BACKGROUND: Only a few clinical trials have been conducted in patients with advanced pancreatic cancer after failure of first-line gemcitabine-based chemotherapy. Therefore, there is no current consensus on the treatment of these patients. We conducted a randomised phase II study of the modified FOLFIRI.3 (mFOLFIRI.3; a regimen combining 5-fluorouracil (5-FU), folinic acid, and irinotecan) and modified FOLFOX (mFOLFOX; a regimen combining folinic acid, 5-FU, and oxaliplatin) regimens as second-line treatments in patients with gemcitabine-refractory pancreatic cancer. METHODS: The primary end point was the 6-month overall survival rate. The mFOlFIRI.3 regimen consisted of irinotecan (70 mg m À2 ; days 1 and 3), leucovorin (400 mg m À2 ; day 1), and 5-FU (2000 mg m À2 ; days 1 and 2) every 2 weeks. The mFOLFOX regimen was composed of oxaliplatin (85 mg m À2 ; day 1), leucovorin (400 mg m À2 ; day 1), and 5-FU (2000 mg m À2 ; days 1 and 2) every 2 weeks. RESULTS: Sixty-one patients were randomised to mFOLFIRI.3 (n ¼ 31) or mFOLFOX (n ¼ 30) regimen. The six-month survival rates were 27% (95% confidence interval (CI) ¼ 13 -46%) and 30% (95% CI ¼ 15 -49%), respectively. The median overall survival periods were 16.6 and 14.9 weeks, respectively. Disease control was achieved in 23% (95% CI ¼ 10 -42%) and 17% patients (95% CI ¼ 6 -35%), respectively. The number of patients with at least one grade 3/4 toxicity was identical (11 patients, 38%) in both groups: neutropenia (7 patients under mFOLFIRI.3 regimen vs 6 patients under mFOLFOX regimen), asthaenia (1 vs 4), vomiting (3 in both), diarrhoea (2 vs 0), and mucositis (1 vs 2). CONCLUSION: Both mFOLFIRI.3 and mFOLFOX regimens were tolerated with manageable toxicity, offering modest activities as second-line treatments for patients with advanced pancreatic cancer, previously treated with gemcitabine.

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A younger age at transplantation and at pregnancy was associated with a greater likelihood of a live birth. Transplantation to conception interval of less than 1 year was not associated with a greater number of adverse pregnancy events when compared with the group with transplantation to conception interval greater than 1 year.

As a new approach to islet transplantation, biocompatible monomethoxy-poly(ethylene glycol) (mPEG) was chemically grafted onto the pancreatic islet capsule. The aim of this study was to determine the optimal conditions for completely covering the islet by the mPEG while maintaining a high viability of islets according to the reaction time and the repeating number of the reaction. By grafting the fluorescein-PEG instead of mPEG, we determined the optimal mPEG grafting time as 1 h, during which time the procedure did not reduce islet viability. Insulin secretion from islets where the mPEG was grafted on for 3 times was similar to that of control islets. Moreover, the mPEG-grafted islets rapidly responded to the changes in the glucose concentration in the same pattern as did control islets. These results showed that mPEG grafting did not damage the function of islets. In conclusion, when the mPEG grafting was performed for 1 h and repeated twice with 1-day culture between each mPEG-grafting step, the mPEG completely covered the islet capsules without any damage to the viability and function of the islets. The main advantage of mPEG grafting on the islet capsule is that it can protect the islet against the host's immune system without increasing the islet size so that it can be administered into the portal vein by the catheter.

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Mesenchymal stem cells (MSCs) are suggested to be immune modulators because of their therapeutic potential in transplantation. In the present study, we evaluated the therapeutic potential of autologous MSCs for preventing graft rejection after allogeneic rat islet transplantation. We assessed the ability of MSCs to elicit an antiproliferative response in alloreactive lymphocytes and tested the immunosuppressive effect of MSCs in allogeneic islet transplantation. In islet allotransplantation, injection of autologous MSCs or a subtherapeutic dose of cyclosporine A (CsA; 5 mg/kg) alone did not prolong allograft survival. However, graft survival was attained for >100 d in 33% of autologous MSC-plus-CsA-treated recipients, indicating that graft acceptance was achieved in a subgroup of allograft recipients. Splenocytes from autologous MSC-plus-CsA-treated rats exhibited a reduced mixed lymphocyte reaction (MLR)-proliferative response to donor stimulators and increased interleukin (IL)-10 release. Interestingly, after excluding host CD11b + cells, splenic T cells from autologous MSC-plus-CsA-treated rats did not produce IL-10 or did not inhibit proliferative responses under the same conditions. The use of autologous MSC-plus-CsA downregulated immune responses, inducing donor-specific T-cell hyporesponsiveness by reducing the production of proinflammatory cytokines and inducing antiinflammatory cytokine production, especially that of IL-10, during the early posttransplantation period. T-regulatory cells made a contribution at a later phase. In conclusion, the combined use of autologous MSCs and low-dose CsA exerted a synergistic immunosuppressive effect in an islet allograft model, suggesting a role for autologous MSCs as an immune modulator.

Stress myocardial perfusion CT provides incremental value over CT angiography in patients with a high calcium score for the detection of myocardial ischemia as defined by FFR.