Hepatocellular carcinoma: Advances in diagnosis,management, and long term outcome

Hepatocellular carcinoma (HCC) remains a common and lethal malignancy worldwide and arises in the setting of a host of diseases. The incidence continues to increase despite multiple vaccines and therapies for viruses such as the hepatitis B and C viruses. In addition, due to the growing incidence of obesity in Western society, there is anticipation that there will be a growing population with HCC due to non-alcoholic fatty liver disease. Due to the growing frequency of this disease, screening is recommended using ultrasound with further imaging using magnetic resonance imaging and multi-detector computed tomography used for further characterization of masses. Great advances have been made to help with the early diagnosis of small lesions leading to potential curative resection or transplantation. Resection and transplantation maybe used in a variety of patients that are carefully selected based on underlying liver disease. Using certain guidelines and clinical acumen patients may have good outcomes with either resection or transplantation however many patients are inoperable at time of presentation. Fortunately, the use of new locoregional therapies has made down staging patients a potential option making them potential surgical candidates. Despite a growing population with HCC, new advances in viral therapies, chemotherapeutics, and an expanding population of surgical and transplant candidates might all contribute to improved long-term survival of these patients.     

Liver transplantation for nonalcoholic fatty liver disease:New challenges and new opportunities

Nonalcoholic fatty liver disease(NAFLD)is becoming rapidly one of the most common indications for orthotopic liver transplantation in the world.Development of graft steatosis is a significant problem during the posttransplant course,which may happen as a recurrence of pre-existing disease or de novo NAFLD.There are different risk factors that might play a role in development of graft steatosis including post-transplant metabolic syndrome,immune-suppressive medications,genetics and others.There are few studies that assessed the effects of NAFLD on graft and patient survival;most of them were limited by the duration of follow up or by the number of patients.With this review article we will try to shed light on post-liver transplantation NAFLD,significance of the disease,how it develops,risk factors,clinical course and treatment options.     

Global Sensitivity Analysis of Chosen Harmonic Drive Parameters Affecting Its Lost Motion

The aim of the presented study was to perform a global sensitivity analysis of various design parameters affecting the lost motion of the harmonic drive. A detailed virtual model of a harmonic drive was developed, including the wave generator, the flexible ball bearing, the flexible spline and the circular spline. Finite element analyses were performed to observe which parameter from the harmonic drive geometry parameter group affects the lost motion value most. The analyses were carried out using 4% of the rated harmonic drive output torque by the locked wave generator and fixed circular spline according the requirements for the high accuracy harmonic drive units. The described approach was applied to two harmonic drive units with the same ratio, but various dimensions and rated power were used to generalize and interpret the global sensitivity analysis results properly. The most important variable was for both harmonic drives the offset from the nominal tooth shape.     

Keratosis reduces sensitivity of anal cytology in detecting anal intraepithelial neoplasia

Objective

To identify factors that may contribute to poor sensitivity of anal cytology in contrast to the sensitivity of anoscopy in heterosexual women.

Methods

We analyzed 324 patients with biopsy confirmed diagnosis of genital intraepithelial neoplasia (either vulva, vaginal, or cervical) from 2006 to 2011 who underwent both anal cytology and anoscopy. Cytology, anoscopy, and biopsy results were recorded. Biopsy specimens underwent independent analysis for quality of specimen. Also, biopsy specimens were analyzed for characteristics that may contribute to correlation, or lack thereof, between anal cytology and anoscopic directed biopsy.

Results

133 (41%) patients had abnormal anoscopy and underwent directed biopsy. 120 patients with normal anal cytology had anoscopy directed biopsies, resulting in 58 cases of AIN (sensitivity 9.4%; 0.039-0.199). This cohort was noted to have extensive keratosis covering the entire dysplastic anal lesion. 18 patients yielded abnormal anal cytology. Of these patients, 13 had anoscopic directed biopsies revealing 6 with AIN and absent keratosis (specificity 88.6%; 0.78-0.95). The κ statistic for anal cytology and anoscopy was − 0.0213 (95% CI = − 0.128-0.086).

Conclusion

Keratosis reduces the sensitivity of anal cytology. Furthermore, anal cytology poorly correlates with anoscopy in the detection of AIN (κ statistic = − 0.0213).     

Natural products for cancer-targeted therapy: citrus flavonoids as potent chemopreventive agents

Targeted therapy has been a very promising strategy of drug development research. Many molecular mechanims of diseases have been known to be regulated by abundance of proteins, such as receptors and hormones. Chemoprevention for treatment and prevention of diseases are continuously developed. Pre-clinical and clinical studies in chemoprevention field yielded many valuable data in preventing the onset of disease and suppressing the progress of their growth, making chemoprevention a challenging and a very rational strategy in future researches. Natural products being rich of flavonoids are those fruits belong to the genus citrus. Ethanolic extract of Citrus reticulata and Citrus aurantiifolia peels showed anticarcinogenic, antiproliferative, co-chemotherapeutic and estrogenic effects. Several examples of citrus flavonoids that are potential as chemotherapeutic agents are tangeretin, nobiletin, hesperetin, hesperidin, naringenin, and naringin. Those flavonoids have been shown to possess inhibition activity on certain cancer cells' growth through various mechanisms. Moreover, citrus flavonoids also perform promising effect in combination with several chemotherapeutic agents against the growth of cancer cells. Some mechanisms involved in those activities are through cell cycle modulation, antiangiogenic effect, and apoptosis induction. Previous studies showed that tangeretin suppressed the growth of T47D breast cancer cells by inhibiting ERK phosphorylation. While in combination with tamoxifen, doxorubicin, and 5-FU, respectively, it was proven to be synergist on several cancer cells. Hesperidin and naringenin increased cytotoxicitity of doxorubicin on MCF-7 cells and HeLa cells. Besides, citrus flavonoids also performed estrogenic effect in vivo. One example is hesperidin having the ability to decrease the concentration of serum and hepatic lipid and reduce osteoporosis of ovariectomized rats. Those studies showed the great potential of citrus fruits as natural product to be developed as not only the source of co-chemotherapeutic agents, but also phyto-estrogens. Therefore, further study needs to be conducted to explore the potential of citrus fruits in overcoming cancer.