Post-hepatectomy liver failure – achievements and challenges

Institutul de chirurgie ”A.V.Vishnevskii”, Moscova, Rusia, Al XII-lea Congres al Asociației Chirurgilor „Nicolae Anestiadi” din Republica Moldova cu participare internațională 23-25 septembrie 2015Introducere: Problema insuficienţei hepatice postrezecţionale (IHPR) rămîne a fi în prezent una destul de actuală. Frecvenţa IHPR nu este în descreştere, oscilînd în limitele 0,7-0,9%. În acelaşi timp introducerea de noi tehnologii în domeniul diagnosticării IHPR poate îmbunătăţi rezultatele tratamentului chirurgical al pacienţilor cu tumori hepatice. Scopul: Studierea posibilităţilor de diagnostic precoce și tratament a IHPR la pacienţii care au suportat intervenţii chirurgicale majore hepatice. Material şi metode: Timp de 5 ani au fost efectuate 204 rezecţii hepatice majore. Pe motivul afectării hepatice secundare au fost operaţi 101 (49,6%) pacienţi, dintre care 75 (36,8%) pacienţi cu metastaze de cancer colorectal; tumori hepatice primare – 54 (26,4%) pacienţi, dintre care 25 (12,3%) – carcinom hepatocelular, 20 (9,8%) – colangiocarcinom, 49 (24%) – tumori benigne şi afecţiuni non-tumorale hepatice. Structura operaţiilor efectuate: hemihepatectomia stîngă – 42 (20%), hemihepatectomia dreaptă – 68 (33,3%), hemihepatectomia stîngă extinsă – 27 (13,3%), hemihepatectomia dreaptă extinsă – 44 (21,5%), rezecţia ≥3 segmente hepatice – 19 (16,3%). În perioada postoperatorie au fost estimaţi indicatorii insuficienţei hepatice în baza datelor clinice, scăderea nivelului de albumină <28 g/l, creşterea bilirubinei ˃50 μmol/l, scăderea indicelui protrombinei (IP) <50%, creşterea INR peste 2,0 în 1-3-a, 7-9-a şi a 5-a zi postoperatorie (criteriul 50/50). Pentru aprecierea gradului de IHPR s-a utilizat clasificarea ISGLS. Rezultate: Majoritatea pacienţilor operaţi au prezentat la 1-3-a zi postoperatorie scăderea nivelului de albumină şi IP, creşterea bilirubinei şi INR. În acelaşi timp, schimbări simultane semnificative ale acestor parametri au fost observate la 64 (31,4%) pacienţi. Aceste modificări s-au rezolvat în urma tratamentului conservativ în termen de 4-8 zile, astfel încît nu au putut fi considerate IHPR. La ziua a 5-a aceste modificări erau observate la 48 (23,5%) pacienţi. Valorile numerice ale parametrilor estimaţi au fost în limitele: albumina – 17-34 (media 29) g/l, INR – 1,4-3,8 (media 2,5), bilirubina totală – 22-99 (media 49) μmol/l. La 31 (15,2%) pacienţi semnele IHPR au cedat în urma terapiei standard, ce a fost interpretat ca clasa A de insuficienţă hepatică după ISGLS. IHPR clinic semnificativă s-a observat la 17 (8,3%) pacienţi, dintre care 11 (5,4%) – clasa B şi 6 (2,9%) – clasa C după ISGLS. Cu toate acestea criteriul 50/50 a fost pozitiv doar la 12 (5,9%) pacienţi. Pe fundalul progresării IHPR au decedat 8 (4,1%) pacienţi, dintre care 3 (1,5%) cu criteriul 50/50 negativ. Concluzii: În pofida ameliorării rezultatelor tratamentului chirurgical al tumorilor hepatice, o problemă importantă rămîne a fi depistarea precoce şi profilaxia apariţiei IHPR. Perfecţionarea metodelor de diagnostic precoce şi prognostic al dezvoltării IHPR la etapa preoperatorie va permite nu doar scăderea letalităţii, dar va spori deasemenea posibilităţile chirurgiei hepatice.Introduction: The issue of posthepatectomy liver failure (PHLF) continues to be very actual. The frequency of the PHLF does not tend to decrease, and varies between 0.7-9.1%. However, the introduction of new technologies in the field of diagnosis of PHLF can improve the results of surgical treatment of patients with liver tumors. Aim of study: To study the possibilities of early diagnosis and treatment of PHLF after major hepatic resection. Material and methods: During 5 years were performed 204 major hepatic resections. 101 (49.6%) patients had secondary hepatic injury – 75 (36.8%) patients with metastases of colorectal cancer; 54 (26.4%) patients had primary liver tumors, including 25 (12.3%) – hepatocellular carcinoma, 20 (9.8%) – cholangiocarcinoma, 49 (24%) – benign tumors and non-tumoral liver diseases. Surgical interventions: left hepatectomy – 42 (20%), right hepatectomy – 68 (33.3%), extended left hepatectomy – 27 (13.3%), extended right hepatectomy – 44 (21.5%), resection of ≥3 segments of liver – 19 (16.3%). In postoperative period, the signs of PHLF were evaluated on clinical data, reduced albumin below 28 g/L, elevated bilirubin levels higher than 50 μmol/l, lower prothrombin index (PTI) below 50%, increasing of INR above 2 at the 1-3 and 7-9-th and 5-th postoperative day (criterion 50/50). To assess the degree of liver failure the ISGLS classification was used. Results: At 1-3 postoperative days most surgical patients presented the decreased levels of albumin and IP, increased bilirubin and INR levels. At the same time, significant simultaneous changes in these parameters were seen in 64 (31.4%) patients. These changes were solved by conservative treatment within 4-8 days, so they could not be considered as PHLF. At the 5-th day, these changes were seen in 48 (23.5%) patients. The numerical values of the estimated parameters ranged: albumin – 17- 34 (average 29) g/L, INR – 1.4-3.8 (average 2.5), total bilirubin – 22-99 (average 49) μmol/L. In 31 (15.2%) cases the signs of PHLF were solved by standard therapy, which was interpreted as a Class A liver failure (ISGLS). Clinically significant PHLF occurred in 17 (8.3%) patients, including 11 (5.4%) – class B and 6 (2.9%) – class C (ISGLS). However, only 12 (5.9%) patients had positive 50/50 criterion. IHPR progression led to the death in 8 (4.1%) cases, of which 3 (1.5%) with negative 50/50 criterion. Conclusions: Despite the amelioration of the surgical treatment of liver tumors, an important problem remains early detection and prevention of the PHLF occurrence. Improved methods of early diagnosis and prediction of PHLF development in preoperative stage will not only reduce mortality, but will also enhance them opportunities of liver surgery

