Medical management of painful achalasia: a patient-driven systematic review.

Achalasia is a rare esophageal disorder characterized by abnormal esophageal motility and swallowing difficulties. Pain and/or spasms often persist or recur despite effective relief of the obstruction. A survey by UK charity 'Achalasia Action' highlighted treatments for achalasia pain/spasms as a key research priority. In this patient-requested systematic review, we assessed the existing literature on pharmacological therapies for painful achalasia. A systematic review of the literature using Medline, Embase and Cochrane databases was performed to identify studies evaluating pharmacological therapies for achalasia. Methodological quality of included randomized controlled trials was assessed using the Cochrane Risk of Bias tool. In total, 70% (40/57) of survey respondents reported experiencing pain/spasms. A range of management strategies were reported. Thirteen studies were included in the review. Seven were randomized controlled trials. Most studies were >30 years old, had limited follow-up, and focussed on esophageal manometry as the key endpoint. Generally, studies found improvements in lower esophageal pressures with medications. Only one study evaluated pain/spasm specifically, precluding meta-analysis. Overall risk of bias was high. The achalasia patient survey identified that pain/spasms are common and difficult to treat. This patient-requested review identified a gap in the literature regarding pharmacological treatments for these symptoms. We provide an algorithm for investigating achalasia-related pain/spasms. Calcium channel blockers or nitrates may be helpful when esophageal obstruction and reflux have been excluded. We advocate for registry-based clinical trials to expand the evidence base for these patients.

Progress with Metabolomic Blood Tests for Gastrointestinal Cancer Diagnosis-An Assessment of Biomarker Translation.

There is an urgent need for cost-effective, non-invasive tools to detect early stages of gastrointestinal cancer (colorectal, gastric, and esophageal cancers). Despite many publications suggesting circulating metabolites acting as accurate cancer biomarkers, few have reached the clinic. In upper gastrointestinal cancer this is critically important, as there is no test to complement gold-standard endoscopic evaluation in patients with mild symptoms that do not meet referral criteria. Therefore, this study aimed to describe and solve this translational gap. Studies reporting diagnostic accuracy of metabolomic blood-based gastrointestinal cancer biomarkers from 2007 to 2020 were systematically reviewed and progress of each biomarker along the discovery-validation-adoption pathway was mapped. Successful biomarker translation was defined as a composite endpoint, including patent protection/FDA approval/recommendation in national guidelines. The review found 77 biomarker panels of gastrointestinal cancer, including 25 with an AUROC >0.9. All but one was stalled at the discovery phase, 9.09% were patented and none were clinically approved, confirming the extent of biomarker translational gap. In addition, there were numerous "re-discoveries," including histidine, discovered in 7 colorectal studies. Finally, this study quantitatively supports the presence of a translational gap between discovery and clinical adoption, despite clear evidence of highly performing biomarkers with significant potential clinical value.

Implementation of the Esophagectomy Complication Consensus Group definitions: the benefits of speaking the same language.

In 2015 the Esophagectomy Complication Consensus Group (ECCG) reported consensus definitions for complications after esophagectomy. This aimed to reduce variation in complication reporting, attributed to heterogeneous definitions. This systematic review aimed to describe the implementation of this definition set, including the effect on complication frequency and variation. A systematic literature review was performed, identifying all observational and randomized studies reporting complication frequencies after esophagectomy since the ECCG publication. Recruitment periods before and subsequent to the index ECCG publication date were included. Coefficients of variance were calculated to assess outcome heterogeneity. Of 144 studies which met inclusion criteria, 70 (48.6%) used ECCG definitions. The median number of separately reported complication types was five per study; only one study reported all ECCG complications. The coefficients of variance of the reported frequencies of eight of the 10 most common complications were reduced in studies which used the ECCG definitions compared with those that did not (P = 0.036). Among ECCG studies, the frequencies of postoperative pneumothorax, reintubation, and pulmonary emboli were significantly reduced in 2020-2021, compared with 2015-2019 (P = 0.006, 0.034, and 0.037 respectively). The ECCG definition set has reduced variation in esophagectomy morbidity reporting. This adds greater confidence to the observed gradual improvement in outcomes with time, and its ongoing use and wider dissemination should be encouraged. However, only a handful of outcomes are widely reported, and only rarely is it used in its entirety.

