Percutaneous radiofrequency ablation of small renal cell carcinoma: technique, complications, and outcomes.

Imaging-guided radiofrequency ablation (RFA) is an option for treatment in patients with early-stage small renal cell carcinomas (RCCs). RFA has been introduced to treat focal renal tumors, particularly incidental lesions <3 cm in elderly patients and those with comorbid conditions. Other uses have included treatment in patients with von Hippel-Lindau syndrome and other diseases that predispose patients to multiple renal carcinomas, where renal parenchymal preservation is desired. It appears that this technique has a low complication rate, preserves renal function, is well tolerated by the patients, and, in a high percentage of patients, can eradicate small renal tumors. Techniques, patient selection, complications, and results are discussed.

Percutaneous imaging-guided radiofrequency ablation of small renal cell carcinoma: techniques and outcomes of 24 treatment sessions in 18 consecutive patients.

PURPOSE: To evaluate the early clinical experience associated with percutaneous imaging-guided radiofrequency ablation (RFA) in patients with renal cell carcinoma (RCC). METHODS: Eighteen consecutive patients with RCC were treated with percutaneous RFA sessions (24 sessions for 19 solitary RCC in 18 patients: 15 patients underwent a single RFA session, 3 had 2 sessions and one 3 sessions). Treatment indications were localized, solid renal mass <4.5 cm, comorbidities precluding surgery, high operation risk, and refusal to perform surgery. During 23 sessions, RFA was performed using computed tomography (CT) guidance and in one session it was guided by ultrasonography. The average patient age was 76.8±7.6 years (range 64-89), and the average renal mass size 3.3 ±0.7 cm (range 2.0-4.5). Follow-up imaging was performed at 3- and 6-month intervals and yearly thereafter. Successful treatment was defined as lack of enhancement of the treated region on follow-up CT studies. RESULTS: RFA was technically successful in all patients. After the last imaging control, 17 of the 19 tumors were completely necrotic according to the imaging criteria (the secondary clinical success rate was 89.5%). Thirteen tumors were not visible on the first follow-up imaging control (the primary clinical success rate was 68.4% - 13 of 19). In 4 of the 6 patients residual tumors were successfully re-ablated, while in 2 patients repeated RFAs were not performed at the time of writing this report. Five patients (20.8%) developed treatmentrelated complications, including mild pain, large perirenal abscess, mild perirenal hematoma and transient elevation of the white blood cell count. The mean follow-up period was 25.3±16.8 months (range 1-51). CONCLUSION: RFA is effective and safe treatment option of exophytic RCC <5 cm in diameter in patients not suitable for surgery due to serious concomitant diseases or advanced age.

Risk of deterministic effects during endovascular aortic stent graft implantation.

Since the 1990s, stent graft implantation for aortic pathology has become an alternative to extensive surgical procedures in some patients. Indeed, many patients with such pathology are now treated endovascularly. Only limited data concerning the risk of a deterministic effect during aortic stent graft implantation are available Accordingly, 179 consecutive patients treated in our institute between October 2002 and July 2008 with endovascular aortic stent grafts were included in this study. Dosimetric data (kerma area product (KAP) and cumulative dose at the interventional reference point (CD(irp))) from radiograph reports were analysed for 172 patients. On a group of 19 patients, GAFCHROMIC XR type dosimetric films were also used to verify the automatic measurements. Readings from the integrated KAP meter were found to be too high and were therefore corrected - KAP to dose area product (DAP) and CD(irp) to entrance skin dose (ESD). Median DAP was 153 Gy cm² (35-700 Gy cm²) and median ESD was 0.44 Gy (0.12-2.73 Gy). Recorded dosimetric quantities were found to be good predictors of the skin dose and highlighted 4 patients (2.3%) who received skin doses that might cause possible deterministic effects. Endovascular stent graft implantation is less invasive than a surgical procedure and is widely used; mid-term results are encouraging. In a small number of patients, deterministic effects can occur even in departments with well-trained staff. Operators should inform the patients of possible skin injury after receiving high doses of ionising radiation and proper support must be available should that occur.

