Biliary atresia and noncardiac polysplenic syndrome: US and surgical considerations

Ten percent of children with biliary atresia have an associated complex of anomalies, including polysplenia, azygous continuation of the inferior vena cava, preduodenal portal vein, hepatic arterial anomalies, and bilaterally bilobed lungs. These abnormalities will not be detected if the preoperative workup is limited to hepatobiliary nuclear scanning. Ultrasonography is important in the preoperative evaluation of patients suspected of having biliary atresia. It is important to identify the associated abnormalities preoperatively because they have an impact on the initial portoenterostomy and may preclude subsequent orthotopic liver transplantation.     

Thickening and nodules in port-wine stains

Port-wine stains are vascular ectasias that can develop thickening or nodules over time. Thickening is a further dilation of the ectatic vessels, and nodules are vascular neoplasms or hyperplasias. The records of 173 subjects with port-wine stains were reviewed for thickening, nodules, and associated characteristics. The incidence of nodules increased with age. Thickening often began in early adulthood, but its intensity and association with nodules continued to increase into older age. Thickening and nodules were most common in the area of the second and third branches of the trigeminal nerve innervating the face and were associated with deepening color. The incidence of thickening alone was greater in male than in female patients.     

Do aluminium-based phosphate binders continue to have a role in contemporary nephrology practice?

Background

Aluminium-containing phosphate binders have long been used for treatment of hyperphosphatemia in dialysis patients. Their safety became controversial in the early 1980's after reports of aluminium related neurological and bone disease began to appear. Available historical evidence however, suggests that neurological toxicity may have primarily been caused by excessive exposure to aluminium in dialysis fluid, rather than aluminium-containing oral phosphate binders. Limited evidence suggests that aluminium bone disease may also be on the decline in the era of aluminium removal from dialysis fluid, even with continued use of aluminium binders.

Discussion

The K/DOQI and KDIGO guidelines both suggest avoiding aluminium-containing binders. These guidelines will tend to promote the use of the newer, more expensive binders (lanthanum, sevelamer), which have limited evidence for benefit and, like aluminium, limited long-term safety data. Treating hyperphosphatemia in dialysis patients continues to represent a major challenge, and there is a large body of evidence linking serum phosphate concentrations with mortality. Most nephrologists agree that phosphate binders have the potential to meaningfully reduce mortality in dialysis patients. Aluminium is one of the cheapest, most effective and well tolerated of the class, however there are no prospective or randomised trials examining the efficacy and safety of aluminium as a binder. Aluminium continues to be used as a binder in Australia as well as some other countries, despite concern about the potential for toxicity. There are some data from selected case series that aluminium bone disease may be declining in the era of reduced aluminium content in dialysis fluid, due to rigorous water testing.

Summary

This paper seeks to revisit the contemporary evidence for the safety record of aluminium-containing binders in dialysis patients. It puts their use into the context of the newer, more expensive binders and increasing concerns about the risks of calcium binders, which continue to be widely used. The paper seeks to answer whether the continued use of aluminium is justifiable in the absence of prospective data establishing its safety, and we call for prospective trials to be conducted comparing the available binders both in terms of efficacy and safety.

     

Hypersensitivity reactions to anticancer agents: Data mining of the public version of the FDA adverse event reporting system, AERS

Background

Cancer-testis antigens (CTAs) are suitable targets for cancer-specific immunotherapy. The aim of the study is to investigate the expression of CTAs in intrahepatic cholagiocarcinoma (IHCC) and evaluate their potential therapeutic values.

Methods

Eighty-nine IHCC patients were retrospectively assessed for their expression of CTAs and HLA Class I by immunohistochemistry using the following antibodies: MA454 recognizing MAGE-A1, 57B recognizing multiple MAGE-A (MAGE-A3/A4), E978 recognizing NY-ESO-1, and EMR8-5 recognizing HLA class I. The clinicopathological and prognostic significance of individual CTA markers and their combination were further evaluated.

Results

The expression rates of MAGE-A1, MAGE-A3/4 and NY-ESO-1 were 29.2%, 27.0% and 22.5%, respectively. The concomitant expression of CTAs and HLA class I antigen was observed in 33.7% of the IHCC tumors. We found that positive MAGE-3/4 expression correlated with larger tumor size (≥ 5 cm), tumor recurrence and poor prognosis. Moreover, we identified 52 cases (58.4%) of IHCC patients with at least one CTA marker expression, and this subgroup displayed a higher frequency of larger tumor size and a shorter survival than the other cases. Furthermore, expression of at least one CTA marker was also an independent prognostic factor in patients with IHCC.

Conclusion

Our data suggest that specific immunotherapy targeted CTAs might be a novel treatment option for IHCC patients.     

Non‐small cell lung cancer metastasis to the oral cavity: a case report

Lung cancer, including non‐small cell lung cancer, remains prevalent in Australia and has a very poor survival rate. Metastases to the oral cavity are a rare occurrence that can arise from lung cancers. This case report describes the presentation of a metastatic lesion from a poorly differentiated lung adenocarcinoma on the mandibular buccal alveolar attached gingivae. The inpatient had terminal disease with known pleural, brain and liver metastases and was receiving palliative care at the time of diagnosis of the oral lesion.     

Essential amino acid deprivation induces monocytic differentiation of the human HL-60 myeloid leukemia cell line

In this study we examine the effects of amino acid deprivation on the growth and differentiation of the human HL-60 myeloid leukemia cell line. The HL-60 cell line was chosen for study because of its ability to differentiate along either a granulocytic or monocytic pathway under appropriate culture conditions. Differentiation was determined by changes in cell morphology, nonspecific esterase (NSE) content, hydrogen peroxide (H2O2) production, and expression of the cell surface differentiation antigens LeuM3 (CD14) and OKM1 (CD11). Using a model system in which HL-60 cells were cultured in medium that selectively lacked one amino acid (AA), it was seen that deprivation of HL-60 cells for essential (but not nonessential) AAs results in decreased cell growth and viability and in differentiation of 30% to 60% of the surviving population of cells specifically along the monocytic pathway. This differentiation is irreversible as well as time- and dose- dependent. Culture of HL-60 cells in essential AA-deficient medium potentiated the differentiative effects of recombinant human interferon- gamma (IFN-gamma), recombinant human tumor necrosis factor (TNF), and dihydroxyvitamin D3 (D3), all of which have previously been shown to induce monocytic differentiation of HL-60 cells. Differentiated cells had decreased DNA and RNA synthesis, but protein synthesis was unchanged compared with control cells. The protein synthesis inhibitor cycloheximide prevented differentiation, indicating the necessity of protein synthesis in this process. Cell cycle analysis revealed that an increased proportion of cells cultured in AA-deficient medium was arrested in G0-G1 (80% and 50% for AA-deficient and control cells, respectively). These results suggest that alterations of AA metabolism and subsequent perturbations in DNA and RNA synthesis may be important in initiating differentiation or in augmenting cytokine-induced differentiation of HL-60 cells into more mature, nonreplicating, monocyte-like cells.