Vascular surgery trainee retention in the UK: how many leave and why? A survey of trainee and Training Programme Directors' perceptions.

BACKGROUND: It is currently not known how many trainees leave vascular surgery, and their reasons for doing so are unclear. This paper is the first to publish the number of UK trainees leaving the training programme and interrogates their reasons for doing so. METHODS: An email survey was distributed to current and recent Training Programme Directors (TPDs) to quantify the number of trainees resigning between 2013 and 2019. Trainees resigning a National Training Number (NTN) were surveyed regarding their reasons for doing so. RESULTS: Since 2013, 23 UK vascular surgery trainees have resigned NTNs, representing 15.4% of the 149 NTNs awarded between 2013 and our analysis. Reasons for leaving, as relayed by TPDs, included availability of an academic career, geography, health and many other reasons classified as "work-life balance" factors. Data from the trainees surveyed also highlighted work-life balance but also identified pressures within the training system and NHS. CONCLUSIONS: UK data of this sort has not previously been available. The authors' primary recommendation is that prospective data collection on trainee retention is carried out, with structured exit interviews with trainees who decide to leave. Our secondary recommendations include improvements to the inter-deanery transfer process and early realistic exposure to vascular surgery for junior doctors to improve trainee retention rates in vascular surgery.

Frozen elephant trunk repair of aortic aneurysms: How to reduce the incidence of endoleak and reintervention.

BACKGROUND: Frozen elephant trunk (FET) enables treatment of arch and proximal descending thoracic aorta aneurysms. In treating patients with single-stage FET, the relationship of distal stent size to endoleak and reintervention has remained unexamined. METHODS: In this retrospective analysis of 63 cases in which FET was used to repair aneurysms between 2008 and 2019, 36 were intended as single-stage procedures. Effective sizing and sealing of distal stents were analyzed by preoperative and postoperative computed tomography angiography (CTA). RESULTS: During a mean of 25.8 ± 5.7 months of CTA follow-up, 10 of 36 (28%) experienced endoleak, and 3 of 36 (8%) had sac expansion. Ultimately, 5 of 13 (38%) underwent thoracic endovascular aneurysm repair. Patients without endoleak or sac expansion were more likely to have stents with >10% oversize and a >30-mm seal in healthy aorta compared with those experiencing these complications (11 of 23 vs 0 of 13; P = .0031). Conversely, 11 of 36 patients (31%) with adequately oversized and sealed stents developed fewer endoleaks compared with those without (0 of 11 vs 10 of 14; P < .0004). Patients with endoleak or sac expansion had smaller mean distal stent oversize and shorter mean sealing length compared with those without endoleak or sac expansion (2.3 ± 3.9% vs 18 ± 2.9% [P = .0023] and 1 ± 0.7 mm vs 34 ± 6 mm [P = .0005], respectively). CONCLUSIONS: We recommend >10% distal stent oversize and >30-mm sealing length to minimize endoleak and reintervention. Increasing multidisciplinary collaboration with endovascular surgeons will improve distal stent planning.

Infection Prophylaxis for Breast Implant Surgery: Could We Do Better?

Objective: Infective complications following breast implant surgery may result in implant removal. This causes patient distress and is costly to treat. A range of precautions is undertaken at the time of surgery to reduce infection, with varying levels of supporting evidence. This study aimed to determine how frequently and consistently infection prevention precautions are used during breast implant surgery. Methods: Multicenter observational study of surgical practice with real-time data collection during breast implant surgery. Results: From 7 NHS breast units, 121 implant procedures were assessed in 94 patients under the care of 22 consultant surgeons. The commonest procedure was immediate reconstruction (58%; 70/121). All patients were methicillin-resistant Staphylococcus aureus (but not methicillin-sensitive Staphylococcus aureus) screened. Antibiotics were given at surgery in all cases; 92% (85/94) received postoperative antibiotics. Other precautions included closed glove technique (67%; 63/94), door signs to reduce theater traffic (72%; 68/94), glove changing prior to implant handling (98%; 119/121), laminar air flow theaters (55%; 52/94), disposable drapes (94%; 88/94) and gowns (74%; 70/94), and cavity washing (89%; 108/121). Among the 14 consultants evaluated on more than 1 procedure (range, 2-22; median = 5), only 1 consistently used exactly the same precautions when siting an implant. Conclusion: Despite national guidance, infection prevention measures are not applied consistently during breast implant surgery, with variability between surgeons and within individual surgeon's practice. The introduction of an infection prevention checklist for all breast implant procedures could improve the reliability with which these precautions are undertaken.

The role of chemerin and ChemR23 in stimulating the invasion of squamous oesophageal cancer cells.

