High Prevalence of Sarcopenia in Older Trauma Patients: A Pilot Study.

Sarcopenia is related to adverse outcomes in various populations. However, little is known about the prevalence of sarcopenia in polytrauma patients. Identifying the number of patients at risk of adverse outcome will increase awareness to prevent further loss of muscle mass. We utilized data from a regional prospective trauma registry of all polytrauma patients presented between 2015 and 2019 at a single level-I trauma center. Subjects were screened for availability of computed tomography (CT)-abdomen and height in order to calculate skeletal mass index, which was used to estimate sarcopenia. Additional parameters regarding clinical outcome were assessed. Univariate analysis was performed to identify parameters related adverse outcome and, if identified, entered in a multivariate regression analysis. Prevalence of sarcopenia was 33.5% in the total population but was even higher in older age groups (range 60-79 years), reaching 82 % in patients over 80 years old. Sarcopenia was related to 30-day or in-hospital mortality (p = 0.032), as well as age (p < 0.0001), injury severity score (p = 0.026), and Charlson comorbidity index (p = 0.001). Log rank analysis identified sarcopenia as an independent predictor of 30-day mortality (p = 0.032). In conclusion, we observed a high prevalence of sarcopenia among polytrauma patients, further increasing in older patients. In addition, sarcopenia was identified as a predictor for 30-day mortality, underlining the clinical significance of identification of low muscle mass on a CT scan that is already routinely obtained in most trauma patients.

SM22 a Plasma Biomarker for Human Transmural Intestinal Ischemia.

OBJECTIVE: To evaluate the diagnostic potential of smooth muscle protein of 22 kDa (SM22) as plasma biomarker for the detection of transmural intestinal ischemia. BACKGROUND: Acute mesenteric ischemia is an abdominal emergency requiring rapid diagnosis and treatment. Especially, detection of transmural damage is imperative because it mandates emergency surgery. Since early clinical and radiological signs are nonspecific, there is an urgent need for accurate biomarkers. SM22 is a potential marker for transmural damage because of its abundant expression in intestinal smooth muscles. METHODS: SM22 concentrations were measured using a newly built enzyme-linked immunosorbent assay. SM22 release was assessed in plasma and intestinal tissue of rats subjected to intestinal ischemia. Blood and tissue were sampled at baseline and followed up to 24 hours of ischemia. Next, organ-specific SM22 arteriovenous concentration differences were studied in both rats and patients. Finally, plasma from patients with intestinal ischemia, other acute abdominal complaints, and healthy volunteers were tested for SM22. RESULTS: SM22 concentrations were significantly elevated in rats from 4 hours of ischemia onwards. Furthermore, SM22 plasma concentrations closely paralleled the histological increasing degree of intestinal smooth muscle damage. Arteriovenous calculations showed that SM22 was specifically released by the intestines and renally cleared. First data of SM22 release in man demonstrated that patients with transmural intestinal ischemia had significantly higher plasma SM22 levels than patients with only ischemic mucosal injury, other acute abdominal diseases, or healthy controls. CONCLUSIONS: This study shows that SM22 is released into the circulation upon severe ischemia of the intestinal muscle layers. Plasma levels of SM22 are potentially useful for the detection of transmural intestinal damage.

Cyclooxygenase-2 Is Essential for Colorectal Anastomotic Healing.

