Late anastomotic breakdown with bevacizumab in colorectal cancers, a case-based review.

BACKGROUND: Bevacizumab is the first angiogenesis inhibitor to be approved for metastatic colorectal cancer. Unfortunately, bevacizumab treatment has been associated with a variety of complications including haemorrhage, poor wound healing and gastrointestinal perforation. Late anastomotic breakdown related to bevacizumab therapy however has rarely been described. CASE REPORT: Here, we present the case of a 56-year-old woman who had a bevacizumab-related anastomotic breakdown 17 months following her primary anastomosis. She initially underwent an emergency Hartmann's procedure and two further laparotomies for significant intra-abdominal haemorrhage. Despite the best efforts of the surgical and intensive care teams, ultimately, the patient passed away. DISCUSSION: There is a small but growing body of literature relating to bevacizumab use and late anastomotic breakdown. It would seem prudent to take extra caution when using bevacizumab in those patients with previous pelvic irradiation, who have a rectal site of anastomosis or have experienced a previous anastomotic leak.

The impact of endovascular repair of ruptured abdominal aortic aneurysm on the gastrointestinal and renal function.

Introduction. Systemic effects of ruptured abdominal aortic aneurysm (rAAA) may be altered by the mode of surgery. This study aimed to determine systemic effects of endovascular aneurysm repair (EVAR) compared to open repair (OR). Patients and Methods. Consecutive patients with rAAA were repaired by OR or EVAR according to computerised tomographic (CT) findings. Renal function was monitored by estimated glomerular filtration rate (eGFR), serum urea and creatinine, and urinary albumin creatinine ratio (ACR). Hepatic function was assessed postoperatively for 5 days. Intestinal function was determined by the paracetamol absorption test. Intestinal permeability was assessed by urinary lactulose/mannitol ratio. Results. 30 rAAA patients were included. Fourteen had eEVAR and sixteen eOR. Serum urea were higher in eOR, while creatinine was similar between groups. Hepatic function showed no intergroup difference. Paracetamol absorption was increased in eEVAR group at day 3 compared to day 1 (P = 0.03), with no similar result in eOR (P = 0.24). Peak lactulose/mannitol ratio was higher in eOR (P = 0.03), with higher urinary L/M ratio in eOR at day 3 (P = 0.02). Clinical intestinal function returned quicker in eEVAR (P = 0.02). Conclusion. EVAR attenuated the organ dysfunction compared to open repair. However, a larger comparative trial would be required to validate this. The clinical trial is registered with reference number EUDRACT: 2013-003373-12.

Effects of early-life exposure to Western diet and wheel access on metabolic syndrome profiles in mice bred for high voluntary exercise.

Experimental studies manipulating diet and exercise have shown varying effects on metabolic syndrome components in both humans and rodents. To examine the potential interactive effects of diet, exercise and genetic background, we studied mice from four replicate lines bred (52 generations) for high voluntary wheel running (HR lines) and four unselected control lines (C). At weaning, animals were housed for 60 days with or without wheels and fed either a standard chow or Western diet (WD, 42% kcal from fat). Four serial (three juvenile and one adult) blood samples were taken to measure fasting total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglycerides and glucose. Western diet was obesogenic for all mice, even after accounting for the amount of wheel running and kilojoules consumed. Western diet significantly raised glucose as well as TC and HDL-C concentrations. At the level of individual variation (repeatability), there was a modest correlation (r = 0.3-0.5) of blood lipids over time, which was reduced with wheel access and/or WD. Neither genetic selection history nor wheel access had a statistically significant effect on blood lipids. However, HR and C mice had divergent ontogenetic trajectories for body mass and caloric intake. HR mice also had lower adiposity, an effect that was dependent on wheel access. The environmental factors of diet and wheel access had pronounced effects on body mass, food consumption and fasting glucose concentrations, interacting with each other and/or with genetic strain. These data underscore the importance (and often unpredictable nature) of genotype-by-environment and environment-by-environment interactions when studying body weight regulation.

