Vries, M.R. de

Re-displacement of stable distal both-bone forearm fractures in children: A randomised controlled multicentre trial (Article)

2012-12-04T00:00:00Z

Introduction: Displaced metaphyseal both-bone fractures of the distal forearm are generally reduced and stabilised by an above-elbow cast (AEC) with or without additional pinning. The purpose of this study was to find out if re-displacement of a reduced stable metaphyseal both-bone fracture of the distal forearm in a child could be prevented by stabilisation with Kirschner wires. Methods: Consecutive children aged <16 years with a displaced metaphyseal both-bone fracture of the distal forearm (n = 128) that was stable after reduction were randomised to AEC with or without percutaneous fixation with Kirschner wires. The primary outcome was re-displacement of the fracture. Results: A total of 67 children were allocated to fracture reduction and AEC and 61 to reduction of the fracture, fixation with Kirschner wires and AEC. The follow-up rate was 96% with a mean follow-up of 7.1 months. Fractures treated with additional pinning showed less re-displacement (8% vs. 45%), less limitation of pronation and supination (mean limitation 6.9 (±9.4)° vs. 14.3 (±13.6)°) but more complications (14 vs. 1). Conclusions: Pinning of apparent stable both-bone fractures of the distal forearm in children might reduce fracture re-displacement. The frequently seen complications of pinning might be reduced by a proper surgical technique.

Contralateral hip fractures and other osteoporosis-related fractures in hip fracture patients: Incidence and risk factors. An observational cohort study of 1,229 patients (Article)

2012-08-01T00:00:00Z

Purpose: To report risk factors, 1-year and overall risk for a contralateral hip and other osteoporosis-related fractures in a hip fracture population. Methods: An observational study on 1,229 consecutive patients of 50 years and older, who sustained a hip fracture between January 2005 and June 2009. Fractures were scored retrospectively for 2005-2008 and prospectively for 2008-2009. Rates of a contralateral hip and other osteoporosis- related fractures were compared between patients with and without a history of a fracture. Previous fractures, gender, age and ASA classification were analysed as possible risk factors. Results: The absolute risk for a contralateral hip fracture was 13.8 %, for one or more osteoporosis-related fracture( s) 28.6 %. First-, second- and third-year risk for a second hip fracture was 2, 1 and 0 %. Median (IQR) interval between both hip fractures was 18.5 (26.6) months. One-year incidence of other fractures was 6 %. Only age was a risk factor for a contralateral hip fracture, hazard ratio (HR) 1.02 (1.006-1.042, p = 0.008). Patients with a history of a fracture (33.1 %) did not have a higher incidence of fractures during follow-up (16.7 %) than patients without fractures in their history (14 %). HR for a contralateral hip fracture for the fracture versus the non-fracture group was 1.29 (0.75-2.23, p = 0.360). Conclusion: The absolute risk of a contralateral hip fracture after a hip fracture is 13.8 %, the 1-year risk was 2 %, with a short interval between the 2 hip fractures. Age was a risk factor for sustaining a contralateral hip fracture; a fracture in history was not.

Below-elbow cast for metaphyseal both-bone fractures of the distal forearm in children: A randomised multicentre study (Article)

2012-07-01T00:00:00Z

Introduction: Minimally displaced metaphyseal both-bone fractures of the distal forearm in children are often treated with an above-elbow cast (AEC). Treatment with a below-elbow cast (BEC) could give more comfort, but might lead to fracture displacement reducing pronation and supination. Because this has not been systematically investigated, we set up a randomised multicentre study. The purpose of this study was to find out whether BEC causes equal limitation of pronation and supination but with higher comfort level, compared with AEC. Patients and methods: In four hospitals, consecutive children aged < 16 (mean 7.1) years with a minimally displaced metaphyseal both-bone fracture of the distal forearm were randomised to 4 weeks BEC (n = 35) or 4 weeks AEC (n = 31). Primary outcome was limitation of pronation and supination 6 months after initial trauma. The secondary outcomes were cast comfort, limitation of flexion/extension of wrist/elbow, complications, cosmetics, complaints, and radiological assessment. Results: A group of 35 children received BEC and 31 children received AEC. All children attended for the final examination at a mean follow-up of 7.0 months (range 5.0-11.6 months). Limitation of pronation and supination 6 months after initial trauma showed no significant difference between the two groups [4.4°(±5.8) for BEC and 5.8°(±9.8) for AEC]. Children treated with BEC had significantly higher cast comfort on a visual analogue scale [5.6 (±2.7) vs. 8.4 (±1.4)] and needed significantly less help with dressing (8.2 days vs. 15.1 days). Six complications occurred in the BEC group and 14 in the AEC group. Other secondary outcomes were similar between the two groups. Conclusions: Children with minimally displaced metaphyseal both-bone fractures of the distal forearm should be treated with a below-elbow cast.