Transjugular intrahepatic portosystemic shunt versus endoscopic sclerotherapy in the elective treatment of recurrent variceal bleeding.

The present study was designed to compare elective transjugular intrahepatic portosystemic shunts (TIPS) and endoscopic sclerotherapy (EST) in terms of their efficacy in preventing recurrent bleeding from gastro-oesophageal varices in patients with advanced liver cirrhosis and portal hypertension. Of 96 patients with at least three gastro-oesophageal variceal rebleeds, 50 were treated with elective TIPS and 46 with EST. Recurrent variceal bleeding was significantly more frequent in patients receiving EST treatment compared with those receiving TIPS (45.7% versus 6.3%, respectively). Cumulative 1- and 4-year survival in the TIPS group was 83.0% and 73.5%, respectively, compared with 69.8% and 39.8% in the EST group, respectively. The rate of portosystemic encephalopathy was 33.3% in the TIPS group and 37.0% in the EST group. Elective TIPS was more effective than EST in the prevention of gastro-oesophageal variceal rebleeding in cirrhotic patients, it improved survival and it was associated with a similar rate of portosystemic encephalopathy.

Infrapopliteal run-off and the outcome of femoropopliteal percutaneous transluminal angioplasty.

BACKGROUND: The outcome of percutaneous transluminal angioplasty (PTA) of peripheral arterial lesions is influenced by several factors, including the haemodynamic conditions. Our study tested: (a) whether infrapopliteal run-off after completed PTA influenced the time course of restenosis/reocclusion of the femoropopliteal arterial segment, and (b) whether worsening of infrapopliteal run-off influenced the long-term femoropopliteal patency after PTA. PATIENTS AND METHODS: Among 245 patients treated by femoropopliteal PTA we enrolled 176 patients who consented to regular follow-up. Concomitant infrapopliteal PTA was performed whenever feasible. The technical success of PTA and the patency of calf arteries were assessed by angiography. Infrapopliteal run-off was scored by a modification of the Society for Vascular Surgery criteria. The treated patients' limbs were divided into a group with good infrapopliteal run-off and a group with compromised run-off. Follow-up examination of the femoropopliteal arterial segment was performed by vascular ultrasonography (US) 1, 6 and 12 months after PTA, and an adverse outcome was defined by a > or = 50 % stenosis, i.e., at least doubling of the maximal systolic velocity, or occlusion - evidenced by the absence of flow. The patency of calf arteries was re-assessed by US 12 months after PTA. RESULTS: One month after femoropopliteal PTA 19 / 83 (23 %) of patients with compromised run-off developed the combined end-point of restenosis or reocclusion in comparison to 10 / 93 (11 %) with good run-off (p = 0.03). After 6 months the incidence of restenosis/reocclusion had increased in both groups at an approximately equal rate, but the differences were no longer significant: 39 / 80 (49 %) in the compromised run-off group vs. 36 / 83 (43 %) in the good run-off group after 6 months, p = 0.49, and 42 / 73 (57 %) vs. 38 / 73 (52 %) after 12 months, p = 0.51. However, in patients' limbs with good periprocedural run-off that deteriorated into compromised run-off in the year after PTA, femoropopliteal restenosis/reocclusion occurred more often than in limbs which retained good run-off: 10 / 14 (71 %) vs. 18 / 51 (35 %), p = 0.02. CONCLUSIONS: Compromised postprocedural infrapopliteal run-off predisposes to early restenosis/reocclusion after femoropopliteal PTA. Deterioration of infrapopliteal run-off in the year after femoropopliteal PTA is accompanied by worsening of long-term femoropopliteal patency.

TRAIL gene-armed oncolytic poxvirus and oxaliplatin can work synergistically against colorectal cancer.

