Prominent subcutaneous oedema as a masquerading symptom of an underlying inflammatory myopathy

The inflammatory myopathies are a group of immune-mediated inflammatory muscle disorders that typically present with marked proximal muscle weakness. We report four cases of inflammatory myopathies with marked subcutaneous oedema as their main complaint. Three of the four patients had normal or low levels of creatine kinase, an enzyme often markedly elevated in these disorders. Magnetic resonance imaging of the muscles, followed by a muscle biopsy were used to make a definitive diagnosis

Midkine Increases Diagnostic Yield in AFP Negative and NASH-Related Hepatocellular Carcinoma

<div><p>Robust biomarkers for population-level hepatocellular carcinoma (HCC) surveillance are lacking. We compared serum midkine (MDK), dickkopf-1 (DKK1), osteopontin (OPN) and AFP for HCC diagnosis in 86 HCC patients matched to 86 cirrhotics, 86 with chronic liver disease (CLD) and 86 healthy controls (HC). Based on the performance of each biomarker, we assessed a separate longitudinal cohort of 28 HCC patients, at and before cancer diagnosis. Serum levels of MDK and OPN were higher in HCC patients compared to cirrhosis, CLD and HC groups. DKK1 was not different between cases and controls. More than half of HCC patients had normal AFP. In this AFP-negative HCC cohort, 59.18% (n = 29/49) had elevated MDK, applying the optimal cut-off of 0.44 ng/ml. Using AFP ≥ 20 IU/ml or MDK ≥ 0.44 ng/ml, a significantly greater number (76.7%; n = 66/86) of HCC cases were detected. The area under the receiver operating curve for MDK was superior to AFP and OPN in NASH-HCC diagnosis. In the longitudinal cohort, MDK was elevated in 15/28 (54%) of HCC patients at diagnosis, of whom 67% had elevated MDK 6 months prior. <b>Conclusion:</b> AFP and MDK have a complementary role in HCC detection. MDK increases the diagnostic yield in AFP-negative HCC and has greater diagnostic performance than AFP, OPN and DKK-1 in the diagnosis of NASH-HCC. Additionally, MDK has a promising role in the pre-clinical diagnosis of HCC.</p></div

Frequency of elevated serum MDK and AFP at HCC diagnosis and 6 months prior to diagnosis.

<p>Frequency of elevated serum MDK and AFP at HCC diagnosis and 6 months prior to diagnosis.</p

Clinical characteristics of HCC patients and controls.

<p>Clinical characteristics of HCC patients and controls.</p

Comparison of the diagnostic performances of serum MDK, OPN and AFP.

<p><b>A) All HCC patients versus non-HCC patients (cirrhotics and chronic liver disease). B) Early HCC patients (BCLC 0-A) versus non-HCC patients (cirrhotic and chronic liver disease). C) HCV-HCC patients versus HCV-cirrhotics. D) HBV-HCC patients versus HBV-cirrhotics and chronic HBV patients. E) NASH-HCC patients versus NASH cirrhotic patients.</b> A) ROC curve for MDK, OPN and AFP for all patients with HCC (n = 86) versus patients with cirrhosis (n = 86) or chronic liver disease (n = 86). B) ROC curve for MDK, OPN and AFP for all patients with early stage (BCLC 0-A) HCC (n = 36) versus patients with cirrhosis (n = 36) or chronic liver disease (n = 36). C) ROC curve for MDK, OPN and AFP for all patients with HCV-related HCC (n = 42) versus all patients with HCV-related cirrhosis (n = 43). D) ROC curve for MDK, OPN and AFP for all patients with HBV-related HCC (n = 14) versus all patients with HBV-related cirrhosis (n = 23) or chronic hepatitis B (n = 86). E) ROC curve for MDK, OPN and AFP for all patients with NASH-related HCC (n = 16) versus all patients with NASH-related cirrhosis (n = 10). Abbreviations: ROC, receiver operating characteristics; MDK, midkine; OPN, osteopontin; DKK1, dickopff-1; AFP, alpha-fetoprotein; HCC, hepatocellular carcinoma; CLD, chronic liver disease; HBV, hepatitis B virus; HCV, hepatitis C virus; NASH, non-alcoholic steatohepatitis.</p

Mean MDK, OPN, DKK1 and AFP levels in HCC patients according to various clinical parameters.

<p>Mean MDK, OPN, DKK1 and AFP levels in HCC patients according to various clinical parameters.</p

Endotrophin, a pro-peptide of Type VI collagen, is a biomarker of survival in cirrhotic patients with hepatocellular carcinoma

AIM: Type VI collagen, is emerging as a signaling collagen originating from different types of fibroblasts. A specific fragment of Type VI collagen, the pro-peptide, is also known as the hormone endotrophin. We hypothesized that this fibroblast hormone would be of particular relevance in cancer types with a high amount of fibrosis activity, namely for outcome in hepatocellular carcinoma (HCC) cirrhotic patients. PATIENTS & METHODS: Plasma C6M, PRO-C6 and alphafeto-protein (AFP) were assessed in 309 patients with mixed etiologies (hepatitis C, hepatitis B, alcohol and nonalcoholic fatty liver) diagnosed as cirrhotics, cirrhotics with HCC, noncirrhotics and healthy controls. Progression-free survival and overall survival (OS) data were collected up to 6120 days after diagnosis. The ability of each marker to predict survival was investigated. RESULTS & CONCLUSION: The level of endotrophin assessed by PRO-C6 was able to separate healthy controls, noncirrhotics and cirrhotics from HCC (p < 0.05–0.0001). Both endotrophin and C6M provided value in the prediction of OS in cirrhotic patients with HCC. In the multivariate analysis for identifying HCC, in patients with high endotrophin (highest quartile) and that were positive for AFP (≥20 IU/ml), the hazard ratio for predicting OS was increased from 3.7 (p = 0.0006) to 14.4 (p = 0.0001) when comparing with AFP positive as a stand-alone marker. In conclusion, plasma levels for markers of Type VI collagen remodeling were associated with survival in cirrhotic patients with HCC. A combination of AFP with endotrophin improved the prognostic value compared with AFP alone for predicting OS in cirrhotic patients with HCC