David Kingsmore

Life threatening pelvic sepsis after stapled haemorrhoidectomy.

We describe a case of severe retroperitoneal sepsis after stapled haemorrhoidectomy. The operation seemed to be technically satisfactory, and we suggest that routine antibiotic prophylaxis may be indicated with this procedure.

Altered sirtuin expression is associated with node-positive breast cancer

Sirtuins are genes implicated in cellular and organismal ageing. Consequently, they are speculated to be involved in diseases of ageing including cancer. Various cancers with widely differing prognosis have been shown to have differing and characteristic expression of these genes; however, the relationship between sirtuin expression and cancer progression is unclear. In order to correlate cancer progression and sirtuin expression, we have assessed sirtuin expression as a function of primary cell ageing and compared sirtuin expression in normal, ‘nonmalignant’ breast biopsies to breast cancer biopsies using real-time polymerase chain reaction (PCR). Levels of SIRT7 expression were significantly increased in breast cancer (P<0.0001). Increased levels of SIRT3 and SIRT7 transcription were also associated with node-positive breast cancer (P<0.05 and P<0.0001, respectively). This study has demonstrated differential sirtuin expression between nonmalignant and malignant breast tissue, with consequent diagnostic and therapeutic implications.

Influence of diabetes mellitus on patient and graft survival in recipients of kidney transplantation

Aims. To investigate the outcomes in patients who have pre‐existing diabetes and those who develop post‐transplant diabetes mellitus (PTDM). 
Methods. We retrospectively reviewed the charts of 939 patients who received a first functioning renal transplant in the cyclosporine (CyA) era between 1984 and 1999. 
Results. Sixty‐six (7%) patients had renal failure due to insulin‐dependent diabetes mellitus (IDDM) and 7 (0.8%) patients due to non‐insulin‐dependent diabetes mellitus (NIDDM). Ten (1.1%) patients had coexistent diabetes and 48 (5.1%) recipients developed PTDM. The mean graft survival for the patients with PTDM was 9.7 yr versus 11.3 yr for the non‐diabetic patients, while mean graft survival was 10.1 yr for patients with IDDM and 2.9 yr with NIDDM and 8.3 yr for those with coexistent diabetes (p=ns). However, there was a statistically significant difference in patient survival between patients who developed PTDM and in those who did not develop this complication. The mean survivals of patients with IDDM, NIDDM, coexistent diabetics and PTDM were 8.4, 3.7, 8.6 and 10.3 yr, respectively. The mean survival of the patients without pre‐existing diabetes or PTDM was 12.8 yr (p<0.001). The survival of patients older than 55 yr with PTDM was no different to the control group. However, in those younger than 55 yr, PTDM was associated with a higher risk of death (relative risk of 2.54, p<0.001). Fifty percent of patients with IDDM developed acute rejection episodes, whereas rejection rate was 57.1% in NIDDM group, 50.0% in the PTDM group, 20.0% in the coexistent diabetes group and 44.3% in the control group (p=ns). 
Conclusion. Patient survival, but not graft survival, was adversely affected by both pre‐existing diabetes and by PTDM, particularly in those with an age less than 55 yr.

Why does specialist treatment of breast cancer improve survival? The role of surgical management

Evidence that the survival of women with breast cancer treated by specialist surgeons is better than that by nonspecialists is limited. Previous reports have not identified the cause of this survival advantage. Our aim was to determine if the survival difference was due to case-mix, adjuvant treatment or the treatment provided by specialist surgeons. The case-records and pathology reports of 2776 women were reviewed. This represented 95% of all those diagnosed with breast cancer between 1/1/1986 and 31/12/1991 in a defined geographical area. Case-mix, surgery, pathology and adjuvant therapies of the 2148 women treated with curative intent were analysed. A standard of adequate surgical management was defined and confirmed as a valid predictor by examining rates of local recurrence, independent of all other prognostic factors. Against this standard, we compared the adequacy of surgical management, local recurrence rates and the survival outcomes of specialists and nonspecialists over an 8-year follow-up period. The inter-relationship between adequacy of surgical management, locoregional recurrence and survival was examined. While the case-mix and prescription of adjuvant therapies were comparable between specialist and nonspecialist surgeons, the efficacy and outcome of local treatment differed widely. Breast cancer patients treated in specialist compared to nonspecialist units had half the risk of inadequate treatment of the breast (24 vs 47%, P<0.001), a five-fold lower risk of inadequate axillary staging (8 vs 40%, P<0.001) and nine times lower risk of inadequate definitive axillary treatment (4 vs 38%, P<0.001). Local recurrence rates were 57% lower (13 vs 23% at eight years, P<0.001) and the risk of death from breast cancer was 20% lower for women treated in specialist units, after allowing for case-mix and adjuvant therapies. Adequacy of surgical management correlated with locoregional recurrence, which in turn correlated with the risk of death. The surgical management in specialised breast units is more often adequate, local and regional recurrence rates are lower, and survival is correspondingly better. We conclude that adequate surgical management of breast cancer is fundamental to improving the outcome from breast cancer irrespective of where it is delivered.