We have explored a unique combination therapy for metastatic colorectal cancer. This strategy combines a potent and new oncolytic poxvirus expressing a membrane-bound tumor necrosis factor-related apoptosis-inducing ligand (TRAIL or TNFSF10) and oxaliplatin (Ox) chemotherapy. We hypothesized that TRAIL expression would increase the efficacy of the oncolytic poxvirus, and that the therapeutic efficacy would be further enhanced by combination with chemotherapy. The cytotoxicity to cancer cells by Ox, oncolytic vaccinia virus (VV) and trail gene-armed VV alone or in combination was tested in vitro. The trail gene armed oncolytic VV-expressed high levels of TRAIL in infected cancer cells and had greater potency as a cytotoxic agent compared with the parent VV. Ox alone exerted concentration-dependent cytotoxicity. In vitro, the combination of the two agents applied at suboptimal concentrations for individual therapy displayed synergy in inducing cancer cells into enhanced levels of apoptosis/necrosis. Western blot analyses were consistent with the notion that TRAIL induced cancer cell death mainly through apoptosis, whereas Ox and vJS6 induced cell death more through non-apoptotic death pathways. In two aggressive colorectal carcinomatosis models derived from human HCT116 and murine MC38 cells, the combination therapy displayed synergistic or additive antitumor activity and prolonged the survival of the tumor-bearing mice compared with either Ox chemotherapy or vvTRAIL-mediated oncolytic gene therapy alone. This combination strategy may provide a new avenue to treating peritoneal carcinomatosis and other types of metastases of colorectal cancer.

Mapping of central visual function by microperimetry and autofluorescence in patients with Best's vitelliform dystrophy.

PURPOSE: To evaluate retinal sensitivity and fixation patterns in patients with Best's dystrophy by microperimetry (MP) and to correlate the results with static perimetry and retinal morphology seen by autofluorescence (AF). METHODS: Central 10 degrees visual fields in 11 patients with Best's dystrophy (VA: 0.5+/-0.38) were recorded by the Octopus M2 TOP program and by MP (MP1, Nidek Technologies). AF was recorded by HRA (Heidelberg Engineering). RESULTS: High correlation (R=0.75, -0.76, -0.48) was found between static perimetry (MS, MD and CLV indices) and MP. Based on MP and AF results, three groups of patients were formed. Patients in the first two groups fixated inside the central nonuniform hypo- and hyperfluorescent AF ring area, next to relative (Group 1) or absolute scotoma (Group 2). Inner parts of the retina close to the fovea were most affected, whereas regions closer to the periphery of the 10 degrees visual field showed near normal function. As the disease progressed, there was an evident shift of fixation to preferential retinal locus (PRL) in eight eyes with visual acuity 0.2 or less (Group 3). Fixation shift was superior in four eyes, temporal in two eyes, and nasal in two eyes. CONCLUSION: MP enabled a highly sensitive topographic monitoring of retinal function, showing central or pericentral fixation in the early stages, until loss of central function, in eyes with VA 0.2 or less, caused evident shift of fixation to PRL. PRL was never situated inside the central uniform hypofluorescent area, but corresponded with the hyperfluorescent ring seen with AF imaging.

The role of interventional radiology in management of patients with end-stage renal disease.

