Чрескожная необратимая электропорация при местно-распространенном раке поджелудочной железы – обзор литературы и клинический случай

Background. The results of local destruction methods in locally advanced pancreatic cancer (LAPCa) are contradictory. Radiation therapy is the most commonly used. Other methods are used much less frequently, irreversible electroporation (IRE) is one of them. Most authors indicate an acceptable level of complications and mortality, but without an improvement in long-term results. The results of two meta-analyses have been published, the authors indicate the possibility of using the IRE in selected patients. The authors also point out that minimally invasive methods of using the IRE be preferred. Some experience has been gained in the use of percutaneous access for IRE in LAPCa. Computed tomography, ultrasound guidance can be used for navigation. The level of complications can reach 50 %. Mortality with percutaneous access, as a rule, is absent or does not exceed 5 %. Long-term results are the same with the results of open IRE.Aim. To share authors experience of using percutaneous irreversible electroporation in pancreatic cancer, because there are no references to the use of percutaneous IRE in LAPCa in Russia.Materials and methods. The IRE was performed for 53-year female patient with LAPCa after successful induction therapy. A step-by-step pulse effect of electrodes installed under ultrasound control on the tumor infiltrate was carried out. Magnetic resonance imaging, computed tomography and other types of studies were used for diagnostic purposes.Results. The involvement of the common hepatic artery and portal vein remained after the induction therapy, which did not allow performing pancreatoduodenal resection. Ultrasonic navigation and flat-detector computed tomography allowed to install the electrodes adequatly and safely. The impact zone almost completely blocked the infiltrate zone, a more optimal location of the electrodes was limited by the wide network of venous collaterals. Magnetic resonance imaging data performed before and after the procedure showed no progression of the disease within more than three months after the procedure, including in the affected area. Tumor shrinkage was noted as a partial response.Conclusion. The first experience confirmed the safety and the absence of subsequent complications when using the percutaneous access method of IRE for LAPCa. Follow-up monitoring of the patient will allow to say more correctly about the possibility of the method to provide long-term local control.Введение. Результаты применения методов локального воздействия при местно-распространенном раке поджелудочной железы (МРРПЖ) противоречивы, наиболее частым методом является лучевая терапия. Другие методы воздействия применяются реже, один из них – необратимая электропорация (НЭП). Большая часть авторов указывают на приемлемый уровень осложнений и летальности, но без улучшения отдаленных результатов. Результаты двух метаанализов указывают на целесообразность применения метода у отобранных пациентов. Акцентируется внимание на том, что следует отдавать предпочтение малоинвазивным способам использования метода, поскольку накоплен определенный опыт применения чрескожного доступа для НЭП при МРРПЖ. Для навигации могут использоваться компьютерная томография, ультразвуковое наведение. Уровень осложнений достигает 50 %. Летальность при чрескожном доступе отсутствует или не превышает 5 %, отдаленные результаты не отличаются от результатов НЭП, выполненной во время лапаротомии.Цель исследования – оценка авторского опыта применения чрескожной НЭП при раке поджелудочной железы в виду отсутствия подобного опыта у коллег в России.Материалы и методы. Процедура чрескожной НЭП при раке поджелудочной железы выполнена у пациентки 53 лет по поводу МРРПЖ после успешной индукционной терапии. Осуществлялось поэтапное импульсное воздействие с помощью установленных под ультразвуковым контролем электродов на опухолевый инфильтрат. В диагностических целях применялись магнитно-резонансная томография, компьютерная томография и другие виды исследований.Результаты. Отмечено уменьшение размеров опухолевого инфильтрата после индукционной терапии при сохранении вовлечения общей печеночной артерии и полного блока воротной и верхней брыжеечной вен с развитием коллатералей, что не позволило выполнить панкреатодуоденальную резекцию. Ультразвуковая навигация с неоднократным контролем расположения электродов с помощью плоскодетекторной компьютерной томографии позволила адекватно и безопасно их установить, а в последующем – убедиться в отсутствии осложнений. Результаты магнитно-резонансной томографии, выполненной до и после процедуры, показали отсутствие прогрессирования заболевания в течение 3,5 мес после процедуры, в том числе в зоне воздействия. Отмечено уменьшение опухоли в рамках частичного ответа.Заключение. Подтверждены безопасность и отсутствие последующих осложнений при применении метода чрескожного доступа для НЭП при МРРПЖ. Наблюдение за пациенткой позволит более корректно высказаться о возможности метода обеспечить длительный локальный контроль заболевания при МРРПЖ

Synthesis, Structures, and Optical Properties of Ruthenium(II) Complexes of the Tris(1-pyrazolyl)methane Ligand

