Use of self-expandable metallic stents in benign GI diseases

BACKGROUND: The self-expandable metallic stent is of proven benefit in patients with malignant disease; however, its use in patients with benign disease is not well established. There are few data available regarding long-term complications and outcomes with use of self-expandable metallic stents in benign disease and virtually none regarding attempted removal once the acute problem is resolved. METHODS: Thirteen patients who had a self-expandable metallic stent placed for benign GI disorders were included in a retrospective analysis. Data collected included patient demographics, indication for procedure, type of stent used, complications, and patient outcomes. RESULTS: Thirteen patients (7 women, 6 men; mean age 67 years, range 34-84 years) had one or more self-expandable metallic stents placed for benign disease and were followed for a mean of 3.4 years (3 weeks to 10 years). Of the 13 patients, 8 had esophageal stents, 4 biliary stents, and 1 had dual stents placed in the pancreaticobiliary tree. Complications developed in 8 (62%) patients; 4 (31%) ultimately died, either from the primary disease process (3) or from stent-related complications (1). CONCLUSIONS: Self-expandable metallic stent placement is effective treatment for benign esophageal leaks, providing the stent can be removed. It also may be used in either the esophagus or biliary tree in patients who are poor candidates for surgery and short expected survival. However, a self-expandable metallic stent should not be placed in a patient with a benign GI disorder who has a significant life expectancy and is a good candidate for surgery.     

Left ventricular remodeling and hypertrophy in patients with aortic stenosis: insights from cardiovascular magnetic resonance

Background

Cardiovascular magnetic resonance (CMR) is the gold standard non-invasive method for determining left ventricular (LV) mass and volume but has not been used previously to characterise the LV remodeling response in aortic stenosis. We sought to investigate the degree and patterns of hypertrophy in aortic stenosis using CMR.

Methods

Patients with moderate or severe aortic stenosis, normal coronary arteries and no other significant valve lesions or cardiomyopathy were scanned by CMR with valve severity assessed by planimetry and velocity mapping. The extent and patterns of hypertrophy were investigated using measurements of the LV mass index, indexed LV volumes and the LV mass/volume ratio. Asymmetric forms of remodeling and hypertrophy were defined by a regional wall thickening ≥13 mm and >1.5-fold the thickness of the opposing myocardial segment.

Results

Ninety-one patients (61±21 years; 57 male) with aortic stenosis (aortic valve area 0.93±0.32cm2) were recruited. The severity of aortic stenosis was unrelated to the degree (r²=0.012, P=0.43) and pattern (P=0.22) of hypertrophy. By univariate analysis, only male sex demonstrated an association with LV mass index (P=0.02). Six patterns of LV adaption were observed: normal ventricular geometry (n=11), concentric remodeling (n=11), asymmetric remodeling (n=11), concentric hypertrophy (n=34), asymmetric hypertrophy (n=14) and LV decompensation (n=10). Asymmetric patterns displayed considerable overlap in appearances (wall thickness 17±2mm) with hypertrophic cardiomyopathy.

Conclusions

We have demonstrated that in patients with moderate and severe aortic stenosis, the pattern of LV adaption and degree of hypertrophy do not closely correlate with the severity of valve narrowing and that asymmetric patterns of wall thickening are common.

Trial registration

ClinicalTrials.gov Reference Number: NCT00930735     

Reduced TGF-beta1 in patients with aplastic anaemia in vivo and in vitro

Transforming growth factor beta (TGF-beta) 1 is a ubiquitous bifunctional cytokine implicated in the regulation of haemopoietic stem cells and bone marrow stromal cells. We analysed sera from 63 patients with aplastic anaemia and describe a significant reduction of TGF-beta1 that was directly related to their treatment status. Untreated patients (n = 35), patients who did not respond (n = 15) and those with a partial response (n = 23) to treatment had significantly lower TGF-beta1 than the normal control group (n = 55), P < 0.0001, P < 0.0001 and P = 0.002 respectively. Patients in complete remission (n = 15) exhibited TGF-beta1 serum levels comparable to the control group. In addition, there was a correlation (r = 0.83, P < 0.0001) between serum TGF-beta1 and platelet count at time of sample. We have demonstrated that the primary source of TGF-beta1 in peripheral blood mononuclear cell (PBMC) cultures was not CD3-positive cells. These data indicate aplastic anaemia is associated with a decreased TGF-beta1 expression in peripheral blood circulation, which may be a direct consequence of thrombocytopenia. In vitro stromal layers grown from aplastic patient bone marrow (n = 14) produced significantly lower levels of TGF-beta1 (P = 0.02) when compared to normal stroma (n = 15). In the aplastic anaemia bone marrow compartment we postulate that accessory cells down-regulate TGF-beta1 expression to allow stem cell cycling to counteract hypoplasia. As TGF-beta1 is important in the regulation of haemopoiesis, dysregulation of this cytokine in combination with previously described abnormal cytokine expression may contribute significantly to the pathophysiology of aplastic anaemia by exacerbating primary stem cell defects.     

