Tumor Necrosis Factor in Isolated Hepatic Perfusion: credits, debits and future directions

Patients with irresectable hepatic malignancies remain an intriguing clinical problem. Hepatocellular carcinoma (HCC) is the most common primary hepatic malignancy and approximately one million individuals will develop this tumor per year. The incidence of these tumors varies widely worldwide, being most common in the Far East [1]. Recent advances in the early detection of these tumors have improved the prognosis and long-term survival has been reported in patients with small, encapsulated malignancy [2-4]. Nevertheless, the overall prognosis of HCC remains poor and usually expressed in months rather than years [5, 6] Metastatic disease from colorectal cancer is the most common hepatic malignancy in the Western countries. Most frequently, the liver is the site of dissemination with many other sites in the body (lung, brain, bone). On the other hand, in as many as 30 % of patients the liver is the sole site of initial cancer recurrence [7]. If left untreated the mean survival rate in these patients is approximately 6 to 9 months. In contrast, 5-year survival rates up to 35 % have been reported for patients amendable to resection [8-11]. Unfortunately in the majority (75 %) of the patients that have been diagnosed with colorectal cancer metastases confined only to the liver, these metastases are considered unresectable. These patients are eligible for other therapies

Surgery for local recurrence of rectal carcinoma

PURPOSE: This study was designed to evaluate results, especially mortality and morbidity, of surgical resection with curative intent for patients with a l

The timing of ankle fracture surgery and the effect on infectious complications; A case series and systematic review of the literature

Purpose: Information about the influence of delayed surgery on infectious wound complications is ambiguous. A clinical audit was performed to test the hypothesis that early surgery lowers the rate of infectious wound complications. Secondly we looked at the influence of surgical delay and complications on patient reported functional outcome. Methods: All consecutive, closed distal fibular fractures treated surgically with a plate were included and retrospectively analysed for the delay in operation and wound complications. In a second cohort of patients with a AO-Weber B-type ankle fracture outcome was measured using the Olerud-Molander ankle score (OMAS), the American Orthopaedic Foot and Ankle Society score (AOFAS) and a visual analog score (VAS) for overall satisfaction. Results: Patients treated within one day experienced no wound complications (zero out of 60), whereas in the delayed group 11 % (16/145) did (p = 0.004). A similar significant difference was found for the patients treated within one week (2/98) versus after one week (14/107). A systematic review of the literature showed a difference in wound complications of 3.6 % (early) versus 12.9 % (late) (p < 0.0001). After 43 months, the median AOFAS was 11.5 points lower in the complication group, the OMAS 10 points, and the VAS 0.5 points, with all differences being statistically significant. Conclusions: Every effort should be made to operate on closed ankle fractures as soon as reasonably possible. A delay in surgery is associated with a significant rise in infectious wound complications, which significantly lowers outcome and patient satisfaction. These fractures should preferably be treated within the first day

Systemic toxicity and cytokine/acute phase protein levels in patients after isolated limb perfusion with tumor necrosis factor-alpha complicated by high leakage

BACKGROUND: Since the introduction of high-dose tumor necrosis factor-alpha (TNFalpha) in the setting of isolated limb perfusion (ILP) in the clinic, prevention of leakage to the body of the patient is monitored with great precision for fear of TNF-mediated toxicity. That we observed remarkably little toxicity in patients with and without leakage prompted us to determine patterns of cytokines and acute phase proteins in patients with high leakage and in patients without any leakage. METHODS: TNFalpha, interleukin (IL)-6, IL-8, C-reactive protein, and secretory (s)-phospholipase A2 were measured at several time points during and after (until 7 days) ILP in 10 patients with a leakage to the systemic circulation varying in percentage from 12% to 65%. As a control, the same measurements, both in peripheral blood and in perfusate, were performed in nine patients without systemic leakage. RESULTS: In patients with systemic leakage, levels of TNFalpha increased during ILP, reaching values to 277 ng/ml. IL-6 and IL-8 peaked 3 hours after ILP with values significantly higher compared with patients without systemic leakage. C-reactive protein and s-phospholipase A2 peaked at day 1 in both patient groups, s-phospholipase A2 with significant higher levels and C-reactive protein, in contrast, with lower levels in the leakage patients. CONCLUSIONS: High leakage of TNFalpha to the systemic circulation, caused by a complicated ILP, led to 10-fold to more than 100-fold increased levels of TNFalpha, IL-6, and IL-8 in comparison with patients without leakage. The increase of the acute phase proteins was limited. Even when high leakage occurs, this procedure should not

