Dose-escalation in prostate cancer: Results of randomized trials.

In 1998, an editorial from the International Journal of Radiation Oncology - Biology - Physics (IJROBP) on the occasion of the publication of Phase I by Zelefsky et al. on 3D radiotherapy dose escalation asked the question: "will more prove better?". More than 20 years later, several prospective studies have supported the authors' conclusions, making dose escalation a new standard in prostate cancer. The data from prospective randomized studies were ultimately disappointing in that they failed to show an overall survival benefit from dose escalation. However, there is a clear and consistent benefit in biochemical recurrence-free survival, which must be weighed on an individual patient basis against the potential additional toxicity of dose escalation. Techniques and concepts have become more and more precise, such as intensity modulated irradiation, simultaneous integrated boost, hypofractionated dose-escalation, pelvic irradiation with involved node boost or focal dose-escalation on gross recurrence after prostatectomy. The objective here was to summarize the prospective data on dose escalation in prostate cancer and in particular on recent advances in the field. In 2022, can we finally say that more has proven better?

Optical gap energy study of poly(thienylene-2,5-dialkoxyphenylene) in solid-state films.

Optical gap energy (Egap) in luminescent π-conjugated polymers presents several difficulties in its determination, particularly when using CW conventional optical spectroscopy, absorption and emission. This happens due to several physicochemical parameter's dependence. Among others, the molecular conformation, intramolecular interactions, structural defects, polymer processability and solvent interaction stand out. In addition, there is a distribution of conjugated segments along the polymeric main chains that differentiate optical absorption transition from emission processes. In other words, these processes do not necessarily occur in the same conjugated segment owing to the very efficient ratios of energy transfer or charge migration in these materials. In this work we present a systematic study of the determination of Egap for the polymer poly(thienylene-2,5-dialkoxyphenylene). We present a comparison between the solution and solid-state film, clearly showing the presence of a polymer-polymer interaction as aggregate species. The goal of this paper is to isolate and aggregate the contribution determination of each species through systematic analysis of optical spectra, as well as to obtain, even on film, the Egap of the isolated polymer which is very similar to the polymer solution at about 2.37 eV. The intersection theory and the voltammetry methods corroborate the experiment and the discussion of the results obtained.

A new designed π conjugated molecule for stable single walled carbon nanotube dispersion in aqueous medium.

A molecule with a π conjugated backbone built from aromatic thiophene and dialkoxyphenylene units and substituted imidazolium groups (TPO) is designed to obtain ultra-stable single walled carbon nanotube (SWCNT) dispersion in aqueous medium. The proposed mechanism of non-covalent interaction is accompanied by individualization of SWCNT and comprises of dominant nondisruptive π-π and cation-π interaction between them and the TPO conjugated oligomer. The individualization of SWCNT and dispersibility and stability of the ultra-stable suspensions were estimated using high resolution transmission electron microscopy, UV-Visible-NIR absorption spectroscopy, Raman spectroscopy, photoluminescence and zeta potential measurement. Nuclear magnetic resonance data provides direct evidence toward possible cation-π interaction.

Interfacial exciplex formation in bilayers of conjugated polymers.

The donor-acceptor interactions in sequential bilayer and blend films are investigated. Steady-state and time-resolved photoluminescence (PL) were measured to characterize the samples at different geometries of photoluminescence collection. At standard excitation, with the laser incidence at 45° of the normal direction of the sample surface, a band related to the aggregate states of donor molecules appears for both blend and bilayer at around 540 nm. For the PL spectra acquired from the edge of the bilayer, with the laser incidence made at normal direction of the sample surface (90° geometry), a new featureless band emission, red-shifted from donor and acceptor emission regions was observed and assigned as the emission from interfacial exciplex states. The conformational complexity coming from donor/acceptor interactions at the heterojunction interface of the bilayer is at the origin of this interfacial exciplex emission.

[Vascular reconstruction for limb preservation during sarcoma surgery: a case series and a management algorithm]. / Reconstrucción vascular durante la cirugía de sarcomas para la preservación de extremidades: serie de casos y algoritmo de manejo.

