Effect of colon cancer and surgical resection on skeletal muscle mitochondrial enzyme activity in colon cancer patients: a pilot study.

BACKGROUND: Colon cancer (CC) patients commonly suffer declines in muscle mass and aerobic function. We hypothesised that CC would be associated with reduced muscle mass and mitochondrial enzyme activity and that curative resection would exacerbate these changes. METHODS: We followed age-matched healthy controls and CC patients without distant metastasis on radiological imaging before and 6 weeks after hemi-colectomy surgery. Body composition was analysed using dual energy X-ray absorptiometry. Mitochondrial enzyme activity and protein concentrations were analysed in vastus lateralis muscle biopsies. RESULTS: In pre-surgery, there were no differences in lean mass between CC patients and age-matched controls (46.1 + 32.5 vs. 46.1 + 37.3 kg). Post-resection lean mass was reduced in CC patients (43.8 + 30.3 kg, P < 0.01). When comparing markers of mitochondrial function, the following were observed: pyruvate dehydrogenase (PDH) activity was lower in CC patients pre-surgery (P < 0.001) but normalized post-resection and cytochrome c oxidase and pyruvate dehydrogenase E2 subunit protein expression were lower in CC patients pre-surgery and not restored to control values post-resection (P < 0.001). Nuclear factor kappa-B, an inflammatory marker, was higher in CC patients pre-surgery compared to controls (P < 0.01), returning to control levels post-resection. CONCLUSION: Muscle mass was affected by surgery rather than cancer per se. PDH activity was however lower in cancer patients, suggesting that muscle mass and mitochondrial enzyme activity are not inextricably linked. This reduction in mitochondrial enzyme activity may well contribute to the significant risks of major surgery to which CC patients are exposed.

Effect of tumor burden and subsequent surgical resection on skeletal muscle mass and protein turnover in colorectal cancer patients.

BACKGROUND: Cachexia is a consequence of tumor burden caused by ill-defined catabolic alterations in muscle protein turnover. OBJECTIVE: We aimed to explore the effect of tumor burden and resection on muscle protein turnover in patients with nonmetastatic colorectal cancer (CRC), which is a surgically curable tumor that induces cachexia. DESIGN: We recruited the following 2 groups: patients with CRC [n = 13; mean ± SEM age: 66 ± 3 y; BMI (in kg/m(2)): 27.6 ± 1.1] and matched healthy controls (n = 8; age: 71 ± 2 y; BMI: 26.2 ± 1). Control subjects underwent a single study, whereas CRC patients were studied twice before and ~6 wk after surgical resection to assess muscle protein synthesis (MPS), muscle protein breakdown (MPB), and muscle mass by using dual-energy X-ray absorptiometry. RESULTS: Leg muscle mass was lower in CRC patients than in control subjects (6290 ± 456 compared with 7839 ± 617 g; P < 0.05) and had an additional decline after surgery (5840 ± 456 g; P < 0.001). Although postabsorptive MPS was unaffected, catabolic changes with tumor burden included the complete blunting of postprandial MPS (0.038 ± 0.004%/h in the CRC group compared with 0.065 ± 0.006%/h in the control group; P < 0.01) and a trend toward increased MPB under postabsorptive conditions (P = 0.09). Although surgical resection exacerbated muscle atrophy (-7.2%), catabolic changes in protein metabolism had normalized 6 wk after surgery. The recovery in postprandial MPS after surgery was inversely related to the degree of muscle atrophy (r = 0.65, P < 0.01). CONCLUSIONS: CRC patients display reduced postprandial MPS and a trend toward increased MPB, and tumor resection reverses these derangements. With no effective treatment of cancer cachexia, future therapies directed at preserving muscle mass should concentrate on alleviating proteolysis and enhancing anabolic responses to nutrition before surgery while augmenting muscle anabolism after resection.

Sarcopenia, dynapenia, and the impact of advancing age on human skeletal muscle size and strength; a quantitative review.

Changing demographics make it ever more important to understand the modifiable risk factors for disability and loss of independence with advancing age. For more than two decades there has been increasing interest in the role of sarcopenia, the age-related loss of muscle or lean mass, in curtailing active and healthy aging. There is now evidence to suggest that lack of strength, or dynapenia, is a more constant factor in compromised wellbeing in old age and it is apparent that the decline in muscle mass and the decline in strength can take quite different trajectories. This demands recognition of the concept of muscle quality; that is the force generating per capacity per unit cross-sectional area (CSA). An understanding of the impact of aging on skeletal muscle will require attention to both the changes in muscle size and the changes in muscle quality. The aim of this review is to present current knowledge of the decline in human muscle mass and strength with advancing age and the associated risk to health and survival and to review the underlying changes in muscle characteristics and the etiology of sarcopenia. Cross-sectional studies comparing young (18-45 years) and old (>65 years) samples show dramatic variation based on the technique used and population studied. The median of values of rate of loss reported across studies is 0.47% per year in men and 0.37% per year in women. Longitudinal studies show that in people aged 75 years, muscle mass is lost at a rate of 0.64-0.70% per year in women and 0.80-00.98% per year in men. Strength is lost more rapidly. Longitudinal studies show that at age 75 years, strength is lost at a rate of 3-4% per year in men and 2.5-3% per year in women. Studies that assessed changes in mass and strength in the same sample report a loss of strength 2-5 times faster than loss of mass. Loss of strength is a more consistent risk for disability and death than is loss of muscle mass.