Lasting Symptoms After Esophageal Resection (LASER): European Multicenter Cross-sectional Study.

OBJECTIVE: To identify the most prevalent symptoms and those with greatest impact upon health-related quality of life (HRQOL) among esophageal cancer survivors. BACKGROUND: Long-term symptom burden after esophagectomy, and associations with HRQOL, are poorly understood. PATIENTS AND METHODS: Between 2010 and 2016, patients from 20 European Centers who underwent esophageal cancer surgery, and were disease-free at least 1 year postoperatively were asked to complete LASER, EORTC-QLQ-C30, and QLQ-OG25 questionnaires. Specific symptom questionnaire items that were associated with poor HRQOL as identified by EORTC QLQ-C30 and QLQ-OG25 were identified by multivariable regression analysis and combined to form a tool. RESULTS: A total of 876 of 1081 invited patients responded to the questionnaire, giving a response rate of 81%. Of these, 66.9% stated in the last 6 months they had symptoms associated with their esophagectomy. Ongoing weight loss was reported by 10.4% of patients, and only 13.8% returned to work with the same activities.Three LASER symptoms were correlated with poor HRQOL on multivariable analysis; pain on scars on chest (odds ratio (OR) 1.27; 95% CI 0.97-1.65), low mood (OR 1.42; 95% CI 1.15-1.77) and reduced energy or activity tolerance (OR 1.37; 95% CI 1.18-1.59). The areas under the curves for the development and validation datasets were 0.81 ±â€Š0.02 and 0.82 ±â€Š0.09 respectively. CONCLUSION: Two-thirds of patients experience significant symptoms more than 1 year after surgery. The 3 key symptoms associated with poor HRQOL identified in this study should be further validated, and could be used in clinical practice to identify patients who require increased support.

Endogenous aldehyde accumulation generates genotoxicity and exhaled biomarkers in esophageal adenocarcinoma.

Volatile aldehydes are enriched in esophageal adenocarcinoma (EAC) patients' breath and could improve early diagnosis, however the mechanisms of their production are unknown. Here, we show that weak aldehyde detoxification characterizes EAC, which is sufficient to cause endogenous aldehyde accumulation in vitro. Two aldehyde groups are significantly enriched in EAC biopsies and adjacent tissue: (i) short-chain alkanals, and (ii) medium-chain alkanals, including decanal. The short-chain alkanals form DNA-adducts, which demonstrates genotoxicity and confirms inadequate detoxification. Metformin, a putative aldehyde scavenger, reduces this toxicity. Tissue and breath concentrations of the medium-chain alkanal decanal are correlated, and increased decanal is linked to reduced ALDH3A2 expression, TP53 deletion, and adverse clinical features. Thus, we present a model for increased exhaled aldehydes based on endogenous accumulation from reduced detoxification, which also causes therapeutically actionable genotoxicity. These results support EAC early diagnosis trials using exhaled aldehyde analysis.

Metabolic Biomarkers of Squamous Cell Carcinoma of the Aerodigestive Tract: A Systematic Review and Quality Assessment.

Introduction. Aerodigestive squamous cell carcinomas (ASCC) constitute a major source of global cancer deaths. Patients typically present with advanced, incurable disease, so new means of detecting early disease are a research priority. Metabolite quantitation is amenable to point-of-care analysis and can be performed in ASCC surrogates such as breath and saliva. The purpose of this systematic review is to summarise progress of ASCC metabolomic studies, with an emphasis on the critical appraisal of methodological quality and reporting. METHOD: A systematic online literature search was performed to identify studies reporting metabolic biomarkers of ASCC. This review was conducted in accordance with the recommendations of the Cochrane Library and MOOSE guidelines. RESULTS: Thirty studies comprising 2117 patients were included in the review. All publications represented phase-I biomarker discovery studies, and none validated their findings in an independent cohort. There was heterogeneity in study design and methodological and reporting quality. Sensitivities and specificities were higher in oesophageal and head and neck squamous cell carcinomas compared to those in lung squamous cell carcinoma. The metabolic phenotypes of these cancers were similar, as was the kinetics of metabolite groups when comparing blood, tissue, and breath/saliva concentrations. Deregulation of amino acid metabolism was the most frequently reported theme. CONCLUSION: Metabolite analysis has shown promising diagnostic performance, especially for oesophageal and head and neck ASCC subtypes, which are phenotypically similar. However, shortcomings in study design have led to inconsistencies between studies. To support future studies and ultimately clinical adoption, these limitations are discussed.