Deficiency of CD73/ecto-5'-nucleotidase in mice enhances acute graft-versus-host disease

Extracellular ATP and adenosine have immunoregulatory roles during inflammation. Elevated extracellular ATP is known to exacerbate GVHD, and the pharmacologic activation of the adenosine A2A receptor is protective. However, the role of endogenous adenosine is unknown. We used gene-targeted mice and a pharmacologic inhibitor to test the role of adenosine generated by CD73/ecto-5'-nucleotidase in GVHD. In allogeneic transplants, both donor and recipient CD73 were protective, with recipient CD73 playing the dominant role. CD73 deficiency led to enhanced T-cell expansion and IFN-γ and IL-6 production, and the migratory capacity of Cd73-/- T cells in vitro was increased. However, the number of regulatory T cells and expression of costimulatory molecules on antigen-presenting cells were unchanged. A2A receptor deficiency led to increased numbers of allogeneic T cells, suggesting that signaling through the A2A receptor via CD73-generated adenosine is a significant part of the mechanism by which CD73 limits the severity of GVHD. Pharmacologic blockade of CD73 also enhanced graft-versus-tumor activity. These data have clinical implications, as both the severity of GVHD and the strength of an alloimmune antitumor response could be manipulated by enhancing or blocking CD73 activity or adenosine receptor signaling depending on the clinical indication.     

Pneumocystis jiroveci pneumonia following rituximab treatment in Wegener's granulomatosis

Objective

Wegener's granulomatosis (WG) is a devastating small‐vessel vasculitis in children. Standard treatment consists of immunosuppressive medications with cyclophosphamide potentially associated with significant infectious side effects, including Pneumocystis jiroveci pneumonia (PCP). Recently, rituximab, a monoclonal antibody against B cells, has successfully been used in refractory disease.

Methods

We describe the first pediatric patient with refractory WG with sinus and lung disease who developed PCP 6 months after treatment with rituximab, while being treated with methotrexate and prednisone. This 9‐year‐old child had no CD20+ B cells at time of infection, with normal lymphocyte and CD4 counts.

Results

This study provides a review of the published literature, including current protocols, which suggest chemoprophylaxis only in WG patients receiving T cell–targeted immunosuppression such as cyclophosphamide. However, clinical and laboratory evidence points toward a possible role of B cells in the defense against PCP.

Conclusion

Routine PCP chemoprophylaxis should be strongly considered in patients with WG treated with rituximab.     

Case Report: Inappropriate Implantable Cardioverter Defibrillator Discharge from Sensing of External Alternating Current Leak

Implantable cardioverter defibrillators (ICDs) are now an accepted and effective therapy for treatment of survivors of sudden cardiac death (SCD) and prevention of SCD in high-risk patients. Normal ICD function and delivery of therapy depends on appropriate sensing and detection of myocardial electrical potentials. Electromagnetic interference resulting in ICD malfunction is a well-documented phenomenon, however, there are less well-known external sources of interference, which may cause life threatening ICD malfunction. We report a unique case of repeated inappropriate ICD shocks in a ten-year old boy caused by the ICD sensing alternating current from an unexpected external source.     