Risk factors for failure to return to the pre-fracture place of residence after hip fracture: a prospective longitudinal study of 444 patients (Article)

2012-06-01T00:00:00Z

Introduction: Long-term place of residence after hip fracture is not often described in literature. The goal of this study was to identify risk factors, known at admission, for failure to return to the pre-fracture place of residence of hip fracture patients in the Wrst year after a hip fracture. Methods: This is a prospective longitudinal study of 444 consecutive admissions of hip fracture patients aged ≥65 years. Place of residence prior to admission, at discharge, after 3 and 12 months was registered. Patients admitted from a nursing home (n = 49) were excluded from statistical analysis. Multivariable logistic regression analysis was performed, using age, gender, presence of a partner, ASAscore, dementia, anaemia at admission, type of fracture, pre-fracture level of mobility and level of activities of daily living (ADL) as possible risk factors. Results: Two hundred eighty-nine patients lived in their own home, 31.8% returned at discharge, 72.9% at 3 months and 72.8% at 12 months. Age, absence of a partner, dementia, and a lower pre-fracture level of ADL or mobility were independent contributors to failure to return to their own home at discharge, 3 or 12 months. 106 patients lived in a residential home; 33.3% returned at discharge, 68.4% at 3 months and 64.4% at 12 months. Age was an independent contributor to failure to return to a residential home. Conclusions: Age, dementia and a lower pre-fracture level of ADL were the main signiWcant risk factors for failure to return to the pre-fracture residence. As the 3- and 12-month return-rates were similar, 3-month follow-up might be used as an endpoint in future research.

Outcome in hip fracture patients related to anemia at admission and allogeneic blood transfusion: An analysis of 1262 surgically treated patients (Article)

2011-11-22T00:00:00Z

Background: Anemia is more often seen in older patients. As the mean age of hip fracture patients is rising, anemia is common in this population. Allogeneic blood transfusion (ABT) and anemia have been pointed out as possible risk factors for poorer outcome in hip fracture patients. Methods. In the timeframe 2005-2010, 1262 admissions for surgical treatment of a hip fracture in patients aged 65 years and older were recorded. Registration was prospective from 2008 on. Anemic and non-anemic patients (based on hemoglobin level at admission) were compared regarding clinical characteristics, mortality, delirium incidence, LOS, discharge to a nursing home and the 90-day readmission rate. Receiving an ABT, age, gender, ASA classification, type of fracture and anesthesia were used as possible confounders in multivariable regression analysis. Results: The prevalence of anemia and the rate of ABT both were 42.5%. Anemic patients were more likely to be older and men and had more often a trochanteric fracture, a higher ASA score and received more often an ABT. In univariate analysis, the 3- and 12-month mortality rate, delirium incidence and discharge to a nursing home rate were significantly worse in preoperatively anemic patients. In multivariable regression analysis, anemia at admission was a significant risk factor for discharge to a nursing home and readmission < 90 days, but not for mortality. Indication for ABT, age and ASA classification were independent risk factors for mortality at all moments, only the mortality rate for the 3-12 month interval was not influenced by ABT. An indication for an ABT was the largest negative contributor to a longer LOS (OR 2.26, 95% CI 1.73-2.94) and the second largest for delirium (OR 1.67, 95% CI 1.28-2.20). Conclusions: This study has demonstrated that anemia at admission and postoperative anemia needing an ABT (PANT) were independent risk factors for worse outcome in hip fracture patients. In multivariable regression analysis, anemia as such had no effect on mortality, due to a rescue effect of PANT. In-hospital, 3- and 12-month mortality was negatively affected by PANT, with the main effect in the first 3 months postoperatively.