De Novo Lipogenesis Alters the Phospholipidome of Esophageal Adenocarcinoma.

The incidence of esophageal adenocarcinoma is rising, survival remains poor, and new tools to improve early diagnosis and precise treatment are needed. Cancer phospholipidomes quantified with mass spectrometry imaging (MSI) can support objective diagnosis in minutes using a routine frozen tissue section. However, whether MSI can objectively identify primary esophageal adenocarcinoma is currently unknown and represents a significant challenge, as this microenvironment is complex with phenotypically similar tissue-types. Here, we used desorption electrospray ionization-MSI (DESI-MSI) and bespoke chemometrics to assess the phospholipidomes of esophageal adenocarcinoma and relevant control tissues. Multivariate models derived from phospholipid profiles of 117 patients were highly discriminant for esophageal adenocarcinoma both in discovery (AUC = 0.97) and validation cohorts (AUC = 1). Among many other changes, esophageal adenocarcinoma samples were markedly enriched for polyunsaturated phosphatidylglycerols with longer acyl chains, with stepwise enrichment in premalignant tissues. Expression of fatty acid and glycerophospholipid synthesis genes was significantly upregulated, and characteristics of fatty acid acyls matched glycerophospholipid acyls. Mechanistically, silencing the carbon switch ACLY in esophageal adenocarcinoma cells shortened glycerophospholipid chains, linking de novo lipogenesis to the phospholipidome. Thus, DESI-MSI can objectively identify invasive esophageal adenocarcinoma from a number of premalignant tissues and unveils mechanisms of phospholipidomic reprogramming. SIGNIFICANCE: These results call for accelerated diagnosis studies using DESI-MSI in the upper gastrointestinal endoscopy suite, as well as functional studies to determine how polyunsaturated phosphatidylglycerols contribute to esophageal carcinogenesis.

Routinely staging gastric cancer with 18F-FDG PET-CT detects additional metastases and predicts early recurrence and death after surgery.

OBJECTIVES: Fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) is typically considered to have minimal yield in gastric cancer, and so is not consistently recommended by international guidelines. However, its yield is considerable in esophageal and junctional cancer, identifying unsuspected metastases and risk-stratifying patients using metabolic nodal stage (mN). We aimed to determine the contemporary utility of routine 18F-FDG PET-CT in gastric cancer. METHODS: We routinely stage patients with non-junctional gastric cancer with PET-CT, provided initial CT does not demonstrate unequivocal metastases. We performed a retrospective study of all such patients staged in our institution from January 2007 to July 2016. Our primary endpoint was detection of incurable disease. Our secondary endpoint was disease-free survival following gastrectomy. Decision theory, economic, and predictive models were generated. RESULTS: The primary tumor was FDG-avid in 225/279 patients (80.6%). Seventy-two (25.8%) had FDG-avid nodes (resectable by D2 lymphadenectomy). This was not influenced by the Lauren classification. Unsuspected metastases were identified in 20 patients (7.2%). In 13 (4.7%), these would not have been otherwise identified. Decision theory and economic modeling supported routine PET-CT. Patients with FDG-avid nodes were more likely to have incurable disease (51.4% versus 15.5%; p < 0.001), and a worse prognosis if not: multivariate hazard ratio 2.19 (1.23-3.91; p = 0.008). Prognosis worsened with mN stage. CONCLUSIONS: PET-CT appears useful when used routinely for non-junctional gastric cancer, and should be considered in international recommendations. Any extra costs appear small and offset by avoiding futile investigations and radical treatment. mN stage identifies patients at risk of early recurrence and death. KEY POINTS: • PET-CT is typically not considered useful when staging gastric cancer. We describe a retrospective study of 279 patients routinely staged with PET-CT in the absence of metastases on CT. • The primary tumor was avid in 80% of patients. Twenty-five percent had resectable avid nodes. PET-CT identified previously unsuspected metastases in 7% of patients, which would likely not have been identified by conventional staging without PET-CT in 5%. These patients were much more likely to have avid nodes. • Beyond avoiding futile investigations and radical treatment in this 5%, we found patients with FDG-avid nodes (metabolic nodal stage, mN) to have a worse disease-free survival after gastrectomy.

