Body composition assessment and sarcopenia in patients with gastric cancer: a systematic review and meta-analysis.

INTRODUCTION: There has recently been increased interest in the assessment of body composition in patients with gastric cancer for the purpose of prognostication. This systematic review and meta-analysis aim to evaluate the current literature on body composition assessment in patients with gastric cancer and its impact on peri-operative outcomes. METHODS: A systematic literature search was conducted for studies reporting assessment of body composition in patients with gastric cancers. Meta-analysis of postoperative outcomes (overall and major complications, anastomotic leaks, pulmonary complications) and survival was performed using random effects models. RESULTS: Thirty-nine studies reported the assessment of body composition in 8402 patients. Methods used to assess body composition in patients with gastric cancers were computerized tomography (n = 26), bioelectrical impedance analysis (n = 9), and dual-energy-X-ray-absorptiometry (n = 3). Only 21 studies reported the impact of pre-operative sarcopenia on post-operative outcomes. Sarcopenic patients have significantly higher rates of postoperative major complications (n = 12, OR 1.67, CI95% 1.14-2.46, p = 0.009), and pulmonary (n = 8, OR 4.01, CI95% 2.23-7.21, p < 0.001) complications after gastrectomy. Meta-analysis of nine studies reporting overall survival after gastrectomy identified significantly worse survival in patients with pre-operative sarcopenia (HR 2.12, CI95% 1.89-2.38, p < 0.001). CONCLUSIONS: Assessment of body composition has the potential to become a clinically useful tool that could support decision-making in patients with gastric cancer. However, variation in methods of assessing and reporting body composition in this patient group limits assessment of current post-operative outcomes.

Correction to: Body composition assessment and sarcopenia in patients with gastric cancer: a systematic review and meta-analysis.

In the original publication of this article, most of the reference citations in Tables 1 and 2 were published incorrectly. The corrected tables are given in this correction.

A Comparison of Mortality Following Emergency Laparotomy Between Populations From New York State and England.

OBJECTIVE: The aim of this study was to compare mortality following emergency laparotomy between populations from New York State and England. SUMMARY OF BACKGROUND DATA: Mortality following emergency surgery is a key quality improvement metric in both the United States and UK. Comparison of the all-cause 30-day mortality following emergency laparotomy between populations from New York State and England might identify factors that could improve care. METHODS: Patient demographics, in-hospital, and 30-day outcomes data were extracted from Hospital Episode Statistics (HES) in England and the New York Statewide Planning and Research Cooperative System (SPARCS) administrative databases for all patients older than 18 years undergoing laparotomy for emergency open bowel surgery between April 2009 and March 2014. The primary outcome measure was all-cause mortality within 30 days of the index laparotomy. Mixed-effects logistic regression was performed to model independent demographic variables against mortality. A one-to-one propensity score matched dataset was created to compare the odd ratios of mortality between the 2 populations. RESULTS: Overall, 137,869 patient records, 85,286 (61.9%) from England and 52,583 (38.1%) from New York State, were extracted. Crude 30-day mortality for patients was significantly higher in the England compared with New York State [11,604 (13.6%) vs 3633 (6.9%) patients, P < 0.001]. Patients undergoing emergency laparotomy in England had significantly higher risk of mortality compared with those in New York State (odds ratio 2.35, confidence interval 2.24-2.46, P < 0.001). CONCLUSION: The risk of mortality at 30 days is higher following emergency laparotomy in England as compared with New York State despite similar patient groups.

A Population-Based Cohort Study of Emergency Appendectomy Performed in England and New York State.