Complications of syndesmotic screw removal (Article)

2011-11-01T00:00:00Z

Background: Currently, the metallic syndesmotic screw is the gold standard in the treatment of syndesmotic disruption. Whether or not this screw needs to be removed remains debatable. The aim of the current study was to determine the complications which occur following routine removal of the syndesmotic screw following operative treatment of unstable ankle fractures. Methods: This was a retrospective study with consecutive cases in a Level-2 Trauma center. All patients with routine removal of a syndesmotic screw, following the treatment of an unstable ankle fracture, between January 1, 2004 and November 30, 2010 were included. Complications recorded were: 1) minor or major wound infection following removal of the syndesmotic screw, 2) recurrent syndesmotic diastasis, and 3) unnecessary removal of a broken screw, not recognized during preoperative planning prior to surgery. Results: A total of 76 patients were included. A wound infection occurred in 9.2% (N=7) of which 2.6% (N=2) were deep infections requiring reoperation. Recurrent syndesmotic diastasis was found in 6.6% (N=5) of patients, and in 6.6% (N=5) screws were broken at the time of implant removal. In the group with recurrent diastasis the screws were removed significantly earlier compared with the group without recurrent diastasis (Mann- Whitney U-test; p = 0.011) and the group with screw breakage had their screws significantly longer in place compared with the group without breakage (p = 0.038). Conclusion: A total of 22.4% complications occurred upon routine removal of the syndesmotic screw. Removal might therefore be considered only in selected cases with complaints, after a minimum of eight to twelve weeks and using antibiotic prophylaxis during removal. Copyright

Determinants of outcome in operatively and non-operatively treated Weber-B ankle fractures (Article)

2011-09-01T00:00:00Z

Introduction: Treatment of ankle fractures is often based on fracture type and surgeon's individual judgment. Literature concerning the treatment options and outcome are dated and frequently contradicting. The aim of this study was to determine the clinical and functional outcome after AO-Weber B-type ankle fractures in operatively and conservatively treated patients and to determine which factors influenced outcome. Patients and methods: A retrospective cohort study in patients with a AO-Weber B-type ankle fracture. Patient, fracture and treatment characteristics were recorded. Clinical and functional outcome was measured using the Olerud-Molander Ankle Score (OMAS), the American Orthopaedic Foot and Ankle Society ankle-hindfoot score (AOFAS) and a Visual Analog Score (VAS) for overall satisfaction (range 0-10). Results: Eighty-two patients were treated conservatively and 103 underwent operative treatment. The majority was female. Most conservatively treated fractures were AO-Weber B1.1 type fractures. Fractures with fibular displacement (mainly AO type B1.2 and Lauge-Hansen type SER-4) were predominantly treated operatively. The outcome scores in the non-operative group were OMAS 93, AOFAS 98, and VAS 8. Outcome in this group was independently negatively affected by age, affected side, BMI, fibular displacement, and duration of plaster immobilization. In the surgically treated group, the OMAS, AOFAS, and VAS scores were 90, 97, and 8, respectively, with outcome negatively influenced by duration of plaster immobilization. Conclusion: Treatment selection based upon stability and surgeon's judgment led to overall good clinical outcome in both treatment groups. Reducing the cast immobilization period may further improve outcome.

Foot and ankle fractures at the supination line (Article)

2011-09-01T00:00:00Z

Background: The supination line is a fictive line along the foot and ankle, on which over twenty fracture types and approximately ten different ligamentous sprain-injuries have been identified. Objective: The current study was conducted to evaluate the incidence of different types of supination line injuries visible at the initial radiographs at the Emergency Department and to determine the type and percentage of misdiagnosed injuries. Method: Retrospective study of consecutive patients who visited the Emergency Department, between January 1 and June 30, 2009, after sustaining an injury of the foot or ankle and had a radiograph taken within 24. h of the incident. Results: In the 6-month study period 1284 patients were included. In these cases the trauma mechanism was a sprain in 780 patients (60.7%). Of these patients 310 suffered from a fracture (40%). There were 36 (4.6%) false-positive cases and in 91 (11.7%) cases the initial diagnosis was false-negative. The number with a missed fracture expressed as a percentage of all patients with a fracture was 29.4% (91/310). Conclusion: Detection of injuries along the supination line remains difficult. This study might aid in decreasing the number of misdiagnosed injuries, which is of value as these might negatively affect outcome.