Prognostic value of cardiovascular screening in potential renal transplant recipients: a single-center prospective observational study.

We assessed the outcome of pretransplant cardiac assessment in a single center. Three hundred patients with end‐stage renal disease underwent electrocardiogram, Bruce exercise testing (ETT) and ventricular assessment by cardiac MRI. Patients with high index of suspicion of coronary artery disease (CAD) underwent coronary angiography and percutaneous coronary intervention (PCI) if indicated. Two hundred and twenty‐two patients were accepted onto the renal transplant waiting list; 80 patients were transplanted during the follow‐up period and 60 died (7 following transplantation). Successful transplantation was associated with improved survival (mean survival 4.5 ± 0.6 years vs. listed not transplanted 4.1 ± 1.4 years vs. not listed 3.1 ± 1.7 years; p < 0.001). Ninety‐nine patients underwent coronary angiography; 65 had normal or low‐grade CAD and 34 obstructive CAD. Seventeen patients (5.6%) were treated by PCI. There was no apparent survival difference between patients who underwent PCI or coronary artery bypass graft compared to those who underwent angiography without intervention or no angiography (p = 0.67). Factors associated with nonlisting for renal transplantation included burden of preexisting cardiovascular disease, poor exercise tolerance and severity of CAD. Pretransplant cardiovascular screening provides prognostic information and information that can be used to restrict access to transplantation. However, if the aim is to identify and treat CAD, the benefits are far from clear.

The impact of late acute rejection after cadaveric kidney transplantation

Background: Acute graft rejection (AR) following renal transplantation results in reduced graft survival. However, there is uncertainty regarding the definition, aetiology and long‐term graft and patient outcome of AR occurring late in the post‐transplant period. 
Aim: To determine if rejection episodes can be classified by time from transplantation by their impact on graft survival into early acute rejection (EAR) and late acute rejection (LAR). 
Materials and methods: 687 consecutive adult renal transplant recipients who received their first cadaveric renal transplant at a single centre. All received cyclosporine (CyA)‐based immunosuppression, from 1984 to 1996, with a median follow‐up of 6.9 yr. Details were abstracted from clinical records, with emphasis on age, sex, co‐morbid conditions, HLA matching, rejection episodes, patient and graft survival. 
Analysis: Patients were classified by the presence and time to AR from the date of transplantation. Using those patients who had no AR (NAR) as a baseline, we determined the relative risk of graft failure by time to rejection. The characteristics of patients who had no rejection, EAR and LAR were compared. 
Results: Compared with NAR, the risk of graft failure was higher for those patients who suffered a rejection episode. A much higher risk of graft failure was seen when the first rejection episode occurred after 90 d. Thus, a period of 90 d was taken to separate EAR and LAR (relative risk of 3.06 and 5.27 compared with NAR as baseline, p<0.001). Seventy‐eight patients (11.4%) had LAR, 271 (39.4%) had EAR and 338 (49.2%) had NAR. The mean age for each of these groups differed (LAR 39.6 yr, EAR 40.8 yr compared with NAR 44 yr, p<0.003). The 5‐yr graft survival for those who had LAR was 45% and 10‐yr survival was 28%. HLA mismatches were more frequent in those with EAR vs. NAR (zero mismatches in HLA‐A: 36 vs. 24%, HLA‐B: 35 vs. 23% and HLA‐DR: 63 vs. 41%, p<0.003). There was no difference in mismatching frequency between NAR and LAR. 
Conclusions: AR had a deleterious impact on graft survival, particularly if occurring after 90 d. AR episodes should therefore be divided into early and late phases. In view of the very poor graft survival associated with LAR, it is important to gain further insight into the main aetiological factors. Those such as suboptimal CyA blood levels and non‐compliance with medication should be further investigated with the aim of developing more effective immunosuppressive regimens in order to reduce the incidence of LAR.