The inflammatory response to ruptured abdominal aortic aneurysm is altered by endovascular repair.

Introduction. Ruptured abdominal aortic aneurysm (rAAA) causes a significant inflammatory response. The study aims to investigate this response following endovascular and open repair of ruptured AAA. Patients and Methods. Consecutive rAAA patients had either endovascular aneurysm repair (EVAR) or open repair (OR). Blood samples were taken for cytokines, lipid hydroperoxides (LOOH), antioxidants, and neutrophil elastase/ α 1-anti-trypsin complexes (NE/AAT) before surgery, 6 hours after clamp release and 1, 3, 5 days postoperatively. Results. 30 patients were included in the study, with 14 undergoing eEVAR and 16 eOR, with comparable baseline comorbidities, age, and parameters. IL-6 peaked higher in eOR patients (P = 0.04), while p75TNFr was similar between groups except at day 5 (P = 0.04). The NE/AAT concentrations were higher in eOR patients (P = 0.01), particularly in the first postoperative day, and correlated with blood (r = 0.398, P = 0.029) and platelet (r = 0.424, P = 0.020) volume transfused. C-reactive protein rose and lipid hydroperoxide fell in both groups without significant intergroup difference. Vitamins C and E, lycopene, and ß -carotene levels were similar between groups. Conclusion. EVAR is associated with lower systemic inflammatory response compared to OR. Its increased future use may thereby improve outcomes for patients.

Spontaneous dissection of the external iliac artery secondary to golf club manufacturing.

Spontaneous dissection of the external iliac artery in the absence of aortic disease is extremely uncommon. We report the conservative treatment of a 46-year-old male patient who presented with acute left lower limb ischemia due to an isolated dissection of the external iliac artery secondary to repetitive swinging movements during golf club manufacturing. Although syndromes of nonatherosclerotic vascular disease secondary to repetitive movements in high-level athletic activity have been previously described in cyclists, long distance runners, and rugby players, we believe this to be the first occupational case associated with golf.

Risedronate in adults with osteogenesis imperfecta type I: increased bone mineral density and decreased bone turnover, but high fracture rate persists.

UNLABELLED: Bisphosphonates can increase bone mineral density (BMD) in children with osteogenesis imperfecta (OI). In this study of adults with OI type I, risedronate increased BMD at lumbar spine (but not total hip) and decreased bone turnover. However, the fracture rate in these patients remained high. INTRODUCTION: Intravenous bisphosphonates given to children with OI can increase BMD and reduce fracture incidence. Oral and/or intravenous bisphosphonates may have similar effects in adults with OI. We completed an observational study of the effect of risedronate in adults with OI type I. METHODS: Thirty-two adults (mean age, 39 years) with OI type I were treated with risedronate (total dose, 35 mg weekly) for 24 months. Primary outcome measures were BMD changes at lumbar spine (LS) and total hip (TH). Secondary outcome measures were fracture incidence, bone pain, and change in bone turnover markers (serum procollagen type I aminopropeptide (P1NP) and bone ALP). A meta-analysis of published studies of oral bisphosphonates in adults and children with OI was performed. RESULTS: Twenty-seven participants (ten males and seventeen females) completed the study. BMD increased at LS by 3.9% (0.815 vs. 0.846 g/cm(2), p = 0.007; mean Z-score, -1.93 vs. -1.58, p = 0.002), with no significant change at TH. P1NP fell by 37% (p = 0.00041), with no significant change in bone ALP (p = 0.15). Bone pain did not change significantly (p = 0.6). Fracture incidence remained high, with 25 clinical fractures and 10 major fractures in fourteen participants (0.18 major fractures per person per year), with historical data of 0.12 fractures per person per year. The meta-analysis did not demonstrate a significant difference in fracture incidence in patients with OI treated with oral bisphosphonates. CONCLUSIONS: Risedronate in adults with OI type I results in modest but significant increases in BMD at LS, and decreased bone turnover. However, this may be insufficient to make a clinically significant difference to fracture incidence.