CASE OF SUCCESSFUL EMERGENCY ENDOVASCULAR REPAIR OF RUPTURED ABDOMINAL AORTIC ANEURYSM IN ANATOMICALLY DIFFICULT CONDITIONS

This report presents a clinical case of emergency endovascular treatment of acute rupture of the abdominal aortic aneurysm in complex anatomically difficult conditions. Although this pathology is rare, it has a high mortality rate. Moreover, according to different authors endovascular repair is safer as compared with open surgery. We demonstrate the decision-making algorithm, show the technical nuances during the intervention which allowed us to achieve an acceptable clinical and angiographic result. Our experience will be interesting and useful for specialists who treat patients with vascular diseases

Endovascular treatment of spurious aneurysm of the aorto-femoral shunt with the use of a stent graft

This report presents a clinical case of endovascular treatment of a rare complication – a spurious aneurysm from a linear aorto-femoral shunt. We performed implantation of a self-expandable stent graft directly into the vascular prosthesis in the projection of the defect of its wall. We tried to foresee possible procedural complications, and in this regard to justify the choice of tactics of treatment and selection of the applied tools. Given the lack of available literature data on the methods and techniques of interventions in this pathology, we believe that our experience will be interesting and useful for professionals involved in the treatment of patients with vascular diseases

DNA metabarcoding of benthic algae and associated eukaryotes from Lake Baikal in the face of rapid environmental changes

Here we report new data describing the biodiversity of phytobenthic communities based on DNA-metabarcoding using the 18S rDNA marker and the Illumina MiSeq system. The study was initiated due to the blooming of filamentous algae (mainly of the genus Spirogyra) and cyanobacteria in the coastal zone of Lake Baikal under climate change and anthropogenic impact. The composition and taxonomic diversity of algae and other organisms associated with them on different sites of Lake Baikal (near Bolshoi Ushkaniy Island, in Listvennichny Bay) and in the Kaya (within the city of Irkutsk, located in the same drainage basin as Lake Baikal) were determined using DNAmetabarcoding. About 15 thousand reads of the 18S rRNA marker were obtained by applying NGS (next-generation sequencing). The species of algae dominating in the number of reads, as well as the difficult-to-identify taxa (Stramenopiles, Alveolata, Euglenozoa, Chromista, Rhizaria, Amoebozoa, etc.), which play an important role in the functioning and formation of the structure of algal communities, were revealed. The Shannon index of the communities studied ranges from 1.56 to 2.72. The advantages and weaknesses of using DNA-metabarcoding based on the 18S rRNA gene fragment for studying the structure of algal communities are shown. The advantage of this method is the possibility to more fully determine the diversity of eukaryotes taxa, which are difficult to identify by morphology, without involving a large number of specialists, while the disadvantage of the method is the distortion that may occur during the PCR. Here, ways of solving this problem are proposed. The results of the study show that the analysis of the minor component of the eukaryotic community in samples (organisms with low biomass) consisting of a mixture of multicellular and unicellular organisms requires a read-depths of at least 100,000 sequences per sample. In general, the DNA-metabarcoding method is recommended for studying the structure of algal communities and eukaryotes associated with them

