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ABSTRACT: Postoperative infectious complications (PICs) are associated with significant morbidity after abdominal surgery. Using multivariate analysis of data from a prospective database, our study focused on the risk factors for PICs and the prevention of these complications after hepatectomy, with the goal of improving outcomes and reducing the length of hospital stays. BACKGROUND: PICs following surgery are associated with significant morbidity, increase the length of hospital stays, and have a negative impact on long-term oncological outcome. The aim of this study was to determine the risk factors for PICs following partial hepatectomy and to validate these results with an external database. METHODS: Between January 2006 and December 2009, 555 patients underwent elective partial hepatectomy. We prospectively collected and retrospectively analyzed demographic data, pathological variables, associated pathological conditions, and preoperative, intraoperative, and postoperative variables. The dependent variables studied were the occurrence of PICs, defined as development of one or more of the following conditions: pneumonia, sepsis, Central line-associated bloodstream infection, urinary tract infection, wound infection, and infected intra-abdominal fluid collection. PICs were devised in medical (PIMCs) and surgical (PISCs) complications. The incidence of PICs and validation of the predictive score were determined using an external prospective database of 342 patients. RESULTS: The multivariate analysis identified three independent risk factors for PICs: the presence of a nasogastric tube (OR = 1.8), blood transfusion (OR = 1.9), and diabetes (OR = 2.4). The multivariate analysis identified only one independent risk factor for PISCs: an associated portal venous resection (OR = 5.5). The multivariate analysis identified four independent risk factors for PIMCs: presence of a biliary drainage (OR = 1.9), blood transfusion (OR = 2.1), diabetes (OR = 2.9), and presence of atrial fibrillation (OR = 3.6). According to the three predictive factors, the observed rates of PICs ranged from 18.8 % to 77.8 % and ranged from 24.2 % to 100 % in the external database. Predicted and observed risks of PICs were not statistically different. CONCLUSIONS: The correction of modifiable risk factors among the identified factors could reduce the incidence of PICs and, as a consequence, improve patient outcomes and reduce the length of hospital stays.
Journal of Gastrointestinal Surgery 05/2013; · 2.83 Impact Factor
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ABSTRACT: To warrant the adoption or rejection of health care interventions in daily practice, it is important to establish the point at which the available evidence is considered sufficiently conclusive. This process must avoid bias resulting from multiple testing and take account of heterogeneity across studies. The present paper addresses the issue of whether the available evidence may be considered sufficiently conclusive to continue or discontinue the current practice of postoperative abdominal drainage after pancreatic resection.
A systematic review was conducted of randomized and non-randomized studies comparing outcomes after routine intra-abdominal drainage with those after no drainage after pancreatic resection. Studies were retrieved from the PubMed, Cochrane Central Trial Register and EMBASE databases and meta-analysed cumulatively, adjusting for multiple testing and heterogeneity using the iterated logarithm method.
Three reports, describing, respectively, one randomized and two non-randomized studies with a comparative design, met the inclusion criteria predefined for primary studies reporting on drain management and complications after pancreatic resection. These studies included 89, 179 and 226 patients, respectively. The absolute differences in rates of postoperative complications in these studies were -6.4%, -9.5% and -6.3%, respectively, in favour of the no-drain groups. The cumulative risk difference in major complications, adjusted for multiple testing and heterogeneity, was -7.8%, with a 95% confidence interval of -20.2% to 4.7% (P = 0.214).
The routine use of abdominal drains after pancreatic resection may result in a higher risk for major complications, but the evidence is inconclusive.
HPB 05/2013; 15(5):337-44. · 1.60 Impact Factor
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ABSTRACT: Enhanced recovery after surgery (ERAS) or fast-track protocols have been implemented in different fields of surgery to attenuate the surgical stress response and accelerate recovery. The objective of this study was to systematically review the literature on outcomes of ERAS protocols applied in liver surgery.
The MEDLINE, EMBASE, PubMed and Cochrane Library databases were searched for randomized controlled trials (RCTs), case-control studies and case series published between January 1966 and October 2011 comparing adult patients undergoing elective liver surgery in an ERAS programme with those treated in a conventional manner. The primary outcome measure was hospital length of stay (LoS). Secondary outcome measures were time to functional recovery, and complication, readmission and mortality rates.