The aim of the paper is to review the role of interventional radiology in the management of hemodialysis vascular access and complications in renal transplantation. The evaluation of patients with hemodialysis vascular access is complex. It includes the radiology/ultrasound (US) evaluation of the peripheral veins of the upper extremities with venous mapping and the evaluation of the central vein prior to the access placement and radiological detection and treatment of the stenosis and thrombosis in misfunctional dialysis fistulas. Preoperative screening enables the identification of a suitable vessel to create a hemodynamically-sound dialysis fistula. Clinical and radiological detection of the hemodynamically significant stenosis or occlusion demands fistulography and endovascular treatment. Endovascular prophylactic dilatation of stenosis greater than 50% with associated clinical abnormalities such as flow-rate reduction is warranted to prolong access patency. The technical success rates are over 90% for dilatation. One-year primary patency rate in forearm fistula is 51%, versus graft 40%. Stents are placed only in selected cases; routinely in central vein after dilatation, in ruptured vein and elastic recoil. Thrombosed fistula and grafts can be declotted by purely mechanical methods or in combination with a lytic drug. The success rate of the technique is 89-90%. Primary patency rate is 8-26% per year and secondary 75% per year. The most frequently radiologically evaluated and treated complications in renal transplantation are perirenal and renal fluid collection and abnormalities of the vasculature and collecting system. US is often the method of choice for the diagnostic evaluation and management of the percutaneous therapeutic procedures in early and late transplantation complications. Computed tomography and magnetic resonance are valuable alternatives when US is inconclusive. Renal and perirenal fluid collection are usually treated successfully with percutaneous drainage. Doppler US, magnetic resonance angiography and digital subtraction angiography have a principle role in the evaluation of vascular complications of renal transplantation and management of the endovascular therapy. Stenosis, the most common vascular complication, occurs in 1-12% of transplanted renal arteries and represents a potentially curable cause of hypertension following transplantation and/or renal dysfunction. Treatment with percutaneous transluminal renal angioplasty (PTRA) or PTRA with stent has been technically successful in 82-92% of the cases, and graft salvage rate has ranged from 80 to 100%. Restenosis occurs in up to 20% of cases, but are usually amenable to repeated PTRA. Complications such as arterial and vein thrombosis are uncommon. Intrarenal A/V fistulas and pseudoaneurysms are occasionally seen after biopsy, the treatment requires superselective embolisation. Urologic complications are relatively uncommon, predominantly they consist of the urinary leaks and urethral obstruction. Interventional treatment consists of percutaneous nephrostomy, balloon dilation, insertion of the double J stents, metallic stent placement and external drainage of the extrarenal collections.

Pattern ERG and psychophysical functions in Best's disease.

The aim of the study was to asses the neurosensory retinal function in 12 patients (24 eyes) with different stages of Best's disease, by determining how pattern and full field flash ERG responses were related to visual acuity, stage of disease and extent of visual field loss. All patients had typically abnormal EOG responses and normal full field-flash ERG responses. Patients were stratified in two groups according to visual acuity. In the first group 12 eyes with visual acuity better than 0.5, all amplitudes and latencies of PERG P50 and N95 responses were in the normal range. Small central scotoma was detected by static perimetry in four of these eyes. In the second group of 12 eyes with visual acuity 0.5 or less, PERG showed reduced both P50 and N95 amplitudes in five eyes, and N95 solely, in two eyes. All patients had central scotomas detected by static perimetry. Progression of the disease, seen in deterioration of visual acuity and progression of central visual field defects, corresponded well with reduction of both PERG P50 and N95 amplitudes. There was no correlation found between visual acuity and EOG responses. Our results show that in Best's distrophy, pattern ERG is getting abnormal with progression of the disease, indicating relative preservation of neurosensory retina in initial stages of the disease. In contrast to EOG - being abnormal in all the patients regardless of the stage of disease - and full field-flash ERG - being normal in most of the patients - PERG gives opportunity for electrophysiological determination of the progression of the disease.

Peripheral blood granulocyte activity following contact sensitization of rats with dinitrochlorobenzene.

Contact hypersensitivity (CHS) reaction is a classic example of a cell-mediated reaction. As the afferent phase of the reaction includes inflammation, CHS is a suitable model for investigating non-specific immunity. Some aspects of granulocyte activity in the afferent phase of experimentally induced CHS to dinitrochlorobenzene (DNCB) in two genetically different rat strains, AO and DA were examined in this study. A shift in the ratio of granulocytes to lymphocytes in favour of granulocytes and an increase in granulocyte survival were noted in DA rats. Granulocytes from both strains demonstrated increased levels of NBT reduction and an increase in their adhesion to plastic. Decreased granulocyte adhesion in the presence of monoclonal antibodies to beta2 integrins (anti-CD11b/c and anti-CD18) points to the contribution of these molecules to granulocyte adhesiveness during the sensitization phase of CHS. Stimulation of adhesion in the presence of anti-CD11a antibody, points to a differential modulation of adhesion molecule activity during the afferent phase of CHS. Changes in functional activity of granulocytes demonstrated in this study might contribute to the development of CHS in rats.