BACKGROUND: To compare selected outcomes (30-day reoperation and total length of hospital stay) following emergency appendectomy between populations from New York State and England. METHODS: This retrospective cohort study used demographic and in-hospital outcome data from Hospital Episode Statistics (HES) and the New York Statewide Planning and Research Cooperative System (SPARCS) administrative databases for all patients aged 18+ years undergoing appendectomy between April 2009 and March 2014. Univariate and adjusted multivariable logistic regression were used to test significant factors. A one-to-one propensity score matched dataset was created to compare odd ratios (OR) of reoperations between the two populations. RESULTS: A total of 188,418 patient records, 121,428 (64.4%) from England and 66,990 (35.6%) from NYS, were extracted. Appendectomy was completed laparoscopically in 77.7% of patients in New York State compared to 53.6% in England (P < 0.001). The median lengths of hospital stay for patients undergoing appendectomy were 3 (interquartile range, IQR 2-4) days versus 2 (IQR 1-3) days (P < 0.001) in England and New York State, respectively. All 30-day reoperation rates were higher in England compared to New York State (1.2 vs. 0.6%, P < 0.001), representing nearly a twofold higher risk of 30-day reoperation (OR 1.88, 95% CI 1.64-2.14, P < 0.001). As the proportion of appendectomy completed laparoscopically increased, there was a reduction in the reoperation rate in England (correlation coefficient -0.170, P = 0.036). CONCLUSIONS: Reoperations and total length of hospital stay is significantly higher following appendectomy in England compared to New York State. Increasing the numbers of appendectomy completed laparoscopically may decrease length of stay and reoperations.

Influence of body composition measures on chyle leak after oesophagectomy.

Background: Chyle leak (CL) is an infrequent but potentially serious complication of oesophagectomy. Sarcopenia is an increasingly recognised prognostic factor in oesophageal cancer surgery. The aim of this study was to identify the influence of body composition measures on CL following oesophagectomy. Methods: Patients who developed CL after oesophagectomy between January 2006-December 2020 were identified retrospectively from a prospectively maintained dataset. A control group of patients undergoing oesophagectomy, who did not experience chyle leak during the same time period, was also collected. Relationships between CL and demographics, operative factors and body composition measures were investigated as primary outcomes. Risk factors for severe CL were evaluated as a secondary outcome. Results: There were 26 patients who developed a CL following an oesophagectomy. On univariate analysis, preoperative body mass index (BMI) (P=0.001), subcutaneous fat index (P=0.001) and total fat index (P=0.004) were significantly associated with CL. On multivariate analysis, a lower preoperative subcutaneous fat index was a significant independent predictor of CL (P=0.003). Sarcopenia, as an overall measure, was not found to be a significant predictor of developing CLs. No significant predictors of severe CL were identified. Conclusions: A reduced preoperative BMI and body fat composition are risk factors for CL after oesophagectomy. Sarcopenia does not predict either the occurrence or severity of CL. This presents potentially modifiable risk factors for CL after oesophagectomy and emphasises the importance of physiological and nutritional optimisation before oesophagectomy.

Critical appraisal on the impact of preoperative rehabilitation and outcomes after major abdominal and cardiothoracic surgery: A systematic review and meta-analysis.

BACKGROUND: There has been increasing interest in the prehabilitation of patients undergoing major abdominal surgery to improve perioperative outcomes. This systematic review and meta-analysis aims to evaluate and compare the current literature on prehabilitation in major abdominal surgery and cardiothoracic surgery METHODS: A systematic literature search was conducted for studies reporting prehabilitation in patients undergoing major abdominal and cardiothoracic surgery. Meta-analysis of postoperative outcomes (overall and major complications, pulmonary and cardiac complications, postoperative pneumonia, and length of hospital stay) was performed using random effects models. RESULTS: Five thousand nine hundred and twenty-one patients underwent prehabilitation in 61 studies, of which 35 studies (n = 3,402) were in major abdominal surgery and 26 studies were in cardiothoracic surgery (n = 2,519). Only 45 studies compared the impact of prehabilitation versus no prehabilitation on postoperative outcomes (abdominal, n = 26; cardiothoracic, n = 19). Quality of evidence for prehabilitation in major abdominal and cardiothoracic surgery appear equivalent. Patients receiving prehabilitation for major abdominal surgery have significantly lower rates of overall (n = 10, odds ratio: 0.61, confidence interval 95%: 0.43-0.86, P = .005), pulmonary (n = 15, odds ratio: 0.41, confidence interval 95%: 0.25-0.67, P < .001), and cardiac complications (n = 4, odds ratio: 0.46, confidence interval 95%: 0.22-0.96, P = .044). Sensitivity analysis including randomized controlled trials only did not alter the findings of this study. CONCLUSION: Prehabilitation has the potential to improve surgical outcomes in patients undergoing major abdominal and cardiothoracic surgery. However, current evidence from randomized studies remains weak owing to variation in prehabilitation regimes, limiting the assessment of current postoperative outcomes.