OBJECTIVE: To evaluate the results of vascular reconstruction in soft tissue sarcoma surgery and establish an algorithm based on current evidence. MATERIAL AND METHODS: We studied patients undergoing soft-tissue sarcoma in a tertiary hospital. A retrospective review of 8 cases was carried out, analysing the demographics, surgical planning, complications, disease-free survival and bypass patency. RESULTS: Successful limb preservation was observed in all patients, and the bypass remained patent in all cases. The mean follow-up was 38.4 months average, with 87.5% survival and no recurrences. CONCLUSIONS: The involvement of major vascular structures in soft tissue sarcomas of the limbs does not necessarily exclude resectability. In selected cases, resection is possible with vascular reconstruction and limb preservation. However, multidisciplinary planning is needed.

Indications of microsurgery in soft tissue sarcomas.

UNLABELLED: Sarcomas are uncommon tumors and free-margin surgical resection remains the single most important treatment in the curative therapy of soft tissue sarcomas. Refinements in surgical techniques have led to increased function preservation and limb salvage. PATIENTS AND METHODS: The records of patients (n = 41) who underwent microsurgical soft tissue reconstruction subsequent to resection of soft tissue sarcoma during the period 1998 to 2010 were reviewed and compared with a general nonmicrosurgery group (n = 188) in relation to clinicopathological characteristics, surgical procedures, postoperative complications, time until start of adjuvant radiation, functional outcome (Toronto Extremity Salvage Score, TESS), local recurrence, free survival, and disease-specific survival. RESULTS: Forty-one patients (age range: 23 to 95 years) received a total of 42 free flaps. When compared with the general nonmicrosurgery group, these patients presented significant differences with regard to location, histological grade, and neoadjuvant treatments. Complications were encountered in 10 cases, including 3 patients with complete flap loss and 1 patient with partial flap loss; other complications were cervical fistulae, knee arthritis, nonconsolidation, and wound infection. Extremity salvage was achieved in 90% (19/21) of limb sarcomas, with these patients showing adequate postoperative ambulation (TESS 77 ± 16) and adequate use of the upper extremity (TESS 66 ± 26). Two patients underwent amputation after recurrence. Disease-specific survival rates at 5 and 10 years were 79.49% and 76.93%, respectively. CONCLUSION: The microsurgical repair of sarcoma defects is a reliable option that, though not free of complications, is necessary in selected cases such as patients receiving neoadjuvant treatments and those with head and neck location and high-grade tumors. The procedure enables both adequate oncosurgical resection and function preservation. Our microsurgical sarcoma reconstruction data, based on an observation period of 12 years and presenting the results of 42 free tissue transfers in 41 patients, adds further evidence to the previously published smaller series.

Theoretical investigations on the electronic and optical properties of bridged oligothiophenes.

A study of the structure, electronic, and optical properties of oligothiophenes is reported. Geometry optimizations of the ground state of derivatives of these molecules were carried out using the density functional theory (DFT) with the B3LYP functional and the 6-31G(d) basis set. Bridged oligothiophenes by C═O, C═S, and C═C(CN)(2) functional groups were found to be planar in their electronic ground states (S(0)). The electronic excitation transitions of the bridged oligothiophenes were investigated using the time-dependent TD-DFT method performed on the ground-state optimized geometries. For all the derivatives, excitation to the S(1) state corresponds mainly to the HOMO → LUMO transition. The excitation energies are found in fair agreement with the experimental values. The optimization (relaxation) of the first singlet excited electronic state (S(1)) has been done using the restricted configuration interaction (singles) (RCIS/6-31G(d) approach. The electronically excited geometries favor a more quinoidic type structure. Emission energies have been obtained from TD-DFT calculations performed on the excited-state optimized geometries S(1). The change of group (C═O, C═S, and C═C(CN)(2)) as well as the incorporation of monomer moieties induce a significant decrease in the excitation and emission energies.

Controlling bandgap energy and multivibronic modes of a poly(2,5-thiophene-1,4-dialkoxyphenylene) derivative by gamma photons.

In this work, the influence of γ radiation on electronic, structural, and vibrational properties of a poly(2,5-thiophene-1,4-dialkoxyphenylene) derivative is studied by optical absorption and photoluminescence. A Gaussian fit of emission spectra within Franck-Condon vertical transitions formalism was carried out in order to understand how vibronic coupling is affected by the dose, because an unexpected luminescence behavior was observed. Aiming to understand the ionizing radiation-matter interaction processes, we employed a molecular modeling procedure, through the use of a semiempirical method (AM1) applied to conjugated oligomers' conformational structure and equilibrium geometries, to clarify the defects induction for the used doses. From AM1 optimized structures, electronic transitions were calculated by ZINDO/S-CI semiempirical method to measure the chain scission degree. Moreover, with the results presented in this work, it is possible to come up with a new physical-chemical route to treat and increase conjugated polymers' efficiency. Finally, we believe that the present paper contributes to the literature about defects on conjugated polymers.