OBJECTIVE: To study the effects of COX-2 on colonic surgical wound healing. BACKGROUND: Cyclooxygenase-2 (COX-2) is a key enzyme in gastrointestinal homeostasis. COX-2 inhibitors have been associated with colonic anastomotic leakage. METHODS: Wildtype, COX-2 knockout and COX-2 heterozygous mice were subjected to a model of colonic anastomotic leakage, and were treated with vehicle, diclofenac, or prostaglandin E2 (PGE2), the most important COX-2 product in the intestine. We assessed anastomotic leakage, mortality, angiogenesis, and inflammation. Furthermore, we investigated the association between anastomotic leakage and a human polymorphism of the COX-2 gene resulting in low COX-2 levels. RESULTS: Diclofenac, a nonsteroidal anti-inflammatory drug inhibiting COX-2, increased anastomotic leakage compared to vehicle-treated mice (100% vs 25%, respectively). Similarly, 92% of COX-2-deficient mice developed anastomotic leakage (P = 0.003) compared to WT. PGE2 partly rescued this severe phenotype because only 46% of PGE2-administered COX-2 knockout mice developed anastomotic leakage (P = 0.02). This may be related to decreased neovascularization, because decreased CD31 staining, indicating less blood vessels, was observed in COX-2 mice (2 vessels/mm vs 6 vessels/mm in controls (P = 0.03)). This effect could partly be reversed by administration of PGE2 to COX-2 mice. No significant differences in inflammation were found. PTGS2-765G>C polymorphism in humans, associated with reduced COX-2 expression, was associated with higher anastomotic leakage rates. CONCLUSIONS: COX-2-induced PGE2 production is essential for intestinal wound healing after colonic surgery, possibly via its effects on angiogenesis. These data emphasize that COX-2 inhibitors should be avoided after colonic surgery, and administration of PGE2 might be favorable for a selection of patients.

Sarcopenia is associated with an increased inflammatory response to surgery in colorectal cancer.

BACKGROUND & AIMS: Sarcopenia in gastrointestinal cancer has been associated with poor clinical outcome after surgery. The effect of low muscle mass on the inflammatory response to surgery has not been investigated, however skeletal muscle wasting in the context of cachexia is associated with a hyperinflammatory state at baseline. Knowledge on this matter can provide new insight into the detrimental effects of sarcopenia on postoperative recovery, possibly leading to novel therapeutic strategies. The aim of this study was to evaluate whether low muscle mass is associated with increased inflammation after resection of colorectal malignancies. METHODS: Eighty-seven consecutive patients undergoing elective resection of a primary colorectal tumor were enrolled. Muscle mass was assessed on routine preoperative computed tomography (CT) scans using image analysis by Osirix(®) by measuring skeletal muscle at the third lumbar vertebra (L3) level. The effect of muscle mass on pre- and postoperative plasma concentrations of C-reactive protein (CRP), calprotectin and interleukin-6 (IL-6) was analyzed. Clinical outcome was assessed by HARM (HospitAl stay, Readmission, and Mortality) scores. RESULTS: Skeletal muscle mass was not predictive of plasma concentrations of CRP and IL-6. However, low skeletal muscle mass was significantly predictive of high plasma concentrations of calprotectin on postoperative days (POD) 2 through 5, reaching highest significance on POD4 (regression beta, -6.06; 95% confidence interval, -10.45 to -1.68; p = 0.007). CONCLUSIONS: Low muscle mass in patients undergoing surgery for colorectal cancer was associated with an increased postoperative inflammatory response. This may be at least part of the explanation for the high incidence of postoperative complications in sarcopenic patients.

Sarcopenia is highly prevalent in patients undergoing surgery for gastric cancer but not associated with worse outcomes.

OBJECTIVES: Aim of this study was to assess the prevalence of sarcopenia and body composition (i.e., subcutaneous and visceral fat) in gastric cancer surgical patients and its association with adverse postoperative outcome. METHODS: Preoperative CT scans were obtained from all patients who underwent surgery for gastric adenocarcinoma between January 2005 and September 2012. Total muscle and adipose tissue cross-sectional area were measured at the level of the third lumbar vertebra (L3) transverse processes. Sarcopenia was defined according to gender- and body mass index (BMI)-specific cutoff points. Primary outcome was in-hospital mortality. Secondary outcomes were severe postoperative complications (i.e., Clavien-Dindo classification ≥3a complications) and 6-month mortality. RESULTS: In 152 out of a total of 180 (84.4%) patients, a CT-scan was available for analysis. In total, 86 (57.7%) of the patients were classified as sarcopenic. Sarcopenia was no predictor for in-hospital mortality (P = 0.52), severe complications (P = 1.00) or 6-month mortality (P = 0.69). Intraabdominal and subcutaneous adipose tissue measurements were not associated with in-hospital mortality, severe complications or 6-month mortality. CONCLUSIONS: In this population of gastric cancer surgical patients, the prevalence of sarcopenia was 57.7%, which is high compared to other abdominal surgical oncology populations. However, sarcopenia was not associated with postoperative morbidity or mortality.

