Adult stem cell activity in naked mole rats for long-term tissue maintenance.

The naked mole rat (NMR), Heterocephalus glaber, the longest-living rodent, provides a unique opportunity to explore how evolution has shaped adult stem cell (ASC) activity and tissue function with increasing lifespan. Using cumulative BrdU labelling and a quantitative imaging approach to track intestinal ASCs (Lgr5+) in their native in vivo state, we find an expanded pool of Lgr5+ cells in NMRs, and these cells specifically at the crypt base (Lgr5+CBC) exhibit slower division rates compared to those in short-lived mice but have a similar turnover as human LGR5+CBC cells. Instead of entering quiescence (G0), NMR Lgr5+CBC cells reduce their division rates by prolonging arrest in the G1 and/or G2 phases of the cell cycle. Moreover, we also observe a higher proportion of differentiated cells in NMRs that confer enhanced protection and function to the intestinal mucosa which is able to detect any chemical imbalance in the luminal environment efficiently, triggering a robust pro-apoptotic, anti-proliferative response within the stem/progenitor cell zone.

The history of surgery and surgical training in the UK.

Surgery has a rich history, and in order to understand the various training pathways for aspiring surgeons one must have an appreciation of the evolution of surgery. This manuscript aims to deliver a brief review of the history of surgery, and explore the historical moments that have shaped the training pathway of surgeons in the United Kingdom (UK), and in doing so disseminate the latest information about surgical training in the UK.

Establishing the need for clinical follow-up after emergency appendicectomy in the modern era: Retrospective case series of 145 patients.

INTRODUCTION: Emergency appendicectomy (EA) is a commonly performed operation, with an increasing number of EAs being performed as day-case. The aim of this study is to establish if there is a need for post-operative follow-up and if this could prevent adverse outcomes. METHODS: A retrospective analysis of patients who underwent EA at multiple centres over a six-month period was undertaken. They were contacted by telephone and a standardised questionnaire was used to ascertain post-operative outcomes, including duration of analgesia use, duration before return to normal daily activity (ADLs), surgical site infection rates (SSI) and rates of re-presentation to medical services. Patients were stratified into those who underwent laparoscopic versus open appendicectomy, smokers versus non-smokers, and body mass index (BMI). RESULTS: A total of 145 patients were included in the study. Patients undergoing open surgery (vs. laparoscopic surgery) required analgesia for significantly longer periods, with a significantly longer return to ADLs. Smokers, when compared to non-smokers experienced a significantly longer return to work/school; and significantly higher risk of SSI and re-presenting to accident & emergency; as did patients with a BMI >30 when compared to those with a BMI <30. CONCLUSION: Most patients do not need formal outpatient assessment after EA. However, there is clearly a subset of higher risk patients who may benefit from this - patients who are smokers or obese. They have prolonged recovery times, and are at greater risk of SSI. Earlier surgical outpatient follow-up of these patients could prevent adverse outcomes.

Diagnosis of ruptured abdominal aortic aneurysm: a multicentre cohort study.

OBJECTIVE: The aim of this study was to describe the presentation of patients with ruptured abdominal aortic aneurysm (rAAA) and identify factors contributing toward misdiagnosis. METHODS: This was an observational study of cases with a final diagnosis of rAAA assessed at nine Emergency Departments and managed at one of two regional vascular centres in the UK. RESULTS: Eighty-five consecutive cases were included. Seventeen [20.0%, 95% confidence interval (CI) 11.5-28.5%] patients reported important symptoms up to 3 weeks before index presentation. In the Emergency Department, most patients complained of abdominal and/or back pain, seven (8.2%, 95% CI 2.4-14.0%) additionally reported atypical pain and ten (11.8%, 95% CI 4.9-18.7%) denied pain altogether. Hypotension (36.5%, 95% CI 26.3-46.7%), tachycardia (18.8%, 95% CI 10.5-27.1%) and syncope (36.5%, 95% CI 26.3-46.7%) were documented in a minority of cases. Distracting symptoms were present in 33 (38.8%, 95% CI 28.4-49.2%) patients. The median time to diagnosis was 17.5 min (range immediate-12 days), and 21 (25.6%, 95% CI 16.3-34.9%) patients were misdiagnosed during clinical assessment. CONCLUSION: The classical signs and symptoms or rAAA are not always present and patients frequently show additional features that may confound the diagnosis. A high level of suspicion should be adopted for rAAA alongside a low threshold for immediate computed tomography. Further research is required to develop an objective clinical risk score or predictive tool for characterizing patients at risk.

