Vegetative plaque on the left superior eyelid.

Herein we present case report of a 73-year-old female who developed a rapidly growing, ulcerated lesion on her left superior eyelid. Despite treatment for suspected infection, symptoms only marginally improved. Physical examination revealed a diffusely ulcerated multinodular tumour with overlying haemorrhagic and serosanguineous exudate. A shave biopsy led to a diagnosis of primary cutaneous anaplastic large cell lymphoma (pcALCL), a rare CD30+ lymphoproliferative disorder. The patient had no extracutaneous involvement on PET-CT and her prognosis is good given the indolent nature of pcALCL. Differential diagnoses included merkel cell carcinoma, periocular sebaceous carcinoma, lymphomatoid papulosis, and extranodal natural killer/T cell lymphoma. Prognosis for pcALCL is generally good. Treatment recommendation for pcALCL is surgical excision with negative margins for localised disease, while intravenous brentuximab vedotin is suggested for widespread, relapsed, and refractory disease.

A novel irinotecan-lipiodol nanoemulsion for intravascular administration: pharmacokinetics and biodistribution in the normal and tumor bearing rat liver.

Colorectal cancer is one of the most common cancers in the United States and treatment options are limited for patients who develop liver metastases. Several chemotherapeutic regimens have been used for transvascular liver-directed therapy in the treatment of colorectal liver metastases without clear evidence of superiority of one therapy over another. We describe the development of a novel nanoemulsion through combining irinotecan (IRI), a first line systemic agent used for the treatment of colon cancer, with lipiodol, an oily contrast medium derived from poppy seed oil, and evaluated its pharmacokinetic and biodistribution profile as a function of portal venous chemoembolization (PVCE) versus transarterial chemoembolization (TACE) delivery. The Tessari technique was used to create a stable emulsion (20 mg IRI mixed with 2 mL lipiodol) with resultant particle size ranging from 28.9 nm to 56.4 nm. Pharmacokinetic profile established through venous sampling in Buffalo rats demonstrate that the area under the curve (AUC0-∞) of IRI was significantly less after PVCE with IRI-lipiodol as compared to IRI alone (131 vs. 316 µg*min/mL, p-value = .023), suggesting significantly higher amounts of IRI retention in the liver with the IRI-lipiodol nanoemulsion via first-pass extraction. Subseqent biodistribution studies in tumor-bearing WAG/Rjj rats revealed more IRI present in the tumor following TACE versus PVCE (29.19 ± 12.33 µg/g versus 3.42 ± 1.62; p-value = .0033) or IV (29.19 ± 12.33 µg/g versus 1.05 ± 0.47; p-value = .0035). The IRI-lipiodol nanoemulsion demonstrated an acceptable hepatotoxicity profile in all routes of administration. In conclusion, the IRI-lipiodol nanoemulsion via TACE showed promise and warrants further investigation as an option for the treatment of metastatic colorectal cancer.

Amyloid precursor protein expression modulates intestine immune phenotype.

Amyloid precursor protein (APP) is widely expressed across many tissue and cell types. Proteolytic processing of the protein gives rise to a plethora of protein fragments with varied biological activities. Although a large amount of data has been generated describing the metabolism of the protein in neurons, its role in regulating the phenotype of other cells remains unclear. Based upon prior work demonstrating that APP regulates the activation phenotype of monocytic lineage cells, we hypothesized that APP can regulate macrophage activation phenotype in tissues other than brain. Ileums of the small intestines from C57BL6/J wild type and APP(-/-) mice were compared as a representative tissue normally associated with abundant macrophage infiltration. APP(-/-) intestines demonstrated diminished CD68 immunoreactivity compared to wild type mice. This correlated with significantly less cyclooxygenase-2 (cox-2), CD68, CD40, CD11c, and ßIII-tubulin protein levels. Peritoneal macrophages from APP(-/-) mice demonstrated decreased in vitro migratory ability compared to wild type cells and diminished basal KC cytokine secretion. Whereas, APP(-/-) intestinal macrophages had an increase in basal KC cytokine secretion compared to wild type cells. Conversely, there was a significant decrease in multiple cytokine levels in APP(-/-) compared to wild type ileums. Finally, APP(-/-) mice demonstrated impaired absorption and increased motility compared to wild type mice. These data demonstrate the APP expression regulates immune cell secretions and phenotype and intestinal function. This data set describes a novel function for this protein or its metabolites that may be relevant not only for Alzheimer's disease but a range of immune-related disorders.