An unusual cause of dysuria.

Laparoscopic adjustable gastric band (LAGB) insertion has become an increasingly common treatment for severe obesity worldwide. As a consequence, LAGB complications are reported in increasing numbers and usually present to acute surgical units. This report describes the development of lower abdominal pain and dysuria in a patient who had undergone LAGB surgery 20 months previously. Repeated symptomatic treatment for a possible urinary tract infection in the community setting had been unsuccessful. The cause was found to be a fracture in the tubing connecting the LAGB device with its subcutaneous adjusting port, which was causing persistent bladder irritation. It is recommended that when LAGB patients present with acute lower abdominal pain, consideration should be made as to whether a tubing disconnection has occurred. Such a complication may be visualised by abdominal radiography. Advice can be sought on this and other complications of bariatric surgery by contacting the regional bariatric surgical centre where definitive management would be undertaken.

Antibiotic therapy for prophylaxis against infection of pancreatic necrosis in acute pancreatitis.

BACKGROUND: Pancreatic necrosis may complicate severe acute pancreatitis, and is detectable by computed tomography (CT). If it becomes infected mortality increases, but the use of prophylactic antibiotics raises concerns about antibiotic resistance and fungal infection. OBJECTIVES: To determine the efficacy and safety of prophylactic antibiotics in acute pancreatitis complicated by CT proven pancreatic necrosis. SEARCH STRATEGY: Searches were updated in November 2008, in The Cochrane Library (Issue 2, 2008), MEDLINE, EMBASE, and CINAHL. Conference proceedings and references from found articles were also searched. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing antibiotics versus placebo in acute pancreatitis with CT proven necrosis. DATA COLLECTION AND ANALYSIS: Primary outcomes were mortality and pancreatic infection rates. Secondary end-points included non pancreatic infection, all sites infection, operative rates, fungal infections, and antibiotic resistance. Subgroup analyses were performed for antibiotic regimen (beta-lactam, quinolone, and imipenem). MAIN RESULTS: Seven evaluable studies randomised 404 patients. There was no statistically significant effect on reduction of mortality with therapy: 8.4% versus controls 14.4%, and infected pancreatic necrosis rates: 19.7% versus controls 24.4%. Non-pancreatic infection rates and the incidence of overall infections were not significantly reduced with antibiotics: 23.7% versus 36%; 37.5% versus 51.9% respectively. Operative treatment and fungal infections were not significantly different. Insufficient data were provided concerning antibiotic resistance.With beta-lactam antibiotic prophylaxis there was less mortality (9.4% treatment, 15% controls), and less infected pancreatic necrosis (16.8% treatment group, 24.2% controls) but this was not statistically significant. The incidence of non-pancreatic infections was non-significantly different (21% versus 32.5%), as was the incidence of overall infections (34.4% versus 52.8%), and operative treatment rates. No significant differences were seen with quinolone plus imidazole in any of the end points measured. Imipenem on its own showed no difference in the incidence of mortality, but there was a significant reduction in the rate of pancreatic infection (p=0.02; RR 0.34, 95% CI 0.13 to 0.84). AUTHORS' CONCLUSIONS: No benefit of antibiotics in preventing infection of pancreatic necrosis or mortality was found, except for when imipenem (a beta-lactam) was considered on its own, where a significantly decrease in pancreatic infection was found. None of the studies included in this review were adequately powered. Further better designed studies are needed if the use of antibiotic prophylaxis is to be recommended.

A pre-operative elevated neutrophil: lymphocyte ratio does not predict survival from oesophageal cancer resection.