Loss of Skeletal Muscle Mass During Neoadjuvant Chemoradiotherapy Predicts Postoperative Mortality in Esophageal Cancer Surgery.

BACKGROUND: Esophageal surgery is associated with complications and mortality. It is highly important to develop tools predicting unfavorable postoperative outcome. Esophageal cancer and neoadjuvant chemoradiotherapy (CRT) induce skeletal muscle wasting, which leads to diminished physiologic reserves. The purpose of this study was to investigate whether the degree of muscle mass lost during neoadjuvant CRT predicts postoperative mortality. METHODS: A total of 123 consecutive patients undergoing surgery for esophageal malignancy in the period 2008-2012 were included, of whom 114 received neoadjuvant CRT. Skeletal muscle mass was measured on routinely performed CT scans by assessing L3 muscle index (according to the Prado method) before and after neoadjuvant CRT, and the amount of muscle mass lost during neoadjuvant CRT (muscle loss index) was calculated. It was investigated whether this amount was associated with postoperative 30-day or in-hospital mortality and morbidity. RESULTS: In the complete cohort, no significant association between loss of muscle mass and mortality was found. However, skeletal muscle mass was significantly lower in patients with stage III-IV tumors compared with stage I-II tumors, prior to neoadjuvant CRT. In the stage III-IV subgroup, the amount of muscle mass lost during neoadjuvant CRT was predictive of postoperative mortality: -13.5 % (standard deviation 6.2 %) in patients who died postoperatively compared with -5.0 % (standard deviation 8.3 %) in surviving patients, p = 0.02. CONCLUSIONS: Measurement of muscle mass loss during neoadjuvant chemoradiotherapy may provide a readily available and inexpensive assessment to identify patients at risk for developing unfavorable postoperative outcome after resection of esophageal malignancies, especially in patients with stage III-IV tumors.

Functional compromise reflected by sarcopenia, frailty, and nutritional depletion predicts adverse postoperative outcome after colorectal cancer surgery.

OBJECTIVE: To determine the association of sarcopenia with postoperative morbidity and mortality after colorectal surgery. BACKGROUND: Functional compromise in elderly colorectal surgical patients is considered as a significant factor of impaired postoperative recovery. Therefore, the predictive value of preoperative functional compromise assessment was investigated. Sarcopenia is a hallmark of functional compromise. METHODS: A total of 310 consecutive patients who underwent oncologic colorectal surgery were included in a prospective digital database. Sarcopenia was assessed using the L3 muscle index utilizing Osirix on preoperative computed tomography. Groningen Frailty Indicator and Short Nutritional Assessment Questionnaire scores were used to assess frailty and nutritional compromise. Predictors for anastomotic leakage, sepsis, and mortality were analyzed by logistic regression analysis. RESULTS: Age was an independent predictor of mortality [P = 0.04; odds ratio, 1.17; 95% confidence interval (CI), 1.01-1.37]. Thirty-day/in-hospital mortality rate in sarcopenic patients was 8.8% versus 0.7% in nonsarcopenic patients (P = 0.001; odds ratio, 15.5; 95% CI, 2.00-120). Sarcopenia was not predictive for anastomotic leakage or sepsis. Combination of high Short Nutritional Assessment Questionnaire score, high Groningen Frailty Indicator score, and sarcopenia strongly predicted sepsis (P = 0.001; odds ratio, 25.1; 95% CI, 5.11-123), sensitivity, 46%; specificity, 97%; positive likelihood ratio, 13 (95% CI, 4.4-38); negative likelihood ratio, 0.57 (95% CI, 0.33-0.97). CONCLUSIONS: Functional compromise in colorectal cancer surgery is associated with adverse postoperative outcome. Assessment of functional compromise by means of a nutritional questionnaire (Short Nutritional Assessment Questionnaire), a frailty questionnaire (Groningen Frailty Indicator), and sarcopenia measurement (L3 muscle index) can accurately predict postoperative sepsis.

