Background and Aims
Liver stiffness measurements (LSM), commonly performed by transient elastography (TE) or two‐dimensional shear wave elastography (2D‐SWE), are used to quantify liver fibrosis. ...Active hepatitis, a hallmark of autoimmune hepatitis (AIH), could bias LSM. This bias might be overcome by measurement spleen 2D‐SWE. Here, we compare liver and spleen 2D‐SWE to TE and liver biopsy (LB) in prospectively recruited patients with AIH.
Methods
We analysed liver and spleen 2D‐SWE in relation to liver TE in 90 patients treated ≥ 6 months for AIH. Liver and spleen 2D‐SWE were also compared to LB in 63 individuals with AIH. Finally, we evaluated these tools in 220 patients with AIH and during 18 months follow‐up.
Results
Liver 2D‐SWE correlated with surrogate markers of active hepatitis (ALT and IgG, both P < .001) but there was no link between spleen 2D‐SWE and ALT. Liver 2D‐SWE, but not spleen 2D‐SWE, was associated with histopathological inflammatory score (P < .01). When compared to LB, the optimal cut‐offs for detecting cirrhosis by liver and spleen 2D‐SWE were 16.1 kPa (AUROC 0.93) and 29.8 kPa (AUROC 0.95), respectively. In patients with active hepatitis the combined diagnostic approach including liver and spleen 2D‐SWE had significantly better AUROC for detecting cirrhosis than liver 2D‐SWE alone.
Conclusions
Liver and spleen 2D‐SWE are reliable complementary methods for the diagnosis of advanced fibrosis in AIH. Spleen 2D‐SWE seems to be less biased by inflammation and could facilitate fibrosis assessment in therapy‐naïve patients or in the presence of active hepatitis.
Chronic fatigue and an impairment of general health‐related quality of life (HRQoL) are frequently reported by patients with primary sclerosing cholangitis (PSC). Studies on patients with primary ...biliary cholangitis (PBC) suggest that, unlike pruritus, fatigue may not be ameliorated by liver transplantation (LT). However, there are few data regarding the assessment of fatigue before and after transplantation in PSC. To investigate the effect of LT on fatigue and HRQoL in patients with PSC, 81 patients with PSC (median age 33 years; 69% men) were prospectively enrolled in this study. The PBC‐40 and Short Form 36 (SF‐36) questionnaires were used for assessment before and twice after LT. A total of 26 patients who received a transplant for PBC were included as controls. The potential impact of the clinical and laboratory parameters was evaluated by univariate and multivariate analyses. Although in addition to other well‐being indexes the median fatigue score improved after LT (P < 0.001), a detailed analysis demonstrated that fatigue persists in one‐third of patients. A significant fatigue reduction was seen in men (P < 0.001) but not women (P = 0.25). Posttransplant fatigue did not depend on concomitant inflammatory bowel disease, laboratory indexes of cholestasis, or disease recurrence. In the multivariate regression model, female sex was the only independent covariate associated with persistent fatigue. In terms of other measures of HRQoL, LT caused a substantial improvement in the majority of SF‐36 and PBC‐40 domains. Recurrent PSC and unemployment negatively affected the well‐being of patients. Patients who received a transplant for PSC had significantly better HRQoL than those patients with PBC. LT improves various measures of HRQoL, but it does not ameliorate fatigue in female patients with PSC.
Bladder cancer is the most common urinary tract malignancy in western countries. In recent years, extensive research has suggested that angiogenesis plays an important role in bladder cancer biology, ...contributing to tumor growth and progression.
In this review, we discuss general mechanisms of angiogenesis and highlight the influence of pro- and anti-angiogenic factors, and cancer stem cells on bladder cancer biology, their relation to disease progression, and potential use in novel targeted therapies.
Expression of a number of proangiogenic factors, including HIF-1, VEGF, bFGF, IL-8 and MMPs, as well as anti-angiogenic factor TSP-1, was found to be altered in bladder tumors. Involvement of cancer stem cells in bladder cancer development was also proposed.
High expression of most pro-angiogenic factors correlated with disease progression and shorter patient survival, but discrepancies between studies urge us to continue evaluating the significance of angiogenesis in bladder cancer.
In aesthetic medicine, there has been an ongoing search for an ideal dermal filler to offer zero complication rate. Polycaprolactone-based dermal filler (PCL) has been available since 2009. The ...purpose of the paper was to present a case of granuloma as a complication of PCL injection, which has not been reported so far by other researchers. A 68-year-old female was injected with PCL. One year later, nodules accompanied by bluish skin discoloration developed within the injection site. Ultrasound and histopathology studies were performed. The examinations confirmed the presence of foreign body granuloma after PCL, which makes it the first reported case worldwide. The published data analyses showed general lack of studies and case reports to address this issue. The PCL, like an injection of any soft tissue filler, may lead to serious complications, such as granuloma formation. This makes further research legitimate and necessary.
