Angiogenesis is essential for tumor growth and metastasis. Although ELR 1 -CXC-chemokines and their corresponding receptor, CXC-receptor 2 (CXCR2), are known mediators of angiogenesis, little is known about their role in pancreatic cancer (PaCa). The aim of our study was to determine the role of ELR 1 -CXCchemokine/CXCR2 biological axis in promoting PaCa angiogenesis. We prospectively collected secretin-stimulated exocrine pancreatic secretions (SSEPS) from normal individuals (NP) and PaCa patients. We showed that summed concentrations of ELR 1 -CXC-chemokines in SSEPS from PaCa patients were significantly higher than in those from NP (p 5 0.002). We measured ELR 1 -CXC-chemokine levels in supernatants from multiple PaCa cell lines and confirmed that BxPC-3, Colo-357 and Panc-28 had significantly higher expression compared with an immortalized human pancreatic ductal epithelial (HPDE) cell line. After confirming lack of autocrine effects of ELR 1 -CXC-chemokines on PaCa cells (due to absence of CXCR2 expression), we investigated paracrine effects of these chemokines on human umbilical vein endothelial cells (HUVEC). Both recombinant ELR 1 -CXC-chemokines and co-culturing with BxPC-3 significantly enhanced proliferation, invasion, and tube formation of HUVEC (p < 0.05). These biological effects were significantly inhibited by treatment with a neutralizing antibody against CXCR2 (anti-CXCR2 Ab) (p < 0.05). Finally, anti-CXCR2 Ab significantly reduced tumor volume (p < 0.05), Ki-67 proliferation index (p 5 0.043) and Factor VIII 1 microvessel density (p 5 0.004) in an orthotopic nude mouse PaCa model. Our results show that ELR 1 -CXC-chemokines promote PaCa tumor-associated angiogenesis through CXCR2, suggesting that CXCR2 is an anti-angiogenic target in PaCa. ' 2009 UICC

Background Few options exist for patients with localized esophageal cancer ineligible for conventional therapies. Endoscopic spray cryotherapy with low-pressure liquid nitrogen has demonstrated efficacy in this setting in early studies. Objective To assess the safety and efficacy of cryotherapy in esophageal carcinoma. Design Multicenter, retrospective cohort study. Setting Ten academic and community medical centers between 2006 and 2009. Patients Subjects with esophageal carcinoma in whom conventional therapy failed and those who refused or were ineligible for conventional therapy. Interventions Cryotherapy with follow-up biopsies. Treatment was complete when tumor eradication was confirmed by biopsy or when treatment was halted because of tumor progression, patient preference, or comorbid condition. Main Outcome Measurements Complete eradication of luminal cancer and adverse events. Results Seventy-nine subjects (median age 76 years, 81% male, 94% with adenocarcinoma) were treated. Tumor stage included T1-60, T2-16, and T3/4-3. Mean tumor length was 4.0 cm (range 1–15 cm). Previous treatment including endoscopic resection, photodynamic therapy, esophagectomy, chemotherapy, and radiation therapy failed in 53 subjects (67%). Forty-nine completed treatment. Complete response of intraluminal disease was seen in 31 of 49 subjects (61.2%), including 18 of 24 (75%) with mucosal cancer. Mean (standard deviation) length of follow-up after treatment was 10.6 (8.4) months overall and 11.5 (2.8) months for T1 disease. No serious adverse events were reported. Benign stricture developed in 10 (13%), with esophageal narrowing from previous endoscopic resection, radiotherapy, or photodynamic therapy noted in 9 of 10 subjects. Limitations Retrospective study design, short follow-up. Conclusions Spray cryotherapy is safe and well tolerated for esophageal cancer. Short-term results suggest that it is effective in those who could not receive conventional treatment, especially for those with mucosal cancer.

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TP results in significant metabolic derangements and exocrine insufficiency, diabetic control and weight maintenance remain a challenge and readmission rates are high. Survival in those with malignant disease remains poor. However, the mortality appears to be decreasing and the morbidities associated with TP appear acceptable compared with the benefits of resection in selected patients.

Cytology brushings are more likely to provide an adequate mucinous epithelium specimen than standard FNA and could aid the diagnosis of CPLs in a selective group of patients.