Cancer review: Cholangiocarcinoma

Cholangiocarcinoma (CCA) is the most common biliary tract malignancy. CCA is classified as intrahepatic, perihilar or distal extrahepatic; the individual subtypes differ in their biologic behavior, clinical presentation, and management. Throughout the last decades, CCA incidence rates had significantly increased. In addition to known established risk factors, novel possible risk factors (i.e. obesity, hepatitis C virus) have been identified that are of high importance in developed countries where CCA prevalence rates have been low. CCA tends to develop on the background of inflammation and cholestasis. In recent years, our understanding of the molecular mechanisms of cholangiocarcinogenesis has increased, thereby, providing the basis for molecularly targeted therapies. In its diagnostic evaluation, imaging techniques have improved, and the role of complementary techniques has been defined. There is a need for improved CCA biomarkers as currently used ones are suboptimal. Multiple staging systems have been developed, but none of these is optimal. The prognosis of CCA is considered dismal. However, treatment options have improved throughout the last two decades for carefully selected subgroups of CCA patients. Perihilar CCA can now be treated with orthotopic liver transplantation with neoadjuvant chemoradiation achieving 5-year survival rates of 68%. Classically considered chemotherapy-resistant, the ABC-02 trial has shown the therapeutic benefit of combination therapy with gemcitabine and cisplatin. The benefits of adjuvant treatments for resectable CCA, local ablative therapies and molecularly targeted therapies still need to be defined. In this article, we will provide the reader with an overview over CCA, and discuss the latest developments and controversies

Review of hepatocellular carcinoma: Epidemiology, etiology, and carcinogenesis

Since the 1970s, the epidemic of hepatocellular carcinoma (HCC) has spread beyond the Eastern Asian predominance and has been increasing in Northern hemisphere, especially in the United States (US) and Western Europe. It occurs more commonly in males in the fourth and fifth decades of life. Among all cancers, HCC is one of the fastest growing causes of death in the US and poses a significant economic burden on healthcare. Chronic liver disease due to hepatitis B virus or hepatitis C virus and alcohol accounts for the majority of HCC cases. Incidence of nonalcoholic fatty liver disease has been on the risem and it has also been associated with the development of HCC. Its pathogenesis varies based on the underlying etiological factor although majority of cases develop in the setting of background cirrhosis. Carcinogenesis of HCC includes angiogenesis, chronic inflammation, and tumor macroenvironment and microenvironment. There is a significant role of both intrinsic genetic risk factors and extrinsic influences such as alcohol or viral infections that lead to the development of HCC. Understanding its etiopathogenesis helps select appropriate diagnostic tests and treatments

Hydropic Gallbladder in Three Patients with Poorly Controlled Diabetes Mellitus: What Constitutes Optimal Management?

Context Long-standing diabetes mellitus results in autonomic nervous system dysfunction, leading to gastroparesis and cholecystoparesis. The latter can result in hydropic gallbladder, a condition that arises from the accumulation of mucinous secretions within the gallbladder, usually caused by obstruction of the cystic duct, but not in the case of the patients with diabetes that we have illustrated. Case report We describe three patients who presented with non-specific abdominal discomfort at the time of admission for complications of poorly controlled diabetes and were subsequently found to have hydropic gallbladder. We theorize that hydropic gallbladder may be a result of a natural progression of gallbladder dysfunction in poorly controlled diabetics with autonomic neuropathy. In our cases the risk of perioperative mortality was high at the time of presentation. No surgical intervention was performed except in one case with the most significant sized gallbladder, and underwent a temporizing cholecystostomy. Conclusions The development of hydropic gallbladder in patients with non-obstructed cystic ducts highlights the complexities of management of patients with functional biliary pain. The rome committee on functional biliary and pancreatic disorders has defined the characteristics of this pain. There is a need for guidelines to direct appropriate assessment of hydropic gallbladder in diabetics and also to determine the indications for cholecystectomy.Image: HIDA scan showing a low ejection fraction of the gallbladder after administration of CCK

Photocatalytic Degradation of Organic Dyes Contaminated Aqueous Solution Using Binary CdTiO₂ and Ternary NiCdTiO₂ Nanocomposites

The synergistic effect of binary CdTiO2 and ternary NiCdTiO2 on the photocatalytic efficiency of TiO2 nanoparticles was investigated. The SEM analysis demonstrates spherical TiO2 NPs of different sizes present in agglomerated form. The structural analysis of the nanocomposites reveals a porous structure for TiO2 with well deposited Cd and Ni NPs. TEM images show NiCdTiO2 nanocomposites as highly crystalline particles having spherical and cubical geometry with an average particle size of 20 nm. The EDX and XRD analysis confirm the purity and anatase phase of TiO2, respectively. Physical features of NiCdTiO2 nanocomposite were determined via BET analysis which shows that the surface area, pore size and pore volume are 61.2 m2/g, 10.6 nm and 0.1 cm3/g, respectively. The absorbance wavelengths of the CdTiO2 and NiCdTiO2 nanocomposites have shown red shift as compared to the neat TiO2 due to coupling with Ni and Cd that results in the enhanced photocatalytic activity. The photocatalytic activity demonstrated that TiO2, CdTiO2 and NiCdTiO2 degrade methylene blue (MB) and methyl green (MG) about 76.59, 82, 86% and 63.5, 88, 97.5%, respectively, at optimum reaction conditions

