Stepwise combination of simple noninvasive fibrosis scoring systems increases diagnostic accuracy in nonalcoholic fatty liver disease.

OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease ranging from simple fatty liver to steatohepatitis, fibrosis, and cirrhosis. We aimed to analyze the diagnostic performance and clinical utility of simple noninvasive tests alone or in combination for the detection of advanced fibrosis in patients with NAFLD. DESIGN AND SUBJECTS: Data from 323 patients with biopsy-proven NAFLD/NASH who presented to the Clinic for Gastroenterology and Hepatology, University Hospital of Cologne between July 1998 and November 2009, were analyzed retrospectively. Sensitivity, specificity, positive predictive values, and negative predictive values were determined along with the area under receiver operating characteristic curves (AUROC) using published formulas for NAFLD, FIB-4, and BARD fibrosis scores. RESULTS: The area under receiver operating characteristic curves were as follows: NAFLD fibrosis score 0.96 [95% confidence interval (CI), 0.92-0.99], FIB-4 0.95 (95% CI, 0.91-1.00), BARD 0.82 (95% CI, 0.71-0.92) with negative predictive values for advanced fibrosis of 96%, 98%, and 96%, respectively. When applying the NAFLD, FIB-4, or BARD scoring systems 25%, 15%, or 26% of cases with advanced fibrosis would have been missed. Combining FIB-4 and BARD in a stepwise fashion, patients would have been correctly classified without biopsy in 67% of cases without missing a single case of advanced fibrosis. CONCLUSIONS: The FIB-4 and NAFLD fibrosis scores perform better than the BARD scoring system. Liver biopsy can securely be replaced only with a stepwise combination of simple noninvasive tests, otherwise the assessment of risk due to advanced fibrosis may be misleading in a clinically meaningful proportion of patients.

Prognostic value of proliferating cell nuclear antigen in parotid gland cancer.

Although cell proliferation is related to tumour aggressiveness and prognosis, there are few studies describing the expression of proliferative markers in salivary gland cancer. Our aim was to assess the long-term prognostic value of the proliferating cell nuclear antigen (PCNA) in a large group of histologically different salivary gland cancers. We analysed the expression of PCNA in 159 patients with parotid gland cancer by means of immunohistochemistry. The mean follow-up time was 56.6 months. A high expression of PCNA showed a significant correlation to the patients' pathological lymph node stage (p = 0.004). A high PCNA expression significantly indicated a poor 5-year disease-free (p = 0.046) and overall survival rate (p = 0.018). The PCNA expression was the only prognostic factor for a worse 5-year disease-free and overall survival in acinic cell carcinomas (p = 0.004, p = 0.022). The correlation between PCNA expression and survival probabilities of salivary gland cancer might make proliferation markers helpful tools in patient follow-up, prognosis and targeted therapy in salivary gland cancer in future.

Cytoplasmic expression of survivin is an independent predictor of poor prognosis in patients with salivary gland cancer.

AIMS: The expression of the inhibitor of apoptosis protein survivin has been shown to be a significant prognostic indicator in various human cancers. The aim was to assess its expression and prognostic value in salivary gland adenocarcinoma and muco-epidermoid carcinoma. METHODS AND RESULTS: Survivin expression was analysed in 48 patients with parotid gland cancer (21 muco-epidermoid, 27 adenocarcinomas) by means of immunohistochemistry. The experimental findings were correlated with clinicopathological and survival parameters. A high cytoplasmic expression of survivin was found in 30% of the examined tumours without any significant correlation with the patients' clinicopathological characteristics (P > 0.05). Within all patients, the estimated overall survival rate of muco-epidermoid carcinomas was significantly better than that of adenocarcinomas (P = 0.013). A high cytoplasmic survivin expression significantly indicated a poor 5-year disease-free survival rate compared to patients with a low cytoplasmic survivin expression in the whole group (P = 0.001) and in adenocarcinomas (P = 0.004). In a multivariate analysis, a high cytoplasmic survivin expression was the only independent prognostic indicator for a significantly poorer 5-year disease-free survival rate (P = 0.001). CONCLUSIONS: The correlation between cytoplasmic survivin expression and survival in salivary gland malignancies might make this an effective tool in patient follow-up, prognosis and targeted therapy in future.

Development of hepatocellular carcinoma associated with anabolic androgenic steroid abuse in a young bodybuilder: a case report.

Introduction. Many different etiological factors are involved in the development of hepatocellular carcinoma (HCC). We report the case of HCC in a 37-year-old male professional bodybuilder with extensive anabolic androgenic (AAS) steroid abuse. Case Presentation. Because of increasing epigastric and abdominal pain, abdominal ultrasound was performed in a 37-year-old male professional bodybuilder. A hyperechoic lesion in the liver was detected in segment VI. The magnetic resonance imaging showed hepatomegaly and confirmed the lesion, which showed features of a hepatocellular adenoma (HCA). Laboratory values were inconspicuous. After laparoscopic segmentectomy the histological examination revealed HCC. Conclusion. While the development of HCA in the liver by chronic intake of AAS is well known, little is known about the association with HCC. The presented case may indicate aetiological association of chronic intake of AAS and the development of HCC.