Displaced midshaft fractures of the clavicle: Non-operative treatment versus plate fixation (Sleutel-TRIAL). A multicentre randomised controlled trial (Article)

2011-08-30T00:00:00Z

Background: The traditional view that the vast majority of midshaft clavicular fractures heal with good functional outcomes following non-operative treatment may be no longer valid for all midshaft clavicular fractures. Recent studies have presented a relatively high incidence of non-union and identified speciic limitations of the shoulder function in subgroups of patients with these injuries. Aim. A prospective, multicentre randomised controlled trial (RCT) will be conducted in 21 hospitals in the Netherlands, comparing fracture consolidation and shoulder function after either non-operative treatment with a sling or a plate fixation. Methods/design. A total of 350 patients will be included, between 18 and 60 years of age, with a dislocated midshaft clavicular fracture. The primary outcome is the incidence of non-union, which will be determined with standardised X-rays (Antero-Posterior and 30 degrees caudocephalad view). Secondary outcome will be the functional outcome, measured using the Constant Score. Strength of the shoulder muscles will be measured with a handheld dynamometer (MicroFET2). Furthermore, the health-related Quality of Life score (ShortForm-36) and the Disabilities of Arm, Shoulder and Hand (DASH) Outcome Measure will be monitored as subjective parameters. Data on complications, bone union, cosmetic aspects and use of painkillers will be collected with follow-up questionnaires. The follow-up time will be two years. All patients will be monitored at regular intervals over the subsequent twelve months (two and six weeks, three months and one year). After two years an interview by telephone and a written survey will be performed to evaluate the two-year functional and mechanical outcomes. All data will be analysed on an intention-to-treat basis, using univariate and multivariate analyses. Discussion. This trial will provide level-1 evidence for the comparison of consolidation and functional outcome between two standardised treatment options for dislocated midshaft clavicular fractures. The gathered data may support the development of a clinical guideline for treatment of clavicular fractures. Trial registration. Netherlands National Trial Register NTR2399.

Delirium risk screening and haloperidol prophylaxis program in hip fracture patients is a helpful tool in identifying high-risk patients, but does not reduce the incidence of delirium (Article)

2011-08-15T00:00:00Z

Background: Delirium in patients with hip fractures lead to higher morbidity and mortality. Prevention in high-risk patients by prescribing low dose haloperidol is currently under investigation. Methods. This prospective cohort surveillance assessed hip fracture patients for risk of developing a delirium with the Risk Model for Delirium (RD) score. High-risk patients (score ≥5 points) were treated with a prophylactic low-dose of haloperidol according to hospital protocol. Primary outcome was delirium incidence. Secondary outcomes were differences between high- and low-risk patients in delirium, length of stay (LOS), return to pre-fracture living situation and mortality. Logistic regression analysis was performed with age, ASA-classification, known dementia, having a partner, type of fracture, institutional residence and psychotropic drug use as possible confounders. Results: 445 hip fracture patients aged 65 years and older were admitted from January 2008 to December 2009. The RD-score was completed in 378 patients, 173 (45.8%) high-risk patients were treated with prophylactic medication. Sensitivity was 71.6%, specificity 63.8% and the negative predictive value (NPV) of a score < 5 was 85.9%. Delirium incidence (27.0%) was not significantly different compared to 2007 (27.8%) 2006 (23.9%) and 2005 (29.0%) prior to implementation of the RD- protocol. Logistic regression analysis showed that high-risk patients did have a significant higher delirium incidence (42.2% vs. 14.1%, OR 4.1, CI 2.43-7.02). They were more likely to be residing at an alternative living situation after 3 months (62.3% vs. 17.0%, OR 6.57, CI 3.23-13.37) and less likely to be discharged from hospital before 10 days (34.9% vs. 55.9%, OR 1.63, CI 1.03-2.59). Significant independent risk factors for a delirium were a RD-score 5 (OR 4.13, CI 2.43-7.02), male gender (OR 1.93, CI 0.99-1.07) and age (OR 1.03, CI 0.99-1.07). Conclusions: Introducing the delirium prevention protocol did not reduce delirium incidence. The RD-score did identify patients with a high risk to develop a delirium. This high-risk group had a longer LOS and returned to pre-fracture living situation less often. The NPV of a score < 5 was high, as it should be for a screening instrument. Concluding, the RD-score is a useful tool to identify patients with poorer outcome.