Accurate prediction of anastomotic leakage after colorectal surgery using plasma markers for intestinal damage and inflammation.

BACKGROUND: Anastomotic leakage is a frequent and life-threatening complication after colorectal surgery. Early recognition of anastomotic leakage is critical to reduce mortality. Because early clinical and radiologic signs of anastomotic leakage are often nonspecific, there is an urgent need for accurate biomarkers. Markers of inflammation and gut damage might be suitable, as these are hallmarks of anastomotic leakage. STUDY DESIGN: In 84 patients undergoing scheduled colorectal surgery with primary anastomosis, plasma samples were collected preoperatively and daily after surgery. Inflammatory markers, C-reactive protein; calprotectin; and interleukin-6, and intestinal damage markers, intestinal fatty acid binding protein; liver fatty acid binding protein; and ileal bile acid binding protein, were measured. Diagnostic accuracy of single markers or combinations of markers was analyzed by receiver operating characteristic curve analysis. RESULTS: Anastomotic leakage developed in 8 patients, clinically diagnosed at median day 6. Calprotectin had best diagnostic accuracy to detect anastomotic leakage postoperatively. Highest diagnostic accuracy was obtained when C-reactive protein and calprotectin were combined at postoperative day 3, yielding sensitivity of 100%, specificity of 89%, positive likelihood ratio = 9.09 (95% CI, 4.34-16), and negative likelihood ratio = 0.00 (95% CI, 0.00-0.89) (p < 0.001). Interestingly, preoperative intestinal fatty acid binding protein levels predicted anastomotic leakage at a cutoff level of 882 pg/mL with sensitivity of 50%, specificity of 100%, positive likelihood ratio = infinite (95% CI, 4.01-infinite), and negative likelihood ratio = 0.50 (95% CI, 0.26-0.98) (p < 0.0001). CONCLUSIONS: Preoperative intestinal fatty acid binding protein measurement can be used for anastomotic leakage risk assessment. In addition, the combination of C-reactive protein and calprotectin has high diagnostic accuracy. Implementation of these markers in daily practice deserves additional investigation.

Improving the outcomes in oncological colorectal surgery.

During the last several decades, colorectal cancer surgery has experienced some major perioperative improvements. Preoperative risk-assessment of nutrition, frailty, and sarcopenia followed by interventions for patient optimization or an adapted surgical strategy, contributed to improved postoperative outcomes. Enhanced recovery programs or fast-track surgery also resulted in reduced length of hospital stay and overall complications without affecting patient safety. After an initially indecisive start due to uncertainty about oncological safety, the most significant improvement in intraoperative care was the introduction of laparoscopy. Laparoscopic surgery for colon and rectal cancer is associated with better short-term outcomes, whereas long-term outcomes regarding survival and recurrence rates are comparable. Nevertheless, long-term results in rectal surgery remain to be seen. Early recognition of anastomotic leakage remains a challenge, though multiple improvements have allowed better management of this complication.

Breast-feeding improves gut maturation compared with formula feeding in preterm babies.

