Feasibility of whole genome and transcriptome profiling in pediatric and young adult cancers.

The utility of cancer whole genome and transcriptome sequencing (cWGTS) in oncology is increasingly recognized. However, implementation of cWGTS is challenged by the need to deliver results within clinically relevant timeframes, concerns about assay sensitivity, reporting and prioritization of findings. In a prospective research study we develop a workflow that reports comprehensive cWGTS results in 9 days. Comparison of cWGTS to diagnostic panel assays demonstrates the potential of cWGTS to capture all clinically reported mutations with comparable sensitivity in a single workflow. Benchmarking identifies a minimum of 80× as optimal depth for clinical WGS sequencing. Integration of germline, somatic DNA and RNA-seq data enable data-driven variant prioritization and reporting, with oncogenic findings reported in 54% more patients than standard of care. These results establish key technical considerations for the implementation of cWGTS as an integrated test in clinical oncology.

In vivo evaluation of the chitosan-based haemostatic agent Omni-stat® in porcine liver resection and in liver injury.

BACKGROUND: Omni-stat®, a polysaccharide made by de-acetylation of chitin, is currently in use as a battlefield topical haemostat. This experimental study undertakes the first evaluation of Omni-stat in an in vivo porcine hepatectomy and liver trauma model. METHODS: A model of sequential liver resection was employed: following liver resection, further resections were undertaken in the same animal provided that there was cessation of bleeding from the earlier resection and that haemodynamic stability was maintained. An additional liver trauma injury was undertaken after completion of all resections. Data were collected on heart rate, blood pressure, haematocrit, resection volumes, blood loss and the efficacy of Omni-stat in haemostasis. RESULTS: Eight minor resections and 12 major resections were undertaken. Topical application of Omni-stat to raw post-transection surfaces immediately upon completion of resection achieved complete haemostasis with a single application in 14 of 15 (93%) resections. There was no recurrence of bleeding during the 5-hour protocol. The median time for cessation of bleeding after resection in the Omni-stat group was 3 min (range 3-6). This was not significantly different from time to cessation of bleeding in 5 control resections. There was no difference in blood loss or haemodynamic parameters. Respiratory rate was significantly faster after application of Omni-stat. In 2 liver lacerations, Omni-stat was effective in achieving cessation of haemorrhage. CONCLUSION: Omni-stat is an effective haemostat in experimental in vivo porcine liver resection and liver trauma. Further evaluation is required to assess its physiological absorption profile in man and its comparative efficacy against commercially established agents.

Impaired CD95 expression predisposes for recurrence in curatively resected colon carcinoma: clinical evidence for immunoselection and CD95L mediated control of minimal residual disease.

BACKGROUND: Loss of CD95 expression in tumour cells occurs frequently in colon carcinoma and may be associated with disease progression. On the other hand, neo-expression of CD95L in tumour cells may contribute to immune evasion. AIMS: We aimed at further exploring the functional role and prognostic significance of the CD95/CD95L death inducing system in colon carcinomas. PATIENTS AND METHODS: CD95 and CD95L expression was examined by immunohistochemistry in 128 R0 resected UICC (International Union against Cancer) stage II/III colon carcinomas and correlated with disease free survival. RESULTS: CD95 expression in tumour cells was observed in only 30 carcinomas (23.4%) whereas the others had at least a minor subpopulation of CD95 negative cells. Loss of CD95 in tumour cells was related to adverse prognosis in uni- and multivariate analysis (p = 0.046 and p = 0.036, respectively). Tumour infiltrating lymphocytes (TIL) were the major source of CD95L in colon carcinomas. CD95L+TIL were present in 83% of cases whereas CD95L was found in tumour cells in only 12% of cases. Moreover, a high rate of CD95L+TIL correlated with prolonged disease free survival in patients with UICC stage II (p = 0.05) but not in those with stage III. CONCLUSIONS: Loss of CD95 in tumour cells may be an independent prognostic factor in colon carcinomas. The CD95L counterattack is not a relevant feature in colon carcinoma but CD95L+TIL may contribute to tumour control in the early stages of the disease, exerting a concurrent selection pressure in the direction of CD95 abrogation/resistance.

Correlation of H. pylori density with grading of chronic gastritis.

Histopathological study of endoscopic gastric mucosa obtained from 251 patients with acid peptic diseases were studied in relation to the degrees of inflammation and the degree of H. Pylori density. Haematoxylin-Eosin and modified Giemsa stains were used. Gastritis grading was done according to Warren and Marshall with slight modification and H. Pylori grading according to our criteria. In this study no definite relationship could be observed between histological grading of chronic gastritis with that of H. Pylori density.