Four new complex salts [Ru^(II)Cl(Tpm)(L^A)_2][PF_6]_n [Tpm = tris(1-pyrazolyl)methane; n = 1, L^A = pyridine (py) 1 or ethyl isonicotinate (EIN) 2; n = 3, L^A = N-methyl-4,4′-bipyridinium (MeQ^+) 3 or N-phenyl-4,4′-bipyridinium (PhQ^+) 4] have been prepared and characterized. Electronic absorption spectra show intense d → π^* metal-to-ligand charge-transfer (MLCT) absorption bands, while cyclic voltammetry reveals a reversible Ru^(III/II) wave, accompanied by quasireversible or irreversible L^A-based reductions for all except 1. Single crystal X-ray structures have been obtained for 1•Me_2CO, 2, and 3•Me_2CO. For 2–4, molecular first hyperpolarizabilities β have been measured in acetonitrile solutions via the hyper-Rayleigh scattering (HRS) technique at 800 nm. Stark (electroabsorption) spectroscopic studies on the MLCT bands in frozen butyronitrile allow the indirect estimation of static first hyperpolarizabilities β_0. The various physical data obtained for 3 and 4 are compared with those reported previously for related cis-{Ru^(II)(NH_3)_4}^(2+) species [Coe, B. J. et al. J. Am. Chem. Soc. 2005, 127, 4845]. TD-DFT calculations on the complexes in 1–4 confirm that their lowest energy absorption bands are primarily Ru^(II) → L^A MLCT in character, while Ru^(II) → Tpm MLCT transitions are predicted at higher energies. DFT agrees with the Stark, but not the HRS measurements, in showing that β_0 increases with the electron-accepting strength of L^A. The 2D nature of the chromophores is evidenced by dominant β_(xxy) tensor components

Kinetics of strain-activated intramolecular Diels-Alder reactions between furan and bicyclopropylidene as well as methylenecyclopropane moieties

The intramolecular Diels-Alder reactions of the furans 1a, 1b, 3a and 3b in dichloromethane solution at pressures up to 3 kbar have been studied by quantitative on-line FT-IR spectroscopy. At identical pressure and temperature cyclization rates are significantly faster, by a factor of 8.1 and 6.8, for the b-type species of 1 and 3, respectively. The activation enthalpies of the four cyclizations are very similar, between 78.5 ± 0.6 and 82.5 ± 2.7 kJ mol-1. The activation volumes, ΔV0 ≠, are in the range -28.4 ± 1.3 (1a) to -40.8 ± 2.0 cm3 mol-1 (3b). These data show that intramolecular Diels-Alder reactions are not necessarily associated with less negative activation volumes than intermolecular Diels-Alder reactions. The size of ΔV0 ≠, however, appears to be clearly correlated with the type and the position of substituents at the diene or dienophile moieties. Replacement of the H atom on the furan ring by the methoxy group turns ΔV0 ≠ more negative by 7.4 ± 2.9 cm3 mol-1 for 1a and 1b and by 8.1 ± 2.0 cm3 mol-1 for 3a and 3b. Varying the dienophile moiety from methylenecyclopropane to bicyclopropylidene lowers ΔV0 ≠ by about 3.5 cm3 mol-1 between 1a and 3a and by about 5.0 cm3 mol-1 between 1b and 3b, which demonstrates the larger steric hindrance due to the tetrasubstitution of the double bond. Comparing the effects on cyclization rate associated with having either one or two cyclopropane units at the dienophile double bond suggests that the rate enhancing influence of strain energy slightly overcompensates a reduction in rate that is expected to go with the increased steric hindrance due to the second cyclopropane unit

(2R,1'S,2'R)- and (2S,1'S,2'R)-3-[2-Mono(di,tri)fluoromethylcyclopropyl]alanines and their incorporation into hormaomycin analogues

Efficient and scalable syntheses of enantiomerically pure (2R,1'S,2'R)- and (2S,1'S,2'R)-3-[2-mono(di,tri)fluoromethylcyclopropyl]alanines 9a-c, as well as allo-D-threonine (4) and (2S,3R)-β-methylphenylalanine (3), using the Belokon' approach with (S)- and (R)-2-[(N-benzylprolyl)amino]benzophenone [(S)- and (R)-10] as reusable chiral auxiliaries have been developed. Three new fluoromethyl analogues of the naturally occurring octadepsipeptide hormaomycin (1) with (fluoromethylcyclopropyl)alanine moieties have been synthesized and subjected to preliminary tests of their antibiotic activity

(2 R

Efficient and scalable syntheses of enantiomerically pure (2R,1'S,2'R)- and (2S,1'S,2'R)-3-[2-mono(di,tri)fluoromethylcyclopropyl]alanines 9a-c, as well as allo-D-threonine (4) and (2S,3R)-β-methylphenylalanine (3), using the Belokon' approach with (S)- and (R)-2-[(N-benzylprolyl)amino]benzophenone [(S)- and (R)-10] as reusable chiral auxiliaries have been developed. Three new fluoromethyl analogues of the naturally occurring octadepsipeptide hormaomycin (1) with (fluoromethylcyclopropyl)alanine moieties have been synthesized and subjected to preliminary tests of their antibiotic activity

Effect of substituents on the 13C-NMR chemical shifts of 3-methylene-4-substituted-1,4-pentadienes. Part I.

Abstract: The principles of linear free energy relationships were applied to the 13C substituent chemical shifts (SCS) of the carbon atoms in the unsaturated chain of 3-methylene-4-substituted-1,4-pentadienes. Correlations of the SCS with the substituent parameters of Swain and Lupton provide a mutually consistent picture of the electronic effects in these compounds. The pattern of the electronic effects can be fully rationalized by a model based on the direct transmission of substituent effects through-space (direct through-space field effects), and via conjugative interactions (resonance effects), or by substituent-induced polarization of the �-system in the unsaturated chain (�-polarization effect). Semi-empirical MNDO-PM3 calculations suggest the s-cis conformation of 3-methylene-4-substituted-1,4--pentadienes as the one with minimal heat of formation