The role of carbohydrate drinks in pre-operative nutrition for elective colorectal surgery.

INTRODUCTION: Traditionally, patients have been fasted from midnight on the night before elective surgery. With the advent of the enhanced recovery programme for elective colorectal surgery, there has been a major change in established practice with patients able to continue with clear fluids up to two hours prior to surgery and solids up to six hours prior to surgery. It has been suggested that nutritional supplements in the immediate pre-operative period enhance post-operative recovery. The aim of this review was therefore critically to appraise the evidence available regarding the use of pre-operative carbohydrate (CHO) supplements for elective colorectal surgery. METHODS: A literature search was performed using: PubMed, MEDLINE(®), Athens and Google Scholar. The following keywords were used: 'pre-operative', 'carbohydrate supplements', 'enhanced recovery' and 'colorectal surgery', singly or in combination. To ensure an up-to-date literature search, the search was restricted to the last ten years. To maximise the search, backward chaining of reference lists from retrieved papers was also undertaken. Only English language articles were included. CONCLUSIONS: The use of CHO drinks pre-operatively in colorectal surgery is both safe and effective. There is no increased risk of aspiration and it results in a shorter hospital stay, a quicker return of bowel function and less loss of muscle mass. On the basis of this evidence, the use of pre-operative CHO drinks should be standard in elective colorectal patients. Further research is nevertheless required for those with diabetes mellitus.

Optimal management of peripheral arterial disease for the non-specialist.

Peripheral arterial disease (PAD) now affects approximately 20% of adults older than 55 years to an estimated total of 27 million people in the Western World. The aim of this paper is to describe the medical management of PAD for the non-vascular specialist, particularly general practitioners, where PAD has now been included in the Northern Ireland Department of Health's Primary Care Service Framework (Directed Enhanced Service).

Bone turnover markers in postmenopausal breast cancer treated with fulvestrant--a pilot study.

BACKGROUND: Tamoxifen has a protective effect on bone metabolism in breast cancer; aromatase inhibitors deleterious and that of fulvestrant is unknown. METHODS: Fourteen locally advanced breast cancers with clinical benefit on fulvestrant (250 mg/month) as first-line primary endocrine therapy had sequential serum bone-specific alkaline phosphatase (BAP), N-terminal propeptide of procollagen type 1 (PINP) and C-terminal telopeptide (CTX) at 0, 1, 6, 12, and 18 months. Mean percentage changes (95% CI) were calculated. RESULTS: Changes from baseline at 1, 6, 12, and 18 months with BAP (3.9-46.8 ng/ml) were +1.5 (-9.8 to +12.9), +2.2 (-22.1 to +26.6), +17.6 (-12.4 to +47.6), +10.8 (-29.9 to +51.7); with PINP (20.6-82.1 ng/ml) were +3.4 (-12.0 to 19.0), +18.8 (-36.7 to +74.2), +47.5 (-21.4 to 116.3), +33.3 (-49.5 to +116.1) and with CTX (0.14-1.35 ng/ml) were +30.8 (0.1 to +61.6), +13.9 (-22.3 to +50.2), +42.9 (-12.7 to +98.5), +45.2 (-28.3 to +118.8). CONCLUSIONS: Long-term (18 months) stability of bone markers may be exploited by using fulvestrant earlier in sequence of endocrine therapies particularly in adjuvant setting in those with pre-existing decreased bone mass.

Endometrial adenocarcinoma: an analysis of treatment and outcome.

