ultrasound (IUS) and advanced modalities (contrast-enhanced ultrasound (CEUS) and shear-wave elastography (SWE)) have the potential for transmural disease evaluation. The STRICTURE study investigated whether (advanced) IUS techniques could distinguish between inflammatory- (IP) and non-inflammatory phenotypes (non-IP) of stricturing CD.
Methods
In this prospective, cross-sectional study consecutive patients with small bowel CD undergoing surgery were included. Patients were eligible if they had a non-passable stricture during endoscopy in the small bowel and/or a stricture at cross-sectional imaging (IUS or MRE)2. Prior to surgery, IUS, CEUS and SWE were performed. Two blinded sonographers scored the cine-loops for IUS and CEUS. After surgery, histological slides were retrieved and location matched with IUS. Two blinded pathologists scored for inflammation, adipocytes and fibrosis. Subsequently the predominant phenotype was determined as: 1 inflammatory (IP; Nancy score 4 with no marked fibrosis/adipocytes), 2 fibrotic (FP; structural changes due to marked fibrosis/adipocytes3) or 3 mixed phenotype (MP; inflammatory and fibrotic aspects but no predominant phenotype). FP and MP were both classified as non-IP.
Results
A total of 36 patients (age: 42±18 years) with a mean BWT of 6.7±1.7 mm were included. Median time between IUS and surgery was 14 3-50 days. A total of 7 patients had an IP, 18 a FP and 11 a MP. For the conventional IUS parameters, loss of wall layer stratification (WLS) was more frequently found in IP strictures(OR: 7.87 1.24-50.00, p=0.029). For CEUS, most parameters were significantly higher in IP versus non-IP (Table 1) and at multi-variable logistic regression Wash-in area under the curve remained the only accurate parameter to distinguish IP from non-IP (OR:1.55 1.03-2.34, p=0.035) Figure 1. SWE inversely correlated with CEUS (Table 1, Figure 1) but did not differentiate between IP and non-IP (33.30 kPa vs 43.49 kPa, p=0.48). The agreement for BWT and loss of WLS was good (ICC: 0.77, p<0.001) and moderate (κ: 0.56, p<0.001), respectively. For CEUS, the most accurate parameters had good to excellent agreement Table 1.
Conclusion
Loss of WLS and CEUS are accurate to distinguish an IP from a non-IP stricture in CD and CEUS inversely correlates with SWE. In addition to accuracy, reproducibility was high and multi-modality IUS could be of additional value in this specific population to select patients most suitable for anti-inflammatory treatment.
Table 1
Figure 1
Inverse melting is the process in which a crystal reversibly transforms into a liquid or amorphous phase when its temperature is decreased. Such a process is considered to be very rare, and the ...search for it is often hampered by the formation of non-equilibrium states or intermediate phases. Here we report the discovery of first-order inverse melting of the lattice formed by magnetic flux lines in a high-temperature superconductor. At low temperatures, disorder in the material pins the vortices, preventing the observation of their equilibrium properties and therefore the determination of whether a phase transition occurs. But by using a technique to 'dither' the vortices, we were able to equilibrate the lattice, which enabled us to obtain direct thermodynamic evidence of inverse melting of the ordered lattice into a disordered vortex phase as the temperature is decreased. The ordered lattice has larger entropy than the low-temperature disordered phase. The mechanism of the first-order phase transition changes gradually from thermally induced melting at high temperatures to a disorder-induced transition at low temperatures.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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