Impact of margin status on survival following pancreatoduodenectomy for cancer: the Leeds Pathology Protocol (LEEPP)

Background

In a previous study we reported an 85% R1 rate for pancreatic cancer following the use of the rigorous, fully standardized Leeds Pathology Protocol (LEEPP). As this significantly exceeded R1 rates observed by others, we investigated the reproducibility of margin assessment using the LEEPP in a larger, prospective, observational cohort study and correlated clinicopathological data with survival.

Methods

Clinicopathological features, including exact site and multifocality of margin involvement, and survival were collated from a prospective series of 83 pancreatoduodenectomies for pancreatic (n = 27), ampullary (n = 24) and bile duct cancer (n = 32). Data were compared with those of the previous study in which the same pathology protocol, based on axial slicing and extensive tissue sampling from the circumferential margin, had been used.

Results

The R1 rate was high in pancreatic (82%) and bile duct (72%) cancer and significantly lower in ampullary cancer (25%). Margin positivity was often multifocal, the posterior margin being most frequently involved. Margin status correlated with survival in the entire cohort (P = 0.006) and the pancreatic subgroup (P = 0.046). These findings were consistent with observations in our previous study.

Conclusions

Margin involvement in pancreatic cancer is a frequent and prognostically significant finding when specimens are assessed using the LEEPP.     

Implementation of population screening for colorectal cancer by repeated fecal occult blood test in the Netherlands

Background  

Colorectal cancer (CRC) is the third most prevalent type of cancer in the world. Its prognosis is closely related to the disease stage at the time of diagnosis. Early detection of symptomless CRC or precursor lesions through population screening could reduce CRC mortality. However, screening programs are only effective if enough people are willing to participate. This study aims to asses the uptake of a second round of fecal occult blood test (FOBt) based screening and to explore factors that could potentially increase this uptake.     

Important role of interleukin‐3 in the early phase of collagen‐induced arthritis

Objective

Activation of basophils contributes to memory immune responses and results in exacerbation of collagen‐induced arthritis (CIA). We undertook the present study to analyze the production and biologic effects of interleukin‐3 (IL‐3), a strong activator of basophils, in CIA.

Methods

Arthritis was induced by immunization with type II collagen. Mice were treated with blocking monoclonal antibodies against IL‐3 or with recombinant IL‐3. Clinical scoring, histologic analysis, fluorescence‐activated cell sorter analysis, enzyme‐linked immunosorbent assay, and cell culturing were performed to assess disease activity and IL‐3 production.

Results

IL‐3 was produced in large quantities by collagen‐specific CD4+ T cells in the spleen and was present in the synovial tissue during onset of arthritis, but was down‐regulated in paws with severe inflammation. Blockade of IL‐3 during the time of arthritis onset resulted in profound improvement of the disease, with reductions in synovial leukocyte and cytokine levels, peripheral blood basophil levels, and anticollagen antibody titers. Blockade of IL‐3 during the late phase of arthritis had no beneficial effect. Administration of recombinant IL‐3 during onset of arthritis induced a marked exacerbation of the disease, with increased peripheral blood basophil and plasma IL‐6 levels and increased titers of anticollagen antibody. In studies of the regulation of IL‐3 expression in CD4+ T cells, IL‐6 and IL‐4 suppressed the release of IL‐3 by activated CD4+ T cells, whereas lipopolysaccharide and CpG DNA up‐regulated IL‐3 secretion in activated CD4+ T cells by acting on costimulatory cells.

Conclusion

Taken together, the present results demonstrate for the first time that IL‐3 has an important role in the early phase of CIA.

     

Structure-Based Design of Conformationally Constrained,Cell-Permeable STAT3 Inhibitors

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