This study aims to review the survival and morbidity in patients treated for endometrial cancer, at a single centre and analyses the effects of co-morbidity on these outcomes. Case notes of all patients referred to the Christie Hospital with endometrial carcinoma from January 1, 1993 to December 31, 1995 (n=499) were reviewed. Twenty patients presented with recurrence and were not included in this analysis. Three hundred and seventy-five patients had previously undergone a total abdominal hysterectomy and bilateral salpingoophorectomy (+/- pelvic lymphadenectomy). Of these, 175 received adjuvant external beam radiotherapy (XRT) only, 49 received XRT and brachytherapy, 30 received brachytherapy alone and 121 patients had no further therapy. One hundred and four patients were referred for primary treatment. Radical radiotherapy was administered to 63 patients who were unfit for surgery, with 10 of these receiving XRT + brachytherapy and 53 receiving brachytherapy alone. Thirteen patients received palliative XRT and 28 supportive care only. The overall 5-year survival for those treated radically was 73.3%. There was no significant survival difference between patients who underwent surgery and adjuvant radiotherapy, in whatever form (p=0.115). Patients who did not undergo surgery did less well as a group, although there was no significant survival difference between those treated with combination therapy or brachytherapy alone (p=0.33). Survival was significantly associated with FIGO stage, tumour grade, age (especially those >75 years) and co-morbidity (ACE-27 score). Late morbidity occurred in 46 patients, with severe toxicity affecting 12 (3.8%). Toxicity was associated with ACE-27 score (p=0.0019), treatment dose and modality, with 50% (n=6) of severe toxicity seen in patients receiving adjuvant XRT + ICT. These data demonstrate that survival in patients with endometrial carcinoma treated radically remains good, with the stage and grade of tumour being significant factors for overall survival. The incidence of severe morbidity related to radiotherapy of any modality was 3.8%. A high co-morbidity (ACE-27) score was significantly associated with poorer survival (p<0.0055) and increased late treatment morbidity (p=0.0019).

Role of endovenous laser treatment in the management of chronic venous insufficiency.

Endovenous laser therapy (EVLT) is a recognized option in the treatment of uncomplicated varicose veins. This uncontrolled case series evaluates its effectiveness in the management of chronic venous insufficiency. Patients with a history of active or healed ulcers were selected for EVLT. The procedure was carried out in an outpatient setting over a period of 12 months. Assessment was carried out for evidence of ulcer healing and recurrence, long saphenous vein occlusion, and patient satisfaction at 3, 12, and 22 months. Results are expressed as means with range. EVLT was used to treat 23 limbs in 20 patients with a median age of 59 years (range 32-76) including 12 females and eight males. All patients had evidence of chronic venous insufficiency, graded at C5 or greater on the CEAP classification (C5 16, C6 7). Patients with long saphenous vein insufficiency were included, whereas those with either deep or combined deep and superficial venous incompetence were excluded. The cumulative 3-, 12-, and 22-month healing rates were 87% (20/23), 100% (23/23), and 95% (21/22), respectively. The only patient having a recurrence of ulcers at 22 months' follow-up (CEAP 6) had mid-calf perforator incompetence with recanalized long saphenous vein. Duplex scan demonstrated long saphenous vein occlusion in 100% (23/23), 96% (22/23), and 91% (20/22) at 3, 12, and 22 months, respectively. In all, 84% (16/19) of patients were satisfied with the results of treatment without any major procedure-related complication. These results demonstrate that EVLT, carried out in an outpatient setting, is effective in the treatment and prevention of chronic venous ulcers, with good patient satisfaction and no major complication.

The low prevalence of abdominal aortic aneurysm in relatives in Northern Ireland.