Особенности клинического течения заболеваний органов дыхания у лиц, участвующих в ликвидации аварии Чернобыльской АЭС

The aerosol radiation damage of airways was registered among Chernobyl catastrophe liquidators. There are few scientific data of aerosol radiation damage of airways. 9 liquidators — males at the age of 33—43 — were examined in our institute. They worked in highly dusted atmosphere that caused the inhalation of radioactive dust. The chronic obstructive bronchitis was diagnosed in 4 cases and chronic bronchitis with purulent sputum- in 4 cases and bronchial asthma — in 1 case. All patients were healthy before 1986. The first symptoms of the disease were found in 3 cases when the patients worked on atomic station in 1986 and in 6 cases — 3—6 years later. The specific feature of the disease was torpide inflammatory process with progressive respiratory failure. The pulmonary function testing demonstrated the obstructive abnormalities and the reduction of diffusing lung capacity. The examination of BAL discovered- the macrophages with polygonal optically dense particles in their cytoplasm. X-ray spectral analysis showed the existence of Np, FR, Pm, Pa, Pu in these particles. Thus, we suppose that inhaled radionuclides may play a significant role in the genesis of respiratory abnormalities for this patients category.Авария на Чернобыльской АЭС явилась одной из самых крупных экологических катастроф в мире за последние десятилетия с поражением обширных территорий страны и населения, проживающего на них. Наряду с воздействием проникающей радиации возникло аэрозольное радионуклидное поражение органов дыхания у лиц, находящихся в зоне загрязнения окружающей среды и, особенно, у ликвидаторов аварии. В доступной литературе данные о клинике, диагностике и лечении патологии бронхолегочной системы при таком виде поражения практически отсутствуют. В НИИ Пульмонологии М3 РФ обследовано 9 мужчин в возрасте от 33 до 43 лет, участвующих в ликвидации последствий катастрофы на ЧАЭС в 1986 году. Выполняемые работы были связаны с высокой запыленностью воздуха, что обусловило преимущественно ингаляционный путь проникновения радионуклидов в организм. Средняя паспортизированная доза облучения составила 22 Р. У 4 больных выявлен хронический обструктивный бронхит, у 4 — хронический гнойно-обструктивный бронхит, у 1 — бронхиальная астма. Все пациенты до 1986 года были практически здоровы. Первые симптомы заболевания у 3 больных возникли во время работы на ЧАЭС, у 6 — в сроки от 3 до 6 лет спустя. Особенностью заболевания у всех больных являлся вялотекущий воспалительный процесс с нарастающими признаками дыхательной недостаточности. При обследовании выявлен обструктивный тип нарушения и снижения диффузионной способности легких. При исследовании клеточного состава БАЛ в цитоплазме большинства альвеолярных макрофагов зарегистрированы оптически плотные полигональные включения. При рентгеноспектральном анализе в составе этих включений у 5 больных обнаружены прометий, франций, протактиний, нептуний, плутоний. Таким образом, предполагается роль ингаляционных радионуклидов в генезе выявленной патологии органов дыхания

Chromosomal-level assembly of the Asian Seabass genome using long sequence reads and multi-layered scaffolding

We report here the ~670 Mb genome assembly of the Asian seabass (Lates calcarifer), a tropical marine teleost. We used long-read sequencing augmented by transcriptomics, optical and genetic mapping along with shared synteny from closely related fish species to derive a chromosome-level assembly with a contig N50 size over 1 Mb and scaffold N50 size over 25 Mb that span ~90% of the genome. The population structure of L. calcarifer species complex was analyzed by re-sequencing 61 individuals representing various regions across the species' native range. SNP analyses identified high levels of genetic diversity and confirmed earlier indications of a population stratification comprising three clades with signs of admixture apparent in the South-East Asian population. The quality of the Asian seabass genome assembly far exceeds that of any other fish species, and will serve as a new standard for fish genomics

Сравнение профиля генной экспрессии колониеформирующих эндотелиальных клеток из периферической крови человека и эндотелиальных клеток коронарной артерии

