Impact on postoperative complications of changes in skeletal muscle mass during neoadjuvant chemotherapy for gastro-oesophageal cancer.

BACKGROUND: Risk assessment is relevant to predict postoperative outcomes in patients with gastro-oesophageal cancer. This cohort study aimed to assess body composition changes during neoadjuvant chemotherapy and investigate their association with postoperative complications. METHODS: Consecutive patients with gastro-oesophageal cancer undergoing neoadjuvant chemotherapy and surgery with curative intent between 2016 and 2019 were identified from a specific database and included in the study. CT images before and after neoadjuvant chemotherapy were used to assess the skeletal muscle index, sarcopenia, and subcutaneous and visceral fat index. RESULTS: In a cohort of 199 patients, the mean skeletal muscle index decreased during neoadjuvant therapy (from 51·187 to 49·19 cm2 /m2 ; P < 0·001) and the rate of sarcopenia increased (from 42·2 to 54·3 per cent; P < 0·001). A skeletal muscle index decrease greater than 5 per cent was not associated with an increased risk of total postoperative complications (odds ratio 0·91, 95 per cent c.i. 0·52 to 1·59; P = 0·736) or severe complications (odds ratio 0·66, 0·29 to 1·53; P = 0·329). CONCLUSION: Skeletal muscle index decreased during neoadjuvant therapy but was not associated with postoperative complications.

ANTECEDENTES: La evaluación de riesgo es importante para predecir los resultados postoperatorios en pacientes con cáncer gastroesofágico. Este estudio de cohortes tuvo como objetivo evaluar los cambios en la composición corporal durante la quimioterapia neoadyuvante e investigar su asociación con complicaciones postoperatorias. MÉTODOS: Los pacientes consecutivos con cáncer gastroesofágico sometidos a quimioterapia neoadyuvante y cirugía con intención curativa entre 2016 y 2019, identificados a partir de una base de datos específica, se incluyeron en el estudio. Se utilizaron las imágenes de tomografía computarizada, antes y después de la quimioterapia neoadyuvante, para evaluar el índice de masa muscular esquelética, la sarcopenia y el índice de grasa visceral y subcutánea. RESULTADOS: En una cohorte de 199 pacientes, el índice de masa muscular esquelética disminuyó durante el tratamiento neoadyuvante (de 51,87 cm2 /m2 a 49,19 cm2 /m2 , P < 0,001) y las tasas de sarcopenia aumentaron (de 42,2% a 54,2%, P < 0,001). Una disminución del índice de masa muscular esquelética > 5% no se asoció con un mayor riesgo de complicaciones postoperatorias globales (razón de oportunidades, odds ratio: 0,908; ic. del 95%: 0,520-1,587, P = 0,736) ni de complicaciones graves (odds ratio: 0,661; i.c. del 95%: 0,286-1,525, P = 0,329). CONCLUSIÓN: El índice de masa muscular esquelética disminuyó durante el tratamiento neoadyuvante, pero no se asoció con complicaciones postoperatorias.

Brachytherapy in the Palliation of Oesophageal Cancer: Effective but Impractical?

Dysphagia in people with advanced oesophageal cancer can be treated by oesophageal stents, external beam radiotherapy (EBRT) and intraluminal brachytherapy. Despite guidelines recommending brachytherapy for patients with a predicted life expectancy exceeding 3 months, its uptake in the UK has been limited. Here we examine the strength of the evidence supporting the use of brachytherapy compared with oesophageal stents and EBRT and possible reasons for its limited uptake. Trials and observational studies suggest brachytherapy alone confers a benefit to patients, but its impact is less immediate than oesophageal stents; the evidence on effectiveness and value-for-money is limited. Moreover, stronger evidence will probably be insufficient to increase uptake, due to the extra complexity of delivery compared with stents and EBRT and a lack of experience among specialists.

Translational study identifies XPF and MUS81 as predictive biomarkers for oxaliplatin-based peri-operative chemotherapy in patients with esophageal adenocarcinoma.