A total of 307 articles were found, six of which were included in the review. These comprised two RCTs, three case-control studies and one retrospective case series. Median LoS ranged from 4 days in an ERAS group to 11 days in a control group. Morbidity, mortality and readmission rates did not differ significantly between the groups. Only two studies assessed time to functional recovery. Functional recovery in these studies was reached 2 days before discharge.
This systematic review suggests that ERAS protocols can be successfully implemented in liver surgery. Length of stay is reduced without compromising morbidity, mortality or readmission rates.
HPB 04/2013; 15(4):245-51. · 1.60 Impact Factor
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ABSTRACT: BACKGROUND: A considerable number of patients develop sinusoidal obstruction syndrome (SOS) after oxaliplatin-based chemotherapy for colorectal liver metastases (CLMs). SOS is associated with adverse outcomes after major hepatectomy. Hyaluronic acid (HA) is a marker of hepatic sinusoidal endothelial cell function and may serve as an accurate marker of SOS. This study aimed to assess the value of systemic HA levels and fractional extraction (FE) of HA by the splanchnic area and liver as markers of SOS after oxaliplatin-based chemotherapy for CLMs. METHODS: Forty patients were studied. The presence of SOS was assessed histopathologically. Blood samples from the radial artery and portal and hepatic veins were collected. HA levels were determined by ELISA and the FE of HA was estimated. RESULTS: SOS was present in 23 patients, 11 of whom demonstrated moderate or severe SOS. Preoperative HA levels were significantly higher in patients with moderate or severe SOS (group B, n = 11) compared to patients with no or mild SOS (group A, n = 29) (51.6 ± 10.2 ng/mL vs. 32.1 ± 3.5 ng/mL, p = 0.030). A cutoff HA level of 44.1 ng/mL yielded a sensitivity of 67 % and specificity of 83 % for detection of SOS. The positive predictive value was 50 % and the negative predictive value 91 %. Both groups exhibited a similar FE of HA by the splanchnic area (-7.9 ± 8.5 % in Group A vs. 7.3 ± 3.6 % in Group B, p = 0.422) and liver (-10.7 ± 6.2 % in Group A vs. 4.6 ± 2.3 % in Group B, p = 0.265). CONCLUSIONS: Systemic HA levels can be used to detect patients at risk of SOS after oxaliplatin-based chemotherapy for CLMs. Additional investigations into the presence of SOS are indicated in patients with elevated HA levels.
Annals of Surgical Oncology 03/2013; · 4.17 Impact Factor
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ABSTRACT: PURPOSE OF REVIEW: Ischemia-reperfusion injury is inevitable during intestinal transplantation and can negatively affect the transplant outcome. Here, an overview is provided of the recent advances in the pathophysiological mechanisms of intestinal ischemia-reperfusion injury and how this may impact graft survival. RECENT FINDINGS: The intestine hosts a wide range of microorganisms and its mucosa is heavily populated by immune cells. Intestinal ischemia-reperfusion results in the disruption of the epithelial lining, affecting also protective Paneth cells (antimicrobials) and goblet cells (mucus), and creates a more hostile intraluminal microenvironment. Consequently, both damage-associated molecular patterns as well as pathogen-associated molecular patterns are released from injured tissue and exogenous microorganisms, respectively. These 'danger' signals may synergistically activate the innate immune system. Exaggerated innate immune responses, involving neutrophils, mast cells, platelets, dendritic cells, as well as Toll-like receptors and complement proteins, may shape the adaptive T-cell response, thereby triggering the destructive alloimmune response toward the graft and resulting in transplant rejection. SUMMARY: Innate immune activation as a consequence of ischemia-reperfusion injury may compromise engraftment of the intestine. More dedicated research is required to further establish this concept in man and to design more effective therapeutic strategies to better tolerize intestinal grafts.
Current opinion in organ transplantation 02/2013; · 1.22 Impact Factor
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ABSTRACT: Both laparoscopic techniques and multimodal enhanced recovery programmes have been shown to improve recovery and reduce length of hospital stay. Interestingly, evidence-based care programmes are not widely implemented, whereas new, minimally invasive surgical procedures are often adopted with very little evidence to support their effectiveness. The present survey aimed to shed light on experiences of the adoption of both methods of optimizing recovery.