Conduit necrosis following esophagectomy: An up-to-date literature review.

Esophageal conduit ischaemia and necrosis is an uncommon but devastating complication of esophagectomy and remains one of the most challenging issues in surgical practice. The incidence, time interval to develop symptoms, and clinical presentation are highly variable with no predictable pattern. Evidence comes from case reports and case series rather than randomized controlled trials. We describe the issues surrounding conduit necrosis affecting the stomach, jejunum and colon as an esophageal replacement and the advantages, disadvantages and challenges of each type of reconstruction. Diagnosis is challenging for the most experienced surgeon. Upper gastrointestinal endoscopy and computed tomography thorax with both oral and intravenous contrast is the gold standard. Management, either conservative or interventional is also a difficult decision. Management options include conservative treatment and more aggressive treatments such as stent insertion, surgical debridement and repair of the esophagus using jejunum, colon or a musculocutaneous flap. In spite of recent advances in surgical techniques, there is no reliable strategy to manage esophageal conduit necrosis. Our review covers the pathophysiology and clinical significance of esophageal necrosis while highlighting current techniques of prevention, diagnosis and treatment of this life-threatening condition.

New genetic signatures associated with cancer cachexia as defined by low skeletal muscle index and weight loss.

BACKGROUND: Cachexia affects the majority with advanced cancer. Based on current demographic and clinical factors, it is not possible to predict who will develop cachexia or not. Such variation may, in part, be due to genotype. It has recently been proposed to extend the diagnostic criteria for cachexia to include a direct measure of low skeletal muscle index (LSMI) in addition to weight loss (WL). We aimed to explore our panel of candidate single nucleotide polymorphism (SNPs) for association with WL +/- computerized tomography-defined LSMI. We also explored whether the transcription in muscle of identified genes was altered according to such cachexia phenotype METHODS: A retrospective cohort study design was used. Analysis explored associations of candidate SNPs with WL (n = 1276) and WL + LSMI (n = 943). Human muscle transcriptome (n = 134) was analysed using an Agilent platform. RESULTS: Single nucleotide polymorphisms in the following genes showed association with WL alone: GCKR, LEPR, SELP, ACVR2B, TLR4, FOXO3, IGF1, CPN1, APOE, FOXO1, and GHRL. SNPs in LEPR, ACVR2B, TNF, and ACE were associated with concurrent WL + LSMI. There was concordance between muscle-specific expression for ACVR2B, FOXO1 and 3, LEPR, GCKR, and TLR4 genes and LSMI and/or WL (P < 0.05). CONCLUSIONS: The rs1799964 in the TNF gene and rs4291 in the ACE gene are new associations when the definition of cachexia is based on a combination of WL and LSMI. These findings focus attention on pro-inflammatory cytokines and the renin-angiotensin system as biomarkers/mediators of muscle wasting in cachexia.

Pre-operative serum albumin and neutrophil-lymphocyte ratio are associated with prolonged hospital stay following colorectal cancer surgery.

AIMS: Colorectal cancer is the third most common cancer in European populations. It has been shown previously that neutrophil-lymphocyte ratio (NLR), pre-operative albumin, and haemoglobin are useful prognostic indicators. The aim of this study was to assess how these factors influence the length of postoperative stay (LOS) following colorectal cancer surgery. METHODOLOGY: All patients undergoing elective colorectal resections for malignancy between 2010 and 2011 in Pilgrim Hospital, Boston, U.K. were considered for the study. Hospital archive systems were used to ascertain pre-operative NLR, albumin and haemoglobin levels. LOS was calculated from electronic discharge documents with day 1 being the day after surgery. Unifactorial and multifactorial analyses were performed to identify independent predictors of prolonged stay. RESULTS: 196 patients were included in the study. Pre-operative haemoglobin was not associated with prolonged hospital stay. On univariate analysis, pre-operative serum albumin and pre-operative NLR were associated with prolonged hospital stay. On multivariate analysis, pre-operative serum albumin >34.5 g/dl (odds ratio, 0.47; 95% confidence interval, 0.24 - 0.92; p = 0.027) retained independent association for prolonged hospital stay .However, pre-operative NLR failed to reach statistical significance on multivariate analysis. CONCLUSIONS: Patients with low albumin and elevated NLR are more likely to have an increased hospital stay following colorectal cancer surgery. This may be useful for surgeons in terms of identifying the 'high-risk' patient post-operatively and allow for early intervention.