CCR5△32 mutation does not influence the susceptibility to HCV infection, severity of liver disease and response to therapy in patients with chronic hepatitis C

AIM: To study whether CCR5△32 mutation was associated with viral infection and severity of liver disease.METHODS: Two hundred and fifty two histologically proven, chronic HCV patients (mean age: 41 ± 14 years;M/F: 164/88) were genotyped. PCR based genotyping of 32 bp deletion at the CCR5 locus was done. Fourhundred and eight matched healthy controls were studied to assess susceptibility to HCV infection. To assess correlation of immune gene polymorphism with severity of HCV related liver disease, patients with chronic HCV infection were divided into those with a fibrosis score of ≤ 2 (mild) or ＞ 2 (severe) and histological activity index (HAI) of ≤ 5 or ＞ 5. For correlation between CCR5△32 mutations and response to therapy, 129 patients who completed therapy were evaluated.RESULTS: The majority (89.4%) of the patients were infected with genotype 3. The frequency of homozygous CCR5△32 mutants was comparable to HCV patients as compared to the healthy controls (0.7% vs 0%, P = 0.1).Further more, the frequency of CCR5△32 mutation was comparable in patients with mild or severe liver disease.(P = NS). There was also no association observed with response to therapy and CCR5△32 mutation.CONCLUSION: CCR5△32 mutation does not have a role in disease susceptibility, severity or response to therapy in patients with chronic hepatitis C infection.     

Are pancreatic IPMN volumes measured on MRI images more reproducible than diameters? An assessment in a large single-institution cohort

Objectives

To assess reproducibility of volume and diameter measurement of intraductal papillary mucinous neoplasms (IPMNs) on MRI images.

Methods

Three readers measured the diameters and volumes of 164 IPMNs on axial T2-weighted images and coronal thin-slice navigator heavily T2-weighted images using manual and semiautomatic techniques. Interobserver reproducibility and variability were assessed.

Results

Interobserver intraclass correlation coefficients (ICCs) for the largest diameter measured using manual and semiautomatic techniques were 0.979 and 0.909 in the axial plane, and 0.969 and 0.961 in the coronal plane, respectively. Interobserver ICCs for the volume measurements were 0.973 and 0.970 in axial and coronal planes, respectively. The highest intraobserver reproducibility was noted for coronal manual measurements (ICC 0.981) followed by axial manual measurements (ICC 0.969). For the diameter measurements, Bland-Altman analysis revealed the lowest interobserver variability for manual axial measurements with an average range of 95% limits of agreement (LOA) of 0.68 cm. Axial and coronal volume measurements showed similar 95% LOA ranges (8.9 cm³ and 9.4 cm³, respectively).

Conclusions

Volume and diameter measurements on axial and coronal images show good interobserver and intraobserver reproducibility. The single largest diameter measured manually on axial images showed the highest reproducibility and lowest variability. The 95% LOA may help define reproducible size changes in these lesions using measurements from different readers.

Key Points

? MRI measurements by different radiologists can be used for IPMN follow-up. ? Both diameter and volume measurements demonstrate excellent interobserver and intraobserver reproducibility. ? Manual axial measurements show the highest interobserver reproducibility in determining size. ? Axial and coronal volume measurements show similar limits of agreement. ? Manual axial measurements show the lowest variability in agreement range.

     

Xanthogranulomatous cholecystitis: What every radiologist should know

Xanthogranulomatous cholecystitis (XGC) is an uncommon variant of chronic cholecystitis characterized by xanthogranulomatous inflammation of the gallbladder. Intramural accumulation of lipid-laden macrophages and acute and chronic inflammatory cells is the hallmark of the disease. The xanthogranulomatous inflammation of the gallbladder can be very severe and can spill over to the neighbouring structures like liver, bowel and stomach resulting in dense adhesions, perforation, abscess formation, fistulous communication with adjacent bowel. Striking gallbladder wall thickening and dense local adhesions can be easily mistaken for carcinoma of the gallbladder, both intraoperatively as well as on preoperative imaging. Besides, cases of concomitant gallbladder carcinoma complicating XGC have also been reported in literature. So, we have done a review of the imaging features of XGC in order to better understand the entity as well as to increase the diagnostic yield of the disease summarizing the characteristic imaging findings and associations of XGC. Among other findings, presence of intramural hypodense nodules is considered diagnostic of this entity. However, in some cases, an imaging diagnosis of XGC is virtually impossible. Fine needle aspiration cytology might be handy in such patients. A preoperative counselling should include possibility of differential diagnosis of gallbladder cancer in not so characteristic cases.