Aim. To compare gene expression profiles of CFEC to human coronary artery endothelial cells, based on the results of whole transcriptome analysis.Methods. CFEC were isolated from peripheral blood of patients during percutaneous coronary intervention. Human coronary artery endothelial cells were purchased from Cell Applications (300K-05a, USA). Cells were lysed with TRIzol with the following total RNA isolation and DNAse treatment. Then rRNA depletion was performed, followed by DNA library preparation. DNA libraries were then quantified by qPCR (CFX96 Touch, Bio-Rad, USA), pooled in equimolar amounts and sequenced (HiSeq 2000, Illumina) using 2 * 125 bp chemistry.Results. RNA-seq demonstrated that CFEC were generally similar to human coronary artery endothelial cells, regarding their global gene expression profile. However, CFEC overexpressed specific markers of all endothelial lineages (NRP2, NOTCH4, LYVE1), in particular, lymphatic EC (LYVE1) and had upregulated extracellular matrix and basement membrane genes (COLlAl, COL1A2, COL4A1, COL4A2).Conclusion. Baseline gene expression in CFEC is close to that of human coronary artery endothelial cells, testifying about their utility for the seeding of tubular scaffolds before the implantation to improve their short- and long-term performance.Цель. Сравнительный анализ профиля генной экспрессии колониеформирующих эндотелиальных клеток и эндотелиальных клеток коронарной артерии человека на основе результатов полнотранскриптомного секвенирования.Материалы и методы. Культура колониеформирующих эндотелиальных клеток получена из периферической крови пациентов, перенесших чрескожное коронарное вмешательство. Первичные эндотелиальные клетки коронарной артерии были приобретены у CellApplications (300K-05a, США). Клетки лизированы тризолом с последующим выделением тотальной РНК и сопутствующей обработкой ДНКазой. Проводилась деплеция рРНК с дальнейшим конструированием ДНК-би-блиотек. Концентрация ДНК-библиотек определялась с помощью количественной полимеразной цепной реакции с детекцией результата в реальном времени на амплификаторе CFX96 Touch (Bio-Rad, США). Далее ДНК-библиотеки смешивались эквимолярно и секвенировались на платформе HiSeq 2000 (Illumina, США) с длиной парно-концевых прочтений 2 я 125 нуклеотидов.Результаты. Полнотранскриптомное секвенирование продемонстрировало, что колониеформирующие эндотелиальные клетки были схожи с первичными эндотелиальными клетками коронарной артерии в отношении их профиля генной экспрессии, при этом гиперэкспрессировали специфичные маркеры всех направлений эндотелиальной дифференцировки (NRP2, NOTCH4, LYVE1), в особенности лимфатической (LYVE1), и обладали повышенной экспрессией генов компонентов внеклеточного матрикса и базальной мембраны (COL1A1, COL1A2, COL4A1, COL4A2).Заключение. Базовый профиль генной экспрессии колониеформирующих эндотелиальных клеток близок к таковому у эндотелиальных клеток коронарной артерии, что свидетельствует о применимости колониеформирующих эндотелиальных клеток для заселения трубчатых полимерных каркасов перед имплантацией для улучшения их кратко- и долгосрочной проходимости

Moscow-Washington Relations during the Final Stage of World War II in Eastern Europe (January - May, 1945)

Рассматривается динамика отношений Белого дома и Кремля на завершающем этапе Второй мировой войны в 1945 г., роль американской военно-политической элиты в реализации стратегического курса Франклина Рузвельта на развитие отношений с СССР.The article studies the evolution of relations between the White House and the Kremlin during the final stage of World War II in 1945, the role of US military and political elite in the realization of Franklin D. Roosevelt's strategy for the development of relationships with the USSR

Development and characterization of novel 2′-F-RNA aptamers specific to human total and glycated hemoglobins

Aptamers are short DNA and RNA fragments which bind their molecular targets with affinity and specificity comparable to those of antibodies. Here, we describe the selection of 2'-F-RNA aptamers against total human hemoglobin or its glycated form HbA1c. After SELEX and high-throughput sequencing of the enriched libraries, affinities and specificities of candidate aptamers and their truncated variants were examined by the solid-phase bioluminescent assay. As a result, we identified aptamers specific to both hemoglobins or only glycated HbA1c. The developed 2'-F-RNA aptamers have shown their applicability for detection of total and glycated hemoglobin in one sample using the solid-phase sandwich assay

Endovascular correction of complicated stenotic lesions in brachycephalic arteries

Most often patients with multifocal sclerosis of brachycephalic arteries are refused to be surgically treated as these cases are complicated due to tandem lesions. The only way out for these patients is endovascular surgery. We have analyzed international experience and applied different methods of endovascular intervention in patients with difficult stenotic lesions of brachycephalic arteries, and became convinced that endovascular correction similar affections is the main means to treat patients with multifocal atherosclerosis. It also could be used as primary treatment as possesses high efficiency, a low complication rate and shows favorable long-term results