INTRA-ARTERIAL CHEMOTHERAPY AS A CLINICAL OPTION FOR METASTATIC COLORECTAL CANCER: CONVERSION OF INOPERABLE LIVER METASTASES TO OPERABLE ILLUSTRATED WITH A CLINICAL CASE.

Colorectal cancer exerts a very high level of liver metastases, even on primary diagnosis, with 80%-90% unresectable nodules. At the same time, the possibility of resection has a significant impact on survival: 5-year survival is 6%-10% without liver surgery and up to 30% upon resection of liver metastases. Finding ways to improve resectability is a topical search for doctors all over the world. One of the promising methods to convert unresectable liver metastases of colorectal cancer into resectable ones is a hepatic artery infusion, or intra-arterial chemotherapy allowing for the delivery of cytotoxic drugs directly to the common hepatic artery via catheter or pump with decreased systemic toxicity and increased local drug concentration. In this article, we discuss the literature data on the impact of intra-arterial chemotherapy on the resectability of colorectal metastases in the liver and present the results of the successful clinical case. The literature shows a positive impact of the hepatic artery infusion on the resectability of hepatic metastases of colorectal cancer. The National Cancer Institute (Ukraine) has its own experience in hepatic artery infusion with further resection of primary-unresectable colorectal metastases in the liver. In our clinical case, a patient with liver-limited metastasis of colorectal cancer was initially inoperable due to the size of tumor lesions and an insufficient residual volume of the liver. Hepatic artery infusion tactics was chosen for this patient. The patient received six cycles of intra-arterial chemotherapy, namely five FOLFOX cycles and one 5-FU cycle, and then met the resectability criteria. Also, it is important to notice that the case demonstrates chemoresistance overcoming, since the patient had disease progression before, following systemically administered XELOX, and the period until readmission of the drugs was less than 6 months. So, hepatic artery infusion can be considered a promising method to convert unresectable liver metastases of colorectal cancer into resectable ones for highly selected patients.

Parenchyma-sparing strategy and oncological prognosis in patients with colorectal cancer liver metastases.

BACKGROUND: Preliminary study results demonstrated parenchyma-sparing surgery (PSS) as an effective approach which allowed to remove colorectal cancer (CRC) metastatic lesions within the central liver cites and increased the probability of the liver re-resections. METHODS: The prospective analysis re-evaluation of the 185 CRC patients surgical treatment has been performed. RESULTS: An overall 5-year survival (OS) of the 185 enrolled patients was 43 ± 7%, and the mean and median value for OS was 48.7 ± 1.9% and 55.2 ± 5 (95% CI: 44.4-66.1) months. The 5-year OS for CRC patients whose metastatic lesions were predominantly located within peripheral and central liver segments was 56 ± 8% and 27 ± 9%, respectively (p = 0.08). A 5-year disease-free survival (DFS) rates of patients with peripheral and central liver cites metastatic lesions were 31 ± 7 % and 15 ± 7%, p = 0,12. And the DFS median was 34.2 and 46.5 months for R1v and R0 cohorts, respectively, p = 0.62. CONCLUSIONS: Parenchyma-sparing surgery should be a priority pathway for complex treatment of patients with deeply located lesions of the right liver lobe. TRIAL REGISTRATION: The study is registered in https://www.researchregistry.com/browse-the-registry#home/registrationdetails/5ed9f60863e9bf0016624456/ , no. 5679.

Eco-friendly synthesis of fused pyrano[2,3-b]pyrans via ammonium acetate-mediated formal oxa-[3 + 3]cycloaddition of 4H-chromene-3-carbaldehydes and cyclic 1,3-dicarbonyl compounds.

Various substituted polycyclic pyrano[2,3-b]pyrans were synthesized via the condensation of 4H-chromene-3-carbaldehydes and their areno-condensed analogues with hetero- and carbocyclic 1,3-dicarbonyl compounds in acetic acid. Ammonium acetate was used as a green catalyst for the reaction. The process also involves the subsequent Knoevenagel condensation and 6π-electrocyclization of the 1-oxatriene intermediates formed. Fused pyridines were isolated as the products of the conjugated addition of ammonia to 1-oxatriene intermediates while using carbocyclic 1,3-dicarbonyl compounds and increasing the reaction time, indicating the reversibility of the electrocyclization stage. The calculated values of the Gibbs free energies and reaction rate constants for the 1-oxatriene - 2H-pyran equilibrium also testified to the irreversibility of pyrano[2,3-b]pyran formation in the case of using of heterocyclic 1,3-dicarbonyl compounds.