Breath Volatile Organic Compound Profiling of Colorectal Cancer Using Selected Ion Flow-tube Mass Spectrometry.

OBJECTIVE: BACKGROUND:: Breath VOCs have the potential to noninvasively diagnose cancer. METHODS: Exhaled breath samples were collected using 2-L double-layered Nalophan bags, and were analyzed using selected-ion-flow-tube mass-spectrometry. Gold-standard test for comparison was endoscopy for luminal inspection and computed tomography (CT) to confirm cancer recurrence. Three studies were conducted: RESULTS:: CONCLUSION:: This study suggests the association of a single breath biomarker with the primary presence and recurrence of CRCa. Further multicenter validation studies are required to validate these findings.

Cancer Risk Following Bariatric Surgery-Systematic Review and Meta-analysis of National Population-Based Cohort Studies.

This study has analyzed results from registry-based population studies to assess the effect of bariatric surgery upon cancer incidence at a population level. Relevant studies were identified and meta-analysis was used to calculate pooled odds ratios (POR) for the incidence of cancer after bariatric surgery compared to controls. Eight population-based studies were included with 635,642 total patients. Bariatric surgery was associated with a significant reduction in overall cancer incidence (POR = 0.72; 95% CI 0.59 to 0.87; p = 0.0007) and incidence of obesity-related cancer (POR = 0.55; 95% CI 0.31 to 0.96; p = 0.04). Bariatric surgery was also protective for breast cancer development (POR = 0.50; 95% CI 0.25 to 0.99; p = 0.045). Bariatric surgery appears to be associated with a reduction in cancer incidence at a population-based level.

Pragmatic and rapid analysis of carbonyl, oxidation and chlorination nucleoside-adducts in murine tissue by UPLC-ESI-MS/MS.

Nucleoside-adduct analysis by liquid chromatography mass spectrometry is a powerful tool in genotoxicity studies. Efforts to date have quantified an impressive array of DNA damage products, although methodological diversity suggests quantification is still a challenging task. For example, inadequate co-examination of normal nucleosides, cumbersome sample preparation and large DNA requirements were identified to be recurring issues. A six-minute ultra-performance liquid chromatography method is presented which adequately separates seven candidate nucleoside-adducts from the four unmodified nucleosides. The method was sensitive to 1 adduct per 108 normal bases with 20 µg DNA input for most targets. The method was shown to be accurate (81-119% across quintuplets of six tissue types) and precise (relative standard deviation 4-13%). The fast method time facilitated a second quantitation for normal nucleosides at an appropriate dilution, allowing DNA damage concentrations to be contextualised accurately sample-to-sample. From DNA samples, the analytical processing time was < 8 h, and 96 samples can easily be prepared in a day. The method was used to quantify carbonyl, chloro- and oxo- adducts in murine tissue samples.

Remote ischemic preconditioning for cardioprotection in elective inpatient abdominal surgery - a randomized controlled trial.

