Photodynamic therapy is a promising antitumor treatment modality approved for the management of both early and advanced tumors. The mechanisms of its antitumor action include generation of singlet oxygen and reactive oxygen species that directly damage tumor cells and tumor vasculature. A number of mechanisms seem to be involved in the protective responses to PDT that include activation of transcription factors, heat shock proteins, antioxidant enzymes and antiapoptotic pathways. Elucidation of these mechanisms might result in the design of more effective combination strategies to improve the antitumor efficacy of PDT. Using DNA microarray analysis to identify stress-related genes induced by Photofrin-mediated PDT in colon adenocarcinoma C-26 cells, we observed a marked induction of heme oxygenase-1 (HO-1). Induction of HO-1 with hemin or stable transfection of C-26 with a plasmid vector encoding HO-1 increased resistance of tumor cells to PDT-mediated cytotoxicity. On the other hand, zinc (II) protoporphyrin IX, an HO-1 inhibitor, markedly augmented PDT-mediated cytotoxicity towards C-26 and human ovarian carcinoma MDAH2774 cells. Neither bilirubin, biliverdin nor carbon monoxide, direct products of HO-1 catalysed heme degradation, was responsible for cytoprotection. Importantly, desferrioxamine, a potent iron chelator significantly potentiated cytotoxic effects of PDT. Altogether our results indicate that HO-1 is involved in an important protective mechanism against PDT-mediated phototoxicity and administration of HO-1 inhibitors might be an effective way to potentiate antitumor effectiveness of PDT.

Background. Simultaneous pancreas and kidney transplantation (SPK) from cadaveric donors has become a widely accepted therapeutic option for insulin-dependent uremic patients. In 1996 the first SPK from a live donor was performed. This procedure offers the advantage of a better immunologic match, reduced cold ischemia injury, and decreased waiting time. As such, it is an attractive alternative treatment for diabetic patients with end-stage nephropathy with an available living donor. Methods. We performed six SPKs from living-related donors. There were four men and two women among the recipients; median age was 34 (range, 29–39) years. All donors were recipients’ siblings with excellent HLA matching. Donors underwent standardized metabolic workup, anti-insulin and anti-islet antibody assays, and computed tomography of the abdomen. Both donors and recipients were treated with octreotide for 5 days perioperatively. After transplantation, the patients were maintained on tacrolimus-based immunosuppression, with the exception of one recipient of SPK from an identical twin, who received cyclosporine monotherapy. Results. All the donors are doing well and have normal renal function and blood glucose levels. One-year patient, renal, and pancreatic graft survival rates were 100%, 100%, and 83%, respectively. Acute kidney rejection was documented in two patients, and both recovered completely after OKT3 therapy. No rejection of pancreatic graft has been documented. Except for one patient who lost the graft because of hemorrhagic pancreatitis, all recipients maintained serum glucose levels at less than 130 mg/dL without insulin therapy. No major surgical complications such as graft thrombosis, intra-abdominal infection, or abscess were reported. Conclusions. Living donor SPK can represent a successful alternative to cadaveric donor SPK. The procedure can be performed safely in the donor and with low morbidity in the recipient.

Objectives: The goal of endovascular repair is to protect the patient from aneurysm rupture. Careful surveillance should be performed postoperatively in order to select patients with aneurysm growth and, therefore, the highest rupture risk. The aim of the study was to present our experience with aneurysm rupture in long-term follow-up after endovascular abdominal aneurysm repair. Methods: Between 1998 and 2006, 445 patients with abdominal aortic aneurysms were treated endovasculary in our Department. All patients were followed-up postoperatively according to the EUROSTAR protocol, with a CT scan performed postoperatively in the 3rd, 6th and 12th month and annually thereafter with good compliance. Because of this we had the opportunity for early treatment of complications, especially endoleaks which may cause aneurysm growth and subsequent rupture. Results: In three presented patients aneurysm rupture occurred in the late follow-up period after endovascular treatment. In all cases open aneurysmectomy was performed without any major complications. We also analyzed the reason for the rupture: in all cases it was due to endoleak type I, that was not present during postoperative CT-scans. The mechanism of its recurrence was proximal cuff migration 29 months after endovascular aneurysm treatment in the first patient. In the second case endoleak type I appeared 32 months postoperatively due to aneurysm lengthening, what could have been the consequence of persistent, small endoleak type II. In the third case the reason of aneurysm rupture was late endoleak type I due to migration of proximal seal of the stentgraft. Conclusions: Although the risk of aneurysm rupture after EVAR is low, all patients treated endovascularly should be routinely monitored, in order to select cases with potential endoleaks or stentgraft migration which may lead to fatal complications. When rupture occurs open aneurysmectomy is feasible, although it requires careful management in these high-risk patients.

Objective: To provide a comprehensive assessment of left ventricle (LV) structure, and function and to detect alterations in cardiac properties in relationship to presence, subtypes and extent of fibromuscular dysplasia (FMD). Methods: We studied 144 patients with FMD. The control group consisted of 50 matched individuals. Office and ambulatory blood pressure levels were evaluated. Echocardiography was employed to assess: left ventricular mass index (LVMI), systolic function including speckle tracking echocardiography and diastolic function assessed by mitral flow and tissue Doppler imaging. Results: There were no differences in LV morphology and function between patients with FMD and the control group. Among 128 patients with renal FMD, there were no differences in LVMI and LV systolic function between patients with unifocal and multifocal FMD. The patients with multifocal FMD were characterized by lower early diastolic velocity (e′) as compared with unifocal FMD and control groups. However, in a multivariate regression model, e′ was not independently correlated with FMD. There were no associations between echocardiographic indexes and vascular involvement of FMD. Also, there were no differences in LV morphology and function in patients with significant renal artery stenosis (RAS) compared with patients with history of significant RAS and patients with nonsignificant RAS. Conclusion: Our study in contrast to those with atherosclerotic RAS, did not show differences in LV morphology and function between FMD patients and matched controls. Although FMD can result in hypertension and serious vascular complications, there is no proof that it can alter LV regardless of FMD type and its extent.