The reliability of lymph-node staging in rectal cancer after preoperative chemoradiotherapy

AimsTo determine the prognostic significance of the nodal stage and number of nodes recovered in the surgical specimen after preoperative synchronous chemoradiation (SCRT) and surgery for locally advanced or unresectable rectal cancer.Materials and MethodsOne hundred and eighty-two consecutive patients with locally advanced or unresectable (T3/T4) rectal carcinomas were entered on a prospective database and treated in this department with preoperative chemoradiation, followed 6–12 weeks later by surgical resection. Most patients received chemotherapy in the form of low-dose folinic acid and 5-fluorouracil (5-FU) 350 mg/m² via a 60-min infusion on days 1–5 and 29–33 of a course of pelvic radiotherapy delivered at a dose of 45 Gy in 25 fractions over 33 days to a planned volume. After resection, patients with a positive circumferential margin (≤1 mm), extranodal deposits or Dukes' C histology received adjuvant 5-FU-based-chemotherapy (n = 40).ResultsAfter SCRT, 161 patients underwent resection. Twenty-one patients remained unresectable or refused an exenterative operation. Median follow-up is 36 months. Down-staging was achieved in most patients, with 19 having a complete pathological response (pT0). The median number of lymph nodes recovered for all patients was five (range 0–21). The 3-year survival rate for node-positive patients is 47%, for node-negative patients with less than three lymph nodes recovered is 62% and for node-negative patients with three or more lymph nodes recovered is 70%. Compared with node-positive patients, simple regression models revealed a reduced hazard ratio (HR) of 0.72 (0.36–1.43) for node-negative patients with less than three nodes recovered and 0.48 (0.26–0.89) for node-negative patients with three or more lymph nodes recovered. In a multivariate model, including nodal status, excision status, age and sex only positive excision margins significantly predicted a poor outcome: HR = 3.05 (1.55–5.97).ConclusionsThe number of nodes found after preoperative chemoradiation is a significant prognostic factor by univariate analysis. In this study, patients with node-negative histology, and at least three nodes recovered, had better long-term survival than patients in whom two or less nodes were recovered or with positive nodes. This effect was attenuated by the inclusion of excision status in multivariate models.     

Evaluation of daclizumab to reduce delayed graft function in non-heart-beating renal transplantation: a prospective, randomized trial

Daclizumab (DZB), an interleukin-2 receptor blocker, has been shown to reduce the rate of acute rejection, while non-heart-beating kidney recipients have high rates of delayed graft function that may be prolonged by high levels of calcineurin inhibitors. This study assessed whether DZB could safely replace calcineurin inhibitors in the immediate postoperative period and promote recovery from ischemic acute tubular necrosis. Patients were randomized into one of two groups: DZB induction and daily mycophenolate mofetil (MMF; 2 g) with steroids (20 mg prednisone) or standard triple therapy with tacrolimus, MMF, and prednisone. Patients in the DZB arm were converted to the control arm when either the serum creatinine dropped to <350 micromol/L or there was biopsy evidence of acute rejection. Over 2 years, Leicester and Newcastle non-heart-beating donor (NHBD) centers recruited 51 patients. There was one patient death in the DZB arm, during the study period, after a nonfunctioning graft was removed. A total of two (8%) grafts in the DZB arm and three (11.5%) grafts in the control arm failed to function. The overall rate of immediate function improved from around 5% (pre-2001) to 28%. There were no significant differences in the incidence of acute rejection or graft function (GFR) at 3 months. Machine-perfused kidneys in DZB-treated recipients had the highest rates of immediate function (53%, P = .015). We found that a calcineurin-sparing regime is safe and may be beneficial for recipients of machine-perfused grafts damaged by warm ischemia.     

Do recipients of kidneys from donors treated with streptokinase develop anti-streptokinase antibodies?

