Clinical significance of circulating anti-p53 antibodies in European patients with hepatocellular carcinoma

p53 alterations are considered to be predictive of poor prognosis in hepatocellular carcinoma (HCC) and may induce a humoral response. Anti-p53 serum antibodies were assessed by enzyme-linked immunosorbent assay (ELISA) using purified recombinant human p53 on 130 European HCC patients before treatment and during the clinical course of the disease. p53 immunohistochemistry was performed on tumours from the 52 patients who underwent surgery, and DNA sequencing analysis was initiated when circulating anti-p53 antibodies were detected. Nine (7%) HCC patients had anti-p53 serum antibodies before treatment. During a mean period of 30 months of follow-up, all the negative patients remained negative, even when recurrence was observed. Of the nine positive patients, eight were still positive 12–30 months after surgery. The presence of anti-p53 serum antibodies was correlated neither with mutation of the p53 gene nor the serum alpha-fetoprotein levels and clinicopathological characterics of the tumours. However, a greater incidence of vascular invasion and accumulation of p53 protein were observed in the tumours of these patients (P < 0.03 and P < 0.01 respectively) as well as a better survival rate without recurrence (P = 0.05). In conclusion, as was recently shown in pancreatic cancer, anti-p53 serum antibodies may constitute a marker of relative ‘good prognosis’ in a subgroup of patients exhibiting one or several markers traditionally thought to be of bad prognosis. © 1999 Cancer Research Campaig

A Delphi Consensus Study

Funding Information: We sincerely thank all the experts who participated in this Delphi study for their time and for sharing their expertise. All Delphi experts qualify for authorship based on the fact that they were involved in data collection and all critically appraised the final manuscript for important intellectual content. See Appendix B for the names of the Delphi experts. Publisher Copyright: © 2021 The AuthorsObjective: No dedicated studies have been performed on the optimal management of patients with an acute stroke related to carotid intervention nor is there a solid recommendation given in the European Society for Vascular Surgery guideline. By implementation of an international expert Delphi panel, this study aimed to obtain expert consensus on the optimal management of in hospital stroke occurring during or following CEA and to provide a practical treatment decision tree. Methods: A four round Delphi consensus study was performed including 31 experts. The aim of the first round was to investigate whether the conceptual model indicating the traditional division between intra- and post-procedural stroke in six phases was appropriate, and to identify relevant clinical responses during these six phases. In rounds 2, 3, and 4, the aim was to obtain consensus on the optimal response to stroke in each predefined setting. Consensus was reached in rounds 1, 3, and 4 when ≥ 70% of experts agreed on the preferred clinical response and in round 2 based on a Likert scale when a median of 7 – 9 (most adequate response) was given, IQR ≤ 2. Results: The experts agreed (> 80%) on the use of the conceptual model. Stroke laterality and type of anaesthesia were included in the treatment algorithm. Consensus was reached in 17 of 21 scenarios (> 80%). Perform diagnostics first for a contralateral stroke in any phase, and for an ipsilateral stroke during cross clamping, or apparent stroke after leaving the operation room. For an ipsilateral stroke during the wake up phase, no formal consensus was achieved, but 65% of the experts would perform diagnostics first. A CT brain combined with a CTA or duplex ultrasound of the carotid arteries should be performed. For an ipsilateral intra-operative stroke after flow restoration, the carotid artery should be re-explored immediately (75%). Conclusion: In patients having a stroke following carotid endarterectomy, expedited diagnostics should be performed initially in most phases. In patients who experience an ipsilateral intra-operative stroke following carotid clamp release, immediate re-exploration of the index carotid artery is recommended.publishersversionpublishe

Fam65b is a new transcriptional target of FOXO1 that regulates RhoA signaling for T lymphocyte migration

Forkhead box Os (FOXOs) transcription factors favor both T cell quiescence and trafficking through their control of the expression of genes involved in cell cycle progression, adhesion and homing. Here, we report that the product of the fam65b gene is a new transcriptional target of FOXO1 that regulates RhoA activity. We show that Fam65b binds the small GTPase RhoA via a non canonical domain and represses its activity by decreasing its GTP loading. As a consequence, Fam65b negatively regulates chemokine-induced responses such as adhesion, morphological polarisation and migration. Therefore, these results show the existence of a new functional link between FOXO1 and RhoA pathways, through which the FOXO1 target Fam65b tonically dampens chemokine-induced migration by repressing RhoA activity

