Stereotactic ablative radiotherapy in the treatment of hepatocellular carcinoma >3 cm

Stereotactic ablative radiotherapy (SABR) is a safe treatment approach for hepatocellular carcinoma (HCC) with comparable results to other local therapies. For lesions larger than 3 cm, no definitive standard treatment is present and several options are available. We retrospectively review local control (LC) and survival results of SABR in patients with HCC lesions >3 cm. Between 2012 and 2015, we treated 29 patients (39 lesions) having histological or radiological diagnosis of HCC and at least one lesion sized >3 cm. Patients were prescribed 36–48 Gy in 3–5 fractions (mainly 16 Gy × 3 fractions or 8 Gy × 5 fractions), in 3–5 consecutive days. A total of 15 lesions (52 %) had complete, while 10 (34 %) had partial remission; 3 (11 %) had a stable disease. Mean time for CR achievement was 5.8 months (range 1–17). One- and two-year actuarial LC was 100 %. Moreover, 1- and 2-year progression-free (PFS), cancer-specific and overall survival were 57.9 % [standard error (SE) 0.09; 95 % CI 36.9–74.2] and 41.2 % (SE 0.12; 95 % CI 17.7–63.5), 80.7 % (SE 0.08; 95 % CI 59.6–91.5) and 63.3 % (SE 0.11; 95 % CI 38.4–80.3), 71.7 % (SE 0.08; 95 % CI 51.2–84.7) and 56.2 % (SE 0.10; 95 % CI 33.8–73.6). On multivariate analysis, achieving a CR within the target lesion had a borderline significance with respect to PFS (HR 0.83; SE = 0.014; z ?1.15; p = 0.095; 95 % CI 0.71–7.45). Time between HCC diagnosis and SABR delivery (< vs >12 months) was significantly correlated with OS (HR 16.5; SE 21.5; z = 2.14; p = 0.032; 95 % CI 1.27–213.3) as CLIP score (score: 0–1 vs 2) (HR 5.6; SE 4.6; z = 2.10; p = 0.036; 95 % CI 1.11–27.8). A total of 6 major toxic events (G3–G4) were recorded (20 %). In 2 patients (6 %), a radiation-induced liver disease was seen. In conclusion, SABR provided LC and survival rates comparable to other local therapies for patients with HCC lesion sized >3 cm, with acceptable toxicity profile.     

Imaging following bariatric procedures: Roux-en-Y gastric bypass, gastric sleeve, and biliopancreatic diversion

Morbid obesity remains as a common and increasing health problem. Due to limited long-term success with nonsurgical weight loss measures for morbid obesity, bariatric surgery is being performed more and more often in both academic and private practice settings and has proven to be an effective treatment option with sustained weight loss, decreased morbidity, reversal of comorbidities, and prolonged life expectancies [Am J Clin Nutr 55:615S-619S, 1992; Brolin, Nutrition 12:403-404, 1996; Fisher and Schauer, Am J Surg 184:9S-16S 2002]. The Roux-en-Y gastric bypass, biliopancreatic diversion, and gastric sleeve will be discussed in terms of their expected imaging appearance and potential complications.     

Pathogen free conditions slow the onset of neurodegeneration in a mouse model of nerve growth factor deprivation

Several studies suggest that systemic infection occurring during aging and chronic neurodegenerative diseases can evoke an exaggerated immune response that contributes to the progression of neurodegeneration and cognitive decline. However, studies directly addressing the relationship between microbial environment and the onset of neurodegeneration in Alzheimer's disease animal models are lacking. Here we show that the onset of neurodegeneration that transgenic mice develop when raised in conventional husbandry slows down when raising anti-nerve growth factor transgenic mice in a murine pathogen free condition.     

A DNA prime-modified vaccinia virus ankara boost vaccine encoding thrombospondin-related adhesion protein but not circumsporozoite protein partially protects healthy malaria-naive adults against Plasmodium falciparum sporozoite challenge

The safety, immunogenicity, and efficacy of DNA and modified vaccinia virus Ankara (MVA) prime-boost regimes were assessed by using either thrombospondin-related adhesion protein (TRAP) with a multiple-epitope string ME (ME-TRAP) or the circumsporozoite protein (CS) of Plasmodium falciparum. Sixteen healthy subjects who never had malaria (malaria-naive subjects) received two priming vaccinations with DNA, followed by one boosting immunization with MVA, with either ME-TRAP or CS as the antigen. Immunogenicity was assessed by ex vivo gamma interferon (IFN-gamma) enzyme-linked immunospot assay (ELISPOT) and antibody assay. Two weeks after the final vaccination, the subjects underwent P. falciparum sporozoite challenge, with six unvaccinated controls. The vaccines were well tolerated and immunogenic, with the DDM-ME TRAP regimen producing stronger ex vivo IFN-gamma ELISPOT responses than DDM-CS. One of eight subjects receiving the DDM-ME TRAP regimen was completely protected against malaria challenge, with this group as a whole showing significant delay to parasitemia compared to controls (P = 0.045). The peak ex vivo IFN-gamma ELISPOT response in this group correlated strongly with the number of days to parasitemia (P = 0.033). No protection was observed in the DDM-CS group. Prime-boost vaccination with DNA and MVA encoding ME-TRAP but not CS resulted in partial protection against P. falciparum sporozoite challenge in the present study.     

Liver Cancer-Specific Isoform of Serine Protease Inhibitor Kazal for the Detection of Hepatocellular Carcinoma: Results from a Pilot Study in Patients with Dysmetabolic Liver Disease

Reliable non-invasive biomarkers for the surveillance of patients at risk of hepatocellular carcinoma (HCC) development represent an unmet medical need. Recently, the liver-cancer-specific isoform of serine protease inhibitor Kazal (LC-SPIK) has been proposed as a valuable biomarker for the detection of HCC in patients with chronic liver disease of viral etiology. In the present study, we assessed the diagnostic accuracy of LC-SPIK, alone or in combination with standard serologic biomarkers (i.e., alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II, PIVKA-II), for the detection of HCC among patients with dysmetabolic liver disease. A total of 120 patients with non-alcoholic fatty liver disease (NAFLD), including 62 patients with a diagnosis of HCC and 58 with cirrhosis but without tumor, were retrospectively analyzed. The serum levels of LC-SPIK were measured by enzyme-linked immunosorbent assay (ImCare Biotech, Doylestown, PA). The serum LC-SPIK values were significantly different between patients with HCC (24.3, 17.6–39.8 ng/mL) and those with cirrhosis but without tumor (11.7, 8.7–18.2 ng/mL) (p < 0.001). By receiver operating characteristic curve analysis, we observed an area under the curve (AUC) of 0.841 for the detection of HCC; the combination with PIVKA-II further increased the accuracy to AUC = 0.926 (cross-validation). The promising results observed in the present pilot study foster additional research to investigate the usefulness of LC-SPIK for the stratification of the risk of HCC development in patients with NAFLD and advanced liver disease.