TNM/Okuda/Barcelona/UNOS/CLIP International Multidisciplinary Classification of Hepatocellular Carcinoma: concepts,perspectives, and radiologic implications

Hepatocellular carcinoma (HCC) is a major health problem worldwide. Moreover, the liver cancer field is evolving rapidly, with early diagnosis, new therapies, and a better understanding of HCC’s biology and development. Accurate staging is important for determining prognosis and selecting the most appropriate treatment for each patient. Surgical intervention remains the most effective treatment for HCC and is the only potentially curative modality. However, in HCC patients, overall survival is also independently affected by underlying liver disease and cirrhosis, which in turn affect the applicability and efficacy of treatment. Although several staging classification and prognostic scoring systems have been proposed for determining the stage and prognosis of HCC, no consensus exists on the best classification method. The most common staging classification systems include tumor-node-metastasis stage, Okuda staging, Cancer of the Liver Italian Program score, Barcelona Clinic Liver Cancer staging classification, the French, the Chinese University Prognostic Index, Japanese Integrated Scoring, and the Tokyo score. Radiologists should be aware of the different staging classification systems for HCC and familiar with the system relevant to their respective referring clinicians, as it will provide pertinent radiological evaluation for multidisciplinary management.     

A novel therapeutic drug (copper nicotinic acid complex) for non-alcoholic fatty liver.

BACKGROUND: Fatty liver is the accumulation of fat in liver cells, which leads to disruption of the normal liver structure and function. METHODS: A non-alcoholic fatty liver rat model received copper (Cu) (I)-nicotinate complex [CuCl(HNA)2] for 4 weeks. RESULTS: Clinical signs and histopathological examinations showed obvious improvements in rats that received Cu complex who were continuously on an (HCFF) diet than those returned to standard diet with Cu complex. The improvement was matched in total lipids in sera and hepatic tissue, with disappearance of fat droplets from liver sections. Furthermore, the gain in body weight and the corresponding decrease in liver weight, decreased liver transaminases and alkaline phosphatase were prominent. The oxidative stress markers such as nitric oxide, lipid peroxides, glutathione and superoxide dismutase were obviously changed to healthy normal levels. CONCLUSION: The Cu complex may serve as a novel chemical restoring agent in fatty degenerated liver cells and for renewal of their structure and functions. However, clinical trials are required for more evaluation of the Cu complex in humans.     

Instant hepatic differentiation of human embryonic stem cells using activin A and a deleted variant of HGF

Human embryonic stem (hES) cells have the ability to differentiate into a variety of different cell lineages and potentially provide a source of differentiated cells for many therapeutic uses. Here we investigated an efficient method of hepatic differentiation from hES cells. A human ES cell line, KhES-1, was used and maintained by a nonfeeder method. KhES-1 cells were cultured for 5 days in the presence of human activin A (50 ng/ml) and then treated with a deleted variant of hepatocyte growth factor (dHGF) at 0, 100, or 500 ng/ml for 7 days. The resultant cells were biologically analyzed. The expression of the endodermal genes SOX17 and FOXA2 increased in KhES-1 cells after activin A treatment. In contrast, Oct4, a self-renewal undifferentiated marker, decreased in a time-dependent manner in KhES-1 cells. Following a 7-day treatment of the resultant cells with dHGF, especially at 500 ng/ml, KhES-1 cells showed an expression of the hepatic makers albumin, AFP, and CK18. Transitional electron microscopy showed well-developed glycogen rosettes and a gap junction in KhES-1 cells treated with 500 ng/ml of dHGF. We developed an efficient method to differentiate KhES-1 cells into hepatocyte-like cells in vitro using 50 ng/ml of activin A and 500 ng/ml of dHGF.     

Diabetes enhances mRNA levels of proapoptotic genes and caspase activity, which contribute to impaired healing

We previously reported that after a bacteria-induced wound in the scalp, type 2 diabetic (db/db) mice had higher levels of apoptosis of fibroblasts and bone-lining cells that are critical for healing compared with normoglycemic controls. To investigate mechanisms by which this might occur, RNA profiling and caspase activity was measured after inoculation of Porphyromonas gingivalis. Diabetes caused a more than twofold induction of 71 genes that directly or indirectly regulate apoptosis and significantly enhanced caspase-8, -9, and -3 activity. The functional significance of diabetes-induced apoptosis was studied by treating diabetic mice with a pancaspase inhibitor, z-VAD-fmk (N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone). Inhibiting apoptosis significantly improved several parameters of healing, including fibroblast density, enhanced mRNA levels of collagen I and III, and increased matrix formation. Improvements were also noted in bone, with an increase in the number of bone-lining cells and new bone formation. Thus, diabetes-enhanced apoptosis represents an important mechanism through which healing is impaired, and this can be explained, in part, by diabetes-increased expression of proapoptotic genes and caspase activity.     

N-acetyl-cysteine is a novel adjuvant to clomiphene citrate in clomiphene citrate-resistant patients with polycystic ovary syndrome

OBJECTIVE: To evaluate the effect of N-acetyl-cysteine (NAC), a mucolytic drug with insulin sensitizing properties, as an adjuvant therapy in subjects with polycystic ovary syndrome (PCOS) resistant to clomiphene citrate (CC). DESIGN: Placebo-controlled, double-blind randomized trial. SETTING: University-based hospital and private infertility practice. PATIENT(S): One hundred fifty women diagnosed with CC-resistant PCOS, aged 18-39 years undergoing therapy for infertility were included. INTERVENTION(S): The patients were assigned randomly to receive either NAC 1.2 g/d (group I) or placebo (group II) with CC 100 mg/d for 5 days starting at day 3 of the cycle. MAIN OUTCOME MEASURE(S): Ovulation rate and pregnancy rate (PR). RESULT(S): Combination of CC and NAC significantly increased both ovulation rate and PR in women with CC-resistant PCOS (49.3% vs. 1.3% and 21.3% vs. 0%, respectively). No cases of ovarian hyperstimulation syndrome (OHSS) were reported in the NAC group; two cases of miscarriage (12.5%) were reported. CONCLUSION(S): The NAC as an adjuvant to CC was more effective than placebo for CC-resistant patients with PCOS. It is safe and well tolerated.     

A Swedish collection of medicinal plants from Cameroon

A collection of 32 botanically identified medicinal plants from the slopes of Mt. Cameroon made by two Swedish settlers in the beginning of the last century is described and the literature is followed up. The drug names were found to be unaltered during the century passed.     

Predicting the risk for dialysis or death in IgA nephropathy

For the individual patient with primary IgA nephropathy (IgAN), it remains a challenge to predict long-term outcomes for patients receiving standard treatment. We studied a prospective cohort of 332 patients with biopsy-proven IgAN patients followed over an average of 13 years. We calculated an absolute renal risk (ARR) of dialysis or death by counting the number of risk factors present at diagnosis: hypertension, proteinuria ≥1 g/d, and severe pathologic lesions (global optical score, ≥8). Overall, the ARR score allowed significant risk stratification (P < 0.0001). The cumulative incidence of death or dialysis at 10 and 20 years was 2 and 4%, respectively, for ARR=0; 2 and 9% for ARR=1; 7 and 18% for ARR=2; and 29 and 64% for ARR=3, in adequately treated patients. When achieved, control of hypertension and reduction of proteinuria reduced the risk for death or dialysis. In conclusion, the absolute renal risk score, determined at diagnosis, associates with risk for dialysis or death.