[Cerebral cryptococcosys with depressive disorder]. / Tserebral'nyi kriptokokkoz s kartinoi trevozhno-depressivnogo rasstroistva.

A case of cerebral cryptococcosis is described. Cryptococcus neoformans is the most pathogenic in humans. It often affects lungs, skin, muscles and tissues of the Central Nervous System (CNS). In case of CNS involvement, the main clinically diagnosed form of the disease is cryptococcal meningitis. The authors describe a patient with non-specific symptoms of anxiety-depressive disorder and further development of neurological symptoms and behavioral deviations.

Intraoperative ultrasonography in pancreatic surgery: staging and resection guidance.

BACKGROUND: Intraoperative ultrasound examination (IOUS) is indispensable part of modern surgical interventions in tumors of hepatopancreatobiliary zone. In this study retrospective analysis of IOUS efficiency in surgical treatment of pancreatic tumors was provided. MATERIALS AND METHODS: In the period from January 2013 till November 2015 in the National Cancer Institute IOUS was applied during 76 surgical interventions: for pancreatic head tumors--in 46 (60.5%) patients, for body/tail pancreatic tumors--in 20 (26.3%) patients, in 10 (13.2%) patients--for periampullary zone neoplasms. In IOUS we performed primary tumor assessment (localization, degree of tumor spreading to superior mesenteric vessels, hepatoduodenal ligament vessels, additional foci occurrence in pancreas), and liver metastases detection. Surgical interventions were performed: pancreatoduodenectomy in 52 (68.4%) patients, radical antegrade modal pancreatosplenectomy--in 14 (18.4%) patients. RESULTS: IOUS allowed determining additional tumor foci in pancreas in 2 (2.6%) patients, in 8 (10.5%) observations tumor invasion into portal or superior mesenteric vein was determined. In 21 (27.6%) patient additional hepatic neoplasms were detected (in half of cases--11.8%, metastases). These findings resulted in change of surgical intervention extent in 23 (30.3%) patients: expansion to combined resections in 14 (18.4%) patients, reduction to symptomatic operations in 5 (6.6%) cases, organ-preserving operations were performed in 4 (5.3%) patients. Variant anatomy of hepatic arterial blood supply was determined in 41 (53.9%) patients that necessitated performance correction of resection stages for preservation of adequate hepatic blood supply. CONCLUSIONS: IOUS is a highly-precise diagnostic method substantively influencing operation course in pancreatic tumors, enabling surgeon to provide adequate staging and permanent correction of operation course.

[PREDICTING FACTORS OF THE LIFE SPAN IN PATIENTS, SUFFERING METASTATIC COLORECTAL CANCER AND SYNCHRONOUS HEPATIC AFFECTION AFTER SURGICAL TREATMENT].

The results of treatment of 125 patients, suffering metastatic hepatic affection in colorectal cancer (pT1--4N0--2M1--in colonic cancer and pT1--3N0--2M1--in cancer recti), to whom in 2008-2015 yrs a one-staged (Group 1) or two-staged (Group II) surgical treatment was done. In affection of 4 regional lymph nodes and more (pN2) late results were less favorable, than in pN1 or pN0, not depending from surgical approach choosed. In 48 (38.4%) patients with one syndromal hepatic metastatic focus, the indices of general three-year and five-year cumulative survival were the best, than in other groups--82 and 63% (p = 0.001) accordingly; in monolobar affection--68 and 49%, and in bilobar--23 and 0%, not depending from method of surgical treatment (p < 0.001) choosed. Predictive factors were established, which impact negatively the indices of general survival in patients, suffering metastatic hepatic affection in colorectal cancer: hepatic metastatic foci number 4 and more, bilobar hepatic metastatic affection.

[SURGICAL TREATMENT OUTCOME IN PATIENTS WITH COLORECTAL CANCER AND CONCOMITANT LIVER METASTASES].