Use of angioscanning in the surgical planning of perforator flaps in the lower extremities.

BACKGROUND: This is one of the few studies in the literature to describe angio-computed tomography (CT) as a planning tool in perforator flap surgery in the lower extremities. METHODS: Eighteen consecutive patients undergoing a perforator flap for lower-extremity reconstruction underwent preoperative CT angiography between September 2007 and November 2009. Eleven received propeller-type flaps, four medial sural artery perforator (MSAP) flaps, two lateral sural artery perforator (LSAP) flaps and one anterolateral thigh (ALT) flap. RESULTS: Preoperative CT angiography was highly specific (100%) and sensitive in mapping and visualising perforators in the lower limb. There were hardly any flap failures after angio-CT, and operative findings always correlated perfectly with preoperative imaging. Postoperative recoveries were uneventful except in three cases of peroneal artery perforator flaps that presented partial necrosis due to venous congestion. CONCLUSIONS: CT angiography is a valuable imaging tool for the preoperative assessment of the donor-site vascular supply for lower-extremity flaps. We recommend use of preoperative angio-CT for imaging vascular anatomy of the lower limb before defect reconstruction, especially in traumatic patients and patients with peripheral vascular disease. Its use can also reduce intra-operative dissection time and minimises surgical error in the identification of the vascular anatomy.

[Relation between cavo-tricuspid isthmus anatomy studied by transesophageal echocardiography and the immediate outcome of radiofrequency ablation of common atrial flutter]. / Relation entre l'anatomie de l'isthme cavo-tricuspide étudiée par échocardiographie trans-oesophagienne et les résultats immédiats de l'ablation par radiofréquence du flutter auriculaire commun.

Radiofrequency ablation is the only curative treatment of common atrial flutter. The aim of the treatment is to create a line of bidirectional block at the level of the cavo-tricuspid isthmus. This objective can be achieved in the vast majority of the patients. However, it may difficult or even not possible to create an isthmus block. The anatomy of the right atrium is subject to important variations, especially at the isthmus level. We therefore tested the hypothesis that these anatomic variations might influence the immediate outcome of cavo-tricuspid isthmus ablation. The anatomy of cavo-tricuspid isthmus was studied by trans-oesophageal echocardiography. The shape of the isthmus (concave or not), the presence of diverticula and the degree of development of the Eustachian ridge were analysed. From these data, the cavo-tricuspid anatomy was classified as simple or complex. The immediate outcome of radiofrequency ablation was reviewed in 94 patients (mean age of 63 years) according to the anatomy, simple or complex. When the anatomy was classified as simple, the success rate of radiofrequency ablation was 95.6%; when the anatomy was complex, the success rate was 76.9% (overall success rate for the entire population equal to 90.4%). The length of the cavo-tricuspid isthmus did not influence the outcome of radiofrequency ablation. In summary, it appears that the anatomy of cavo-tricuspid isthmus seems to play a role in the immediate outcome of radiofrequency ablation of cavo-tricuspid isthmus.

Lattice dynamics of oligo(phenylenethienylene)s: a far-infrared and inelastic neutron scattering study.

New promising oligo(phenylenethienylene)s have been synthesized to realize suitable materials for improving electronic transport properties, particularly in organic field effect transistors (OFETs). Far-infrared and incoherent neutron scattering measurements have been performed to assign their phonon modes. The assignment of the main low-frequency phonon modes of these materials has been performed experimentally by using a filiation procedure. Assuming a small frequency dispersion of the high-frequency modes, the main intramolecular phonon modes of a model oligomer have been assigned by using first-principles calculations on its isolated molecule. These assignments constitute the preliminary work for a better understanding of these new promising materials in electronic and opto-electronics applications.

Correlations between structure and far-infrared active modes in polythiophenes.