Oxaliplatin-based chemotherapy is used to treat patients with esophageal adenocarcinoma (EAC), but no biomarkers are currently available for patient selection. We performed a prospective, clinical trial to identify potential biomarkers associated with clinical outcomes. Tumor tissue was obtained from 38 patients with resectable EAC before and after 2 cycles of oxaliplatin-fluorouracil chemotherapy. Pre-treatment mRNA expression of 280 DNA repair (DNAR) genes was tested for association with histopathological regression at surgery, disease-free survival (DFS) and overall survival (OS). High expression of 13 DNA damage repair genes was associated with DFS less than one year (P < 0.05); expression of 11 DNAR genes were associated with worse OS (P < 0.05). From clinical associations with outcomes, two genes, ERCC1 and EME1, were identified as candidate biomarkers. In cell lines in vitro, we showed the mechanism of action related to repair of oxaliplatin-induced DNA damage by depletion and knockout of protein binding partners of the candidate biomarkers, XPF and MUS81 respectively. In clinical samples from the clinical trial, pre-treatment XPF protein levels were associated with pathological response, and MUS81 protein was associated with 1-year DFS. XPF and MUS81 merit further validation in prospective clinical trials as biomarkers that may predict clinical response of EAC to oxaliplatin-based chemotherapy.

A comparison of the left thoracoabdominal and Ivor-Lewis esophagectomy.

The purpose of this study was to assess the oncological outcomes of a large multicenter series of left thoracoabdominal esophagectomies, and compare these to the more widely utilized Ivor-Lewis esophagectomy. With ethics approval and an established study protocol, anonymized data from five centers were merged into a structured database. The study exposure was operative approach (ILE or LTE). The primary outcome measure was time to death. Secondary outcome measures included time to tumor recurrence, positive surgical resection margins, lymph node yield, postoperative death, and hospital length of stay. Cox proportional hazards models provided hazard ratios (HR) with 95% confidence intervals (CI) adjusting for age, pathological tumor stage, tumor grade, lymphovascular invasion, and neoadjuvant treatment. Among 1228 patients (598 ILE; 630 LTE), most (86%) had adenocarcinoma (AC) and were male (81%). Comparing ILE and LTE for AC patients, no difference was seen in terms of time to death (HR 0.904 95%CI 0.749-1.1090) or time to recurrence (HR 0.973 95%CI 0.768-1.232). The risk of a positive resection margin was also similar (OR 1.022 95%CI 0.731-1.429). Median lymph node yield did not differ between approaches (LTE 21; ILE 21; P = 0.426). In-hospital mortality was 2.4%, significantly lower in the LTE group (LTE 1.3%; ILE 3.6%; P = 0.004). Median hospital stay was 11 days in the LTE group and 14 days in the ILE group (P < 0.0001). In conclusion, this is the largest series of left thoracoabdominal esophagectomies to be submitted for publication and the only one to compare two different transthoracic esophagectomy strategies. It demonstrates oncological equivalence between operative approaches but possible short- term advantages to the left thoracoabdominal esophagectomy.

Metabolic nodal response as a prognostic marker after neoadjuvant therapy for oesophageal cancer.

BACKGROUND: The ability to predict recurrence and survival after neoadjuvant chemotherapy (NAC) and surgery for oesophageal cancer remains elusive. This study evaluated the role of [18 F]fluorodeoxyglucose (FDG) PET-CT in assessing tumour and nodal response as a prognostic marker. METHODS: This was a single-centre UK cohort study. From 2006 to 2014, patients with oesophageal cancer staged with PET-CT before NAC, and restaged by CT or PET-CT before resection, were included. Pathological tumour response was evaluated using Mandard regression grades. Metabolic tumour and nodal responses (mTR and mNR respectively) were quantified using absolute and threshold reductions. RESULTS: Among 294 included patients, mTR and mNR independently predicted prognosis before surgery. After surgery, mNR (but not mTR), pathological tumour response, resection margin status and pathological node category predicted prognosis. Patients with FDG-avid nodal disease after NAC were at high risk of recurrence/death at 1 and 2 years (43 and 71 per cent respectively; P = 0·030 and P = 0·025 versus patients without avid nodes), and had a worse prognosis than patients with non-avid nodal metastases: hazard ratio 4·19 (95 per cent c.i. 1·87 to 9·40) and 2·11 (1·12 to 3·97) respectively versus patients without nodal metastases. Considering mTR and mNR response separately improved prognostication. CONCLUSION: mNR is a novel prognostic factor, independent of conventional N status. Primary and nodal tumours may respond discordantly and patients with FDG-avid nodes after NAC have a poor prognosis.