An international, web-based, 18-question, electronic survey was composed in 2010. The survey was sent out to 673 hepatopancreatobiliary (HPB) centres worldwide in June 2010 to investigate international experiences with laparoscopic liver surgery, fast-track recovery programmes and surgery-related equipoise in open and laparoscopic techniques and to assess opinions on strategies for adopting laparoscopic liver surgery in HPB surgical practice.
A total of 507 centres responded (response rate: 75.3%), 161 of which finished the survey completely. All units reported performing open liver resections, 24.2% performed open living donor resections, 39.1% carried out orthotopic liver transplantations, 87.6% had experience with laparoscopic resections and 2.5% performed laparoscopic living donor resections. A median of 50 (range: 2-560) open and 9.5 (range: 1-80) laparoscopic liver resections per surgical unit were performed in 2009. Patients stayed in hospital for a median of 7 days (range: 2-15 days) after uncomplicated open liver resection and a median of 4 days (range: 1-10 days) after uncomplicated laparoscopic liver resection. Only 28.0% of centres reported having experience with fast-track programmes in liver surgery. The majority considered the instigation of a randomized controlled trial or a prospective register comparing the outcomes of open and laparoscopic techniques to be necessary.
Worldwide dissemination of laparoscopic liver resection is substantial, although laparoscopic volumes are low in the majority of HPB centres. The adoption of enhanced recovery programmes in liver surgery is limited and should be given greater attention.
HPB 12/2012; 14(12):818-27. · 1.60 Impact Factor
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ABSTRACT: BACKGROUND: Manipulation of the liver during liver surgery results in profound hepatocellular damage. Experimental data show that mobilization-induced hepatocellular damage is related to hepatic inflammation. To date, information on this link in humans is lacking. As it is possible to modulate inflammation, it is clinically relevant to unravel this relationship. AIM: This observational study aimed to establish the association between liver mobilization and hepatic inflammation in humans. METHODS: Consecutive patients requiring mobilization of the right hemi-liver during liver surgery were studied. Plasma samples and liver biopsies were collected prior to and directly after mobilization and after transection of the liver. Hepatocellular damage was assayed by liver fatty acid-binding protein (L-FABP) and aminotransferase levels. Hepatic inflammation was determined by (a) immunohistochemical identification of myeloperoxidase (MPO) and CD68- positive cells and (b) hepatic gene expression of inflammatory and cell adhesion molecules (IL-1β, IL-6, IL-8, VCAM-1 and ICAM-1). RESULTS: A total of 25 patients were included. L-FABP levels increased significantly during mobilization (301 ± 94 ng/ml to 1599 ± 362 ng/ml, P = 0.008), as did ALAT levels (36 ± 5 IU/L to 167 ± 21 IU/L, P < 0.001). A significant increase in MPO (P = 0.001) and CD68 (P = 0.002) positive cells was noticed in the liver after mobilization. The number of MPO-positive cells correlated with the duration of mobilization (Pearson correlation=0.505, P = 0.033). Hepatic gene expression of pro-inflammatory cytokines IL-1β and IL-6, chemo-attractant IL-8 and adhesion molecule ICAM-1 increased significantly during liver manipulation. CONCLUSIONS: Liver mobilization is associated with hepatocellular damage and liver inflammation, as shown by infiltration of inflammatory cells and upregulation of genes involved in acute inflammation.
