Tissue-specific inflammation and insulin sensitivity in subjects with obesity.

Obesity is associated with low-grade inflammation and insulin resistance (IR). The contribution of adipose tissue (AT) and hepatic inflammation to IR remains unclear. We conducted a study across three cohorts to investigate this relationship. The first cohort consists of six women with normal weight and twenty with obesity. In women with obesity, we found an upregulation of inflammatory markers in subcutaneous and visceral adipose tissue, isolated AT macrophages, and the liver, but no linear correlation with tissue-specific insulin sensitivity. In the second cohort, we studied 24 women with obesity in the upper vs lower insulin sensitivity quartile. We demonstrated that several omental and mesenteric AT inflammatory genes and T cell-related pathways are upregulated in IR, independent of BMI. The third cohort consists of 23 women and 18 men with obesity, studied before and one year after bariatric surgery. Weight loss following surgery was associated with downregulation of multiple immune pathways in subcutaneous AT and skeletal muscle, alongside notable metabolic improvements. Our results show that obesity is characterised by systemic and tissue-specific inflammation. Subjects with obesity and IR show a more pronounced inflammation phenotype, independent of BMI. Bariatric surgery-induced weight loss is associated with reduced inflammation and improved metabolic health.

Impact of Body Composition on Surgical Outcome in Rectal Cancer Patients, a Retrospective Cohort Study.

BACKGROUND: Obesity is becoming a bigger health problem every year. Current research shows that the obesity-related metabolic problems are strongly associated with visceral fat and not subcutaneous fat. Visceral obesity (VO) is associated with a worse postoperative outcome in multiple fields of abdominal surgery. On the other hand, muscle mass is related to better postoperative outcome. In rectal cancer patients, we studied the influence of visceral obesity and muscle mass on postoperative complications. METHODS: The visceral fat area (VFA) and skeletal muscle area (SMA) were determined on preoperative CT scans in 406 patients. The preoperative comorbidity, per-operative outcome and postoperative complications were extracted retrospectively from the patient files. VO was defined as a VFA > 100 cm2. Correlations between body composition, postoperative complications and LOS were studied. RESULTS: In our study, 67% of the patients were classified as visceral obese. Mean body mass index (BMI) was higher in the VO group (26.6 ± 3.5 vs 23.5 ± 2.8; p < 0.001). Visceral obese patients had a higher prevalence of cardiac comorbidity (29% vs 13% p = 0.001), hypertension (36% vs 20% p = 0.002) and diabetes mellitus (16% vs 5% p = 0.002). In addition, VO patients had more operative blood loss (431 vs 310 mL; p = 0.008), longer operating time (166 vs 149 min p = 0.003) and more wound infections (14% vs 8% p = 0.048). Visceral obesity was associated with more complications (OR: 1.63 p = 0.043) and longer LOS (risk estimate: 1.18 p = 0.009). CONCLUSION: VO patients more often had a history of cardiac disease, hypertension and diabetes mellitus. Visceral obesity correlated with a worse outcome after surgery for rectal cancer.

Mini Nutritional Assessment and Mortality after Hip Fracture Surgery in the Elderly.

BACKGROUND: Hip fracture surgery in elderly patients is associated with a poor postoperative outcome and a high mortality. Malnutrition is a frequent problem in elderly patients and may be associated with mortality after hip fracture surgery. The Mini Nutritional Assessment (MNA) is a valuable tool to identify malnourished patients and those at risk for malnutrition. OBJECTIVE: To evaluate the association between the preoperative MNA score and mortality after surgery for hip fractures in elderly patients. METHODS: Patients with a hip fracture and an indication for surgery were included in our study. This study was part of a randomized trial on the effect of taurine on postoperative outcome in elderly hip fracture patients. The MNA was assessed on admission before surgery. Length of stay, postoperative complications and mortality were documented. The association of the MNA score on postoperative outcome and mortality was analyzed using Cox regression analysis. RESULTS: The one-year survival rate in 226 elderly hip fracture patients was 79%. In-hospital mortality rates and 1-year mortality were 27% and 46% in malnourished patients, 12% and 26% in patients at risk for malnutrition and 7% and 17% in well-nourished patients as assessed by MNA. CONCLUSION: Preoperative malnutrition measured by the MNA is associated with mortality in elderly hip fracture patients.