Pragmatic staging of oesophageal cancer using decision theory involving selective endoscopic ultrasonography, PET and laparoscopy.

BACKGROUND: Following CT, guidelines for staging oesophageal and gastro-oesophageal junction (GOJ) cancer recommend endoscopic ultrasonography (EUS), PET-CT and laparoscopy for T3-T4 GOJ tumours. These recommendations are based on generic utilities, but it is unclear whether the test risk outweighs the potential benefit for some patients. This study sought to quantify investigation risks, benefits and utilities, in order to develop pragmatic, personalized staging recommendations. METHODS: All patients with a histological diagnosis of oesophageal or GOJ cancer staged between May 2006 and July 2013 comprised a development set; those staged from July 2013 to July 2014 formed the prospective validation set. Probability thresholds of altering management were calculated and predictive factors identified. Algorithms and models (decision tree analysis, logistic regression, artificial neural networks) were validated internally and independently. RESULTS: Some 953 patients were staged following CT, by [(18) F]fluorodeoxyglucose PET-CT (918), EUS (798) and laparoscopy (458). Of these patients, 829 comprised the development set (800 PET-CT, 698 EUS, 397 laparoscopy) and 124 the validation set (118 PET-CT, 100 EUS, 61 laparoscopy). EUS utility in the 71.8 per cent of patients with T2-T4a disease on CT was minimal (0.4 per cent), its risk exceeding benefit. EUS was moderately accurate for pT1 N0 disease. A number of factors predicted metastases on PET-CT and laparoscopy, although none could inform an algorithm. PET-CT altered management in 23.0 per cent, and laparoscopy in 7.1 per cent, including those with T2 and distal oesophageal tumours. CONCLUSION: Although EUS provided additional information on T and N category, its risk outweighed potential benefit in patients with T2-T4a disease on CT. Laparoscopy seemed justified for distal oesophageal tumours of T2 or greater.

The effect of formalizing enhanced recovery after esophagectomy with a protocol.

Enhanced recovery after surgery (ERAS) pathways aim to accelerate functional return and discharge from hospital. They have proven effective in many forms of surgery, most notably colorectal. However, experience in esophagectomy has been limited. A recent study reported significant reductions in pulmonary complications, mortality, and length of stay following the introduction of an ERAS protocol alone, without the introduction of any clinical changes. We instituted a similar change 16 months ago, introducing a protocol to provide a formal framework, for our existing postoperative care. This retrospective analysis compared outcome following esophagectomy for the 16 months before and 20 months after this change. Data were collected from prospectively maintained secure web-based multidisciplinary databases. Complication severity was classified using the Clavien-Dindo scale. Operative mortality was defined as death within 30 days of surgery, or at any point during the same hospital admission. Lower respiratory tract infection was defined as clinical evidence of infection, with or without radiological signs. Respiratory complications included lower respiratory tract infection, pleural effusion (irrespective of drainage), pulmonary collapse, and pneumothorax. Statistical analysis was performed using SPSS v21. One hundred thirty-two patients underwent esophagectomy (55 protocol group; 77 before). All were performed open. There were no differences between the two groups in terms of age, gender, operation, use of neoadjuvant therapy, cell type, stage, tumor site, or American Society of Anesthesiologists grade. Median length of stay was 14.0 days (protocol) compared with 12.0 before (interquartile range 9-19 and 9.5-15.5, respectively; P = 0.073, Mann-Whitney U-test). Readmission within 30 days of discharge occurred in five (9.26%) and six (8.19%; P = 1.000, Fisher's exact test). There were four in-hospital deaths (3.03%): one (1.82%) and three (3.90%), respectively (P = 0.641). There were no differences in the severity of complications (P = non-significant; Pearson's chi-squared). There were no differences in the type of complications occurring in either group. The protocol was completed successfully by 26 (47.3%). No baseline factors were predictive of this. In contrast to previous studies, we did not demonstrate any improvement in outcome by formalizing our existing pathway using a written protocol. Consequently, improvements in short-term outcome from esophagectomy within ERAS would seem to be primarily due to improvements in components of perioperative care. Consequently, we would recommend that centers introducing new (or reviewing existing) ERAS pathways for esophagectomy focus on optimizing clinical aspects of such standardized pathways.

Attempted validation of the NUn score and inflammatory markers as predictors of esophageal anastomotic leak and major complications.