Liver international: official journal of the International Association for the Study of the Liver 11/2012; · 3.82 Impact Factor
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ABSTRACT: BACKGROUND: Sustainability of hepatic glutathione (GSH) homeostasis is an important cellular defense against oxidative stress. Therefore, knowledge of liver GSH status is important. However, measurement of plasma GSH and tissue is difficult due to its instability. Alternatively, ophthalmate (OPH), an endogenous tripeptide analog of GSH, has been suggested as a potential indicator to assess GSH depletion. AIM: To provide an overview of present knowledge with respect to the usefulness of OPH as a biomarker for oxidative stress and hepatic GSH homeostasis. METHODS: A systematic, computerized search combined with a cross-reference search of the literature described in PubMed (January 1975 to January 2012) was conducted, key words: 'ophthalmate' and 'ophthalmic acid'. RESULTS: Twenty-two articles were included. Hepatic OPH levels increase inversely proportional to a drop in hepatic GSH in mice with paracetamol (PCM) induced hepatotoxicity. Little is known about the stability of OPH in human plasma. To measure the very low physiological concentrations of plasma OPH, liquid chromatography-mass spectrometry techniques can be employed. OPH synthesis can be measured in humans, using stable isotope labeling with a deuterated water ((2)H(2)O) load. CONCLUSION: OPH may be a promising biomarker to indicate hepatic glutathione depletion, but the suggested biological pathways need further unraveling.
Clinical nutrition (Edinburgh, Scotland) 10/2012; · 3.27 Impact Factor
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ABSTRACT: BACKGROUND: Although the safety of liver surgery has improved enormously, hepatic surgery continues to face challenging complications. Therefore, improvements supported by evidence-based guidelines are still required. The conduct of randomized controlled trials in liver surgery using dichotomous outcomes requires a large sample size. The use of surrogate endpoints (SEPs) reduces sample size but SEPs should be validated before use. AIM: The aim of this review was to summarize the SEPs used in hepatic surgery related trials, their definitions and recapitulating the evidence validating their use. METHOD: A systematic computerized literature search in the biomedical database PubMed using the MeSH terms 'hepatectomy' or 'liver resection' or 'liver transection' was conducted. Search was limited to papers written in the English language and published between 1 January 2000 and 1 January 2010. RESULTS: A total of 593 articles met the search terms and 49 articles were included in the final selection. Standard biochemical liver functions tests were the most frequently used SEP (32 of 49 the studies). The used definitions of SEPs varied greatly among the studies. Most studies referred to earlier published material to justify their choice of SEP. However, no validating studies were found. CONCLUSION: Many SEPs are used in liver surgery trials however there is little evidence validating them.
HPB 10/2012; · 1.60 Impact Factor
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Kristoffer Lassen,
Marielle M E Coolsen,
Karem Slim,
Francesco Carli,
José E de Aguilar-Nascimento,
Markus Schäfer,
Rowan W Parks,
Kenneth C H Fearon,
Dileep N Lobo,
Nicolas Demartines,
Marco Braga,
Olle Ljungqvist, Cornelis H C Dejong
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ABSTRACT: BACKGROUND: Protocols for enhanced recovery provide comprehensive and evidence-based guidelines for best perioperative care. Protocol implementation may reduce complication rates and enhance functional recovery and, as a result of this, also reduce length-of-stay in hospital. There is no comprehensive framework available for pancreaticoduodenectomy. METHODS: An international working group constructed within the Enhanced Recovery After Surgery (ERAS(®)) Society constructed a comprehensive and evidence-based framework for best perioperative care for pancreaticoduodenectomy patients. Data were retrieved from standard databases and personal archives. Evidence and recommendations were classified according to the GRADE system and reached through consensus in the group. The quality of evidence was rated "high", "moderate", "low" or "very low". Recommendations were graded as "strong" or "weak". RESULTS: Comprehensive guidelines are presented. Available evidence is summarised and recommendations given for 27 care items. The quality of evidence varies substantially and further research is needed for many issues to improve the strength of evidence and grade of recommendations. CONCLUSIONS: The present evidence-based guidelines provide the necessary platform upon which to base a unified protocol for perioperative care for pancreaticoduodenectomy. A unified protocol allows for comparison between centres and across national borders. It facilitates multi-institutional prospective cohort registries and adequately powered randomised trials.