Absence of correlation between serum CRP levels and mitochondrial D-loop DNA mutations in gastro-oesophageal adenocarcinoma.

INTRODUCTION: Both inflammation and mitochondrial DNA (mtDNA) mutation are thought to play a role in the many human cancers. The aim of this study was to evaluate the relationship between inflammation and accumulation of mitochondrial DNA (mtDNA) mutations in the D-loop region in carcinogenesis of gastro-oesophageal adenocarcinomas. MATERIALS AND METHODS: Blood samples of 20 patients with gastro-oesophageal adenocarcinoma were taken for measurement of serum C-reactive protein (CRP) concentration. Direct sequencing of mtDNA in the D-loop region was done in the 20 adenocarcinoma samples and their corresponding surrounding non-cancerous tissue. Sequences were compared with existing mtDNA databases to identify mutations. RESULTS: mtDNA mutations in the D-loop region occur commonly with almost identical frequency in both non-cancerous tissue (3.0 ± 1.6) and adenocarcinoma (3.1 ± 1.9) (P = 0.916, paired t-test). CRP levels are not predictive of the number of D-loop mutations in both adenocarcinoma (ß: -0.131; 95% CI: -2.354-1.364; P = 0.583) and non-cancerous tissue samples (ß: 0.130; 95% CI: -1.125-1.933; P = 0.586). Five new mutations were identified that were not recorded previously in mtDNA databases. CONCLUSION: D-loop mtDNA mutations are common in both gastro-oesophageal adenocarcinoma and surrounding non-cancerous tissue. However, the accumulation of such mutations appears to occur independent of systemic inflammation. The frequency of D-loop mutations is likely not useful as a marker for carcinogenesis in gastro-oesophageal adenocarcinoma.

P-selectin genotype is associated with the development of cancer cachexia.

The variable predisposition to cachexia may, in part, be due to the interaction of host genotype. We analyzed 129 single nucleotide polymorphisms (SNPs) in 80 genes for association with cachexia based on degree of weight loss (>5, >10, >15%) as well as weight loss in the presence of systemic inflammation (C-reactive protein, > 10 mg/l). 775 cancer patients were studied with a validation association study performed on an independently recruited cohort (n = 101) of cancer patients. The C allele (minor allele frequency 10.7%) of the rs6136 (SELP) SNP was found to be associated with weight loss >10% both in the discovery study (odds ratio (OR) 0.52; 95% confidence intervals (CI), 0.29-0.93; p = 0.026) and the validation study (OR 0.09, 95% CI 0.01-0.98, p = 0.035). In separate studies, induction of muscle atrophy gene expression was investigated using qPCR following either tumour-induced cachexia in rats or intra-peritoneal injection of lipopolysaccharide in mice. P-selectin was found to be significantly upregulated in muscle in both models. Identification of P-selectin as relevant in both animal models and in cachectic cancer patients supports this as a risk factor/potential mediator in cachexia.

Identification of possible genetic polymorphisms involved in cancer cachexia: a systematic review.