Colorectal cancer with synchronous liver metastasis (sm-CRC) is extremely unfavorable prognostic factor. Surgery remains is most effective method, able to extend the life of these patients. The results of treatment of 126 patients with sm-CRC were analyzed, whom performed simultaneous (group I) or staged (group II) surgery. Simultaneous resection of 3 segments of liver or less with metastases and primary tumor is a safe surgical strategy (complicatios level was 4.8%); simultaneous resection of 3 segments of liver or more increase the complicatios level to 20.9%. Simultaneous resection ensure reduction of hospital stay terms in 58.1% and duration of surgery in 71.3% (p < 0.001). The average cost of treatment patient treating with staged strategy exceeded in simultaneous surgical treatment in 40.9%.

[Combination of in-situ hepatic split and portal ligation in patients with colorectal cancer and metastatic hepatic spread].

In up to 50% of patients, suffering colorectal cancer (CRC), a hepatic metastatic affection was revealed, in 20-34% of them the metastases have occurred synchroniously with primary tumor. The main problem in estimation of resectability of metastatic CRC (mCRC) is a possibility to preserve a sufficient volume of the organ parenchyma, because an acute hepatic insufficiency (AHI) constitute one of the main risk factors for occurrence of complications and mortality in early postoperative period after extended hemihepatectomy. The expediency of application in National Cancer Institute of the insitu hepatic split in conjunction with a portal ligation (ISHS-PL), elaborated by surgical group in Regensburg, was studied up. The results of treatment of mCRC, using ISHS-PL--in 3 patients and of a standard two-staged hepatic resection--in 3, were analyzed. Duration of a gap period between the ISHS-PL stages have constituted on average (10 +/- 1) days, and for a standard two-staged hepatic resection--(56 +/- 11.3) days (p = 0.001). The investigation results witness a safety of performance of the ISHS-PL in patients, suffering mCRC. Application of such a surgical tactics have permitted to reduce the risk of an AHI occurrence after performance of the extended hepatic resection in patients, suffering bilobar metastatic hepatic affection.

Imaging the anisotropic nonlinear meissner effect in nodal YBa2 Cu3 O7-δ thin-film superconductors.

We have directly imaged the anisotropic nonlinear Meissner effect in an unconventional superconductor through the nonlinear electrodynamic response of both (bulk) gap nodes and (surface) Andreev bound states. A superconducting thin film is patterned into a compact self-resonant spiral structure, excited near resonance in the radio-frequency range, and scanned with a focused laser beam perturbation. At low temperatures, direction-dependent nonlinearities in the reactive and resistive properties of the resonator create photoresponse that maps out the directions of nodes, or of bound states associated with these nodes, on the Fermi surface of the superconductor. The method is demonstrated on the nodal superconductor YBa2Cu3O7-δ and the results are consistent with theoretical predictions for the bulk and surface contributions.

[The method of the isolated reconstruction by gastropancreatoduodenal resection].

The modification of the reconstructive stage of gastropancreatoduodenal resection aims to increase the security of the pancreatojejunoanastomosis by minimizing the impact of such aggressive substances as bile and pancreatic juice. The modification represents the isolated pancreatojejunoanastomosis on the Roux-en-Y intestinal loop and gastro- and hepaticojejunoanastomoses on the second intestinal loop, separated with the use of the stub. Thus, the method allows the separate passage of pancreatic juice, bile and gastric contents, excluding their impact on other anastomoses. The described modification was performed in 6 patients. There were no cases of the anastomotic insufficiency. The mean hospital stay was 10,5 days. Thus. The method proved to be effective and safe, providing good initial results.

Measuring the temperature dependence of individual two-level systems by direct coherent control.

We demonstrate a new method to directly manipulate the state of individual two-level systems (TLSs) in phase qubits. It allows one to characterize the coherence properties of TLSs using standard microwave pulse sequences, while the qubit is used only for state readout. We apply this method to measure the temperature dependence of TLS coherence for the first time. The energy relaxation time T1 is found to decrease quadratically with temperature for the two TLSs studied in this work, while their dephasing time measured in Ramsey and spin-echo experiments is found to be T1 limited at all temperatures.

Improved powder filters for qubit measurements.