Acute-phase response patterns in isolated hepatic perfusion with tumour necrosis factor α (TNF-α) and melphalan in patients with colorectal liver metastases

Background. In this study, we have evaluated hepatotoxicity, secondary cytokine production and hepatic acute-phase response (APR) in patients who underwent isolated hepatic perfusion (IHP) with tumour necrosis factor (TNF) α and melphalan for irresectable colorectal liver metastases. Design. An extracorporeal veno-venous bypass was used to shunt blood from the lower body and intestines to the heart. Inflow catheters were placed in the hepatic artery and portal vein, and an outflow catheter in the inferior caval vein. The liver was perfused for 60 min with 0.4 mg of TNF-α plus 1 mg kg-1 melphalan (IHP(TM) group, n = 6) or 1 mg kg-1 melphalan (IHP(M) group, n = 3). The liver was washed with macrodex before restoring vascular continuity. Results. After the washout procedure, a TNF-α peak (169 ± 38 pg mL-1) was demons

Early mobilisation versus plaster immobilisation of simple elbow dislocations: Results of the FuncSiE multicentre randomised clinical trial

Background/aim To compare outcome of early mobilisation and plaster immobilisation in patients with a simple elbow dislocation. We hypothesised that early mobilisation would result in earlier functional recovery. Methods From August 2009 to September 2012, 100 adult patients with a simple elbow dislocation were enrolled in this multicentre randomised controlled trial. Patients were randomised to early mobilisation (n=48) or 3 weeks plaster immobilisation (n=52). Primary outcome measure was the Quick Disabilities of the Arm, Shoulder, and Hand (Quick-DASH) score. Secondary outcomes were the Oxford Elbow Score, Mayo Elbow Performance Index, pain, range of motion, complications and activity resumption. Patients were followed for 1 year. Results Quick-DASH scores at 1 year were 4.0 (95% CI 0.9 to 7.1) points in the early mobilisation group versus 4.2 (95% CI 1.2 to 7.2) in the plaster immobilisation group. At 6 weeks, early mobilised patients reported less disability (Quick-DASH 12 (95% CI 9 to 15) points vs 19 (95% CI 16 to 22); p<0.05) and had a larger arc of flexion and extension (121° (95% CI 115° to 127°) vs 102° (95% CI 96° to 108°); p<0.05). Patients returned to work sooner after early mobilisation (10 vs 18 days; p=0.020). Complications occurred in 12 patients; this was unrelated to treatment. No recurrent dislocations occurred. Conclusions Early active mobilisation is a safe and effective treatment for simple elbow dislocations. Patients recovered faster and returned to work earlier without increasing the complication rate. No evidence was found supporting treatment benefit at 1 year

ARIA 2016: Care pathways implementing emerging technologies for predictive medicine in rhinitis and asthma across the life cycle

The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma a

Colorectal liver metastases: Surgery versus thermal ablation (COLLISION) - a phase III single-blind prospective randomized controlled trial

Background: Radiofrequency ablation (RFA) and microwave ablation (MWA) are widely accepted techniques to eliminate small unresectable colorectal liver metastases (CRLM). Although previous studies labelled thermal ablation inferior to surgical resection, the apparent selection bias when comparing patients with unresectable disease to surgical candidates, the superior safety profile, and the competitive overall survival results for the more recent reports mandate the setup of a randomized controlled trial. The objective of the COLLISION trial is to prove non-inferiority of thermal ablation compared to hepatic resection in patients with at least one resectable and ablatable CRLM and no extrahepatic disease. Methods: In this two-arm, single-blind multi-center phase-III clinical trial, six hundred and eighteen patients with at least one CRLM (≤3cm) will be included to undergo either surgical resection or thermal ablation of appointed target lesion(s) (≤3cm). Primary endpoint is OS (overall survival, intention-to-treat analysis). Main secondary endpoints are overall disease-free survival (DFS), time to progression (TTP), time to local progression (TTLP), primary and assisted technique efficacy (PTE, ATE), procedural morbidity and mortality, length of hospital stay, assessment of pain and quality of life (QoL), cost-effectiveness ratio (ICER) and quality-adjusted life years (QALY). Discussion: If thermal ablation proves to be non-inferior in treating lesions ≤3cm, a switch in treatment-method may lead to a reduction of the post-procedural morbidity and mortality, length of hospital stay and incremental costs without compromising oncological outcome for patients with CRLM. Trial registration:NCT03088150 , January 11th 2017

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection ar