We have investigated the experimental X-ray and far-infrared responses of three polythiophenes synthesized from a thiophene, alpha-bithiophene, and alpha-quaterthiophene monomer. The X-ray data show that the crystallinity of the different polythiophene samples depends on the synthesis conditions. An excellent correlation between the crystallinity of polythiophenes and their far-infrared signatures is demonstrated. In addition, the assignment of the far-infrared phonon modes in polythiophenes is given by using both an experimental filiation procedure and first-principles calculations. In particular, the ring libration inside the polymeric chain, directly involved in the electron-phonon coupling, is assigned.

Human dendritic cells genetically engineered to express a melanoma polyepitope DNA vaccine induce multiple cytotoxic T-cell responses.

PURPOSE: To assess the therapeutic potential of a melanoma polyepitope vaccine in human cells. Polyepitope DNA vaccines encoding T-cell epitopes have been demonstrated in murine systems to generate multiple cytotoxic T-cell responses to different antigens. Here, for the first time we demonstrate the ability of a melanoma polyepitope to stimulate lymphocytes from normal human donors to simultaneously generate multiple antigen-specific responses. EXPERIMENTAL DESIGN: Human dendritic cells (DC), transduced with a melanoma-polyepitope cDNA, were used to activate autologous lymphocytes from naïve donors as an in vitro model of DNA vaccination. Lymphocytes were primed with polyepitope or mock-transduced DC, boosted with peptide, then measured for antigen-specific cytotoxicity. RESULTS: Lymphocytes primed with polyepitope-transduced DC and boosted with peptide generated multiple cytotoxic responses. By contrast lymphocytes primed with mock-transfected DCs and boosted with peptide gave no specific cytotoxicity. However, when lymphocytes were repeatedly stimulated with polyepitope-transduced DCs immunodominance was seen with CTLs being generated to only one epitope, MART(27-35). CONCLUSIONS: We show in a human system that a melanoma polyepitope primes CTL to multiple epitopes. However, repeated stimulation by the polyepitope restricts the response to only the MART1 epitope. Thus, although polyepitope vaccines are an effective way of priming multiple naïve T-cell responses, continual boosting with polyepitope vaccines may, as a result of immunodominance, restrict the CTL. These findings have important implications for the use of DNA polyepitope vaccines in cancer immunotherapy.

[Rupture of a sinus of Valsalva aneurysm in the left atrium]. / Rupture d'un anévrisme des sinus de Valsalva dans l'oreillette gauche.

Ruptures of sinus of Valsalva aneurysms are a rare complication, and very few cases of rupture in the left atrium have been described. In this clinical case we report the case of a patient hospitalised with a scenario of cardiac insufficiency revealing a very large posterior sinus of Valsalva aneurysm, associated with a bicuspid aortic valve, and rupture in the left atrium. The diagnosis was by transthoracic and transoesophageal multiplan echocardiography, and the treatment surgical, with a good result.

The COP9/signalosome complex is conserved in fission yeast and has a role in S phase.

The COP9/signalosome complex is conserved from plant to mammalian cells. In Arabidopsis, it regulates the nuclear abundance of COP1, a transcriptional repressor of photomorphogenic development [1] [2]. All COP (constitutive photomorphogenesis) mutants inappropriately express genes that are normally repressed in the dark. Eight subunits (Sgn1-Sgn8) of the homologous mammalian complex have been purified [3] [4]. Several of these have been previously identified through genetic or protein interaction screens. No coherent model for COP9/signalosome function has yet emerged, but a relationship with cell-cycle progression by transcriptional regulation, protein localisation or protein stability is possible. Interestingly, the COP9/signalosome subunits possess domain homology to subunits of the proteasome regulatory lid complex [5] [6]. Database searches indicate that only Sgn5/JAB1 is present in Saccharomyces cerevisiae, precluding genetic analysis of the complex in cell-cycle regulation. Here we identify a subunit of the signalosome in the fission yeast Schizosaccharomyces pombe through an analysis of the DNA-integrity checkpoint. We provide evidence for the conservation of the COP9/signalosome complex in fission yeast and demonstrate that it functions during S-phase progression.

Occlusive and aneurysmal peripheral arterial disease: assessment of a stent-graft system.