Biochemical and functional characterization of a molecule expressed by a subset of thymic medullary epithelial cells.

A monoclonal antibody (mAb), named TE-4F 10, was produced by fusing P3X-Ag8 myeloma cells with splenocytes of BALB/c mice immunized with a rat medullary thymic epithelial cell (TEC) line, (TE-R 2.5), previously established in our Institute. Flow cytometry showed that 85-95% TE-R 2.5 cells expressed the TE-4F10 antigen. The mAb immunoprecipitated a 29 kDa molecule from the TE-R2.5 cell lysate. Immunohistochemical analysis using single and double staining of the thymus with anti-cytokeratin (CK) mAb, showed that TE- 4F10 mAb selectively stains a subpopulation of medullary TEC. Hematopoietic and lymphoid cells were negative. The expression of the TE-4F10 antigen on TE-R 2.5 cells in vitro was significantly upregulated by interleukin 1 (IL-1) and tumor necrosis factor (TNFalpha). Other cytokines IL-4, IL-6, IL-10 and granulocyte - macrophage colony stimulating factor (GM-CSF) showed lesser stimulation on its expression, whereas interferon gamma (IFN) and dexamethasone were without significant effect. The TE-R 2.5 cell line strongly bound and induced apoptosis of a rat / mouse thymocyte heterohybridoma (BWRT8), phenotypically alphabetaTCRhiCD4hiCD8lo. TE-4F10 mAb significantly inhibited binding (40-50%) of both BWRT8 cells and the BWRT8 - MDP.1 subclone to TE-R 2.5 cells. The inhibition was enhanced when TEC were stimulated with IL-1 + TNFalpha. The mAb also significantly blocked apoptosis of BWRT8 but did not modulate cell death of the BWRT8 - MDP.1 subclone, which was resistant to TEC-induced apoptosis. These findings indicate that the TE-4F10 antigen might be selectively involved in adhesion and selection processes in the medullary thymic microenvironment. The mAb of the same characteristics has not been described so far.

[Importance of determining the absolute CD3+ lymphocyte count during induction therapy with antithymocyte globulin in kidney transplantation patients]. / Znacaj odredjivanja apsolutnog broja CD3+ limfocita tokom indukcione terapije antitimocitnim globulinom kod bolesnika sa transplantovanim bubregom.

Antithymocyte globulin (ATG) is successfully applied in prophylaxis and treatment of renal allograft rejection. However, it is an expensive mode of therapy, associated with increased risk of opportunistic infections and lymphoproliferative diseases. For this reason, monitoring of ATG immunosuppressive effects as well as individual dose adjustment represent an important therapeutic approach. Here we report our results of ATG dose titration according to total lymphocyte count (< 300/microliter) and absolute CD3+ count (< 50/microliter) in seven renal transplant patients. Monitoring of absolute CD3+ count enabled reduction of the mean daily dose from the recommended dosage in all patients. Our results have also shown that the absolute CD3+ count is a more reliable parameter than the total lymphocyte count for monitoring of ATG biological effects on T cells. When rapid, significant and stable decrease of absolute CD3+ count is reached, ATG dose can be further adjusted according to the total lymphocyte count. With this approach, ATG treatment becomes rational and safe, with well established immunosuppressive effect, reduced risk of overimmunosuppression and considerable cost benefit.

Significance of de-novo IgD and IgM synthesis in CSF of patients with relapsing-remitting form of disseminated demyelinating disease of CNS.