Cancer cachexia is a polygenic and complex syndrome. Genetic variations in regulation of the inflammatory response, muscle and fat metabolic pathways, and pathways in appetite regulation are likely to contribute to the susceptibility or resistance to developing cancer cachexia. A systematic search of Medline and EmBase databases, covering 1986-2008 was performed for potential candidate genes/genetic polymorphisms relating to cancer cachexia. Related genes were then identified using pathway functional analysis software. All candidate genes were reviewed for functional polymorphisms or clinically significant polymorphisms associated with cachexia using the OMIM and GeneRIF databases. Genes with variants which had functional or clinical associations with cachexia and replicated in at least one study were entered into pathway analysis software to reveal possible network associations between genes. A total of 184 polymorphisms with functional or clinical relevance to cancer cachexia were identified in 92 candidate genes. Of these, 42 polymorphisms (in 33 genes) were replicated in more than one study with 13 polymorphisms found to influence two or more hallmarks of cachexia (i.e. inflammation, loss of fat mass and/or lean mass and reduced survival). Thirty-three genes were found to be significantly interconnected in two major networks with four genes (ADIPOQ, IL6, NFKB1 and TLR4) interlinking both networks. Selection of candidate genes and polymorphisms is a key element of multigene study design. The present study provides an initial framework to select genes/polymorphisms for further study in cancer cachexia, and to develop their potential as susceptibility biomarkers of developing cachexia.

Cancer cachexia: a systematic literature review of items and domains associated with involuntary weight loss in cancer.

BACKGROUND: The concept of cancer-related anorexia/cachexia is evolving as its mechanisms are better understood. To support consensus processes towards an updated definition and classification system, we systematically reviewed the literature for items and domains associated with involuntary weight loss in cancer. METHODS: Two search strings (cachexia, cancer) explored five databases from 1976 to 2007. Citations, abstracts and papers were included if they were original work, in English/German language, and explored an item to distinguish advanced cancer patients with variable degrees of involuntary weight loss. The items were grouped into the 5 domains proposed by formal expert meetings. RESULTS: Of 14,344 citations, 1275 abstracts and 585 papers reviewed, 71 papers were included (6325 patients; 40-50% gastrointestinal, 10-20% lung cancer). No single domain or item could consistently distinguish cancer patients with or without weight loss or having various degrees of weight loss. Anorexia and decreased nutritional intake were unexpectedly weakly related with weight loss. Explanations for this could be the imprecise measurement methods for nutritional intake, symptom interactions, and the importance of systemic inflammation as a catabolic drive. Data on muscle mass and strength is scarce and the impact of cachexia on physical and psychosocial function has not been widely assessed. CONCLUSIONS: Current data support a modular concept of cancer cachexia with a variable combination of reduced nutritional intake and catabolic/hyper-metabolic changes. The heterogeneity in the literature revealed by this review underlines the importance of an agreed definition and classification of cancer cachexia.

Cytokine gene polymorphisms and susceptibility to cachexia.

PURPOSE OF REVIEW: Cachexia is a progressive deterioration of body habitus associated with chronic diseases. The finding that only a proportion of patients with chronic disease develop cachexia has prompted studies looking for genetic polymorphisms that may underlie differential susceptibility. The aim of this review is to explore how inflammation and gene polymorphisms influence susceptibility to cachexia. RECENT FINDINGS: There has been evidence that certain cytokine gene polymorphisms are associated with cachexia. However, only the IL10 -1082 G allele, which is associated with an increased risk of developing cachexia has been replicated in more than one study. Variation in genes outwith inflammation pathways (e.g. genes involved in protein metabolism) is also likely to contribute the susceptibility of developing cachexia. The insertion/deletion angiotensin converting enzyme (ACE) gene polymorphism has recently been linked with lower lean body mass in cancer patients with cachexia. SUMMARY: Although there is an increasing body of evidence of genetic susceptibility to cachexia, most studies so far have only focussed on a small number of polymorphisms and have small sample sizes. Large-scale candidate gene studies or genome-wide association studies are required to further elucidate the link between genotype and cachexia.

Endoscopic mucosal resection of colorectal polyps in typical UK hospitals.