INTRODUCTION: Mortality from ruptured abdominal aortic aneurysm (AAA) remains high and has given impetus to screening. Targeted screening towards high-risk groups would increase efficacy. Relatives of previous AAA patients have been suggested as one such group. The aim of this study was therefore to determine the prevalence of AAA in relatives of previous patients in Northern Ireland. PATIENTS AND METHODS: All living AAA patients, who underwent surgery between August 2001 and December 2005 in our unit, or were attending for follow-up of small aneurysms were contacted and asked for details of siblings and their family history. Screening by ultrasound was offered to the siblings and children over 50 years, with a defining threshold diameter for an aneurysm of 3.0 cm. Overall prevalence of AAA in the relatives was calculated. Separate prevalence rates were calculated according to relationship and gender of the patient and relative. RESULTS: 513 previous patients were contacted. 132 gave details of living relatives, resulting in a total of 405 relatives suitable for screening. 105 declined a scan, leaving 300 in the study. Overall mean age of the group was 63.0+/-8.7 years and 68% were siblings of male patients. Overall ten AAAs were detected by screening, giving a prevalence of 3.3%. No aneurysms were found in the subgroup of children, while the highest prevalence (12.5%) was found in brothers of female patients. 20 additional AAAs were reported in these 132 families, resulting in 14 of the 132 families (10.6%) having two or more members with AAA. CONCLUSION: The prevalence of screening detected AAA in this study is lower than anticipated. The reason is unclear, but demonstrates the multifactorial nature of the aetiology and genetic complexities yet to be unravelled by future research.

Endovenous laser treatment for long saphenous vein incompetence.

BACKGROUND: Endovenous laser treatment is a percutaneous technique used for the treatment of long saphenous vein (LSV) incompetence. This paper presents the results of an uncontrolled case series undertaken to assess the feasibility, safety and efficacy of this technique. METHODS: Some 145 incompetent LSVs in 136 patients with saphenofemoral reflux were treated with endovenous laser. The data were evaluated prospectively. Assessment was carried out at 1 week, 3 and 12 months for LSV occlusion and symptomatic relief. RESULTS: Primary procedural success was achieved in 124 (85.5 per cent) of 145 LSVs. Reasons for primary failure included failed cannulation, failure to pass the guidewire and patient discomfort. At 3 months' follow-up, 105 (89.7 per cent) of 117 veins were totally and nine (7.7 per cent) were partially occluded. At 12 months, 63 (76 per cent) of 83 veins were totally and 15 (18 per cent) were partially occluded. At this stage 73 (88 per cent) of 83 patients remained satisfied, but 26 (31 per cent) had residual or recurrent varicosities. Of these, only five required further treatment. Complications included saphenous nerve injury in one patient and superficial skin burns in a second. CONCLUSION: Endovenous laser treatment for LSV reflux is safe and can be carried out under local anaesthesia in an outpatient setting with good patient satisfaction and low complication rates.

Changes in bone mineral density, body composition and biochemical markers of bone turnover during weight gain in adolescents with severe anorexia nervosa: a 1-year prospective study.

Osteoporosis is a serious complication of anorexia nervosa and in affected adolescents may result in a permanent deficit in bone mass. The pathophysiology of this bone disease has not been clearly defined. In this prospective study of 26 young women with anorexia nervosa aged 13-20 years (mean 16.5) we have measured changes in bone mineral density, total body composition and biochemical indices of bone turnover over 1 year. Over this period there was a mean weight gain of 10 kg and significant height gain with baseline and final values for body mass index of 14.2+/-1.7 and 17.6+/-2.3 kg/m2 (P<0.001). However, no significant changes were seen in bone mineral density in the spine or proximal femur during the study; total body bone mineral content was significantly higher than baseline at 3 months and 12 months (P=0.001 and P<0.0001), but total body bone mineral density at 3 months was significantly lower than baseline (P=0.003). Serum osteocalcin and bone-specific alkaline phosphatase values increased significantly and remained higher than baseline at all time points whereas urinary NTX/creatinine excretion showed a non-significant increase over the first 6 months of the study, but at 12 months, the mean value was significantly lower than baseline. Mean serum 25-hydroxyvitamin D levels showed a significant decrease at 6 months (P<0.05), but returned towards baseline thereafter. There was a significant increase in serum parathyroid hormone levels at all time points compared to baseline, these occurring within the normal range. These results indicate that although weight gain in young anorexics is associated with linear growth, bone mineral density does not increase. Whether this deficit can be corrected subsequently requires longer-term prospective studies.