Disseminated demyelinating disease of the central nervous system (DDD CNS) is immunologically mediated, with confirmed significant intrathecal immunoglobulin production. According to recently known immunopathogenic occurrences and activation of humoral immune response, we have assumed that the presence of oligoclonal immunoglobulins of M and D classes can be confirmed in cerebrospinal fluid (CSF) of patients with DDD CNS. With the aim of its further determination in CSF of relapsing-remitting DDD CNS patients in either remission and relapse phase, respectively, we have confirmed the presence of oligoclonal IgD and IgM bands, the association of this production and the presence of new demyelinating zones found by MRI of endocranium, as the time elapsed from the last relapse until the obtaining of CSF for further analyses. Method of isoelectric focusing with Western blott procedure was used for the confirmation of oligoclonal IgM and IgD bands presence in CSF. Significant presence of intrathecally synthetized oligoclonal IgM and IgD in patients with DDD CNS in exacerbation phase was presented. Almost in all patients in this phase was found at least one indicator of acute phase (positive MRI finding, presence of oligoclonal IgM or IgD bands). Significant decrease of positive findings of oligoclonal Ig bands in CSF was correlated with the time elapsed from the onset of relapse until the obtaining of CSF for the analysis due to short half-life of those Ig in CSF.

Comparison of signaling pathways involved in apoptosis of a thymocyte hybridoma triggered by a rat thymic medullary epithelial cell line, dexamethasone or T-cell receptor cross-linking.

Using an in vitro co-culture assay we found that a rat medullary thymic epithelial cell (TEC) line (TE-R2.5) induces apoptosis of the BWRT8 thymocyte hybridoma (TH) (CD4(hi)CD8(low) alphabetaTCR(hi)). TH apoptosis induced by this TEC line was predominantly mediated by direct cell-cell contacts and was potentiated by cross-linking of the T cell receptor (TCR) by R73 monoclonal antibody (mAb). Dexamethasone (Dx) also triggered TH apoptosis but inhibited death of these cells induced by TE-R2.5 cells or immobilized R73 mAb. The TEC-induced apoptosis was independent of the LFA-1/ICAM-1 interaction but partly depended on a novel 29 kDa molecule expressed on TE-R2.5 cells. All three types of TH apoptosis were followed by the cleavage of poly-(ADP-ribose)-polymerase and were blocked by a caspase inhibitor Z-Val-Ala-Asp(OMe)-CH(2)F.PKC stimulation by phorbol myristate acetate interfered with the TH apoptosis induced by TE-R2.5 and Dx, but did not modulate the effect of R73 mAb. On the contrary, inhibition of calcineurin with cyclosporine A did not influence the apoptosis induced by TE-R2.5 and Dx, but completely prevented the R73-triggered TH cell death. The TE-R2.5-mediated BWRT8 apoptosis was suppressed by Na-orthovanadate, an inhibitor of protein tyrosine phosphatases (PTP) as well as by genistein, a protein tyrosine kinase (PTK) inhibitor, while both compounds potentiated the effect of Dx. Blocking PTP, but not PTK decreased the proapoptotic effect of R73 mAb. These results, including those using a BWRT8 subclone (BWRT8-MDP.2) which is resistant to TCR-triggered apoptosis, but sensitive to apoptosis stimulated by TE-R2.5 and Dx, indicate that TE-R2.5-induced TH apoptosis in our model is different from apoptosis in other TEC co-culture models, published so far.

Modulatory effect of 7-thia-8-oxoguanosine on proliferation of rat thymocytes in vitro stimulated with concanavalin A.

7-thia-8-oxoguanosine (immunosine) is a guanosine analogue showing immunostimulatory activity on different components of the immune system, including B lymphocytes, natural killer cells and macrophages. However, little is known about its effect on T-cell functions. In this work it was demonstrated that immunosine at concentrations between 10 microM and 1 mM stimulated proliferation of rat thymocytes in vitro triggered by suboptimal concentrations of concanavalin A (Con A). The effect correlated with increased interleukin 2 (IL-2) production, upregulation of the IL-2 receptor alpha (IL-2Ralpha) expression and decreased apoptosis of thymocytes in comparison to the effect of Con A alone.