Does surgery have a role in managing incurable gastric cancer?

Although the incidence of gastric cancer is decreasing, the outcomes of this disease are among the poorest of all solid-organ tumours, predominantly due to the frequent presence of stage IV metastatic disease at primary presentation. Stage IV gastric cancer is incurable and carries a very poor prognosis (5-year survival rate of ∼4%); palliative chemotherapy remains the standard of care, but increasing evidence indicates that palliative surgery can provide a prognostic and symptomatic benefit, particularly in combination with chemotherapy and/or radiotherapy. Ongoing prospective trials should further clarify the efficacy of palliative surgery in comparison with other treatment modalities. Until such data are available, surgery should not be offered as a standard first-line treatment, but can be considered in selected cases after thorough multidisciplinary discussions involving the patient. Patient selection for both gastrectomy and nonresectional surgery must include consideration of various factors that predict quality of life after surgery. This Perspectives summarizes the available evidence and discusses the utility of palliative surgery in relation to other therapeutic modalities in the management of incurable gastric cancer.

Locoregional anesthesia for endovascular aneurysm repair.

OBJECTIVE: This was a systematic review and meta-analysis of the mode of anesthesia and outcome after endovascular aneurysm repair (EVAR). METHODS: Review methods were according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Published and unpublished literature was searched. The primary outcome was 30-day mortality. Secondary outcomes were categorized for patient selection, perioperative outcomes, and postoperative outcomes. Weighted mean differences (WMD) were calculated for continuous variables, such as length of stay, and pooled odds ratios (OR) were calculated for discrete variables such as major morbidity. RESULTS: Ten studies of 13,459 patients given local anesthesia (LA) or general anesthesia (GA) were eligible for analysis. There was no difference in 30-day mortality. The LA patients were older than the GA patients (WMD, 0.17; P = .006), with an increased burden of cardiac (LA vs GA: OR, 1.28; P = .011) and respiratory (LA vs GA: OR, 1.28; P = .006) comorbidity. LA EVAR was reported with shorter operative time (WMD, -0.54; P = .001) and hospital stay (WMD, -0.27; P = .001) vs GA. LA patients developed fewer postoperative complications than GA patients (OR, 0.54; P < .001). CONCLUSIONS: The absence of randomized data is a major hurdle to understanding the effect of anesthetic technique on morbidity after EVAR. The data presented are encouraging in selected patients. The use of locoregional anesthesia for EVAR should be further investigated with better reporting of aneurysm morphology to clarify its potential benefits and identify the subgroups that will derive greatest benefit.

Current evidence is insufficient to define an optimal threshold for intervention in isolated type II endoleak after endovascular aneurysm repair.

PURPOSE: To report a systematic review and meta-regression of the association between the threshold for intervention in patients with isolated type II endoleak after endovascular aneurysm repair (EVAR) and the fate of the aneurysm sac. METHODS: Medline, trial registries, conference proceedings, and article reference lists were searched to identify case series reporting sac outcomes following a specific treatment threshold for isolated type II endoleak. Articles were classified by the threshold for intervention as conservative, selective (intervention for >5-mm sac expansion or persistent type II endoleak >6 months), or aggressive (any type II endoleak or persistent for >3 months) and sac outcomes were extracted for review. Standard meta-regression to estimate the pooled odds ratios (OR), presented with the 95% confidence interval (CI), was performed to identify whether an aggressive, selective, or conservative threshold for intervention was associated with sac expansion or sac regression. RESULTS: Ten series were analyzed that reported the outcomes of isolated type II endoleak in 231 patients; of these, 56 patients were treated at an aggressive threshold, 104 at a selective threshold, and 71 at a conservative threshold. The majority (194/231, 84.0%) demonstrated either stable or shrinking sacs during follow-up. No ruptures occurred. Meta-regression demonstrated no evidence that any strategy, compared to using a conservative approach, reduced sac expansion (aggressive estimated OR 0.70, 95% CI 0.15 to 3.31, p = 0.60; selective estimated OR 1.72, 95% CI 0.49 to 6.00, p = 0.34) or improved sac regression (aggressive estimated OR 0.55, 95% CI 0.02 to 16.94, p = 0.69; selective estimated OR 5.54, 95% CI 0.39 to 79.21, p = 0.17). CONCLUSION: There is inadequate information to support any one threshold for intervention. The rarity of rupture and sac expansion confirms the predominantly benign nature of isolated type II endoleak. In the absence of statistical support for a uniform approach to this problem, patient and physician preference remain key. Prospective data are still needed to investigate whether an optimum management algorithm can be devised.