A hinged external fixator for complex elbow dislocations: A multicenter prospective cohort study (Article)

2011-06-09T00:00:00Z

Background: Elbow dislocations can be classified as simple or complex. Simple dislocations are characterized by the absence of fractures, while complex dislocations are associated with fractures of the radial head, olecranon, or coronoid process. The majority of patients with these complex dislocations are treated with open reduction and internal fixation (ORIF), or arthroplasty in case of a non-reconstructable radial head fracture. If the elbow joint remains unstable after fracture fixation, a hinged elbow fixator can be applied. The fixator provides stability to the elbow joint, and allows for early mobilization. The latter may be important for preventing stiffness of the joint. The aim of this study is to determine the effect of early mobilization with a hinged external elbow fixator on clinical outcome in patients with complex elbow dislocations with residual instability following fracture fixation. Methods/Design. The design of the study will be a multicenter prospective cohort study of 30 patients who have sustained a complex elbow dislocation and are treated with a hinged elbow fixator following fracture fixation because of residual instability. Early active motion exercises within the limits of pain will be started immediately after surgery under supervision of a physical therapist. Outcome will be evaluated at regular intervals over the subsequent 12 months. The primary outcome is the Quick Disabilities of the Arm, Shoulder, and Hand score. The secondary outcome measures are the Mayo Elbow Performance Index, Oxford Elbow Score, pain level at both sides, range of motion of the elbow joint at both sides, radiographic healing of the fractures and formation of periarticular ossifications, rate of secondary interventions and complications, and health-related quality of life (Short-Form 36). Discussion. The outcome of this study will yield quantitative data on the functional outcome in patients with a complex elbow dislocation and who are treated with ORIF and additional stabilization with a hinged elbow fixator. Trial Registration. The trial is registered at the Netherlands Trial Register (NTR1996).

Demographics and Functional Outcome of Toe Fractures (Article)

2011-05-01T00:00:00Z

Toe fractures are common; however, there are few data on demographics and functional outcome. We studied outcomes in 339 consecutive patients with toe fractures treated between January 2006 and September 2008. Two hundred and sixty-four patients, aged 16 to 75, were mailed an outcome questionnaire, and overall subjective satisfaction with the outcome of treatment was measured using a visual analog scale (VAS). Most frequently affected were the first (38%) and fifth (30%) toes, and most (75.6%) of the fractures were caused by stubbing or crush injury. More than 95% of the fractures were displaced less than 2 mm, and all of the fractures were treated conservatively. The questionnaire was returned by 141 (53%) patients with a median follow-up of 27 months. Respondents were female in 57.4% of cases and had a median age of 45 years. The median AOFAS score was 100 (P25, P75= 93,100) points; the median VAS was 10 (P25, P75= 8, 10) points. Univariate regression analysis revealed no statistically significant associations between outcome and the particular toe or phalanx involved, number of fractured toes, fracture type and location, articular involvement, gender, age, body mass index, smoking habits, and the presence of diabetes mellitus. Satisfaction VAS was dependent on age (P = .047) and gender (P = .049) in the multivariate analysis. The AOFAS midfoot score was not influenced by any of the covariates. This is the first epidemiological investigation using 2 outcome-scoring systems to determine function and satisfaction following treatment of toe fractures.

