Лапароскопічна холедохолітотомія в лікуванні хворих на гострий панкреатит з жовчною гіпертензією

The aim of the work: to improve the results of treatment of patients with acute biliary pancreatitis (ABP) with biliary hypertension (BH) by using laparoscopic choledocholithotomy. Materials and Methods. The study involved 50 patients (6 men and 44 women with an average age of 58.4 years) with moderate severity ABP and BH induced by choledocholithiasis. In all patients, the biliary origin of pancreatitis was diagnosed according to the criteria proposed by the Dutch Pancreatitis Research Group. Hospitalization of patients in the hospital took place from 2 to 48 hours from the onset of the disease. Most patients (60 %) were hospitalized not later than 24 hours after the onset of the disease. Concomitant illnesses were found in 36 (72 %) patients: coronary heart disease – in 28 (56 %), hypertensive illness of different severity – in 27 (54 %), chronic hepatitis – in 15 (30 %), increase in body mass index, which corresponded to obesity – in 1 (2 %), diabetes – in 2 (4%), anemia – in 1 (2 %). The personalized algorithm of surgical treatment was applied, which allowed to choose a method of elimination of biliary hypertension in the first 12–72 h after the occurrence of a pain attack. Results and Discussion. In the first 12–72 hours of the disease performed: ERCP (n = 33), laparoscopic cholecystectomy, choledochoscopy and lioextraction with external drainage of extrahepatic bile ducts (n = 13), percutaneous peritoneal puncture of the biliary tract (n = 7). Laparoscopic lioextraction was used in 26 % of patients, which made it possible to simultaneously eliminate the cause of BH and perform cholecystectomy. Mortality was 2 % (1 patient). The average length of stay in a hospital is 12.46 days.Цель работы: улучшить результаты лечения больных острым билиарным панкреатитом (ОБП) с желчной гипертензией (ЖГ) путем применения лапароскопической холедохолитотомии. Материалы и методы. В исследование вовлечены 50 пациентов (6 мужчин и 44 женщины, средний возраст – 58,4 года) с ОБП и ЖГ средней степени тяжести, вызванной холедохолитиазом. У всех пациентов билиарное происхождение панкреатита диагностировано согласно критериям, предложенным Голландской исследовательской группой по изучению панкреатита. Госпитализация больных в больницу происходила в сроки от 2 до 48 ч от начала заболевания. Большинство пациентов (60 %) госпитализированы не позднее 24 ч от начала заболевания. Сопутствующие заболевания выявлены у 36 (72 %) пациентов: ишемическая болезнь сердца – у 28 (56 %), гипертоническая болезнь различной степени тяжести – у 27 (54 %), хронический гепатит – у 15 (30 %), повышение индекса массы тела, которое соответствовало ожирению – у одного (2 %), сахарный диабет – у 2 (4 %), анемия – в одного (2 %). Применен персонализированный алгоритм хирургического лечения, который позволил выбрать метод устранения билиарной гипертензии в первые 12–72 ч после возникновения болевого приступа. Результаты исследования и их обсуждение. В первые 12–72 ч заболевания выполнили: ФЭГДС с ЭПСТ (n = 33), лапароскопическую холецистэктомию, холедохоскопию и литоэкстракцию с наружным дренированием внепеченочных желчных протоков (n = 13), перкутанную черезпеченочную пункцию желчных путей (n = 7). Лапароскопическую литоэкстракцию использовали в 26 % больных, что позволило одномоментно ликвидировать причину ЖГ и выполнить холецистэктомию. Летальность составляла 2 % (один больной). Средний срок пребывания в стационаре – 12,46 сутки.Мета роботи: поліпшити результати лікування хворих на гострий біліарний панкреатит (ГБП) із жовчною гіпертензією  (ЖГ) шляхом застосування лапароскопічної холедохолітотомії. Матеріали і методи. У дослідження залучено 50 пацієнтів (6 чоловіків та 44 жінки, середній вік – 58,4 року) з ГБП та ЖГ середнього ступеня тяжкості, спричиненою холедохолітіазом. В усіх пацієнтів біліарне походження панкреатиту діагностовано згідно із критеріями, запропонованими Нідерландською дослідницькою групою з вивчення панкреатиту. Госпіталізація хворих у лікарню відбувалася в строки від 2 до 48 год від початку захворювання. Більшість пацієнтів (60 %) госпіталізовано не пізніше 24 год від початку захворювання. Супутні захворювання виявлено у 36 (72 %) пацієнтів: ішемічну хворобу серця – у 28 (56 %), гіпертонічну хворобу різного ступеня тяжкості – в 27 (54 %), хронічний гепатит – у 15 (30 %), підвищення індексу маси тіла, яке відповідало ожирінню, – в одного (2 %), цукровий діабет – у 2 (4 %), анемію – в одного (2 %). Застосовано персоналізований алгоритм хірургічного лікування, який дав змогу обрати метод усунення біліарної гіпертензії в перші 12–72 год після виникнення больового нападу. Результати досліджень та їх обговорення. В перші 12–72 год захворювання виконали: ФЕГДС з ЕПСТ (n=33),  лапароскопічну холецистектомію, холедохоскопію та літоекстракцію із зовнішнім дренуванням позапечінкових жовчних проток (n=13), перкутанну крізьпечінкову пункцію жовчних шляхів (n=7). Лапароскопічну літоекстракцію виконали в 26 % хворих, що дало змогу одномоментно ліквідувати причину ЖГ та виконати холецистектомію. Летальність становила 2 % (один хворий). Середній термін перебування в стаціонарі – 12,46 доби