Gallbladder perforation: case series and systematic review.

BACKGROUND: Gallbladder perforation is a serious complication of acute cholecystitis. Its management has evolved considerably since its classification by Niemeier in 1934. This review summarises the evidence surrounding the natural progression of this condition and potential problems with Niemeier's classification, and proposes a management algorithm for the more complex type II perforation. METHODS: Data from a retrospective case series and a systematic review were combined. The case series included all patients with gallbladder perforations from 2004 to 2008 at a British teaching hospital. The systematic review searched for gallbladder perforation using the MEDLINE, Embase, Web of Science and Cochrane Library (2011 Issue 4) databases, as well as recent conference abstracts. The outcome data were analysed using SPSS version 15. No adjustments were made for multiple testing. RESULTS: 198 patients (including 19 patients from the present series) with a mean age of 62.1+/-9.7 years and male gender proportion of 55.4% (range 33.3-76.7%) were included. The most common gallbladder perforations were type II (median 46.2%, range 7.4-83.3%), followed by type I (median 40.6%, range 16.7-70.0%) and type III (median 10.1%, range 0-48.1%). Perforation was associated with cholelithiasis in 86.6% (range 78.9-90.6%) of patients, and the overall median mortality rate was 10.8% (range 0-12.5%). Male gender was weakly associated with mortality (p = 0.089) but age (p = 0.877) and cholelithiasis (p = 0.425) were not. Mortality did not vary significantly with perforation type. CONCLUSIONS: Gallbladder perforation should be reported according to the original Neimeier's classification to avoid heterogeneity in data (e.g. varying rates of perforation types). The algorithm proposed in this study aims to guide the management of complex type II gallbladder perforations to minimise subsequent morbidity and mortality.

Unexpected outcome from Trousseau syndrome.

BACKGROUND: Unprovoked superficial thrombophlebitis and subsequent venous thromboembolism are well-described albeit rare presenting features of advanced visceral malignancy that often manifest too late for curative intervention to be beneficial. CASE PRESENTATION: We present the first reported case of early gastric carcinoma presenting with these paraneoplastic phenomena in an otherwise healthy farmer. The early presentation allowed for a curative partial gastrectomy, which itself was complicated by the presence of a deep vein thrombosis extending into the inferior vena cava. Fortunately, stabilization of the clot allowed for surgery to proceed without the need for a caval filter. The patient was referred for adjuvant chemotherapy and has since made an excellent recovery. CONCLUSIONS: This case provides new evidence for the presentation of superficial thrombophlebitis in early gastric carcinoma and the potential for curative surgery in such instances. A high index of suspicion and a prompt diagnostic workup are essential for timely planning and execution of surgery in these early albeit rare presentations.

Solitary colonic metastasis from renal cell carcinoma presenting as a surgical emergency nine years post-nephrectomy.

Late colonic metastasis following curative surgery for renal cell carcinoma has rarely been described. We present the first reported case of solitary colonic renal cell carcinoma metastasis presenting as an intra-abdominal bleed, nine years post-nephrectomy.

The surgical management of pancreaticoduodenal tumours in multiple endocrine neoplasia type 1.

A 48-year-old man was admitted under the care of urologists with acute renal failure and septicaemia secondary to pyelonephritis. Upon investigation, he was found to have renal stone disease secondary to a parathyroid adenoma. Further tests revealed high pituitary hormone and gastrin values, confirming the diagnosis of multiple endocrine neoplasia type 1 (MEN 1) and Zollinger-Ellison syndrome. Soon after this he experienced a series of renal complications due to his renal stone disease and multiple complications of his gastrinoma, including two gastrointestinal perforations and three episodes of significant upper gastrointestinal bleeds (two of which required laparotomies), and a full length oesophageal stricture-all within the span of 9 months. His complications were managed appropriately and the oesophageal stricture was treated with a full length metallic stent. He was discharged home in a reasonably good condition with normal swallowing, but unfortunately died of aspiration pneumonia 3 weeks later.