PURPOSE: To assess the use of a recently developed stent-graft system for treatment of occlusive lesions and aneurysms in the iliac and femoropopliteal arteries. MATERIALS AND METHODS: The stent-graft consisted of a nitinol stent framework covered by a thin-walled polyester fabric. The device was used in 105 patients with symptomatic peripheral vascular disease. Implant locations were iliac artery (n = 38), femoral artery (n = 62), and popliteal artery (n = 5). RESULTS: Initial technical success was achieved in all patients except one with occlusive disease and one with aneurysmal disease. Residual stenosis after stent-graft implantation was 0.5% +/- 3. Mean ankle-brachial index increased from 0.53 to 0.98. Complications were hematoma (n = 3), pseudoaneurysm (n = 2), puncture site thrombosis (n = 1), early graft thrombosis (n = 8), graft misplacement (n = 1), distal embolization (n = 2), delayed thrombosis (n = 14), pain and fever (n = 27). At the iliac level, primary patency was 97% and secondary patency was 100%. At the femoral level, primary patency was 59% and secondary patency was 81%. CONCLUSION: Endoluminal bypass with a percutaneously delivered stent-graft is feasible. Technical results are good, and the number of complications is few at the iliac level. At the femoropopliteal level, patency is not as good and the number of complications is higher.

[5 years results of percutaneous mitral commissurotomy. Apropos of a series of 606 patients; late results after mitral dilatation]. / Résultats à 5 ans de la commissurotomie mitrale percutanée. A partir d'une série de 606 patients; résultats tardifs après dilatation mitrale.

The long-term results of percutaneous mitral commissurotomy were evaluated in 606 patients with a mean age of 48 +/- 14 years. One hundred and eleven patients (48%) had a history of surgical commissurotomy. At echocardiography, 91 patients (15%) had flexible leaflets and little subvalvular apparatus, and 180 (30%) have calcified valves. The procedure was performed with a single balloon in 21 patients, a double balloon in 402 patients and Inoue's balloon in 183 patients. A good immediate, result, defined as a mitral valve surface area > or = 1.5 cm2 without > 2/4 mitral regurgitation, was obtained in 528 patients (87%). Five hundred and eighty patients (96%) were followed up for an average of 30 +/- 18 months. The actuarial 5 year rates were: survival 94 +/- 4%; survival without surgery 74 +/- 6%; survival without surgery with a good functional result (NYHA Classe I and II) 66% +/- 6%. Factors predictive of a good functional result were the valvular anatomy (p = 0.01), the NYHA Class before the procedure (p = 0.02), the cardiothoracic ratio before the procedure (p = 0.005) and mitral valve surface area after the procedure (p = 0.007). The type of balloon had no influence on the result (p = 0.54). The authors conclude that the 5 year results of percutaneous mitral commissurotomy are good in a population of patients with varied characteristics. The persistence of good functional results depends on anatomical and functional data and the quality of the initial result, but not on variables related to the procedure.

Immediate results of percutaneous mitral commissurotomy. A predictive model on a series of 1514 patients.

BACKGROUND: The wide use of percutaneous mitral commissurotomy (PMC) underlines the need to identify the predictive factors of the results. Using a large series allowed us to develop a multivariate model that can be applied to improve patient selection. METHODS AND RESULTS: Between 1986 and 1995. PMC was undertaken in 1514 patients. Mean age was 45 +/- 15 years. Echocardiography showed that 245 patients (16%) had pliable valves and mild chordal thickening (group 1), 886 (59%) had extensive subvalvular disease (group 2), and 383 (25%) had calcified valves (group 3). PMC failed in 22 patients; it was performed with a single balloon in 30 patients, a double balloon in 586, and the Inoue balloon in 876. Good immediate results were defined as a valve area > or = 1.5 cm2 with mitral regurgitation Sellers' grade < or = 2 and were obtained in 1348 patients (89%). A logistic model developed from the first 1088 cases identified the following predictors of immediate results: age (P = .004), echocardiographic group (P < .0001), valve area (P < .0001), and effective balloon dilating area (EBDA) (P = .03). Two interactions were significant: age at previous commissurotomy (P = .013) and EBDA by initial mitral regurgitation (P = .034). The type of balloon was of borderline significance (P = .09). The model was validated on an independent sample comprising the subsequent 426 procedures. For a threshold of probability of good results of .75, sensitivity was 92%, specificity 25%, and predictive accuracy 87%. CONCLUSIONS: Prediction of the immediate results of PMC is multifactorial. The predictive model developed and validated can be contributive in decision making for individual patients.