Characterization of the CXCR4 Signaling in Pancreatic Cancer Cells

CXCL12 and its receptor, CXCR4, are emerging as promising targets for modulating growth, angiogenesis, and metastasis in several human cancers. Indeed, blocking the receptor is sufficient to prevent metastasis and angiogenesis in experimental breast cancer xenografts. Recently, the biological effect of the CXCR4 in pancreatic cancer, one of the most deadly neoplastic diseases, has been reported. However, the molecular mechanism by which CXCR4 contributes to these properties is not completely understood. In this paper, we characterize the signaling pathways activated by CXCR4 in pancreatic cancer. We show that after CXCR4 activation, EGFR becomes tyrosine phosphorylated, and the kinase activity of this receptor, together with the activation of MMPs, Src, and PI3-Kinase, is required for CXCR4-mediated ERK activation. Analysis of this cascade in pancreatic cancer cells revealed that the ERK-mediated pathway regulates genes involved in angiogenesis, such as VEGF, CD44, HIF1α, and IL-8. Furthermore, ERK blockage inhibits the migration and tube formation of endothelial cells induced by CXCL12. Considering that inhibitors for several components of this pathway, including CXCR4 itself, are at different stages of clinical trials, this study provides theoretical justification for the clinical testing of these drugs in pancreatic cancer, thus extending the list of potential targets for treating this dismal disease.     

Comparison of ThinPrep versus conventional smear cytopreparatory techniques for fine-needle aspiration specimens of head and neck masses.

OBJECTIVES: Diagnostic accuracy of the ThinPrep process (Cytyc, Boxborough, MA) was compared with that of conventional (smear) cytopreparation for fine-needle aspiration (FNA) of head and neck masses. METHODS: In a prospective, randomized, single-blinded study, 209 patients served as their own controls and underwent 236 FNAs using ThinPrep and conventional (smear) cytopreparatory techniques. RESULTS: ThinPrep produced less air-drying artifact and less mechanical distortion than the conventional method. The conventional technique was diagnostic in 63% of samples; the ThinPrep technique was diagnostic in 55% of samples. When all results were combined, pathologists subjectively preferred the conventional technique but accepted use of ThinPrep as the only cytopreparatory technique for most head and neck masses. CONCLUSIONS: For adequately experienced cytopathologists, ThinPrep is acceptable for FNA of salivary masses, neck cysts, metastatic lymph nodes, and thyroid lesions. Conventional smear technique should be used for FNA of nonmetastatic lymphoid lesions. Use of ThinPrep can complement use of the conventional (smear) cytopreparatory technique when aspirate is nondiagnostic or bloody, when the patient has a blood-borne infectious disease, when the clinician is inexperienced, or when aspirate has entered the syringe.     

Comparison of Laparoscopic vs Open Sigmoid Colectomy for Benign and Malignant Disease at Academic Medical Centers

Few studies have examined outcomes of laparoscopic and open sigmoid colectomy performed at US academic centers. Using ICD-9 diagnosis and procedural codes, data was obtained from the University HealthSystem Consortium (UHC) Clinical Database of 10,603 patients who underwent laparoscopic or open sigmoid colectomy for benign and malignant disease between 2003–2006. A total of 1,092 patients (10.3%) underwent laparoscopic sigmoid colectomy. Laparoscopic sigmoid colectomy was associated with a significantly shorter length of stay (5.4 vs 7.4 days), lower overall complication rate (19.7 vs 26.0%), lower 30-day readmission rate (3.4 vs 4.6), and a lower hospital cost ($13,814 vs $15,626). When a subset analysis of malignant and benign groups was performed, a significantly shorter length of stay in both the malignant laparoscopic group (6.4 ± 6.4 vs 7.8 ± 6.6 days) and in the benign laparoscopic groups (5.1 ± 3.5 vs 7.2 ± 7.6) exists. A lower wound complication rate (2.1 vs 5.5%, malignant and 4.0 vs 6.1, benign) is also evident. Laparoscopic sigmoid colectomy was associated with a shorter length of stay, less complications, and a lower 30-day readmission rate. The shorter length of stay and wound infection rate maintain significance when comparing laparoscopic vs open sigmoid resections for malignant and benign disease. Presented at the 48th annual meeting of the Society for Surgery of the Alimentary Tract at Digestive Disease Weak, Washington, DC, May 21st 2007. The information contained in this article was based on the Clinical Data Base provided by the University HealthSystem Consortium.     

Exacerbation of occult femoral hernia during laparoscopic prostatectomy.

Laparoscopic prostatectomy has been accepted as an appropriate treatment for prostate cancer because of the shorter hospital stay and quicker recovery. We present a rare complication of groin hernia with incarceration and necrosis of small bowel following laparoscopic prostatectomy. Occult hernias and small fascia defects may not always be apparent pre-operatively, but extension of pneumoperitoneal insufflation to extraperitoneal compartments should alert the surgeon to the possible presence of such a defect.