The number and ratio of positive lymph nodes affect pancreatic cancer patient survival after neoadjuvant therapy and pancreaticoduodenectomy.

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 American Joint Committee on Cancer (AJCC) staging of PDAC patients.

Superior Mesenteric Artery Margin of Posttherapy Pancreaticoduodenectomy and Prognosis in Patients With Pancreatic Ductal Adenocarcinoma.

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.

Antibody-mediated p53 protein therapy prevents liver metastasis in vivo.

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 +/- 1.3, whereas mice treated with Fv-p53 had an average metastasis score of 0.8 +/- 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.

Fontan operation: a comparison of lateral tunnel with extracardiac conduit.

BACKGROUND: The purpose of this report is to compare the outcome of the extracardiac (EC) with the lateral tunnel (LT) Fontan. METHODS: From January 1990 to October 2004, the Fontan operation was performed in 162 patients, of which 49 were EC and 113 were LT. Cardiac morphology and ventricular dominance were similar, except EC patients were older and had a greater frequency of heterotaxy syndrome, and LT patients had a higher incidence of hypoplastic left heart syndrome. Preoperative transpulmonary gradient, ventricular end-diastolic pressure, McGoon index, room air saturation, and cardiac rhythm were similar. EC patients underwent superior caval pulmonary connection, and LT patients underwent hemi-Fontan. Cardiopulmonary bypass time was similar, but fewer EC patients needed aortic cross-clamping. Fenestration was more frequent in LT patients (EC, 16% versus LT, 73%; p < 0.01). RESULTS: Overall operative mortality was 1.8% (EC, 1 versus LT, 2; p = NS). Postoperative transpulmonary gradient, readmission for chylous effusion, and change in ejection fraction relative to preoperative level did not differ between cohorts. Resource utilization was higher in the EC group. The loss of sinus rhythm and the frequency of all neurologic events did not differ. There were seven late deaths (EC 4 versus LT 3; p = NS). Actuarial survival at 5 years was not significantly different (EC, 90% versus LT, 95%; p = 0.08). CONCLUSIONS: The EC and LT operation had comparable early and late mortality, readmission for chylous effusion, preservation of sinus rhythm, and frequency of all neurologic events. The more frequently fenestrated LT cohort used fewer resources.

Comparison of angioplasty and surgery for neonatal aortic coarctation.

BACKGROUND: The efficacy of balloon dilatation as primary treatment for neonatal aortic coarctation remains controversial. METHODS: A retrospective comparison between balloon angioplasty and surgery for the treatment of neonatal aortic coarctation was undertaken on 57 neonates younger than 40 days of age (angioplasty, 23 patients; surgery, 34 patients) treated between 1994 and 2004. RESULTS: Cohorts were similar with respect to the preinterventional variables of age, weight, upper extremity systolic blood pressure, coarctation gradient, degree of aortic arch hypoplasia, associated conditions, and mean follow-up (angioplasty, 36 months; surgery, 38 months). Among the angioplasty group, 13 patients (57%) required surgery, and 8 required a second balloon dilatation, of whom 3 patients had an aortic aneurysm. Among the surgery cohort, 6 patients experienced recurrence (18%) after either SFA (3) or XETE anastomosis repair (3). All were successfully treated with balloon angioplasty. Actuarial freedom from any intervention was significantly greater in the surgery cohort as was the degree of aortic arch growth. At latest follow-up, antihypertensive medication was required in 3 of 9 angioplasty patients (33%) and 2 of 27 surgery patients (7%). No repeat intervention was required in the 13 patients who underwent angioplasty followed by surgery. CONCLUSIONS: Primary angioplasty is palliative treatment for neonatal aortic coarctation, but it is the treatment of choice for recurrence after surgery. Surgery for neonatal aortic coarctation is associated with fewer reinterventions, improved aortic arch growth, no aortic aneurysm formation, and decreased need for antihypertensive medication when compared with neonates treated primarily with balloon angioplasty.