Defining Major Surgery: A Delphi Consensus Among European Surgical Association (ESA) Members

Background: Major surgery is a term frequently used but poorly defined. The aim of the present study was to reach a consensus in the definition of major surgery within a panel of expert surgeons from the European Surgical Association (ESA). Methods: A 3-round Delphi process was performed. All ESA members were invited to participate in the expert panel. In round 1, experts were inquired by open- and closed-ended questions on potential criteria to define major surgery. Results were analyzed and presented back anonymously to the panel within next rounds. Closed-ended questions in round 2 and 3 were either binary or statements to be rated on a Likert scale ranging from 1 (strong disagreement) to 5 (strong agreement). Participants were sent 3 reminders at 2-week intervals for each round. 70% of agreement was considered to indicate consensus. Results: Out of 305 ESA members, 67 (22%) answered all the 3 rounds. Significant comorbidities were the only preoperative factor retained to define major surgery (78%). Vascular clampage or organ ischemia (92%), high intraoperative blood loss (90%), high noradrenalin requirements (77%), long operative time (73%) and perioperative blood transfusion (70%) were procedure-related factors that reached consensus. Regarding postoperative factors, systemic inflammatory response (76%) and the need for intensive or intermediate care (88%) reached consensus. Consequences of major surgery were high morbidity (>30% overall) and mortality (>2%). Conclusion: ESA experts defined major surgery according to extent and complexity of the procedure, its pathophysiological consequences and consecutive clinical outcomes

Complete response for advanced liver cancer during sorafenib therapy: Case Report

<p>Abstract</p> <p>Background</p> <p>Hepatocellular carcinoma (HCC) is the fifth most common neoplasia in the world. In the past, treatment of advanced HCC with conventional antineoplastic drugs did not result in satisfactory outcomes: recently, in this patient population the oral multikinase inhibitor sorafenib has been able to induce a statistically significant improvement of overall survival. Similarly to other anti-angiogenic drugs employed in other tumour types, also sorafenib seldom induces the dimensional tumour shrinking usually observed with conventional cytotoxic drugs: data gathered from studies carried out with sorafenib and other competitors under development do not report any complete response in HCV-induced HCC.</p> <p>Case presentation</p> <p>An 84-year old man with a long-lasting history of chronic HCV hepatitis was referred to our Institution for an ultrasonography investigation of a focal hepatic lesion. To better characterize the liver disease and clearly define the diagnosis of the focal hepatic lesion, the patient was hospitalized in our department. Laboratory and instrumental investigations confirmed the clinical picture of HCV-related liver cirrhosis and identified a hepatic lesion of about 6 cm featuring infiltrating HCC with thrombosis of the portal trunk. Due to the advanced stage of the disease, therapy with sorafenib 400 mg bid was started. Right from one month after the treatment was started, a reduction of alpha-fetoprotein level was observed which, by the third month, turned down within the normal limits. In addition the CT scan showed 50% reduction of the neoplastic lesion along with canalization of the portal trunk. At the sixth month the normalization of the alpha-fetoprotein level at the lower limit of normality was confirmed and the MRI showed complete disappearance of the neoplasia. In addition a reduction of a metallo-proteinase serum level was obserdved. At the twelfth month a further MRI confirmed complete response had been maintained. At present the patient is in a follow-up program to evaluate the duration of the complete response.</p> <p>Conclusions</p> <p>This case is worth mentioning since, to the best of our knowledge, it represents the first evidence of complete response to sorafenib in an elderly patient with advanced HCV-related HCC.</p

Improvement in Survival after Paraquat Ingestion Following Introduction of a New Formulation in Sri Lanka

Martin Wilks and colleagues compared the outcome of paraquat self-poisoning with the standard formulation against a new formulation following its introduction into Sri Lanka