BACKGROUND: Perioperative myocardial injury (PMI) is common in elective inpatient abdominal surgery and correlates with mortality risk. Simple measures for reducing PMI in this cohort are needed. This study evaluated whether remote ischemic preconditioning (RIPC) could reduce PMI in elective inpatient abdominal surgery. METHODS: This was a double-blind, sham-controlled trial with 1:1 parallel randomization. PMI was defined as any post-operative serum troponin T (hs-TNT) > 14 ng/L. Eighty-four participants were randomized to receiving RIPC (5 min of upper arm ischemia followed by 5 min reperfusion, for three cycles) or a sham-treatment immediately prior to surgery. The primary outcome was mean peak post-operative troponin in patients with PMI, and secondary outcomes included mean hs-TnT at individual timepoints, post-operative hs-TnT area under the curve (AUC), cardiovascular events and mortality. Predictors of PMI were also collected. Follow up was to 1 year. RESULTS: PMI was observed in 21% of participants. RIPC did not significantly influence the mean peak post-operative hs-TnT concentration in these patients (RIPC 25.65 ng/L [SD 9.33], sham-RIPC 23.91 [SD 13.2], mean difference 1.73 ng/L, 95% confidence interval - 9.7 to 13.1 ng/L, P = 0.753). The treatment did not influence any secondary outcome with the pre-determined definition of PMI. Redefining PMI as > 5 ng/L in line with recent data revealed a non-significant lower incidence in the RIPC cohort (68% vs 81%, P = 0.211), and significantly lower early hs-TnT release (12 h time-point, RIPC 5.5 ng/L [SD 5.5] vs sham 9.1 ng/L [SD 8.2], P = 0.03). CONCLUSIONS: RIPC did not at reduce the incidence or severity of PMI in these general surgical patients using pre-determined definitions. PMI is nonetheless common and effective cardioprotective strategies are required. TRIAL REGISTRATION: This trial was registered with Clinicaltrials.gov, NCT01850927 , 5th July 2013.

Assessment of a Noninvasive Exhaled Breath Test for the Diagnosis of Oesophagogastric Cancer.

Importance: Early esophagogastric cancer (OGC) stage presents with nonspecific symptoms. Objective: The aim of this study was to determine the accuracy of a breath test for the diagnosis of OGC in a multicenter validation study. Design, Setting, and Participants: Patient recruitment for this diagnostic validation study was conducted at 3 London hospital sites, with breath samples returned to a central laboratory for selected ion flow tube mass spectrometry (SIFT-MS) analysis. Based on a 1:1 cancer:control ratio, and maintaining a sensitivity and specificity of 80%, the sample size required was 325 patients. All patients with cancer were on a curative treatment pathway, and patients were recruited consecutively. Among the 335 patients included; 172 were in the control group and 163 had OGC. Interventions: Breath samples were collected using secure 500-mL steel breath bags and analyzed by SIFT-MS. Quality assurance measures included sampling room air, training all researchers in breath sampling, regular instrument calibration, and unambiguous volatile organic compounds (VOCs) identification by gas chromatography mass spectrometry. Main Outcomes and Measures: The risk of cancer was identified based on a previously generated 5-VOCs model and compared with histopathology-proven diagnosis. Results: Patients in the OGC group were older (median [IQR] age 68 [60-75] vs 55 [41-69] years) and had a greater proportion of men (134 [82.2%]) vs women (81 [47.4%]) compared with the control group. Of the 163 patients with OGC, 123 (69%) had tumor stage T3/4, and 106 (65%) had nodal metastasis on clinical staging. The predictive probabilities generated by this 5-VOCs diagnostic model were used to generate a receiver operator characteristic curve, with good diagnostic accuracy, area under the curve of 0.85. This translated to a sensitivity of 80% and specificity of 81% for the diagnosis of OGC. Conclusions and Relevance: This study shows the potential of breath analysis in noninvasive diagnosis of OGC in the clinical setting. The next step is to establish the diagnostic accuracy of the test among the intended population in primary care where the test will be applied.

Imaging of Esophageal Lymph Node Metastases by Desorption Electrospray Ionization Mass Spectrometry.