Demographics and Functional Outcome of Toe Fractures (Article)

2011-05-01T00:00:00Z

Functional treatment versus plaster for simple elbow dislocations (FuncSiE): A randomized trial (Article)

2010-11-16T00:00:00Z

Background. Elbow dislocations can be classified as simple or complex. Simple dislocations are characterized by the absence of fractures, while complex dislocations are associated with fractures. After reduction of a simple dislocation, treatment options include immobilization in a static plaster for different periods of time or so-called functional treatment. Functional treatment is characterized by early active motion within the limits of pain with or without the use of a sling or hinged brace. Theoretically, functional treatment should prevent stiffness without introducing increased joint instability. The primary aim of this randomized controlled trial is to compare early functional treatment versus plaster immobilization following simple dislocations of the elbow. Methods/Design. The design of the study will be a multicenter randomized controlled trial of 100 patients who have sustained a simple elbow dislocation. After reduction of the dislocation, patients are randomized between a pressure bandage for 5-7 days and early functional treatment or a plaster in 90 degrees flexion, neutral position for pro-supination for a period of three weeks. In the functional group, treatment is started with early active motion within the limits of pain. Function, pain, and radiographic recovery will be evaluated at regular intervals over the subsequent 12 months. The primary outcome measure is the Quick Disabilities of the Arm, Shoulder, and Hand score. The secondary outcome measures are the Mayo Elbow Performance Index, Oxford elbow score, pain level at both sides, range of motion of the elbow joint at both sides, rate of secondary interventions and complication rates in both groups (secondary dislocation, instability, relaxation), health-related quality of life (Short-Form 36 and EuroQol-5D), radiographic appearance of the elbow joint (degenerative changes and heterotopic ossifications), costs, and cost-effectiveness. Discussion. The successful completion of this trial will provide evidence on the effectiveness of a functional treatment for the management of simple elbow dislocations. Trial Registration. The trial is registered at the Netherlands Trial Register (NTR2025).

Demographics and outcome of metatarsal fractures (Article)

2010-01-01T00:00:00Z

Introduction: Although metatarsal fractures are amongst the most common injuries of the foot, this is the first study on outcome after metatarsal fractures. Method: All consecutive patients with metatarsal fractures treated between January 2006 and September 2008 were re-evaluated. Patients aged 16 to 75 were sent a questionnaire consisting of the American Orthopaedic Foot Ankle Society midfoot score and a Visual Analogue Scale (VAS) for patient satisfaction. Results: Four-hundred metatarsal fractures were identified in 322 patients. The fifth metatarsal was involved in more than 50% of patients. Most fractures were caused by an inversion injury or fall from height (75%). Out of 247 patients between 16 and 75 years, a total of 166 patients (67.2%) returned the questionnaire with a median follow-up of 33 months. All patients were treated conservatively. The median AOFAS score was 100 points (P25-P75, 87-100), the median VAS was 9 points (P25-P75, 8-10). The AOFAS and VAS scores correlated negatively with the body mass index (BMI) (Rs = -0.409 and -0.305; p < 0.001). Patients with diabetes reported lower VAS (p = 0.010) and AOFAS scores (p = 0.020). Females reported a lower AOFAS score (p = 0.034). An increase in dislocation (>2 mm) resulted in a decrease in VAS score (p = 0.017). Multivariable analysis indicated that the VAS score was significantly affected by BMI and dislocation >2 mm (p = 0.013). The AOFAS score was affected by BMI (p = 0.011). Conclusion: This is the first investigation using two validated outcome scoring systems to determine functional outcome in metatarsal fractures. Overall outcome in metatarsal fractures is high, as almost all fractures healed without complaints at 33 months. Outcome is dependent on BMI, diabetes, gender, and dislocation at the fracture site.

Tumor Necrosis Factor in Isolated Hepatic Perfusion: credits, debits and future directions (Doctoral Thesis)

2003-06-12T00:00:00Z

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.

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

2000-01-01T00:00:00Z

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 lead to fatal complications. The most prominent clinical toxicity was hypotension (grade III in four patients), which was easily corrected. No pulmonary or renal toxicity was observed in any patient. It is our experience that, even in the rare event of significant leakage during a TNFa-based ILP, postoperative toxicity is usually mild and can be easily managed by the use of fluid and, in some cases, vasopressors.