The ability to predict complications following esophagectomy/extended total gastrectomy would be of great clinical value. A recent study demonstrated significant correlations between anastomotic leak (AL) and numerical values of C-reactive protein (CRP), white cell count (WCC) and albumin measured on postoperative day (POD) 4. A predictive model comprising all three (NUn score >10) was found to be highly sensitive and discriminant in predicting AL and complications. We attempted a retrospective validation in our center. Data were collected on all resections performed during a 5-year period (April 2008-2013) using prospectively maintained databases. Our biochemistry laboratory uses a maximum CRP value (156 mg/L), unlike that of the original study; otherwise all variables and outcome measures were comparable. Analysis was performed for all patients with complete blood results on POD4. Three hundred twenty-six patients underwent resection, of which 248 had POD4 bloods. There were 21 AL overall (6.44%); 16 among those with complete POD4 blood results (6.45%). There were 8 (2.45%) in-hospital deaths; 7 (2.82%) in those with POD4 results. No parameters were associated with AL or complication severity on univariate analysis. WCC was associated with AL in multivariate binary logistic regression with albumin and CRP (OR 1.23 [95% CI 1.03-1.47]; P = 0.021). When a binary variable of CRP ≥ 156 mg/L was used rather than an absolute value, no factors were significant. Mean NUn was 8.30 for AL, compared with 8.40 for non-AL (P = 0.710 independent t-test). NUn > 10 predicted 0 of 16 leaks (sensitivity 0.00%, specificity 94.4%, receiver operator curve [ROC] area under the curve [AUC] 0.485; P = 0.843). NUn > 7.65 was 93% sensitive and 21.6% specific. ROC for WCC alone was comparable with NUn (AUC 0.641 [0.504-0.779]; P = 0.059; WCC > 6.89 93.8% sensitive, 20.7% specific; WCC > 15 6.3% sensitive and 97% specific). There were no associations between any parameters and other complications. In a comparable cohort with the original study, we demonstrated a similar multivariate association between WCC alone on POD4 and subsequent demonstration of AL, but not albumin or CRP (measured up to 156 mg/L). The NUn score overall (calculated with this caveat) and a threshold of 10 was not found to have clinical utility in predicting AL or complications.

Metabolic response at repeat PET/CT predicts pathological response to neoadjuvant chemotherapy in oesophageal cancer.

OBJECTIVES: Reports have suggested that a reduction in tumour 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) examination during or after neoadjuvant chemotherapy may predict pathological response in oesophageal cancer. Our aim was to determine whether metabolic response predicts pathological response to a standardised neoadjuvant chemotherapy regimen within a prospective clinical trial. METHODS: Consecutive patients staged with potentially curable oesophageal cancer who underwent treatment within a non-randomised clinical trial were included. A standardised chemotherapy regimen (two cycles of oxaliplatin and 5-fluorouracil) was used. PET/CT was performed before chemotherapy and repeated 24-28 days after the start of cycle 2. RESULTS: Forty-eight subjects were included: mean age 65 years; 37 male. Using the median percentage reduction in SUV(max) (42%) to define metabolic response, pathological response was seen in 71% of metabolic responders (17/24) compared with 33% of non-responders (8/24; P = 0.009, sensitivity 68%, specificity 70%). Pathological response was seen in 81% of subjects with a complete metabolic response (13/16) compared with 38% of those with a less than complete response (12/32; P = 0.0042, sensitivity 52%, specificity 87%). There was no significant histology-based effect. CONCLUSIONS: There was a significant association between metabolic response and pathological response; however, accuracy in predicting pathological response was relatively low.

Role of positron emission tomography-computed tomography in predicting survival after neoadjuvant chemotherapy and surgery for oesophageal adenocarcinoma.

