Multi-omic cross-sectional cohort study of pre-malignant Barrett's esophagus reveals early structural variation and retrotransposon activity.

Barrett's esophagus is a pre-malignant lesion that can progress to esophageal adenocarcinoma. We perform a multi-omic analysis of pre-cancer samples from 146 patients with a range of outcomes, comprising 642 person years of follow-up. Whole genome sequencing reveals complex structural variants and LINE-1 retrotransposons, as well as known copy number changes, occurring even prior to dysplasia. The structural variant burden captures the most variance across the cohort and genomic profiles do not always match consensus clinical pathology dysplasia grades. Increasing structural variant burden is associated with: high levels of chromothripsis and breakage-fusion-bridge events; increased expression of genes related to cell cycle checkpoint, DNA repair and chromosomal instability; and epigenetic silencing of Wnt signalling and cell cycle genes. Timing analysis reveals molecular events triggering genomic instability with more clonal expansion in dysplastic samples. Overall genomic complexity occurs early in the Barrett's natural history and may inform the potential for cancer beyond the clinically discernible phenotype.

Ninety day mortality following pancreatoduodenectomy in England: has the optimum centre volume been identified?

BACKGROUND: Mortality following pancreatoduodenectomy is related to centre volume although the optimal volume is not defined. METHODS: Patients undergoing PD between 2001 and 2016 were identified from UK national databases. The effects of patient variables, centre volume and time period upon 90 day mortality were studied. RESULTS: 90 day mortality (970/14,935, 6.5%) was related to advanced age, comorbidity, diagnosis, ethnicity, deprivation, centre volume and time period. Mortality rates fell markedly from 10.0% in 2001-4 to 4.1% in 2013-16. There was no difference in 90 day mortality between high (36 -60 PD per year) and very high volume (>60) centres. However, patients operated upon at very high volume centres were more elderly (66, 58 -73 vs 65, 56 -72; median, IQR; p = 0.006), deprived (38.7 vs 34.6%; p < 0.001) and co morbid (48.9 vs 46.1%; p = 0.027). CONCLUSION: Although a plateau in the centre volume and mortality relationship appears to have been demonstrated those patients treated at the highest volume centres were at higher risk of mortality. This data suggests therefore that to further understand outcomes from specialist centres characteristics of the patient population should be defined, not just centre volume.

[Leiomyoma of the stomach]. / Leiomioma na stomakha.

A case of a 72-year-old man with a leiomyoma of the stomach is presented. The clinical course and the X-ray examination resembled that of a stomach cancer with hemorrhagic complications. The patient died. While alive, he refused fiber gastroscopic examination and biopsy which could have led to the correct diagnosis and to gastric resection, thus this benign tumor was not recognized before the postmortem examination.

[Changes in the serum enzymes and clinical and clinico-biochemical indices of cows with subclinical ketosis]. / Promeni na niakoi serumni enzimi, klinichni i kliniko-biokhimichni pokazateli pri kravi sus subklinichna ketoza.

Investigations were carried out with a total of 276 high-producing and clinically healthy cows that had freshly calved on 11 farms, being divided into groups according to the extent to which ketonuria was present if al all. Whole blood and blood serum were sampled to determine the ketone bodies, blood sugar, erythrocyte and leukocyte counts, hemoglobin, inorganic phosphorus, Ca, Mg, total protein, carotene, and activity of the GOT and GPT enzymes as well as the activity of lactic acid dehydrogenase, alkaline phosphatase, aldolase, and leucine aminopeptidase. Studied were the body temperature, the pulse rate, and the respiration rate. It was found that on farms with ketosis in cows ketonuria was manifested most often after the ketone bodies in the blood rose to 10-12 mg%. At the same time the blood sugar level was lowered and as a rule it showed reverse correlation with the levels of ketonemia and ketonuria. In such cows there was a lowering trend with the Ca and carotene contents and the erythrocyte count, and the respiration rate was higher. There were no changes in the body temperature, pulse rate, leukocyte count, Ca, Mg, hemoglobin, protein, and the activity of aldolase. The activity of the other enzymes mentioned was higher, and it correlated positively with the rise of ketonemia and ketonuria. With diseased cows the activity of alkaline phosphatase only was shown to be lower, negatively correlating with ketonuria.

[Diagnosis of infectious anemia in horses using the Coggins test]. / Diagnostika na infektsioznata anemiia po konete s testa na Coggins.

Coggins' immune diffusion test was modified, and was applied as a screening one in the study of the epizootic status. The positive reactions were characterized by the production of a precipitation line between the antigen and the respective serum that was tested. The appearance of such a line was associated with that formed with the use of the positive control serum, pointing to a reaction of identity. With the weakly positive reactions the ends of the precipitin lines, formed with the use of the positive control serum, were found to deviate slightly toward the site where the antigen had been placed. The specificity of the test was confirmed through biological experiments and clinical, morphological, and hematological investigations.