Ward based goal directed fluid therapy (GDFT) in acute pancreatitis (GAP) trial: A feasibility randomised controlled trial.

BACKGROUND: Goal-directed fluid therapy (GDFT) reduces complications in patients undergoing major general surgery. There are no reports of cardiac output evaluation being used to optimise the fluid administration for patients with acute pancreatitis (AP) in a general surgery ward. METHOD: 50 patients with AP were randomised to either ward-based GDFT (n = 25) with intravenous (IV) fluids administered based on stroke volume optimisation protocol or standard care (SC) (n = 25), but with blinded cardiac output evaluation, for 48-h following hospital admission. Primary outcome was feasibility. RESULTS: 50 of 116 eligible patients (43.1%) were recruited over 20 months demonstrating feasibility. 36 (72%) completed the 48-h of GDFT; 10 (20%) discharged within 48-h and 4 withdrawals (3 GDFT, 1 SC). Baseline characteristics were similar with only 3 participants having severe disease (6%, 1 GDFT, 2 SC). Similar volumes of IV fluids were administered in both groups (GDFT 5465 (1839) ml, SC 5211 (1745) ml). GDFT group had a lower heart rate, blood pressure and respiratory rate and improved oxygen saturations. GDFT was not associated with any harms. There was no evidence of difference in complications of AP (GDFT 24%, SC 32%) or in the duration of stay in intensive care (GDFT 0 (0), SC 0.7 (3) days). Length of hospital stay was 5 (2.9) days in GDFT and 6.3 (7.6) in SC groups. CONCLUSION: Ward-based GDFT is feasible and shows a signal of possible efficacy in AP in this early-stage study. A larger multi-site RCT is required to confirm clinical and cost effectiveness.

Ward-based Goal-Directed Fluid Therapy (GDFT) in Acute Pancreatitis (GAP) trial: study protocol for a feasibility randomised controlled trial.

INTRODUCTION: Acute pancreatitis is an inflammatory disease of the pancreas with high risk of developing multiorgan failure and death. There are no effective pharmacological interventions used in current clinical practice. Maintaining fluid and electrolyte balance is the mainstay of supportive management. Goal-directed fluid therapy (GDFT) has been shown to decrease morbidity and mortality in surgical conditions with systemic inflammatory response. There is currently no randomised controlled trial (RCT) investigating the role of GDFT based on cardiac output parameters in patients with acute pancreatitis in the ward setting. A feasibility trial was designed to determine patient and clinician support for recruitment into an RCT of ward-based GDFT in acute pancreatitis, adherence to a GDFT protocol, safety, participant withdrawal, and to determine appropriate endpoints for a subsequent larger trial to evaluate efficacy. METHODS AND ANALYSIS: The GDFT in Acute Pancreatitis trial is a prospective two-centre feasibility RCT. Eligible adults admitted with new onset of acute pancreatitis will be enrolled and randomised into ward-based GDFT (n=25) or standard fluid therapy (n=25) within 6 hours from the diagnosis and continuing for the following 48 hours. Cardiac output parameters will be monitored with a non-invasive device (Cheetah NICOM; Cheetah Medical). The intervention group will consist of a protocolised GDFT approach consisting of stroke volume optimisation with crystalloid fluid boluses, while the control group will receive standard care fluid therapy as advised by the clinical team. The primary endpoint is feasibility. Secondary endpoints will include safety of the intervention, complications, mortality, admission to intensive care unit, cost and quality of life. ETHICS AND DISSEMINATION: Ethics approval was granted by the London Central Research Ethics Committee (17/LO/1235, project ID: 221872). The results of this trial will be presented to international conference with interest in general surgery and acute care and published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ISRCTN36077283.

The Neutrophil-to-Lymphocyte Ratio as a Marker of Lymph Node Status in Patients with Rectal Cancer.

AIM: The aim of the study was to investigate the role of the neutrophil-to-lymphocyte ratio (NLR) as a prognostic marker of rectal cancers. METHODS: We undertook a retrospective review of patients with rectal cancer. Pre-treatment NLR was assessed for association and predictive values against clinicopathological staging and post-treatment outcomes. RESULTS: A total of 140/180 cases were included in the final analysis [male:female 2:1; mean age 68 years (interquartile range 58-75)]. The pre-operative mean NLR was 5.4 ± 6.8. There was a strong positive correlation between NLR and C-reactive protein (Spearman's rho 64.3%, p < 0.001). A high NLR was associated with a positive nodal status on MRI (5.2 vs. 3.8, p = 0.03) and histopathological (4.8 vs. 3.8, p = 0.02) assessment. The NLR showed an average value for predicting MRI and pathological nodal status on receiver operating characteristic analysis [area under the curve = 0.72 (95% CI = 0.54-0.91), p = 0.031 and area under the curve = 0.64 (95% CI = 0.52-0.077), p = 0.021, respectively]. On multivariate analysis, the total lymph node retrieved at operation was the best predictor of pathological nodal involvement; NLR did not show any predictive value. Patients with an NLR >4 showed reduced recurrence-free (60 vs. 86 months, p = 0.52) and overall survival (57 vs. 84 months, p = 0.40) without statistical significance. CONCLUSION: Raised pre-treatment NLR may indicate nodal involvement in patients with rectal cancer.

Hemophagocytic lymphohistiocytosis caused by primary Epstein-Barr virus in patient with Crohn's disease.

We present a case of a 19-year-old man with a 6-year history of Crohn's disease (CD), previously treated with 6-mercaptopurine, who was admitted to our department for Epstein-Barr virus (EBV) infection and subsequently developed a hemophagocytic lymphohistiocytosis (HLH). HLH is a rare disease which causes phagocytosis of all bone marrow derived cells. It can be a primary form as a autosomic recessive disease, or a secondary form associated with a variety of infections; EBV is the most common, the one with poorer prognosis. The incidence of lymphoproliferative disorders was increased in patients with inflammatory bowel disease (IBD) treated with thiopurines. Specific EBV-related clinical and virological management should be considered when treating a patient with IBD with immunosuppressive therapy. Moreover EBV infection in immunosuppressed patient can occur with more aggressive forms such as encephalitis and diffuse large B cell lymphoma. Our case confirms what is described in the literature; patients with IBD, particularly patients with CD receiving thiopurine therapy, who present 5 d of fever and cervical lymphadenopathy or previous evidence of lymphopenia should be screened for HLH.