Biological and Physicochemical Characterization of Self-Adhesive Protective Coating Dental Restorative Material after Incorporation of Antibacterial Nanoparticles

This study evaluated the physicochemical and antibacterial properties of EQUIATM coat liquid (E) after incorporation of zinc oxide (ZnO) and titanium dioxide (TiO2) nanoparticles. ZnO and TiO2 (1 wt.% and 2 wt.%) were dispersed in EQUIA coat. Principal component analysis (PCA) and cluster analysis were performed to visualize systemic variation. Antibacterial activity was evaluated by colony-forming units and crystal violet staining using Streptococcusmutans and Lactobacillusacidophilus after 24 h, 48 h, and 72 h, and the microstructure was studied by scanning electron microscopy. The weight change was analyzed at 1 and 21 days. The PCA for TiO2- and ZnO-based groups showed 100% variance at all spectral ranges at 600–800/cm and 800–1200/cm, whereas 1200–1800/cm and 2700–3800/cm spectral regions demonstrated 99% variance. The absorbance values were significant (p < 0.05) for both nanoparticles-based adhesives, and the specimens with 2 wt.% ZnO showed the maximum response by minimum bacterial attachment, and the control group showed the least response by maximum attachment. The weight change percentage was reduced after the incorporation of antibacterial nanoparticles. It is suggested that EQUIATM coat containing nanoparticles exhibits promising results, and it may be recommended to clinically use as an improved coating material

Structural, Physical, and Mechanical Analysis of ZnO and TiO₂ Nanoparticle-Reinforced Self-Adhesive Coating Restorative Material

This study aimed to modify an EQUIA coat (EC; GC, Japan) by incorporating 1 and 2 wt.% of zinc oxide (ZnO; EC-Z1 and EC-Z2) and titanium dioxide (TiO2; EC-T1 and EC-T2) nanoparticles, whereby structural and phase analyses were assessed using Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD), respectively. Thermogravimetric analysis/differential scanning calorimetry, micro-hardness, and water absorption analyses were conducted, and the microstructure was studied by scanning electron microscopy/energy-dispersive spectroscopy. FTIR spectra showed a reduction in peak heights of amide (1521 cm−1) and carbonyl (1716 cm−1) groups. XRD showed peaks of ZnO (2θ ~ 31.3°, 34.0°, 35.8°, 47.1°, 56.2°, 62.5°, 67.6°, and 68.7°) and TiO2 (2θ ~ 25.3°, 37.8°, 47.9, 54.5°, 62.8°, 69.5°, and 75.1°) corresponding to a hexagonal phase with a wurtzite structure and an anatase phase, respectively. Thermal stability was improved in newly modified materials in comparison to the control group. The sequence of obtained glass transitions was EC-T2 (111 °C), EC-T1 (102 °C), EC-Z2 (98 °C), EC-Z1 (92 °C), and EC-C (90 °C). EC-T2 and EC-T1 showed the highest (43.76 ± 2.78) and lowest (29.58 ± 3.2) micro-hardness values. EC showed the maximum water absorption (1.6%) at day 7 followed by EC-T1 (0.82%) and EC-Z1 (0.61%). These results suggest that EC with ZnO and TiO2 nanoparticles has the potential to be used clinically as a coating material

Phase 1 study of the immunotoxin LMB-100 in patients with mesothelioma and other solid tumors expressing mesothelin

BACKGROUND: LMB-100 is an antibody-toxin conjugate with an anti-mesothelin Fab linked to a 24 kDa portion of Pseudomonas exotoxin A with mutations that decrease immunogenicity. The objective of this first-in-human Phase I study was to determine the maximum tolerated dose (MTD) and safety in patients with advanced solid tumors expressing mesothelin. METHODS: Cohorts of 1–7 patients received intravenous LMB-100 at 7 dose levels from 40 to 250 mcg/kg intravenously on days 1, 3 and 5 of a 21-day cycle. RESULTS: Of 25 subjects accrued, 17 had mesothelioma, 3 each had ovarian or pancreatic cancer and 2 had gastric cancer. Dose limiting toxicity (DLT) occurred in 2 of 4 treated at 250 mcg/kg (capillary leak syndrome) and 3 of 7 treated at 170 mcg/kg (creatinine increase). The MTD of LMB-100 was 140 mcg/kg. Of 10 mesothelioma patients treated at 170 or 140 mcg/kg, 8 had stable disease and 2 progressive disease. Peak LMB-100 plasma concentrations were dose-dependent during cycle 1. Development of anti-drug antibodies (ADAs) decreased LMB-100 blood levels in 8 of 21 (38%) patients who received cycle 2 and 9 of 11 patients (81.8%) receiving cycle 3. CONCLUSIONS: The MTD for single agent LMB-100 is 140 mcg/kg given on a QOD x 3 schedule. Although less immunogenic than the first generation anti-mesothelin immunotoxin SS1P, the majority of patients developed ADAs after 2 cycles and LMB-100 has limited anti-tumor efficacy as a single agent. Phase II studies of LMB-100 plus pembrolizumab are ongoing for patients with mesothelioma and lung cancer