Targeted Cyclo[8]pyrrole-Based NIR-II Photoacoustic Tomography Probe for Suppression of Orthotopic Pancreatic Tumor Growth and Intra-abdominal Metastases.

Pancreatic cancer is highly lethal. New diagnostic and treatment modalities are desperately needed. We report here that an expanded porphyrin, cyclo[8]pyrrole (CP), with a high extinction coefficient (89.16 L/g·cm) within the second near-infrared window (NIR-II), may be formulated with an αvß3-specific targeting peptide, cyclic-Arg-Gly-Asp (cRGD), to form cRGD-CP nanoparticles (cRGD-CPNPs) with promising NIR-II photothermal (PT) therapeutic and photoacoustic (PA) imaging properties. Studies with a ring-array PA tomography system, coupled with analysis of control nanoparticles lacking a targeting element (CPNPs), revealed that cRGD conjugation promoted the delivery of the NPs through abnormal vessels around the tumor to the solid tumor core. This proved true in both subcutaneous and orthotopic pancreatic tumor mice models, as confirmed by immunofluorescent studies. In combination with NIR-II laser photoirradiation, the cRGD-CPNPs provided near-baseline tumor growth inhibition through PTT both in vitro and in vivo. Notably, the combination of the present cRGD-CPNPs and photoirradiation was found to inhibit intra-abdominal metastases in an orthotopic pancreatic tumor mouse model. The cRGD-CPNPs also displayed good biosafety profiles, as inferred from PA tomography, blood analyses, and H&E staining. They thus appear promising for use in combined PA imaging and PT therapeutic treatment of pancreatic cancer.

Evaluation of defecative function 5 years or longer after laparoscopic-assisted pull-through for imperforate anus.

BACKGROUND: Laparoscopic anorectoplasty was introduced in 2000, but the procedure has not yet gained universal acceptance. Previous studies, including ours, reported satisfactory early postoperative outcome as compared with posterior sagittal anorectoplasty (PSARP), but mid- to long-term results are not available. Here, we aim to evaluate the mid- to long-term defecative function in these patients. MATERIALS AND METHODS: A retrospective study was carried out and included all patients who underwent laparoscopic-assisted anorectoplasty for high-/intermediate-type imperforate anus between 2001 and 2005. Their degree of continence was graded according to the Krickenbeck classification and compared with historical controls treated with PSARP. The results were compared using χ(2) test, and P < .05 was considered statistically significant. RESULTS: There were 18 patients who underwent laparoscopic anorectoplasty (LAR) in the study period. They were compared with 20 historical PSARP patients. For defecation sensation, 16 of the 18 LAR patients were positive, whereas there were 16 of 20 PSARP patients. Eight LAR patients were clean without any fecal soiling or incontinence (11/20 PSARP). Only 3 of 18 LAR had constipation as compared with 7 of 20 PSARP. The need for rectal enema for evacuation was seen in 1 of 20 LAR patients and 2 of 20 PSARP patients (for all categories, P > .05). CONCLUSIONS: Mid- to long-term follow-up study revealed satisfactory defecative function for patients with high-/intermediate-type imperforate anus after LAR. The outcome is at least as good as PSARP. Longer term follow-up with larger sample size is necessary to demonstrate the benefits of LAR over PSARP.

ω-3 fatty acids suppress inflammatory cytokine production by macrophages and hepatocytes.

OBJECTIVE: Long-term total parenteral nutrition (TPN) in children is often complicated by parental nutrition-associated liver disease and may even lead to liver failure. Recently, the addition of ω-3 fatty acids to TPN has been shown to reduce the risk of parental nutrition-associated liver disease. The purpose of this study was to explore the anti-inflammatory effects of ω-3 fatty acids (eicosapentaenoic acid [EPA]) to demonstrate the protection of the liver against hepatic steatosis and damage. MATERIALS AND METHODS: Lipopolysaccharide (LPS) and prostaglandin E(2) (PGE(2)) were used to stimulate human macrophages and hepatocytes (THLE-3) to induce in vitro inflammatory condition. The cells were then incubated with either ω-3 (EPA) or ω-6 (arachidonic acid) fatty acids. Supernatants were collected at different time points for the measurement of tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and interleukin 10 (IL-10) using enzyme-linked immunosorbent assay. Furthermore, pretreated macrophages by LPS stimulation and after incubation with EPA were added to prestimulated hepatocytes for the subsequent measurement of cytokine response. RESULTS: Eicosapentaenoic acid effectively reduced LPS-induced or PGE(2)-induced TNF-α and IL-6 expression, and increased IL-10 expression significantly when compared with arachidonic acid. Furthermore, supernatant collected after co-culturing EPA with macrophages also suppressed the levels of TNF-α and IL-6 in hepatocytes. This would suggest that EPA not only had an anti-inflammatory effect on macrophages and hepatocytes directly, it could indirectly reduce hepatocyte inflammation through activated macrophages. CONCLUSIONS: The addition of ω-3 fatty acids in TPN suppresses the inflammatory response via direct and indirect routes. The findings may help explain the clinical benefits of EPA in pediatric patients receiving long-term TPN.