Streptokinase is used for preflush for non-heart-beating donors (NHBDs) in our center. The aim of this study was to evaluate whether the use of thrombolytic streptokinase results in the production of anti-streptokinase antibodies in the recipients after renal transplantation. Recipient sera taken prior to and at 1 and 6 months posttransplant were tested for the presence of antibodies to streptokinase using an enzyme-linked immunosorbent assay assay. No differences were detected between a group of 18 recipients who had kidneys from thrombolytic-treated NHBDs and a further group of 18 who received NHBD kidneys without such treatment.     

Factors predicting duration of delayed graft function in non-heart-beating donor kidney transplantation

Non-heart-beating donors (NHBDs) are an important potential source of donor organs, but kidneys from such donors are prone to delayed graft function (DGF) and primary nonfunction, which are multifactorial in origin but believed to be mainly due to warm ischemic injury. This retrospective study examined a series of 88 transplants from Maastricht category II and III NHBDs to examine the role of factors to predict the duration of DGF. The main factors affecting duration of DGF were total warm ischemic time, cold ischemic time, product of perfusate GST concentration and donor age, quality of postoperative graft perfusion, incidence of acute rejection, recipient cardiovascular risk score, maximum pressure on machine perfusion, and weight gain during machine perfusion. Primary nonfunction was not accurately predicted from these factors for kidneys that had passed the viability assessment.     

Prospective study comparing three-dimensional computed tomography and magnetic resonance imaging for evaluating the renal vascular anatomy in potential living renal donors

OBJECTIVE: To prospectively compare the accuracy of multislice spiral computed tomographic angiography (CTA) and magnetic resonance angiography (MRA) in evaluating the renal vascular anatomy in potential living renal donors. SUBJECTS AND METHODS: Thirty-one donors underwent multislice spiral CTA and gadolinium-enhanced MRA. In addition to axial images, multiplanar reconstruction and maximum intensity projections were used to display the renal vascular anatomy. Twenty-four donors had a left laparoscopic donor nephrectomy (LDN), whereas seven had right open donor nephrectomy (ODN); LDN was only considered if the renal vascular anatomy was favourable on the left. CTA and MRA images were analysed by two radiologists independently. The radiological and surgical findings were correlated after the surgery. RESULTS: CTA showed 33 arteries and 32 veins (100% sensitivity) whereas MRA showed 32 arteries and 31 veins (97% sensitivity). CTA detected all five accessory renal arteries whereas MRA only detected one. CTA also identified all three accessory renal veins whereas MRA identified two. CTA had a sensitivity of 97% and 47% for left lumbar and left gonadal veins, whereas MRA had a sensitivity of 74% and 46%, respectively. CONCLUSION: Multislice spiral CTA with three-dimensional reconstruction was more accurate than MRA for both renal arterial and venous anatomy.     

How PEDF prevents angiogenesis: a hypothesized pathway

Pigment epithelium-derived factor (PEDF) is a multiple functional protein, coded by the serine proteinase inhibitor, clade F, member 1 (SERPINF1) gene, which has both anti-angiogenic activity and neurotrophic activity at the same time. Its antiangiogenic activity in the mammalian eye is the most potent known at this time. However, the mechanism(s) by which PEDF works in vivo is still uncertain. Some observations suggest that PEDF can simultaneously inhibit the migration and proliferation induced by vascular endothelial growth factor (VEGF), and then further inhibits angiogenesis by interacting with specific cell surface receptors, but no such receptor has been reported to date. Here we propose a hypothesis that PEDF exerts its function by binding with intergrins. Intergrin can therefore serve as the receptor of PEDF.     

Neurosyphilis: the most common things are most common.

Reports published in the past twenty years include many purporting to show, without much reason, that classic presentations of neurosyphilis are the exception rather than the rule. We join the few who take another view, and discuss here the reasons underlying the conflict of opinions.     

Determinants of response to a parent questionnaire about development and behaviour in 3 year olds: European multicentre study of congenital toxoplasmosis

Background  

We aimed to determine how response to a parent-completed postal questionnaire measuring development, behaviour, impairment, and parental concerns and anxiety, varies in different European centres.