Dexa Body Composition Assessment in 10-11 Year Healthy Children.

INTRODUCTION: Obesity is a growing health problem associated with metabolic derangements and cardiovascular disease. Accumulating evidence links the accumulation of visceral adipose tissue (VAT) to these obesity related health risks in adults. Childhood obesity is associated with a lifetime risk of cardiovascular disease and poses a serious challenge to future health care. In children, there is much less data on the prevalence and gender differences of visceral obesity than in adults. This study aims to provide reference values for VAT in children 10-11 years of age. METHODS: In a cross-sectional study performed in the north western part of theNetherlands, healthy children of 10-11 years of age, were recruited from primary schools. Anthropometric data consisting of height, weight, waist circumference (WC) and BMI were measured. Body composition was measured using DXA, providing measures for bone mineral content, total fat mass (TFM), lean body mass (LBM) and VAT. RESULTS: 217 children were eligible for this study. Girls appeared to have a greater TFM (31.4% vs 27.5% of total body weight (TBW); P < .01) but lower VAT (0.3% vs 0.5% of TBW;P < .01) than boys, whereas boys had higher LBM (65.4% vs 69.3% TBW;P < .01). Median VAT area (cm2) was 41.1 for boys and 22.4 for girls (P < .01). Moderate to strong correlations were found for WC and BMI with VAT (boys: r = .664 and r = .630; Girls r = .699 and r = .546 respectively all P < .001). DISCUSSION: This study shows gender specific differences in VAT percentiles in healthy non-obese 10-11 year old children as measured by DXA that may serve as reference values in children. Independent of BMI and WC, girls tend to have more TFM but less VAT and LBM than boys.

An unexpected finding in the resection specimen of a carcinoma of the oral cavity: A case report.

INTRODUCTION: The occurrence of two synchronous, primary cancers is rare. Thyroid carcinoma is incidentally found in the resection specimen after surgery for head and neck cancer in 0.3-1.9% of the patients. PRESENTATION OF CASE: In this report, we describe the case of a 72-year-old patient in whom a primary (synchronous) papillary thyroid carcinoma was found coincidentally upon pathologic examination of lymph nodes recovered from the cervical neck lymph node dissection specimen after a 'commando' procedure for carcinoma of the oral cavity. DISCUSSION AND CONCLUSION: There is no gold standard concerning treatment of the incidentally discovered thyroid gland carcinoma. The decision to perform surgery depends on the life expectancy of the patient, whether the thyroid gland demonstrates clinical or radiologic lesions, the already completed treatment for the head and neck cancer and should always be adjusted to the specific patient.

Preoperative Methods to Reduce Liver Volume in Bariatric Surgery: a Systematic Review.

BACKGROUND: Patients qualified for gastric bypass surgery have an enlarged and fatty liver. An essential step in gastric bypass surgery is elevation of the left liver lobe to expose the gastroesophageal junction. An enlarged and fatty liver complicates the surgical procedure and increases the risk for laceration of the liver. The aim of our study was to evaluate methods to reduce liver volume in patients prior to gastric bypass surgery. METHODS: A systematic literature search of multiple databases, including PubMed, EMBASE.com, and the Cochrane Library and a hand search of reference lists, was performed. We used the search terms morbid obesity and liver, including their synonyms and controlled terms. Inclusion criteria were as follows: patients with morbid obesity who qualified for bariatric surgery, the use of a preoperative treatment to reduce liver volume, and the use of imaging techniques before and after treatment. RESULTS: In total, 281 patients in 11 different studies were included. Preoperative diets reduced liver size by an average of 14%, alternative methods including nutritional supplements, reduced liver size between 20 and 43%, and an intragastric balloon by 32%. CONCLUSIONS: This review showed that nutritional supplements and intragastric balloon are more effective than low calorie diets in reducing liver volume prior to gastric bypass surgery. However, low calorie diet is the preferable method to reduce liver volume, considering the level of evidence and practical applicability. There is a need for well-designed randomized studies with sufficient power in order to confirm the effectiveness of preoperative methods to reduce liver volume.

Extensive cervicomediastinal hematoma due to spontaneous hemorrhage of a parathyroid adenoma: a case report.