Published data regarding lymphangiomatous cysts of the adrenal glands (also known as adrenal cystic lymphangiomas) are limited to case reports and a few small case series. We analyzed the ...clinicopathologic features and histomorphologic spectrum of 37 cases of adrenal cystic lymphangiomatous lesions. There were 26 females and 11 males ranging from 12 to 67 years old (median, 34 years). Twenty two lesions (59.5%) were diagnosed incidentally on imaging studies for unrelated causes, while 15 cases (40.5%) were symptomatic: 8 patients presented with abdominal or flank pain and 7 patients presented with arterial hypertension. Clinically, 4 lesions (10.8%) were reported to have concurrent hormonal hypersecretion. Follow-up data were available for 23 patients (62.2%), ranging from 6 to 156 months (median, 52 mo). One of the 22 patients showed local recurrence at 12 months after partial adrenalectomy. The median size of the adrenal lymphangiomatous cysts was 4.5 cm (range, 1.5 to 10 cm). Based on the histopathologic findings these lesions were grouped into three, morphologically distinct types: typical multicystic lymphatic malformation (n = 16), typical unilocular lymphangiomatous cyst (n = 14) and lymphangiomatous cyst with papillary endothelial proliferation (n = 7). The median patient age of the first group was significantly higher than that of the other groups and calcifications in these cysts were more common than in the other two groups. The unilocular lymphangiomatous cysts were more frequently associated with a history of previous intra-abdominal surgical procedures and/or inflammatory processes than the other two groups. Cysts with papillary endothelial proliferation were significantly larger than other cysts and shared some microscopic features with a vascular neoplasm known as papillary intralymphatic angioendothelioma (PILA). In conclusion, adrenal lymphangiomatous cysts are usually asymptomatic, incidentally diagnosed lesions with a female predominance. They may imitate other adrenal tumors, both radiologically and clinically. Despite being non-functioning lesions, they should be considered as a possible cause of pseudopheochromocytoma. Although most adrenal lymphangiomatous cysts seem to be non-neoplastic, vascular abnormalities (malformations or lymphangiectasias), those with papillary endothelial proliferations may represent true neoplastic lesions.
Wilson's disease (WD) is an inherited disorder involving copper accumulation in the liver and brain. An important mechanism responsible for hepatocyte injury in WD is mitochondria destruction, ...although damage may also be caused by oxidative stress and lipid peroxidation.
The study included 54 treated patients with WD without liver cirrhosis and 10 healthy controls. All patients had liver biopsy and immunohistochemical analysis of liver samples was performed using targeted staining for markers of mitochondrial injury (thioredoxin-2 TRX2, cytochrome c oxidases subunit 2 COX2, and cytochrome c oxidases complex IV subunit 4 isoform 1 COX4-1), of oxidative stress (peroxiredoxin-1 PRDX1 and 8-hydroxyguanosine 8-OHdG), and of lipid peroxidation (4-hydroxynonenal 4-HNE).
Expression, measured as mean strengths of intensity (SI) of immunohistochemical reactions per 5 fields of view, was significantly lower in patients with WD compared to controls for COX2 (2.9 vs 8.3), 8-OHdG (0.05 vs 3.8), TRX2 (4.9 vs 10.1), and PRDX1 (4.6 vs 10.1) (all P < 10−5). COX4-1 expression was undetected in patients with WD but detected in control specimens (8.1) (P < 10−5). 4-HNE was overexpressed in patients with WD compared to controls (10.1 vs 9.1; P < 0.07).
Negligible COX4-1 and low COX2 expression in liver specimens may serve as markers of inner mitochondrial membrane injury in treated patients with WD and early stages of liver fibrosis.
Objective
The promotion of neovascularisation is a crucial aspect of carcinogenesis. The study evaluates the microvascular density (MVD) and expression of hypoxia-induced factor (HIF-1α) in ...hypertrophic vocal fold (VF) lesions of different histopathological states including non-dysplastic, low-grade, high-grade dysplasia and invasive glottic cancer.
Materials and methods
Histological specimens collected from patients diagnosed and treated in a single centre with different histological grades were immunohistochemically stained with CD31, CD34 and HIF-1α. Of the total number of 77 analysed VF specimens, 20 were non-dysplastic, 20 had low-grade dysplasia, 17 high-grade dysplasia and 20 were invasive cancers.
Results
The highest mean value for MVD evaluated with expression of CD31 (MVD CD31) was 21.23 ± 14.46 and identified in the low-grade dysplasia group. The average MVD CD31 was 13.74 ± 5.56 and 20.11 ± 9.28 in the high-grade dysplasia and invasive cancer group, respectively. The highest MVD evaluated with CD34 (MVD CD34) was revealed for invasive cancer 35.64 ± 17.21. The MVD CD34 was higher for low-grade than in high-grade dysplasia (25.87 ± 12.30 vs 24.65 ± 15.92, respectively). The expression of HIF-1α was strong or very strong in 60% of non-dysplastic lesions, 100% of low-grade dysplasia cases, 53% of high-grade dysplasia cases and 50% of invasive cancer cases. The comparison of MVD CD31 with MVD CD34 revealed a strong positive correlation (
ρ
value 0.727). The comparison of both MVD CD31 and MVD CD34 with HIF-1α resulted in no linear relationship (
ρ
value of 0.143 and 0.165, respectively).
Conclusion
The stage of low-grade dysplasia in intraepithelial vocal fold lesions is related to significant advancement of angiogenesis together with the highest hypoxia level.
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