OBJECTIVE: The incidence of necrotizing enterocolitis (NEC) is higher in formula-fed babies than in breast-fed babies, which may be caused by breast-feeding-induced gut maturation. The effect of breast-feeding on gut maturation has been widely studied in animal models. This study aimed to assess the effects of breast-feeding on intestinal maturation in prematurely born babies by evaluating postnatal changes in urinary intestinal fatty acid binding protein (I-FABP) levels, a specific enterocyte marker. METHODS: Gut maturation in 40 premature babies (<37 weeks of gestation) without gastrointestinal morbidity was studied, of whom 21 were exclusively breast-fed and 19 were formula-fed infants. Urinary I-FABP levels as the measure of gut maturation were measured at 5, 12, 19, and 26 days after birth. RESULTS: In breast-fed infants, there was a significant increase in median urinary I-FABP levels between 5 and 12 days after birth (104 [78-340] pg/mL to 408 [173-1028] pg/mL, P = 0.002), whereas I-FABP concentration in formula-fed infants increased between 12 and 19 days after birth (105 [44-557] pg/mL, 723 [103-1670] pg/mL, P = 0.004). Breast-fed babies had significantly higher median urinary I-FABP levels at postnatal day 12 (P = 0.01). CONCLUSIONS: The time course of the postnatal increase in urinary I-FABP levels reflecting gut maturation was significantly delayed in formula-fed babies, suggesting a delayed physiological response in formula-fed compared with breast-fed infants.

Intestinal fatty acid-binding protein: a possible marker for gut maturation.

BACKGROUND: Gut immaturity is linked with postnatal intestinal disorders. However, biomarkers to assess the intestinal developmental stage around birth are lacking. The aim of this study was to gain more insight on intestinal fatty acid-binding protein (I-FABP) as an indicator of gut maturity. METHODS: Antenatal I-FABP distribution and release was investigated in extremely premature, moderately premature, and term lambs, and these findings were verified in human urinary samples. Ileal I-FABP distribution was confirmed in autopsy material within 24 h postnatally. RESULTS: Median (range) serum I-FABP levels were lower in extremely premature lambs compared with moderately premature lambs (156 (50.0-427) vs. 385 (100-1,387) pg/ml; P = 0.02). Contrarily, median early postnatal urine I-FABP levels in human infants were higher in extremely premature compared with moderately premature and term neonates (1,219 (203-15,044) vs. 256 (50-1,453) and 328 (96-1,749) pg/ml; P = 0.008 and P = 0.04, respectively). I-FABP expression was most prominent in nonvacuolated enterocytes and increased with rising gestational age (GA) in ovine and human tissue samples. The epithelial distribution pattern changed from a phenotype displaying I-FABP-positive enterocytes merely in the crypts early in gestation into a phenotype with I-FABP expressing cells exclusively present in the villus tips at term in ovine and human tissue. CONCLUSION: In this ovine and human study, increasing GA is accompanied by an increase in I-FABP tissue content. Cord I-FABP levels correlate with gestation in ovine fetuses, identifying I-FABP as a marker for gut maturation. Raised postnatal urine I-FABP levels in preterm human infants may indicate intestinal injury and/or inflammation in utero.

Non-invasive serum amyloid A (SAA) measurement and plasma platelets for accurate prediction of surgical intervention in severe necrotizing enterocolitis (NEC).