Prognostic value of survivin expression in parotid gland cancer in consideration of different histological subtypes.

BACKGROUND: Cancer of the major salivary glands comprises a morphological diverse group of rare tumours of largely unknown cause. Survivin, an inhibitor of apoptosis has shown to be a significant prognostic indicator in various human cancers. The aim of this study was to assess the long-term prognostic value of survivin in a large group of histological different salivary gland cancers. METHODS: We analysed the survivin expression in 143 patients with parotid gland cancer by means of immunohistochemistry and tissue micro array. Survivin expression was categorised into a low and a high expressing group. The experimental findings were correlated with clinicopathological and survival parameters. The mean follow-up time was 54.8 months. RESULTS: A positive cytoplasmic expression of survivin was found in 61.5%, a high expression in 25.9% of all specimens. In the whole group, high cytoplasmic survivin expression significantly indicated a poor 5-year disease-free and overall survival rate (p < 0.0001, p = 0.003). This applied for all adeno-, adenoid cystic and undifferentiated carcinomas whereas in mucoepidermoid carcinomas an analogical non-significant trend could be observed. A high cytoplasmic survivin expression significantly indicated a poor survival in high grade but not in low grade tumours. A multivariate analysis revealed that high cytoplasmic survivin expression was the only significant negative prognostic indicator for a poor 5-year disease-free survival rate in all patients (p = 0.042). CONCLUSION: The correlation between cytoplasmic survivin expression and survival probabilities of salivary gland cancer might make this an effective tool in patient follow-up, prognosis and targeted therapy in future.

Noise exposure during ambulance flights and repatriation operations.

OBJECTIVES: Although ambulance flights are routine work and thousands of employees work in repatriation organizations, there is no data on noise exposure which may be used for preventive advice. We investigated the noise exposure of crews working in ambulance flight organizations for international patient repatriation to get the data for specific guidelines concerning noise protection. MATERIAL AND METHODS: Noise levels inside Learjet 35A, the aircraft type which is most often used for repatriation operations, were collected from locations where flight crews typically spend their time. A sound level meter class 1 meeting the DIN IEC 651 requirements was used for noise measurements, but several factors during the real flight situations caused a measurement error of ~3%. Therefore, the results fulfill the specifications for class 2. The data was collected during several real repatriation operations and was combined with the flight data (hours per day) regarding the personnel to evaluate the occupationally encountered equivalent noise level according to DIN 45645-2. RESULTS AND CONCLUSIONS: The measured noise levels were safely just below the 85 dB(A) threshold and should not induce permanent threshold shifts, provided that additional high noise exposure by non-occupational or private activities was avoided. As the levels of the noise produced by the engines outside the cabin are significantly above the 85 dB(A) threshold, the doors of the aircraft must be kept closed while the engines are running, and any activity performed outside the aircraft - or with the doors opened while the engines are running - must be done with adequate noise protection. The new EU noise directive (2003/10/EG) states that protective equipment must be made available to the aircrew to protect their hearing, though its use is not mandatory.

Pro12Ala polymorphism of the peroxisome proliferator-activated receptor γ2 in patients with fatty liver diseases.

AIM: To test the occurrence of the Pro12Ala mutation of the peroxisome proliferator-activated receptor-γ (PPARγ)2-gene in patients with non-alcoholic fatty liver disease (NAFLD) or alcoholic fatty liver disease (AFLD). METHODS: DNA from a total of 622 specimens including 259 blood samples of healthy blood donors and 363 histologically categorized liver biopsies of patients with NAFLD (n = 263) and AFLD (n = 100) were analyzed by Real-time polymerase chain reaction using allele-specific probes. RESULTS: In the NAFLD and the AFLD collective, 3% of the patients showed homozygous occurrence of the Ala12 PPARγ2-allele, differing from only 1.5% cases in the healthy population. In NAFLD patients, a high incidence of the Ala12 mutant was not associated with the progression of fatty liver disease. However, we observed a significantly higher risk (odds ratio = 2.50, CI: 1.05-5.90, P = 0.028) in AFLD patients carrying the mutated Ala12 allele to develop inflammatory alterations. The linkage of the malfunctioning Ala12-positive PPARγ2 isoform to an increased risk in patients with AFLD to develop severe steatohepatitis and fibrosis indicates a more prominent anti-inflammatory impact of PPARγ2 in progression of AFLD than of NAFLD. CONCLUSION: In AFLD patients, the Pro12Ala single nuclear polymorphism should be studied more extensively in order to serve as a novel candidate in biomarker screening for improved prognosis.