The dynamic geophysical environment of (101955) Bennu based on OSIRIS-REx measurements

The top-shaped morphology characteristic of asteroid (101955) Bennu, often found among fast-spinning asteroids and binary asteroid primaries, may have contributed substantially to binary asteroid formation. Yet a detailed geophysical analysis of this morphology for a fast-spinning asteroid has not been possible prior to the Origins, Spectral Interpretation, Resource Identification, and Security-Regolith Explorer (OSIRIS-REx) mission. Combining the measured Bennu mass and shape obtained during the Preliminary Survey phase of the OSIRIS-REx mission, we find a notable transition in Bennu’s surface slopes within its rotational Roche lobe, defined as the region where material is energetically trapped to the surface. As the intersection of the rotational Roche lobe with Bennu’s surface has been most recently migrating towards its equator (given Bennu’s increasing spin rate), we infer that Bennu’s surface slopes have been changing across its surface within the last million years. We also find evidence for substantial density heterogeneity within this body, suggesting that its interior is a mixture of voids and boulders. The presence of such heterogeneity and Bennu’s top shape are consistent with spin-induced failure at some point in its past, although the manner of its failure cannot yet be determined. Future measurements by the OSIRIS-REx spacecraft will provide insight into and may resolve questions regarding the formation and evolution of Bennu’s top-shape morphology and its link to the formation of binary asteroids

Evidence for widespread hydrated minerals on asteroid (101955) Bennu

Early spectral data from the Origins, Spectral Interpretation, Resource Identification, and Security-Regolith Explorer (OSIRIS-REx) mission reveal evidence for abundant hydrated minerals on the surface of near-Earth asteroid (101955) Bennu in the form of a near-infrared absorption near 2.7 µm and thermal infrared spectral features that are most similar to those of aqueously altered CM-type carbonaceous chondrites. We observe these spectral features across the surface of Bennu, and there is no evidence of substantial rotational variability at the spatial scales of tens to hundreds of metres observed to date. In the visible and near-infrared (0.4 to 2.4 µm) Bennu’s spectrum appears featureless and with a blue (negative) slope, confirming previous ground-based observations. Bennu may represent a class of objects that could have brought volatiles and organic chemistry to Earth

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing

Chromothripsis is a mutational phenomenon characterized by massive, clustered genomic rearrangements that occurs in cancer and other diseases. Recent studies in selected cancer types have suggested that chromothripsis may be more common than initially inferred from low-resolution copy-number data. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we analyze patterns of chromothripsis across 2,658 tumors from 38 cancer types using whole-genome sequencing data. We find that chromothripsis events are pervasive across cancers, with a frequency of more than 50% in several cancer types. Whereas canonical chromothripsis profiles display oscillations between two copy-number states, a considerable fraction of events involve multiple chromosomes and additional structural alterations. In addition to non-homologous end joining, we detect signatures of replication-associated processes and templated insertions. Chromothripsis contributes to oncogene amplification and to inactivation of genes such as mismatch-repair-related genes. These findings show that chromothripsis is a major process that drives genome evolution in human cancer

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Signatures of positive selection reveal a universal role of chromatin modifiers as cancer driver genes.

Tumors are composed of an evolving population of cells subjected to tissue-specific selection, which fuels tumor heterogeneity and ultimately complicates cancer driver gene identification. Here, we integrate cancer cell fraction, population recurrence, and functional impact of somatic mutations as signatures of selection into a Bayesian model for driver prediction. We demonstrate that our model, cDriver, outperforms competing methods when analyzing solid tumors, hematological malignancies, and pan-cancer datasets. Applying cDriver to exome sequencing data of 21 cancer types from 6,870 individuals revealed 98 unreported tumor type-driver gene connections. These novel connections are highly enriched for chromatin-modifying proteins, hinting at a universal role of chromatin regulation in cancer etiology. Although infrequently mutated as single genes, we show that chromatin modifiers are altered in a large fraction of cancer patients. In summary, we demonstrate that integration of evolutionary signatures is key for identifying mutational driver genes, thereby facilitating the discovery of novel therapeutic targets for cancer treatment