AIM: To evaluate the outcomes of endoscopic mucosal resection (EMR) for colorectal polyps, with particular regard to procedural complications and recurrence rate, in typical United Kingdom (UK) hospitals that perform an average of about 25 colonic EMRs per year. METHODS: A total of 239 colorectal polyps (≥ 10 mm) resected from 199 patients referred to Rochdale Infirmary, Salford Royal Hospital and Royal Oldham Hospital for EMR between January 2003 and January 2009 were studied. RESULTS: The mean size of polyps resected was 19.6 ± 12.4 mm (range 10-80 mm). The overall major complication rate was 2.1%. Complications were less frequent with non-adenomas compared with the other groups (Pearson's χ(2) test, P < 0.0001). Resections of larger-sized polyps were more likely to result in complications (unpaired t-test, P = 0.021). Recurrence was associated with histology, with carcinoma-in-situ more likely to recur compared with low-grade dysplasia [hazard ratio (HR) 186.7, 95% confidence interval (95% CI): 8.81-3953.02, P = 0.001]. Distal lesions were also more likely to recur compared with right-sided and transverse colon lesions (HR 5.93, 95% CI: 1.35-26.18, P = 0.019). CONCLUSION: EMR for colorectal polyps can be performed safely and effectively in typical UK hospitals. Stricter follow-up is required for histologically advanced lesions due to increased recurrence risk.

A review of mesothelioma information on the World Wide Web.

INTRODUCTION: The Internet is a widely used information resource for patients with mesothelioma. The goal of this study is to assess the content and quality of mesothelioma information presented on the internet using Google as a search engine, as well as to test the hypothesis that more popular sites (i.e., higher Google rank) are of higher quality. METHODS: The top 100 websites appearing in Google using the terms "mesothelioma" were included in the study. Websites were evaluated using (a) JAMA benchmarks (authorship, references, currency, and disclosure), and (b) an Information score (IS) that awarded websites points (0-100) for specific information on various aspects of mesothelioma. RESULTS: Of the top 100 websites identified, 84 websites were suitable for scoring. Only 5 (6.0%) sites met all 4 criteria of the JAMA benchmarks. The mean IS was 23.8 (range, 0-86). There was a weak but significant positive correlation with Google ranking of websites and IS (r = 0.275, p = 0.006). CONCLUSIONS: There is marked variation in the quality, integrity, and currency of the information in educational websites for mesothelioma patients. Google ranking has shown a weak but significant positive correlation to the quality of medical information relating to mesothelioma.

Sarcopenia in an overweight or obese patient is an adverse prognostic factor in pancreatic cancer.

PURPOSE: The average weight-losing pancreatic cancer patient undergoing palliative therapy is frequently overweight rather than underweight, and this can confound conventional measures used for risk stratification. The aim of this study was to evaluate if weight and body composition, specifically sarcopenia, assessed from diagnostic computed tomography (CT) scans, is of prognostic value in patients with pancreatic cancer. The nature and extent of tissue loss over subsequent months was also evaluated. EXPERIMENTAL DESIGN: A total of 111 patients entering a palliative therapy program, who had CT images and had undergone nutritional screening, were studied. In patients for whom follow-up scans were available (n = 44), longitudinal changes in body composition were studied at a mean of 230 +/- 62 and 95 +/- 60 days prior to demise. RESULTS: Sixty-two patients (55.9%) were sarcopenic, 44 (39.6%) were overweight/obese, and 18 (16.2%) were both. Age > or =59 years (hazard ratio, 1.71; 95% confidence interval, 1.10-2.66; P = 0.018), and overweight/obese sarcopenia (hazard ratio, 2.07; 95% confidence interval, 1.23-3.50; P = 0.006) were identified as independent predictors of survival on multivariate analysis. Longitudinal analysis revealed that total fat-free mass index decreased from 15.5 +/- 2.5 kg/m(2) to 14.5 +/- 2.0 kg/m2 (P = 0.002), and total fat mass index decreased from 7.5 +/- 2.0kg/m2 to 6.0 +/- 1.5kg/m2 (P < 0.0001) over 135 days. CONCLUSIONS: Sarcopenia in overweight/obese patients with advanced pancreatic cancer is an occult condition but can be identified using CT scans. This condition is an independent adverse prognostic indicator that should be considered for stratification of patients' entering clinical trials, systemic therapy, or support care programs.

Frequency of the mitochondrial DNA 4977bp deletion in oesophageal mucosa during the progression of Barrett's oesophagus.