Histopathological assessment of lymph node metastases (LNM) depends on subjective analysis of cellular morphology with inter-/intraobserver variability. In this study, LNM from esophageal adenocarcinoma was objectively detected using desorption electrospray ionization-mass spectrometry imaging (DESI-MSI). Ninety lymph nodes (LN) and their primary tumor biopsies from 11 esophago-gastrectomy specimens were examined and analyzed by DESI-MSI. Images from mass spectrometry and corresponding histology were coregistered and analyzed using multivariate statistical tools. The MSIs revealed consistent lipidomic profiles of individual tissue types found within LNs. Spatial mapping of the profiles showed identical distribution patterns as per the tissue types in matched IHC images. Lipidomic profile comparisons of LNM versus the primary tumor revealed a close association in contrast to benign LN tissue types. This similarity was used for the objective prediction of LNM in mass spectrometry images utilizing the average lipidomic profile of esophageal adenocarcinoma. The multivariate statistical algorithm developed for LNM identification demonstrated a sensitivity, specificity, positive predictive value, and negative predictive value of 89.5%, 100%, 100%, and 97.2%, respectively, when compared with gold-standard IHC. DESI-MSI has the potential to be a diagnostic tool for perioperative identification of LNM and compares favorably with techniques currently used by histopathology experts. Cancer Res; 76(19); 5647-56. ©2016 AACR.

Diagnostic Metabolomic Blood Tests for Endoluminal Gastrointestinal Cancer--A Systematic Review and Assessment of Quality.

Advances in analytics have resulted in metabolomic blood tests being developed for the detection of cancer. This systematic review aims to assess the diagnostic accuracy of blood-based metabolomic biomarkers for endoluminal gastrointestinal (GI) cancer. Using endoscopic diagnosis as a reference standard, methodologic and reporting quality was assessed using validated tools, in addition to pathway-based informatics to biologically contextualize discriminant features. Twenty-nine studies (15 colorectal, 9 esophageal, 3 gastric, and 2 mixed) with data from 10,835 participants were included. All reported significant differences in hematologic metabolites. In pooled analysis, 246 metabolites were found to be significantly different after multiplicity correction. Incremental metabolic flux with disease progression was frequently reported. Two promising candidates have been validated in independent populations (both colorectal biomarkers), and one has been approved for clinical use. Networks analysis suggested modulation of elements of up to half of Edinburgh Human Metabolic Network subdivisions, and that the poor clinical applicability of commonly modulated metabolites could be due to extensive molecular interconnectivity. Methodologic and reporting quality was assessed as moderate-to-poor. Serum metabolomics holds promise for GI cancer diagnostics; however, future efforts must adhere to consensus standardization initiatives, utilize high-resolution discovery analytics, and compare candidate biomarkers with peer nonendoscopic alternatives.

Direct detection and quantification of malondialdehyde vapour in humid air using selected ion flow tube mass spectrometry supported by gas chromatography/mass spectrometry.

RATIONALE: It has been proposed that malondialdehyde (MDA) reflects free oxygen-radical lipid peroxidation and can be useful as a biomarker to track this process. For the analysis of MDA molecules in humid air by selected ion flow tube mass spectrometry (SIFT-MS), the rate coefficients and the ion product distributions for the reactions of the SIFT-MS reagent ions with volatile MDA in the presence of water vapour are required. METHODS: The SIFT technique has been used to determine the rate coefficients and ion product distributions for the reactions of H3O(+), NO(+) and O2 (+•) with gas-phase MDA. In support of the SIFT-MS analysis of MDA, solid-phase microextraction, SPME, coupled with gas chromatography/mass spectrometry, GC/MS, has been used to confirm the identification of MDA. RESULTS: The primary product ions have been identified for the reactions of H3O(+), NO(+) and O2 (+•) with MDA and the formation of their hydrates formed in humid samples is described. The following combinations of reagent and the analyte ions (given as m/z values) have been adopted for SIFT-MS analyses of MDA in the gas phase: H3O(+): 109; NO(+): 89, 102; O2 (+•): 72, 90, 108, 126. The detection and quantification of MDA released by a cell culture by SIFT-MS are demonstrated. CONCLUSIONS: This detailed study has provided the kinetics data required for the SIFT-MS analysis of MDA in humid air, including exhaled breath and the headspace of liquid-phase biogenic media. The detection and quantification by SIFT-MS of MDA released by a cell culture are demonstrated.

Minimally invasive esophagectomy: Lateral decubitus vs. prone positioning; systematic review and pooled analysis.