BACKGROUND: Positron emission tomography combined with computed tomography (PET-CT) is increasingly being used in the staging of oesophageal cancer. Some recent reports suggest it may be used to predict survival. None of these studies, however, reported on the prognostic value of PET-CT performed before neoadjuvant chemotherapy and surgery. The aim of this study was to determine whether pretreatment PET-CT could predict survival. METHODS: Consecutive patients with oesophageal adenocarcinoma who underwent PET-CT before neoadjuvant chemotherapy and resection were included. Maximum standardized uptake value (SUV(max)), fluorodeoxyglucose (FDG)-avid tumour length and the presence of FDG-avid local lymph nodes were determined for all patients. Kaplan-Meier survival analysis was performed and multivariable analysis used to identify independent prognostic factors. RESULTS: A total of 121 patients were included (mean age 63 years, 97 men) of whom 103 underwent surgical resection. On an intention-to-treat basis, overall survival was significantly worse in patients with FDG-avid local lymph nodes (P < 0·001). SUV(max) and FDG-avid tumour length did not predict survival (P = 0·276 and P = 0·713 respectively). The presence of FDG-avid local lymph nodes was an independent predictor of poor overall survival (hazard ratio (HR) 4·75, 95 per cent confidence interval 2·14 to 10·54; P < 0·001) and disease-free survival (HR 2·97, 1·40 to 6·30; P = 0·004). CONCLUSION: The presence of FDG-avid lymph nodes, but not SUV(max) or FDG-avid tumour length, was an independent adverse prognostic factor.

Additional benefit of ¹8F-fluorodeoxyglucose integrated positron emission tomography/computed tomography in the staging of oesophageal cancer.

OBJECTIVE: ¹8F-fluorodeoxyglucose positron emission tomography (FDG PET) has been shown to improve the accuracy of staging in oesophageal cancer. We assessed the benefit of PET/CT over conventional staging and determined if tumour histology had any significant impact on PET/CT findings. METHODS: A retrospective cohort study, reviewing the results from 200 consecutive patients considered suitable for radical treatment, undergoing routine PET/CT staging comparing the results from CT and endoscopic ultrasound, as well as multi-disciplinary team records. Adenocarcinoma and squamous cell carcinoma were compared for maximum Standardised Uptake Value (SUV(max)), involvement of local lymph nodes and distant metastases. RESULTS: PET/CT provided additional information in 37 patients (18.5%) and directly altered management in 34 (17%): 22 (11%) were upstaged; 15 (7.5%) were downstaged, 12 of whom (6%) received radical treatment. There were 11 false negatives (5.5%) and 1 false positive (0.5%). SUV(max) was significantly lower for adenocarcinoma than squamous cell carcinoma (median 9.1 versus 13.5, p = 0.003). CONCLUSIONS: Staging with PET/CT offers additional benefit over conventional imaging and should form part of routine staging for oesophageal cancer. Adenocarcinoma and squamous cell carcinoma display significantly different FDG-avidity.

Left thoracoabdominal esophagectomy: results from a single specialist center.

The left thoracoabdominal approach to esophagectomy is not widely performed, despite offering excellent exposure to tumors of the esophagogastric junction. Criticisms of the approach have focused on historically high rates of mortality, complications, and positive resection margins. Our aim was to determine whether left thoracoabdominal esophagectomy could combine a radical oncological resection with acceptably low mortality and morbidity. A retrospective cohort study of all left thoracoabdominal esophagectomies was performed at a single specialist center over an 11-year period. Primary outcomes were in-hospital mortality, complications, resection margin involvement, and lymph node yield; secondary outcomes were 1-year and 5-year survival. Two hundred eleven esophagectomies were performed. In-hospital mortality was 5.7% (12/211). One hundred one subjects (47.9%) had an uncomplicated recovery; 110 subjects (52.1%) developed at least one complication. There were 15 clinically significant anastomotic leaks (7.1%). Twenty-four subjects (11.4%) required emergency reoperation, the most common indication being anastomotic leakage. Complete tumor excision (R0 resection) was achieved in 151 of 211 cases (71.6%); median lymph node yield was 24. One-year and 5-year survival rates were 70% (147/211) and 21% (24/116), respectively. Left thoracoabdominal esophagectomy can combine a radical oncological resection with acceptably low mortality and morbidity.

Oxford experience with neoadjuvant chemotherapy and surgical resection for esophageal adenocarcinomas and squamous cell tumors.

