1,721,043 research outputs found
Surgical leadership: the British concept
No full textIn the UK all surgeons need to have leadership skills as, despite the increasing importance of team management, the consultant surgeon still has overall responsibility for the patient under their care. Poor care is evident when clinical leadership fails. The UK hospital system is non-hierarchical within the consultant body. The clinical surgical manager in a hospital may not be the most senior clinician and the role will often rotate. The manager may or may not have the characteristics of a leader, and very often surgical leaders in a hospital may have no formal role. They are, however, essential to the functioning of the service. Nationally the roles in which professional leadership may reside are numerous. The country has multiple Surgical Royal Colleges and innumerable specialty associations and sub specialty associations all of which have councils and presidents and the multiple specialty and sub-specialty associations normally will have an annual meeting. In the long term this is probably unsustainable and although consolidation is desirable it is hard to achieve. In summary, good surgical leadership is found in many settings in the UK, some in formal roles within hospitals, some in the colleges and specialty associations and sometimes in individuals with no formal role but the capacity to make things happen.</p
p53-independent activation of the hdm2-P2 promoter through multiple transcription factor response elements results in elevated hdm2 expression in estrogen receptor alpha-positive breast cancer cells
No full textThe negative-regulatory feedback loop between p53 and hdm2 forms part of a finely balanced regulatory network of proteins that controls cell cycle progression and commitment to apoptosis. Expression of hdm2, and its mouse orthologue mdm2, is known to be induced by p53, but recent evidence has demonstrated mdm2 expression can also be regulated via p53-independent pathways. However the p53 independent mechanisms that control transcription of the human hdm2 gene have not been studied. Differential levels of hdm2 mRNA and protein expression have been reported in several types of human malignancy, including breast cancers in which hdm2 expression correlates with positive estrogen receptor {alpha} (ER{alpha}) status. Experimental models have demonstrated that hdm2 overexpression can promote breast cancer development. Here, we show that the elevated level of hdm2 protein in ER{alpha}+ve breast cancer cell lines such as MCF-7 and T47D is because of transcription from the p53-inducible P2 promoter of hdm2. The P2 promoter is inactive in ER{alpha}-ve cell lines such as SKBr3. Hdm2-P2 promoter activity in T47D cells is independent of p53, as well as of known regulators of the mouse mdm2-P2 promoter, including ER{alpha} and ras-raf-mitogen-activated protein/extracellular signal-regulated kinase (MEK) mitogen-activated protein kinase (MAPK) signaling. We show that hdm2-P2 activity in T47D cells is dependent on the integrity of both an evolutionarily conserved composite binding site for AP1 and ETS family transcription factors (AP1-ETS) and a nonconserved upstream (nnGGGGC)5 repeat sequence. Lack of hdm2-P2 activity in ER{alpha}-ve cells is shown to be a consequence of reduced transcriptional activation through the AP1-ETS element. Overexpression of ETS2 in SKBr3 cells reconstitutes AP1-ETS element-dependent hdm2-P2 promoter activity, resulting in increased levels of hdm2 protein in the cells. Our findings support the hypothesis that the elevated levels of hdm2 expression reported in cancers such as ER{alpha}+ve breast tumors play an important role in the development of these tumors
Circulating tumour DNA as a biomarker in resectable and irresectable stage IV colorectal cancer; a systematic review and meta-analysis
No full textBackground: For patients with metastatic colorectal cancer, stratification for treatment (surgery or chemotherapy) is often based on crude clinicopathological characteristics like tumour size and number of lesions. Circulating tumour DNA (ctDNA) acts as a potential biomarker of disease trajectory and biology, allowing better stratification. This study aims to systematically review ctDNA in stage IV colorectal cancer to assess its potential role as a prospective biomarker to guide management decisions. Methods: A literature search was performed to identify studies where the measurement of ctDNA in stage IV colorectal cancer was correlated with a clinical outcome (radiological response, secondary resection rate, PFS, DFS or OS). Results: Twenty-eight studies were included, reporting on 2823 patients. Circulating tumour DNA was detectable in between 80% and 90% of patients prior to treatment. Meta-analysis identified a strong correlation between detectable ctDNA after treatment (surgery or chemotherapy) and overall survival (HR 2.2, 95% CI 1.79–2.69, p < 0.00001), as well as progression-free survival (HR 3.15, 95% CI 2.10–4.73, p < 0.00001). ctDNA consistently offered an early marker of long-term prognosis in irresectable disease, with changes after one cycle of systemic therapy demonstrating prognostic value. In resectable disease treated with curative intent, detection of ctDNA offered a lead time over radiological recurrence of 10 months. Conclusion: Circulating tumour DNA is detectable in the majority of resectable and irresectable patients. The presence of ctDNA is clearly associated with shorter overall survival, with changes in ctDNA an early biomarker of adverse disease behaviour. Prospective trials are essential to test its clinical efficacy.</p
Exploring the role of laparoscopic surgery in two-stage hepatectomy for bilobar colorectal liver metastases
No full textBACKGROUND: The role of laparoscopy in two-stage hepatectomy for bilobar colorectal liver metastases (CRLMs) has not yet been extensively investigated.PATIENTS AND METHODS: We reviewed a prospectively collected database of 302 consecutive patients undergoing laparoscopic liver resection at our institution between 2003 and 2011.RESULTS: Eight patients undergoing laparoscopic first/second-stage hepatectomy for bilobar CRLMs (male/female 6:2; median age, 64 years) were analyzed. The first stage consisted of laparoscopic clearance of the left lobe in all patients with no postoperative morbidity and mortality. Seven patients underwent portal vein embolization or ligation. The median interval between first- and second-stage hepatic resections was 89 days (range, 36-123 days). Second-stage hepatectomy with right lobar clearance (open, n=5; laparoscopic, n=2; laparoscopic to open, n=1) was associated with no mortality and an operative morbidity rate of 50%. Adhesions were judged to be minimal or absent during the second-stage procedure. Complications included intra-abdominal collection (n=2), bleeding requiring re-operation (n=1), and bile leak (n=1). R0 resection was obtained in 7 of 8 cases after first-stage resection and in 8 of 8 cases after second-stage resection. Three patients (38%) died from disease recurrence. Of the remaining 5 patients, 4 are disease-free at a median follow-up of 24 months (range, 9-27 months).CONCLUSIONS: The well-recognized advantages of laparoscopy may play a favorable role in the management of patients with bilobar CRLMs candidate for a two-stage resection. The first-stage laparoscopic clearance of the left lobe could progressively become the "gold standard." Laparoscopic second-stage hepatectomy should be limited to selected cases
Site and stage of colorectal cancer influence the likelihood and distribution of disease recurrence and postrecurrence survival: data from the FACS randomized controlled trial
Full text linkThe likelihood and site of recurrence, and survival, are influenced by the site and stage of the primary tumor. Those with rectal cancers benefited most from follow-u
T cells but not NK cells are associated with a favourable outcome for resected colorectal liver metastases
No full textT cells, but not NK cells, are preferentially recruited to colorectal liver metastases. NK cells within colorectal metastases have an intrahepatic and potentially tolerogenic, rather than a peripheral, phenotype. Similar to primary tumours, the magnitude of the T cell infiltrate in colorectal metastases is positively associated with surviva
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