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Negative-margin resection is crucial to favorable prognosis in patients with pancreatic ductal adenocarcinoma. However, the definition of a negative superior mesenteric artery margin (SMAM) varies. The College of American Pathologists defines positive SMAM as the presence of tumor cells at the margin, whereas the European protocol is based on a 1 mm clearance. In this study, we examined the prognostic significance of the SMAM distance in 411 consecutive pancreatic ductal adenocarcinoma patients who completed neoadjuvant therapy and pancreaticoduodenectomy. Per College of American Pathologists criteria, 32 (7.8%) had positive margins, and 379 (92.2%) had negative margins. Among margin-negative group, SMAM was ≤ 1, 1.0 to 5.0, and >5.0 mm in 66, 145, and 168 patients, respectively. There was no difference in either disease-free survival (DFS) or overall survival (OS) between the positive-margin group and SMAM ≤ 1 mm (P > 0.05). However, patients with SMAM 1.0 to 5.0 mm had better OS than those with positive margins or SMAM ≤ 1 mm (P = 0.02). Patients with SMAM > 5.0 mm had better DFS and OS than those with SMAM 1.0 to 5.0 mm and those with positive margins or SMAM ≤ 1 mm (P < 0.01). By multivariate analysis, the SMAM distance, tumor differentiation, lymph node metastasis, and histopathologic tumor response grade were independent prognostic factors for both DFS and OS. SMAM distance correlated with lower ypT and AJCC stages, smaller tumor size, better histopathologic tumor response grade, fewer lymph node metastases, and recurrences (P < 0.05). Thus our results strongly support use of SMAM > 1 mm for R0 resection in posttherapy pancreaticoduodenectomy specimens.

Aims This study is to examine the significance of the number and ratio of positive nodes in post neoadjuvant therapy pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC). Methods and results Our study population consisted of 398 consecutive PDAC patients, who completed neoadjuvant therapy and PD between 1999 and 2012. Lymph node status was classified as ypN0 (node negative), ypN1 (1–2 positive nodes) and ypN2 (≥3 positive nodes) and correlated with disease-free survival (DFS) and overall survival (OS). The ypN0, ypN1 and ypN2 was present in 183 (46.0%), 117 (29.4%) and 98 (24.6%) patients respectively. Additionally, 162 (40.7%) had a lymph node ratio (LNR) ≤ 0.19 and 53 (13.3%) had a LNR > 0.19. Patients with ypN1 disease had shorter DFS and OS than those with ypN0 disease, but better DFS and OS than those with ypN2 disease (P<0.05). Similarly, patients with a LNR≤0.19 had better DFS and OS than those with a LNR≤0.19 (P<0.001). In multivariate analysis, both the number of positive nodes and LNR were independent prognostic factors for DFS and OS. Conclusions Subclassification of post-therapy node positive group into ypN1 (1–2 positive nodes) and ypN2 (≥ 3 positive nodes) should be incorporated into the AJCC staging of PDAC patients.

To evaluate the clinical efficacy of monoclonal antibody (mAb) 3E10 Fv antibody-mediated p53 protein therapy, an Fv-p53 fusion protein produced in Pichia pastoris was tested on CT26.CL25 colon cancer cells in vitro and in vivo in a mouse model of colon cancer metastasis to the liver. In vitro experiments showed killing of CT26.CL25 cells by Fv-p53 but not Fv or p53 alone, and immunohistochemical staining confirmed that Fv was required for transport of p53 into cells. Prevention of liver metastasis in vivo was tested by splenic injection of 100 nmol/L Fv-p53 10 min and 1 week after injection of CT26.CL25 cancer cells into the portal vein of BALB/c mice. Mice were sacrificed 1 week after the second injection of Fv-p53 and assigned a quantitative metastasis score. Control mice had an average metastasis score of 3.3 F 1.3, whereas mice treated with Fv-p53 had an average metastasis score of 0.8 F 0.4 (P = 0.004). These results indicate that Fv-p53 treatment had a profound effect on liver metastasis and represent the first demonstration of effective full-length p53 protein therapy in vivo. mAb 3E10 Fv has significant clinical potential as a mediator of intracellular and intranuclear delivery of p53 for prevention and treatment of cancer metastasis. [Cancer Res 2007;67(4):1769-74]

uvenile polyposis (JP or JPS for juvenile polyposis syndrome) is an autosomal dominant disorder that often presents in childhood. It is characterized by the presence of hamartomatous (juvenile) polyps that vary in number from fi ve to several hundred (1, 2). Th e polyps are found primarily in the colorectum, but they can be present throughout the gastrointestinal tract, from the stomach to the rectum (2). Even though these polyps are normally benign, patients have an increased risk of gastrointestinal cancer (1-3). Th is disease occurs in approximately 1 in 100,000 people (4), and in 50% to 60% of the patients a germline mutation in SMAD4 (5) or bone morphogenic protein receptor 1A (BMPR1A) (6) genes can be found. Hereditary hemorrhagic telangiectasia (HHT; Osler-Weber-Rendu syndrome) is another autosomal dominant disorder distinguished by vascular dysplasia in multiple organs that can result in excessive bleeding. Th is syndrome was initially described by Osler in 1901 in a report of a familial form of recurrent mucous membrane bleeding from telangiectasias (3). Characteristic features include telangiectasias of the skin and oral and nasal mucosa, epistaxis, and arteriovenous malformations (AVMs) of the lungs, liver, brain, and gastrointestinal tract that can lead to hemorrhage and stroke (7-9). Th e frequency of this syndrome diff ers between populations, but it ranges from 1 in every 1300 Afro-Caribbeans in the Netherlands Antilles (10) to 1 in every 40,000 people in northern England (4). Approximately 80% of the families have a mutation in the endoglin (ENG) (5) or activin receptor-like kinase 1 (ALK1) (6) genes, while the remaining 20% of patients have a mutation in the SMAD4 gene (7) or in new loci mapped to chromosome 5 and chromosome 7 (8). A syndrome that combines JP and HHT was fi rst described in 1980 (9, 10). Th ese patients exhibit symptoms of both

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