The Medical Research Council trial for oesophageal cancer (OEO2) trial demonstrated a clear survival benefit from neoadjuvant chemotherapy in resectable esophageal carcinoma. Since February 2000 it has been our practice to offer this chemotherapy regime to patients with T2 and T3 or T1N1 tumors. We analyzed prospectively collected data of patients who received neoadjuvant chemotherapy prior to esophageal resection under the care of a single surgeon. Complications of treatment and overall outcomes were evaluated. A total of 194 patients had cisplatin and 5-fluorouracil prior to esophageal resection. Six patients (5.7%) had progressive disease and were inoperable (discovered in four at surgery). During chemotherapy one patient died and one perforated (operated immediately). Complications including severe neutropenia, coronary artery spasm, renal impairment and pulmonary edema led to the premature cessation of chemotherapy in 12 patients (6.2%). A total of 182 patients with a median age of 63 (range 30-80), 41 squamous and 141 adenocarcinomas underwent surgery. Operations were 91 left thoracoabdominal (50%), 45 radical transhiatal (25%), 40 Ivor-Lewis (22%) and six stage three (3%), and 78.6% had microscopically complete (R0) resections. Median survival was 28 months with 77.3% surviving for 1 year and 57.7% for 2 year. In hospital mortality was 5.5% and anastomotic leak rate 7.7%. A radical surgical approach to the primary tumor in combination with OEO2 neoadjuvant chemotherapy has led to a high R0 resection rate and good survival with acceptable morbidity and mortality.

Proposals for the management of gastrointestinal stromal tumours of the stomach.

BACKGROUND AND AIMS: It has been reported that gastric gastrointestinal stromal tumours (GIST) are aggressive, rare and difficult to treat. Some have advocated radical resection as the only potential cure. We present data to support treatment of gastric GISTs with a limited surgical approach and minimal morbidity. Furthermore, we propose that surveillance for recurrence is unnecessary based upon the follow-up of a cohort of patients with gastric GISTs. METHODS: Database and case notes analysis of 20 patients diagnosed with gastric GIST (1998-2004) and managed by one surgeon in a single centre over seven years. Main outcome measures were inpatient adverse events, positive resection margins and symptom free survival. OUTCOMES: Three cases have been managed with surveillance only. Successful resection was performed in 17 patients without mortality. No patient had positive margins on histological assessment. Fifteen out of seventeen samples were positive for the c-Kit proto-oncogene (CD117) and 14117 positive for CD34. Only two patients required en-bloc resections due to the tumour size and involvement of adjacent structures. One patient developed metastatic disease during follow-up of 19-86 months. CONCLUSIONS: We recommend local excision of gastric GISTs to allow macroscopically clear margins. This policy then allows symptomatic follow-up due to the indolent nature of the majority of the tumours resected. A tailored follow-up with endoscopy and radiological imaging has been advocated by others but appears unnecessary in most cases. Imatinib (anti c-Kit) can now be offered to patients presenting with recurrent GIST, if further surgery is deemed inappropriate.

Liver function and splanchnic ischemia in critically ill patients.

STUDY OBJECTIVE: To investigate the concept that splanchnic ischemia leads to hepatic dysfunction in the critically ill. DESIGN: Prospective study and analysis of patient data. SETTING: A general ICU in an inner-city London teaching hospital. PATIENTS: Twenty-seven consecutive critically ill patients with evidence of inadequate tissue perfusion requiring pulmonary artery catheterization and mechanical ventilation. MEASUREMENTS: In all patients, we measured the hepatic metabolism of lidocaine (lignocaine) to monoethylglycinexylidide (MEGX) and the clearance of indocyanine green (both dynamic, flow-dependent tests of hepatic function) over the first 3 days following admission to the ICU. These were compared with results of standard liver function tests and related to tonometric assessment of gastric intramucosal pH (pHim) and outcome. RESULTS: There were no significant differences in bilirubin, aspartate aminotransferase, alkaline phosphatase, and prothrombin levels, or in indocyanine green clearance between survivors and nonsurvivors. On day 3, the median MEGX level was higher in survivors than in nonsurvivors (16 vs 2.4 ng/mL, p < 0.001), and the median MEGX level in nonsurvivors fell over the 3 days (20.6 to 2.4 ng/mL, p < 0.002). MEGX levels were significantly correlated with pHim (Spearman rank correlation coefficient [Rs] = 0.69, p < 0.001) as were the changes in the two measurements over the 3 days (Rs = 0.46, p < 0.02). The MEGX formation test and gastric pHim were the most discriminatory with regard to death and survival. CONCLUSIONS: Our findings suggest that critically ill patients develop significant hepatic dysfunction that is associated with a poor outcome. This is likely to be due to a mismatch between hepatic metabolic demand and blood flow, and the MEGX formation test appears to be an extremely effective means of assessing liver function and flow in this group of patients.