Spontaneous extracapsular hemorrhage is a rare but potentially life-threatening manifestation of parathyroid gland adenomas. We present a case demonstrating that even in a patient with increased bleeding tendency due to anticoagulants, combined with compression of trachea and esophagus, conservative treatment can be successful.

Eight years of experience with Enhanced Recovery After Surgery in patients with colon cancer: Impact of measures to improve adherence.

BACKGROUND: Perioperative treatment of patients with colorectal cancer according to the Enhanced Recovery After Surgery (ERAS) protocol has proven to reduce complications and duration of stay. However, strict adherence remains a challenge and the benefits may decrease with lower adherence. In this study, we report on 8 years of adherence to the ERAS protocol and its effect on postoperative outcome in patients with colon cancer. METHODS: In 2006, the ERAS protocol was introduced for treatment of colon cancer patients in the Medical Center Alkmaar, a large teaching hospital. Patients scheduled for elective colon cancer resection were included in this study. Adherence to ERAS items was monitored and along with clinical data prospectively gathered in a database. In 2011, several measures to improve adherence were implemented. RESULTS: In total, 816 patients were included. Mean adherence rate was 73% in 2006 and 2007, 66% in 2008 and 2009, 63% in 2010 and 2011, and 82% in 2012 and 2013. There was a shorter duration of stay in the years with high adherence (5.7 days) compared with the years with low adherence (7.3 days; P < .001). The ERAS items that were the strongest predictors for a shorter duration of stay were no nasogastric tube, early mobilization, early oral nutrition, early removal of epidural, early removal of catheter, and nonopioid oral analgesia. CONCLUSION: It is possible to improve adherence to the ERAS protocol and related outcomes with specific measures. Adherence to the ERAS protocol was related inversely to duration of stay. Only postoperative items of the ERAS protocol were predictive for a shorter duration of stay. Keeping adherence optimal remains an ongoing challenge that requires repeated training and dedicated personnel.

Adherence to Enhanced Recovery After Surgery and length of stay after colonic resection.

AIM: The Enhanced Recovery After Surgery (ERAS) programme is a multimodal approach to improve peri-operative care in colon surgery. The aim of this study was to report on the adherence to and outcomes of ERAS in the first years after implementation. METHOD: Data of patients undergoing elective colon resections for malignancy in 2006 until 2010 were compared with patients receiving conventional care in 2005. Retrospective analysis was performed including length of stay (LOS), protocol adherence and complications. The predictive values of ERAS items and baseline characteristics on LOS and complications were analysed using univariate and multivariate analysis. RESULTS: Length of stay (LOS) was significantly shorter in 2006 and 2007 (P ≤ 0.009 and P ≤ 0.004) but not in 2008 and 2009. The mean adherence rate to the ERAS items was 84.1% in 2006 and 2007 and 72.4% in 2008 and 2009 (P < 0.001). In 2005, 2008 and 2009 LOS was significantly shorter for laparoscopically operated patients than for patients with open resections (P < 0.002, P < 0.001 and P < 0.004 respectively). Multivariate analysis showed that age, laparoscopic surgery, removal of nasogastric tube before extubation, mobilization within 24 h after surgery, starting nonsteroidal anti-inflammatory drugs at day 1 and removal of thoracic epidural analgesia at day 2 were independent predictors of LOS. CONCLUSION: Strict adherence to the ERAS protocol was associated with reduced LOS and improved outcome in elective colon surgery for malignancy. These benefits were lost when protocol adherence was lower. Embedding the ERAS protocol into an organization and repetitive education are vital to sustain its beneficial effects on LOS and outcome.

The role of a disturbed arginine/NO metabolism in the onset of cancer cachexia: a working hypothesis.