We designed and fabricated miniature low-pass metal powder filters suitable for noise-sensitive measurements at cryogenic temperatures. In comparison with previous powder filters, our filters have a much better frequency response and significantly smaller dimensions (0.7 cm(3) including the plugs) and can also be used as hermetic feedthroughs at low temperatures. Their transmission characteristics are smooth, contain no ripples, and have a steep decay above the cutoff frequency. At 4.2 K the cutoff frequency of a single filter is f(c)=1 MHz and the roll-off is -50 dB per decade. All of the fabricated filters have identical frequency responses at 4.2 K and their characteristics are reliably reproducible.

Temperature dependence of coherent oscillations in Josephson phase qubits.

We experimentally investigate the temperature dependence of Rabi oscillations and Ramsey fringes in superconducting phase qubits. In a wide range of temperatures, we find that both the decay time and the amplitude of these coherent oscillations remain nearly unaffected by thermal fluctuations. In the two-level limit, coherent qubit response rapidly vanishes as soon as the energy of thermal fluctuations k(B)T becomes larger than the energy level spacing variant Planck's over h omega of the qubit. In contrast, a sample of much shorter coherence times displayed semiclassical oscillations very similar to Rabi oscillation, but showing a qualitatively different temperature dependence. Our observations shed new light on the origin of decoherence in superconducting qubits. The experimental data suggest that, without degrading already achieved coherence times, phase qubits can be operated at temperatures much higher than those reported till now.

Enhanced macroscopic quantum tunneling in Bi2Sr2CaCu2O8 + delta intrinsic Josephson-junction stacks.

We have investigated macroscopic quantum tunneling in Bi(2)Sr(2)CaCu(2)O(8 + delta) intrinsic Josephson junctions at millikelvin temperatures using microwave irradiation. Measurements show that the escape rate for uniformly switching stacks of Nu junctions is about Nu(2) times higher than that of a single junction having the same plasma frequency. We argue that this gigantic enhancement of the macroscopic quantum tunneling rate in stacks is boosted by current fluctuations which occur in the series array of junctions loaded by the impedance of the environment.

Quantum dynamics of a single vortex.

Vortices occur naturally in a wide range of gases and fluids, from macroscopic to microscopic scales. In Bose-Einstein condensates of dilute atomic gases, superfluid helium and superconductors, the existence of vortices is a consequence of the quantum nature of the system. Quantized vortices of supercurrent are generated by magnetic flux penetrating the material, and play a key role in determining the material properties and the performance of superconductor-based devices. At high temperatures the dynamics of such vortices are essentially classical, while at low temperatures previous experiments have suggested collective quantum dynamics. However, the question of whether vortex tunnelling occurs at low temperatures has been addressed only for large collections of vortices. Here we study the quantum dynamics of an individual vortex in a superconducting Josephson junction. By measuring the statistics of the vortex escape from a controllable pinning potential, we demonstrate the existence of quantized levels of the vortex energy within the trapping potential well and quantum tunnelling of the vortex through the pinning barrier.

Multiphoton transitions between energy levels in a current-biased Josephson tunnel junction.

The escape of a current-biased Josephson tunnel junction from the zero-voltage state in the presence of weak microwave radiation is investigated experimentally at low temperatures. The measurements of the junction switching current distribution indicate the macroscopic quantum tunneling of the phase below a crossover temperature of T small star, filled approximately 280 mK. At temperatures below T small star, filled we observe both single-photon and multiphoton transitions between the junction energy levels by applying microwave radiation in the frequency range between 10 and 38 GHz to the junction. These observations reflect the anharmonicity of the junction potential containing only a small number of levels.

Quantum dissociation of a vortex-antivortex pair in a long josephson junction.

The thermal and the quantum dissociation of a single vortex-antivortex (VAV) pair in an annular Josephson junction is experimentally observed and theoretically analyzed. In our experiments, the VAV pair is confined in a pinning potential controlled by external magnetic field and bias current. The dissociation of the pinned VAV pair manifests itself in a switching of the Josephson junction from the superconducting to the resistive state. The observed temperature and field dependence of the switching current distribution is in agreement with the analysis. The crossover from the thermal to the macroscopic quantum tunneling mechanism of dissociation occurs at a temperature of about 100 mK. We also predict the specific magnetic field dependence of the oscillatory energy levels of the pinned VAV state.