The effect of pravastatin on intima media thickness of the carotid artery in patients with normal cholesterol.

OBJECTIVE: Carotid intima media thickness (IMT) is a good indicator of the severity of atherosclerotic disease. Statins have been found to reduce carotid IMT in patients with hypercholesterolaemia. The aim of this study was to investigate if pravastatin is effective in reducing IMT in normocholesterolaemic patients with carotid artery disease. METHODS: Patients with carotid artery stenosis and normal cholesterol levels who were not on a statin, were recruited. Patients were randomised to receive pravastatin or placebo daily. Serum concentration of cholesterol and IMT of common carotid arteries were measured before randomisation and at 3 monthly intervals thereafter, for 9 months. IMT was analysed to give the mean of a standardised 2 cm of the common carotid artery (CCA). Results are expressed as median (IQR) and comparison made using the Wilcoxon signed ranks test. RESULTS: Fifty-four patients were examined. Twenty-eight patients were randomised to active treatment. There was no difference in demographic details and co-morbid states between the two groups. A significant reduction in cholesterol concentration was observed from 3 months in patients randomised to the pravastatin group [5.14(4.72-5.88) vs. 4.11(3.44-5.33), p < 0.05], while there was also a significant decrease in combined IMT form 6 months [1.53(1.36-1.87) vs. 1.41 (1.33-1.78), p < 0.05]. CONCLUSIONS: The results demonstrate that pravastatin reduces intima media thickness of the common carotid artery in normocholesterolaemic patients with moderate carotid stenosis.

Endovascular repair of abdominal aortic aneurysm in a patient with renal transplant.

Patients with functioning renal transplant who develop abdominal aortic aneurysm can safely be treated with endovascular repair. Endovascular repair of aneurysm avoids renal ischemia associated with cross-clamping of aorta.

Relationship of early changes in bone resorption to the reduction in fracture risk with risedronate.

Changes in the level of biochemical markers of bone resorption with risedronate treatment for osteoporosis were examined as a surrogate for the decrease in fracture risk. Greater decreases in bone resorption markers were associated with greater decreases in vertebral (and nonvertebral) fractures. Antifracture efficacy of antiresorptive therapies is only partially explained by increases in bone mineral density. Early decreases in bone resorption may also play a role. We tested this hypothesis by measuring two bone resorption markers, the C-telopeptide of type I collagen (CTX) and the N-telopeptide of type I collagen (NTX), in osteoporotic patients in risedronate vertebral fracture trials. We studied 693 women with at least one vertebral deformity (mean age, 69 +/- 7 years) who received calcium (and vitamin D if required) and placebo or risedronate 5 mg daily for 3 years. The reductions in urinary CTX (median, 60%) and NTX (51%) at 3-6 months with risedronate therapy were significantly associated (p < 0.05) with the reduction in vertebral fracture risk (75% over 1 year and 50% over 3 years). The changes in both CTX and NTX accounted for approximately one-half (CTX, 55%; NTX, 49%) of risedronate's effect in reducing the risk of vertebral fractures in the first year and approximately two-thirds (CTX, 67%; NTX, 66%) over 3 years compared with placebo. The changes in CTX and NTX accounted for 77% and 54%, respectively, of risedronate's effect in reducing the risk of nonvertebral fractures over 3 years compared with placebo. The relationships between vertebral fracture risk and changes from baseline in CTX and NTX were not linear (p < 0.05). There was little further improvement in fracture benefit below a decrease of 55-60% for CTX and 35-40% for NTX. The decrease in bone resorption in patients taking risedronate accounts for a large proportion of the reduction in fracture risk. There may be a level of bone resorption reduction below which there is no further fracture benefit.