B‐type natriuretic peptide predicts cardiac morbidity and mortality after major surgery

The objective of this study was to determine whether measurement of B‐type natriuretic peptide (BNP) concentration before operation could be used to predict perioperative cardiac morbidity.

Cellular senescence in pretransplant renal biopsies predicts postoperative organ function

Older and marginal donors have been used to meet the shortfall in available organs for renal transplantation. Post‐transplant renal function and outcome from these donors are often poorer than chronologically younger donors. Some organs, however, function adequately for many years. We have hypothesized that such organs are biologically younger than poorer performing counterparts. We have tested this hypothesis in a cohort of pre‐implantation human renal allograft biopsies (n = 75) that have been assayed by real‐time polymerase chain reaction for the expression of known markers of cellular damage and biological aging, including CDKN2A, CDKN1A, SIRT2 and POT1. These have been investigated for any associations with traditional factors affecting transplant outcome (donor age, cold ischaemic time) and organ function post‐transplant (serum creatinine levels). Linear regression analyses indicated a strong association for serum creatinine with pre‐transplant CDKN2A levels (p = 0.001) and donor age (p = 0.004) at 6 months post‐transplant. Both these markers correlated significantly with urinary protein to creatinine ratios (p = 0.002 and p = 0.005 respectively), an informative marker for subsequent graft dysfunction. POT1 expression also showed a significant association with this parameter (p = 0.05). Multiple linear regression analyses for CDKN2A and donor age accounted for 24.6% (p = 0.001) of observed variability in serum creatinine levels at 6 months and 23.7% (p = 0.001) at 1 year post‐transplant. Thus, these data indicate that allograft biological age is an important novel prognostic determinant for renal transplant outcome.

Predictive value of plasma brain natriuretic peptide for cardiac outcome after vascular surgery

Vascular surgery is associated with a substantial risk of cardiovascular events and death.1,2 There is no effective method for determining cardiac risk preoperatively: validated risk prediction instruments are limited by complexity and poor predictive value, and other cardiac investigations such as nuclear stress testing and coronary angiography are limited by time and resources. For these reasons, alternative methods that can predict outcome of at risk patients would be an important advance. Plasma brain natriuretic peptide (BNP) has counter-regulatory vasodilator and natriuretic properties. Plasma BNP concentrations are often increased in cardiac disorders, such as angina and heart failure. The plasma concentrations of BNP are related to prognosis in these conditions.3 Many of these cardiovascular conditions occur in patients with peripheral vascular disease. We investigated the predictive value of preoperative plasma BNP concentration for the occurrence of perioperative fatal or non-fatal myocardial infarction (MI) in high risk vascular surgical patients. We also compared the predictive value of plasma BNP concentration with the Eagle score, a conventional surgical risk assessment instrument.1,2 We screened consecutive patients undergoing major surgery for aortic or peripheral arterial occlusive disease in Gartnavel General Hospital, Glasgow, between April and September 2004. All patients at high risk, defined according to the American Society of Anesthesiology …

Specialisation and breast cancer survival in the screening era

It is recommended that specialist surgeons treat all breast cancer, although the limited evidence to support this is based on treatment patterns prior to the introduction of screening. Whether a specialist survival advantage exists in the post-screening era is uncertain, as referral and treatment patterns may have changed, in addition to the effect of screening on the natural history of breast cancer. Our aim was to determine the impact of screening on the caseload and case-mix of specialist surgeons, to determine if the survival advantage associated with specialist care is maintained with longer follow-up and persists after the introduction of screening. Using the West of Scotland Cancer Registry, all 7197 women treated for breast cancer in a 15-year time period (1980–1994) in a geographically defined cohort were followed up for an average of 9 years, and pathological stage and socioeconomic status were linked with mortality data. We show that the caseload of specialists has increased substantially (from 11 to 59% of the total workload) and that smaller cancers have been selectively referred. However, even after allowing for pathological stage, socioeconomic status and method of detection, specialist treatment was associated with a significantly lower risk of dying (prescreening: relative risk of dying=0.83, 95% CI=0.75–0.92; post-screening: relative risk of dying=0.89, 95% CI=0.78–1.00). We conclude that this survival benefit is most consistent with effective surgical management rather than selective referral, the influx of screen-detected cancers or adjuvant therapies.