OBJECTIVE: To evaluate the value of biomarkers to detect severe NEC. SUMMARY BACKGROUND DATA: The time point of surgery in necrotizing enterocolitis (NEC) is critical. Therefore, there is a need for markers that detect severe NEC, because clinical signs of severe NEC often develop late. This study evaluated the value of biomarkers reflecting intestinal cell damage and inflammation to detect severe NEC. METHODS: 29 neonates with NEC were included. Two definitions of moderate versus severe NEC were analyzed: medical NEC (n = 12) versus surgical or fatal NEC (n = 17); and Bell stage II NEC (n = 13) versus stage III NEC (n = 16). Urinary intestinal fatty acid binding protein (I-FABP), serum amyloid A (SAA), C3a and C5a, and fecal calprotectin were measured. C-reactive protein (CRP), white blood cell count (WBC) and platelet count data were measured in blood. RESULTS: In both definitions of moderate versus severe NEC, urinary SAA levels were significantly higher in severe NEC. A cut-off value of 34.4 ng/ml was found in surgical NEC versus medical NEC (sensitivity, 83%; specificity, 83%; LR+, 4.88 (95% CI, 1.37-17.0); LR-, 0.20 (95% CI, 0.07-0.60)) at diagnosis of NEC and at one day prior to surgery in neonates who were operated later on. Combination of urinary SAA and platelet count increased the accuracy, with a sensitivity, 94%; specificity, 83%; LR+, 5.53 (95% CI, 1.57-20.0); and LR-, 0.07 (95% CI, 0.01-0.48). CONCLUSION: Urinary SAA is an accurate marker in differentiating severe NEC from moderate NEC; particularly if combined with serum platelet count.

Word of caution before implementing ketotifen for gastrointestinal transit improvement.

The therapeutic potential of long-term ketotifen in irritable bowel syndrome and postoperative ileus is currently under investigation. Ambiguous results of prolonged postoperative ketotifen use on gastrointestinal passage have been found. The current data point at a hampered gastrointestinal transit after prolonged postoperative ketotifen use in a rodent ileus induction model. Therefore, caution should be taken when administering ketotifen in the perioperative phase.

Sarcopenia negatively affects preoperative total functional liver volume in patients undergoing liver resection.

OBJECTIVES: Sarcopenia may negatively affect short-term outcomes after liver resection. The present study aimed to explore whether total functional liver volume (TFLV) is related to sarcopenia in patients undergoing partial liver resection. METHODS: Analysis of total liver volume and tumour volume and measurements of muscle surface were performed in patients undergoing liver resection using OsiriX(®) and preoperative computed tomography. The ratio of TFLV to bodyweight was calculated as: [TFLV (ml)/bodyweight (g)]*100%. The L3 muscle index (cm(2) /m(2) ) was then calculated by normalizing muscle areas (at the third lumbar vertebral level) for height. RESULTS: Of 40 patients, 27 (67.5%) were classified as sarcopenic. There was a significant correlation between the L3 skeletal muscle index and TFLV (r= 0.64, P < 0.001). Median TFLV was significantly lower in the sarcopenia group than in the non-sarcopenia group [1396 ml (range: 1129-2625 ml) and 1840 ml (range: 867-2404 ml), respectively; P < 0.05]. Median TFLV : bodyweight ratio was significantly lower in the sarcopenia group than in the non-sarcopenia group [2.0% (range: 1.4-2.5%) and 2.3% (range: 1.5-2.5%), respectively; P < 0.05]. CONCLUSIONS: Sarcopenic patients had a disproportionally small preoperative TFLV compared with non-sarcopenic patients undergoing liver resection. The preoperative hepatic physiologic reserve may therefore be smaller in sarcopenic patients.

Noninvasive measurement of intestinal epithelial damage at time of refeeding can predict clinical outcome after necrotizing enterocolitis.

BACKGROUND: Reintroduction of enteral nutrition in neonates with necrotizing enterocolitis (NEC) should take place when the gut is ready for its normal function. Too early a start of oral feeding might lead to disease relapse, whereas prolonged discontinuation of enteral nutrition is associated with impaired gut function and parenteral nutrition-related complications. This study evaluated whether noninvasive urinary measurement of intestinal fatty acid binding protein (I-FABP) at the time of refeeding can predict clinical outcome in neonates with NEC. METHODS: Urinary I-FABP concentrations were measured in 21 infants with NEC just before reintroducing enteral nutrition. Poor outcome was defined as unsuccessful reintroduction of enteral feeding (EF), (re)operation for NEC, or death related to NEC after reintroduction of EF. RESULTS: Median urinary I-FABP levels in neonates with poor outcome (n = 5) were significantly higher as compared with I-FABP levels in neonates with good outcome (n = 16) (P < 0.01). A clinically significant cutoff value of 963 pg/ml was found to discriminate between infants with poor outcome and those with good outcome (sensitivity 80%, specificity 94%). CONCLUSION: Noninvasive urinary I-FABP measurement at time of refeeding differentiates neonates with poor outcome from neonates with good outcome in NEC. Urinary I-FABP measurement may therefore be helpful in the timing of EF in neonates with NEC.