BACKGROUND: Elevated pre-operative neutrophil: lymphocyte ratio (NLR) has been identified as a predictor of survival in patients with hepatocellular and colorectal cancer. The aim of this study was to examine the prognostic value of an elevated preoperative NLR following resection for oesophageal cancer. METHODS: Patients who underwent resection for oesophageal carcinoma from June 1997 to September 2007 were identified from a local cancer database. Data on demographics, conventional prognostic markers, laboratory analyses including blood count results, and histopathology were collected and analysed. RESULTS: A total of 294 patients were identified with a median age at diagnosis of 65.2 (IQR 59-72) years. The median pre-operative time of blood sample collection was three days (IQR 1-8). The median neutrophil count was 64.2 x 10-9/litre, median lymphocyte count 23.9 x 10-9/litre, whilst the NLR was 2.69 (IQR 1.95-4.02). NLR did not prove to be a significant predictor of number of involved lymph nodes (Cox regression, p = 0.754), disease recurrence (p = 0.288) or death (Cox regression, p = 0.374). Furthermore, survival time was not significantly different between patients with high (>or= 3.5) or low (< 3.5) NLR (p = 0.49). CONCLUSION: Preoperative NLR does not appear to offer useful predictive ability for outcome, disease-free and overall survival following oesophageal cancer resection.

E-learning in surgical education and training.

For most surgeons and surgical educators, e-learning is relatively new and confusing. This article attempts to explain the key concepts behind e-learning, as well as its benefits and risks. E-learning has become a fixed feature within Higher and Professional Education and has been prioritized by Universities around the world, as well as all six Surgical Royal Colleges. Trainees have grown up with virtual learning environments and expect similar provision for their postgraduate studies, but have a greater need for basic science learning. Dispersal of trainees across duty rotas and geographically makes e-learning more attractive, but preserving peer and trainer communication is as important as content. Recent changes in surgical education and training have also made electronic and distance learning more attractive than previously. Initial work by the Colleges is now being evaluated and important lessons have emerged. The UK Department of Health has made medical e-learning a priority and it is now the largest e-learning provider in Europe. Changes in the World Wide Web, with a shift to more social-networking activity in education and to web-based delivery to small, ubiquitous portable devices will increase opportunities for surgical e-learning.

Management of infected pancreatic necrosis.

The past two decades have seen major advances in the understanding and clinical management of acute pancreatitis, yet it still lacks a specific treatment, and management is largely supportive and reactive. Surgery is seeing a diminishing role in the early phase of acute pancreatitis but still predominates in the management of infected pancreatic necrosis--the most lethal complication. This review focuses on recent literature but begins with an account of the evolution of infected necrosis management, which serves to place current treatment into context. Although surgeons initially emphasized less invasive approaches to pancreatic necrosis, they now compete with new techniques developed by pioneering physicians, radiologists, and interventional endoscopists. Clinicians adopting the new techniques will need to emulate the dedication and commitment that the current pioneers demonstrate. Although new techniques are still evolving, they should be evaluated against existing standards of treatment.

Large bowel obstruction due to sesame seed bezoar: a case report.

We report a case of a 79 year old man with a known benign anastomotic stricture presenting with large bowel obstruction. At laparotomy the obstruction was found to be caused by a large sesame seed bezoar. Seed bezoars are well known to cause impaction in the rectum but have never been previously reported to cause large bowel obstruction. We recommend that patients with known large bowel strictures should be advised not to eat seeds as this could ultimately lead to obstruction, ischaemia or perforation.

Hypocalcemia in patients with acute pancreatitis: a putative role for systemic endotoxin exposure.

INTRODUCTION: Hypocalcemia is not uncommon during acute pancreatitis and is associated with a poor outcome. Whilst the mechanisms responsible for its development remain unclear, there is evidence to implicate endotoxemia in other models of sepsis. AIM: To investigate the potential role of systemic endotoxin exposure in the development of hypocalcemia in patients with acute pancreatitis. METHODOLOGY: Adjusted serum calcium was measured daily, and the lowest value within 72 hours of admission for acute pancreatitis was determined. Serum endotoxin and both IgG and IgM antiendotoxin core antibodies (EndoCAbs) were measured on admission. Attacks were classified as mild (n = 51) or severe (n = 21) according to the criteria of the Atlanta International Symposium of 1992. RESULTS: Hypocalcemia was significantly more frequent (86% versus 39%, p < 0.001) and reached significantly lower levels during severe attacks than during mild attacks (median [interquartile range], 2.06 [1.78-2.17] mmol/L, versus 2.23 [2.15-2.30] mmol/L; p < 0.001). Endotoxemia was present in a significantly greater proportion of patients with severe disease (71% versus 41%; p = 0.037), and serum IgM and IgG EndoCAbs were significantly depleted during severe attacks in comparison with mild attacks (p = 0.007 and p = 0.039, respectively). A negative and significant correlation was observed between endotoxemia and both the admission and lowest serum concentrations of adjusted calcium (r = -0.424 and p = 0.022; r = -0.383 and p = 0.037, respectively), and the latter correlated significantly with serum IgG EndoCAb concentrations (r = 0.251; p = 0.036). CONCLUSION: Systemic endotoxin exposure appears to play a significant role in the development of hypocalcemia in patients with acute pancreatitis.