BACKGROUND: Stromal cells, including cancer-associated myofibroblasts (CAMs), are recognised to be determinants of cancer progression, but the mechanisms remain uncertain. The chemokine-like protein, chemerin, is upregulated in oesophageal squamous cancer (OSC) CAMs compared with adjacent tissue myofibroblasts (ATMs). In this study, we hypothesised that chemerin stimulates OSC cell invasion. METHODS: Expression of the chemerin receptor, ChemR23, in OSC was examined by immunohistochemistry. The invasion of OSC cells was studied using Boyden chambers and organotypic assays, and the role of chemerin was explored using siRNA, immunoneutralisation and a ChemR23 receptor antagonist. Matrix metalloproteinases (MMPs) were detected by western blot, enzyme assays or immunohistochemistry. RESULTS: Immunohistochemistry indicated expression of the putative chemerin receptor ChemR23 in OSC. It was also expressed in the OSC cell line, OE21. Chemerin stimulated OE21 cell migration and invasion in Boyden chambers. Conditioned medium (CM) from OSC CAMs also stimulated OE21 cell invasion and this was inhibited by chemerin immunoneutralisation, the ChemR23 antagonist CCX832, and by pretreatment of CAMs with chemerin siRNA. In organotypic cultures of OE21 cells on Matrigel seeded with either CAMs or ATMs, there was increased OE21 cell invasion by CAMs that was again inhibited by CCX832. Chemerin increased MMP-1, MMP-2 and MMP-3 abundance, and activity in OE21 cell media, and this was decreased by inhibiting protein kinase C and p44/42 MAPK kinase but not PI-3 kinase. CONCLUSIONS: The data indicate that OSC myofibroblasts release chemerin that stimulates OSC cell invasion. Treatments directed at inhibiting chemerin-ChemR23 interactions might be therapeutically useful in delaying progression in OSC.

Increased expression of chemerin in squamous esophageal cancer myofibroblasts and role in recruitment of mesenchymal stromal cells.

Stromal cells such as myofibroblasts influence tumor progression. The mechanisms are unclear but may involve effects on both tumor cells and recruitment of bone marrow-derived mesenchymal stromal cells (MSCs) which then colonize tumors. Using iTRAQ and LC-MS/MS we identified the adipokine, chemerin, as overexpressed in esophageal squamous cancer associated myofibroblasts (CAMs) compared with adjacent tissue myofibroblasts (ATMs). The chemerin receptor, ChemR23, is expressed by MSCs. Conditioned media (CM) from CAMs significantly increased MSC cell migration compared to ATM-CM; the action of CAM-CM was significantly reduced by chemerin-neutralising antibody, pretreatment of CAMs with chemerin siRNA, pretreatment of MSCs with ChemR23 siRNA, and by a ChemR23 receptor antagonist, CCX832. Stimulation of MSCs by chemerin increased phosphorylation of p42/44, p38 and JNK-II kinases and inhibitors of these kinases and PKC reversed chemerin-stimulated MSC migration. Chemerin stimulation of MSCs also induced expression and secretion of macrophage inhibitory factor (MIF) that tended to restrict migratory responses to low concentrations of chemerin but not higher concentrations. In a xenograft model consisting of OE21 esophageal cancer cells and CAMs, homing of MSCs administered i.v. was inhibited by CCX832. Thus, chemerin secreted from esophageal cancer myofibroblasts is a potential chemoattractant for MSCs and its inhibition may delay tumor progression.

Mapping proteolytic processing in the secretome of gastric cancer-associated myofibroblasts reveals activation of MMP-1, MMP-2, and MMP-3.

Cancer progression involves changes in extracellular proteolysis, but the contribution of stromal cell secretomes to the cancer degradome remains uncertain. We have now defined the secretome of a specific stromal cell type, the myofibroblast, in gastric cancer and its modification by proteolysis. SILAC labeling and COFRADIC isolation of methionine containing peptides allowed us to quantify differences in gastric cancer-derived myofibroblasts compared with myofibroblasts from adjacent tissue, revealing increased abundance of several proteases in cancer myofibroblasts including matrix metalloproteinases (MMP)-1 and -3. Moreover, N-terminal COFRADIC analysis identified cancer-restricted proteolytic cleavages, including liberation of the active forms of MMP-1, -2, and -3 from their inactive precursors. In vivo imaging confirmed increased MMP activity when gastric cancer cells were xenografted in mice together with gastric cancer myofibroblasts. Western blot and enzyme activity assays confirmed increased MMP-1, -2, and -3 activity in cancer myofibroblasts, and cancer cell migration assays indicated stimulation by MMP-1, -2, and -3 in cancer-associated myofibroblast media. Thus, cancer-derived myofibroblasts differ from their normal counterparts by increased production and activation of MMP-1, -2, and -3, and this may contribute to the remodelling of the cancer cell microenvironment.

Transdermal oestrogen therapy as a second-line hormonal intervention in prostate cancer: a bad experience.

OBJECTIVE: To compare transdermal oestrogen with oral diethylstilbestrol (DES) as a second- or third-line hormonal therapy in the treatment of prostate cancer. PATIENTS AND METHODS: In all, 32 assessable patients who, having already had a relapse on at least one line of hormonal therapy, received transdermal oestrogen therapy as an alternative to oral DES, when DES became unavailable. RESULTS: Whereas DES had controlled the prostate-specific antigen (PSA) level for a median of 29 weeks in a group of 15 patients in remission, all but one had an increase in PSA level (median 86% increase above the starting PSA level) within a median of 8 weeks after introducing transdermal therapy. This increase was reversed in seven of the 12 patients who recommenced DES therapy. CONCLUSION: Although the use of transdermal oestrogen is currently attracting enthusiasm as a first-line treatment for prostate cancer, these results show that for second- or third-line therapy further cautious research with careful monitoring is necessary.