Noninvasive measurement of fecal calprotectin and serum amyloid A combined with intestinal fatty acid-binding protein in necrotizing enterocolitis.

BACKGROUND: Diagnosis of necrotizing enterocolitis (NEC), prevalent in premature infants, remains challenging. Enterocyte damage in NEC can be assessed by intestinal fatty acid-binding protein (I-FABP), with a sensitivity of 93% and a specificity of 90%. Numerous markers of inflammation are known, such as serum amyloid A (SAA) and fecal calprotectin. PURPOSE: The aim of the present study was to evaluate which combination of noninvasive measurement of inflammatory markers and I-FABP improves the diagnostic accuracy in neonates suspected for NEC. METHODS: In 62 neonates with clinical suspicion of NEC (29 with final diagnosis of NEC), urinary I-FABP, urinary SAA, and fecal calprotectin levels were determined quantitatively. Diagnostic accuracy was calculated for the combinations I-FABP-SAA and I-FABP-fecal calprotectin, using a multivariable logistic regression model. RESULTS: The combination of SAA and I-FABP did not increase the diagnostic accuracy of I-FABP. However, the combination of fecal calprotectin and I-FABP improved accuracy significantly. The combination of urinary I-FABP and fecal calprotectin measurement produced a sensitivity of 94%, a specificity of 79%, a positive likelihood ratio of 4.48, and a negative likelihood ratio of 0.08. CONCLUSION: The combination of noninvasive measurement of I-FABP and fecal calprotectin seems promising for diagnosing NEC at an early time point. Prospective analysis is required to confirm this finding and to evaluate better treatment strategies based on noninvasive measurement of I-FABP and calprotectin.

Total intermittent Pringle maneuver during liver resection can induce intestinal epithelial cell damage and endotoxemia.

OBJECTIVES: The intermittent Pringle maneuver (IPM) is frequently applied to minimize blood loss during liver transection. Clamping the hepatoduodenal ligament blocks the hepatic inflow, which leads to a non circulating (hepato)splanchnic outflow. Also, IPM blocks the mesenteric venous drainage (as well as the splenic drainage) with raising pressure in the microvascular network of the intestinal structures. It is unknown whether the IPM is harmful to the gut. The aim was to investigate intestinal epithelial cell damage reflected by circulating intestinal fatty acid binding protein levels (I-FABP) in patients undergoing liver resection with IPM. METHODS: Patients who underwent liver surgery received total IPM (total-IPM) or selective IPM (sel-IPM). A selective IPM was performed by selectively clamping the right portal pedicle. Patients without IPM served as controls (no-IPM). Arterial blood samples were taken immediately after incision, ischemia and reperfusion of the liver, transection, 8 hours after start of surgery and on the first post-operative day. RESULTS: 24 patients (13 males) were included. 7 patients received cycles of 15 minutes and 5 patients received cycles of 30 minutes of hepatic inflow occlusion. 6 patients received cycles of 15 minutes selective hepatic occlusion and 6 patients underwent surgery without inflow occlusion. Application of total-IPM resulted in a significant increase in I-FABP 8 hours after start of surgery compared to baseline (p<0.005). In the no-IPM group and sel-IPM group no significant increase in I-FABP at any time point compared to baseline was observed. CONCLUSION: Total-IPM in patients undergoing liver resection is associated with a substantial increase in arterial I-FABP, pointing to intestinal epithelial injury during liver surgery. TRIAL REGISTRATION: ClinicalTrials.gov NCT01099475.