PURPOSE: The mechanisms of the progression of Barrett's oesophagus (BO) to oesophageal adenocarcinoma (OA) are poorly understood. The frequency of the 4977bp deletion in mitochondrial DNA (mtDNA) was investigated in specimens ranging from normal oesophageal tissue to OA in order to investigate whether this deletion represents a useful biomarker of disease progression. METHODS: The presence of the 4977bp deletion was screened by PCR amplification from 70 specimens in total. RESULTS: The frequency of specimens with the 4977bp deletion increased in relation to the degree of dysplasia (8.3% in normal squamous epithelium; 15.4% in BO; 40% in low grade dysplasia (LGD); 69.2% in high-grade dysplasia and 90% in para-tumoural tissue). However, the frequency of the deletion reduced sharply in OA specimens (16.7%; p<0.001). CONCLUSION: The mtDNA 4977bp deletion may be useful as a biomarker to detect the severity of dysplasia but not the presence of OA.

Cancer cachexia is associated with the IL10 -1082 gene promoter polymorphism in patients with gastroesophageal malignancy.

BACKGROUND: The genetic predisposition of the host to local or systemic inflammation may contribute to the effect of cancer cachexia. OBJECTIVE: We investigated the relation between cytokine polymorphisms (IL1B -511, IL6 -174, IL10 -1082, TNFA -308, and LTA +252) and markers of nutritional status among patients with gastroesophageal cancer to determine whether any such association was reflected by cytokine concentrations in the tumor or plasma compartments. DESIGN: Patients (n = 203) with a diagnosis of gastroesophageal cancer underwent nutritional assessment (body mass index, anthropometric measures, dysphagia scoring, and estimation of dietary intake). Single nucleotide polymorphism genotyping was performed by TaqMan allelic discrimination genotyping. Serum cytokine and C-reactive protein concentrations were determined by enzyme-linked immunosorbent assay. Tumor tissue cytokine protein concentrations (n = 56) were determined by using the Cytometric Bead Array System. RESULTS: IL10 GG and IL6 CC polymorphisms were associated with elevated serum C-reactive protein concentrations, and the IL6 CC genotype was also associated with elevated tumor tissue cytokine concentrations. At diagnosis, the IL10 GG, but not the IL6, genotype was linked with increased total weight loss: 4.9% for AA, 7.1% for AG, and 12.0% for GG (P = 0.007). Serum C-reactive protein concentrations correlated with increased weight loss (r = 0.24, P < 0.001). Compared with other genotypes, the IL10 GG genotype retained an independent association in determining the extent of weight loss on multivariate analysis (95% CI: 0.52, 3.43; P = 0.008). Possession of the GG allele was associated with a 2.3 times increased risk of developing cachexia (95% CI: 1.2, 4.3; P = 0.014). CONCLUSION: These data suggest that the IL10 genotype of the host can influence the development of cachexia among patients with gastroesophageal malignancy.

Cachexia: prevalence and impact in medicine.

PURPOSE OF REVIEW: Cachexia is a progressive deterioration of body habitus associated with certain chronic diseases (e.g., cancer, chronic obstructive pulmonary disease, chronic heart failure, and chronic kidney disease). The aim of this article is to describe the prevalence and impact of cachexia (and precachexia) in such patients. RECENT FINDINGS: Owing to the wide spectrum of clinical presentation and lack of an 'all-inclusive' definition, it is difficult to estimate the true prevalence of cachexia. Perhaps 2% of the population suffer from precachexia (characterized by weight loss in association with a chronic disease). The significant increase in obesity of the general population (which can mask significant muscle wasting) confounds such simple estimates of the true prevalence of cachexia. In contrast, a multidimensional characterization of the cachectic state (including weight loss, reduced food intake, and systemic inflammation) may be more meaningful in terms of altered clinical outcomes. Such a multidimensional view of cachexia has been shown to impact on patients' survival and quality of life and therefore constitutes a major public health issue. SUMMARY: There is a high prevalence of (pre)cachexia in patients with chronic diseases. The cachexia syndrome is probably less frequent but has a significant impact in terms of morbidity and mortality.