Cancer cachexia is a complex catabolic state in patients with a malignancy, associated with increased morbidity and mortality. This syndrome is characterized by a redistribution of the body's protein content and a subsequent muscle wasting. The aetiology of this syndrome seems multifactorial, but remains unclear. It is suggested that this catabolic state occurs in response to the alterations in immune interactions between tumor and host. The amino acid arginine and its derivate nitric oxide (NO) play various roles in anti-tumor immune response and the body's homeostasis. Glutamine is the precursor for arginine de novo synthesis and the most abundant amino acid in the body, mainly stored in skeletal muscle. Tumors develop a protection mechanism against the specific anti-tumor attack of the immune system by recruiting myeloid derived suppressor cells (MDSC). The MDSC deplete arginine levels and disturb NO production. We here hypothesize that the perturbation of the arginine/NO metabolism plays a significant role in the aetiology of cancer cachexia. Arginine/ NO metabolism is disturbed in patients with cancer. The body will try to correct this perturbation by mobilizing arginine and glutamine from muscles. The decreased arginine levels and the disturbed NO production activate several cascades, which in turn inhibit protein synthesis and promote proteolysis, leading to cachexia. Cachexia remains one of the most frequent and damaging opportunistic syndromes in cancer patients. In this review we will elaborate on a new hypothesised concept and the underlying mechanisms of this syndrome. New studies are essential to ground this hypothesis and to develop interventions to break through the pathological mechanisms underlying cachexia.

Laparoscopically assisted transhiatal resection for malignancies of the distal esophagus.

BACKGROUND: Resection of the esophagus remains the only curative therapy for esophageal cancer. Conventional resections are right-side thoracotomy in combination with laparotomy, gastric tube creation, and the transhiatal approach according to Orringer. This study evaluated laparoscopically assisted transhiatal esophagus resection, which offers perfect visualization of the esophagus during mediastinal dissection without the necessity of a thoracotomy. METHODS: In this study, 25 laparoscopically assisted transhiatal esophagus resections were compared with a historical control group consisting of 20 open transhiatal esophagus resections. RESULTS: Nine laparoscopically assisted resections (36%) were converted to open procedures. The operating time was longer in the laparoscopically assisted group (300 vs 257 min; p < 0.05), but laparoscopically assisted esophagus resection was associated with less blood loss (600 vs 900 ml; p < 0.05) and shorter intensive care unit stay (1 vs 2 days; p < 0.05). There were no differences in morbidity, mortality, and hospital stay. During a shorter follow-up time for the laparoscopic group (17 vs 54 months), 11 patients (44%) in the laparoscopically assisted group and 10 (50%) patients in the open group had recurrence of the disease. CONCLUSIONS: Laparoscopically assisted transhiatal esophagus resection is a safe procedure with important advantages, as compared with the open procedure, such as less blood loss and shorter intensive care unit stay. At this point, the oncologic consequences are not clear.

Primary immune response to keyhole limpet haemocyanin following trauma in relation to low plasma glutamine.

Severe trauma can lead to a compromised immune response, thereby increasing susceptibility to infections. Here we will study to what extent these early changes in the immune status upon trauma affect a primary immune response to keyhole limpet haemocyanin (KLH). Because glutamine is the preferred respiratory substrate for immune competent cells and known to be depleted after trauma, we studied the immune status and the primary sensitization in relation to the glutamine plasma concentration in a group of severe trauma patients [injury severity score (ISS) >17]. Trauma patients (n = 31) were sensitized with KLH within 12 h after trauma; plasma glutamine concentrations and immune parameters were determined, after which KLH-specific immune responsiveness was evaluated on days 9 and 14. Low plasma glutamine concentrations were found after trauma. Significantly elevated numbers of granulocytes and CD14-positive leucocytes were found, whereas the HLA-DR expression on CD14-positive cells was significantly lower in trauma patients than in healthy controls. Trauma did not change the in vitro proliferative capacity of lymphocytes when cultured with glutamine; however, when lymphocytes were cultured without glutamine, trauma resulted in lower proliferation than healthy controls. Phytohaemagglutinin-(PHA)-induced interferon (IFN)-gamma and interleukin (IL)-10 production was significantly lower after trauma, whereas IL-4 production was not affected. KLH sensitization following trauma resulted in poor skin test reactivity and low in vitro KLH-induced lymphocyte proliferation compared to controls. In contrast, the development of anti-KLH IgM, IgG, IgA, IgG1, IgG2, IgG3 and IgG4 production on days 9 and 14 following trauma was not different from that in healthy controls. Major trauma was associated with a reduced cell-mediated immune response, correlating with low plasma glutamine concentrations, while no effects of trauma were found on the development of a primary humoral immune response.