The uptake of minimally invasive esophagectomy (MIE) has increased vastly over the last decade, with proven short-term benefits over an open approach. The aim of this pooled analysis was to compare clinical outcomes of Minimally Invasive Esophagectomy (MIE) performed in the prone and lateral decubitus positions. A systematic literature search (2000-2015) was undertaken for publications that compared patients who underwent MIE in the lateral decubitus (LD) or prone (PR) positions. Weighted mean difference (WMD) was calculated for the effect size of LD positioning on continuous variables and Pooled odds ratios (POR) for discrete variables. Ten relevant publications comprising 723 patients who underwent minimally invasive esophagectomy were included; 387 in the LD group and 336 in the PR group. There was no significant difference between the groups in terms of in-hospital mortality, total morbidity, anastomotic leak, chylothorax, laryngeal nerve palsy, average operative time, and length hospital stay. LD MIE was associated with a non-significant increase in pulmonary complications (POR = 1.65; 95% C.I. 0.93 to 2.92; P = 0.09), and significant increases in estimated blood loss (WMD = 36.03; 95% 14.37 to 57.69; P = 0.001) and a reduced average mediastinal lymph node harvest (WMD = -2.17; 95% C.I. -3.82 to -0.52; P = 0.01) when compared to prone MIE. Pooled analysis suggests that prone MIE is superior to lateral decubitus MIE with reduced pulmonary complications, estimated blood loss and increased mediastinal lymph node harvest. Further studies are needed to explain performance-shaping factors and their influence on oncological clearance and short-term outcomes.

Tyrosine, phenylalanine, and tryptophan in gastroesophageal malignancy: a systematic review.

Gastroesophageal cancer has a rapidly increasing incidence worldwide and reliable biomarkers are urgently required to facilitate earlier diagnosis and improve survival. The aromatic amino acids tyrosine, phenylalanine, and tryptophan represent potential biomarkers and their relation to gastroesophageal cancer will be evaluated in this review. An electronic literature search was performed to identify all published research relating to the measurement of tyrosine, phenylalanine, or tryptophan in the biofluids or tissues of patients with gastroesophageal cancer. Sixteen studies were included in this systematic review. Six studies investigated serum concentrations, which all found decreased concentrations of these aromatic amino acids, except one study that found increased phenylalanine. Five studies reported increased concentrations within gastric content of these patients and two reported increased urinary concentrations. Tissue concentrations of these aromatic amino acids were increased in three studies. Tyrosine, phenylalanine, and tryptophan represent potential biomarkers of gastroesophageal cancer, and further research is necessary to definitively establish the mechanism responsible for altered concentrations of these compounds in patients with gastroesophageal cancer.

Prdm6 is essential for cardiovascular development in vivo.

Members of the PRDM protein family have been shown to play important roles during embryonic development. Previous in vitro and in situ analyses indicated a function of Prdm6 in cells of the vascular system. To reveal physiological functions of Prdm6, we generated conditional Prdm6-deficient mice. Complete deletion of Prdm6 results in embryonic lethality due to cardiovascular defects associated with aberrations in vascular patterning. However, smooth muscle cells could be regularly differentiated from Prdm6-deficient embryonic stem cells and vascular smooth muscle cells were present and proliferated normally in Prdm6-deficient embryos. Conditional deletion of Prdm6 in the smooth muscle cell lineage using a SM22-Cre driver line resulted in perinatal lethality due to hemorrhage in the lungs. We thus identified Prdm6 as a factor that is essential for the physiological control of cardiovascular development.

Spontaneous presacral haematoma mimicking rectal malignancy--an unusual consequence of anticoagulation.

An 81-year-old man on warfarin was admitted to hospital after 3 days of constipation, straining and mild rectal bleeding. A large, boggy mass was felt posteriorly on direct rectal examination. Investigations revealed a normocytic anaemia and a supratherapeutic international normalised ratio (INR). Fearing a late presentation of malignancy, an urgent CT of abdomen and pelvis was arranged which showed a homogeneous mass arising between the sacrum and the rectum. Given the anaemia in the presence of anticoagulation, and subsequent widespread perineal and scrotal ecchymosis, the patient was diagnosed with atraumatic presacral haematoma. Following resuscitation, the patient was managed non-operatively and was discharged several days later following stabilisation of the haemoglobin and INR. At 3 months, he had complete clinical and radiological resolution of this haematoma.