World Journal of Surgery 09/2012; · 2.36 Impact Factor
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ABSTRACT: Measurement of the incorporation or conversion of infused stable isotope enriched metabolites in vivo such as amino acids plays a key role in metabolic research. Specific routes are frequently probed in knockout mouse models limiting the available amount of sample. Although less precise as compared to combustion-isotope ratio mass spectrometry (C-IRMS), gas chromatography-mass spectrometry (GC-MS) or liquid chromatography-mass spectrometry (LC-MS) techniques are therefore often the method of choice to measure isotopic enrichment of target metabolites. However, under conditions of metabolic depletion, the precision of these systems becomes limiting. In this paper, studies were performed to enhance the sensitivity and precision of isotope enrichment measurements using LC-MS. Ion-statistics and resolution were identified as critical factors for this application when using a linear trap mass spectrometer. The combination with an automated pre-column derivatization and a carefully selected solvent mix allowed us to measure isotopic enrichments down to 0.005% at plasma concentrations as low as 5μmol/l, an improvement by a factor of 100 compared to alternative methods. The resulting method now allowed measurement of the in vivo conversion of the amino acid arginine into citrulline as a marker for the production of nitric oxide in an in vivo murine endotoxemia model with depleted plasma levels of arginine and citrulline.
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 08/2012; 905:31-6. · 2.78 Impact Factor
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ABSTRACT: BACKGROUND & AIMS: Increased gastrointestinal (GI) permeability is an important hallmark of many conditions, potentially leading to antigen exposure and sepsis. Current permeability tests are hampered by analytical limitations. This study aims to compare the accuracy of our multi-sugar (MS) and the classical dual sugar (DS) test for detection of increased GI permeability. METHODS: Ten volunteers received permeability analysis using MS (1 g sucrose, lactulose, sucralose, erythritol, 0.5 g rhamnose in water) or DS (5 g lactulose, 0.5 g rhamnose), after indomethacin or placebo. Blood and urine were analyzed by isocratic LC-MS. RESULTS: MS testing revealed significantly elevated urinary lactulose/rhamnose (L/R) ratios after indomethacin, due to enhanced lactulose excretion (P < .01) and unaltered rhamnose excretion. The DS test showed increased L/R ratios, due to increased lactulose excretion and decreased rhamnose excretion (both P < .05). After indomethacin, plasma L/R increased in both assays (P < .05 and P < .01). Urinary and plasma L/R ratios correlated significantly. Indomethacin increased sucrose excretion and 0-1 h sucrose/rhamnose. Colon permeability was unchanged. CONCLUSIONS: Sensitive permeability analysis is feasible in plasma and urine using MS or DS test. In contrast to the DS test, monosaccharide excretion is not decreased by the MS test. In short, the MS test provides accurate, site-specific information on gastroduodenal, small, and large intestinal permeability. Registered at US National Library of Medicine (http://www.clinicaltrials.gov, NCT00943345).
Clinical nutrition (Edinburgh, Scotland) 08/2012; · 3.27 Impact Factor
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ABSTRACT: Based on animal experimentations, ophthalmate (OPH) has recently been suggested as a potential plasma biomarker to probe hepatic GSH homeostasis. Up until now, the inability to accurately determine OPH concentrations in human plasma prohibited further studies of OPH metabolism in humans. This study therefore aimed to study the influence of delayed sample preparation on OPH concentrations using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Venous plasma samples from 5 healthy human volunteers were incubated for varying times (5, 30, 60 and 120 min) at temperatures of 4 °C and 37 °C to investigate potential enzymatic degradation. At 37 °C, the decrease in OPH reached significance after 120 min (74.6% (range: 56.2-100.0%; p<0.0001)). At 4 °C, the same trend was observed but did not reach significance. These findings indicate ongoing enzymatic activity, stressing the need for immediate sample deproteinization to obtain reliable plasma concentrations. To investigate the feasibility of the here developed method, baseline arterial plasma values of 21 patients scheduled for partial liver resection were determined to be 0.06±0.03 μmol/l (mean±s.d.). In addition, in pooled samples from 3 patients, an OPH calibration curve was spiked to arterial plasma, arterial whole blood and liver biopsy material, resulting in a linear calibration curve in all cases. Individual measurements of baseline samples revealed that both arterial whole blood and liver biopsy material contained significant levels of endogenous OPH, namely 16.1 (11.8-16.4) μmol/l and 80.0 (191.8-349.2) μmol/kg, respectively. In conclusion, the present LC-MS/MS assay enables the accurate measurement of OPH in human plasma, whole blood and liver biopsies. Freshly prepared samples and immediate deproteinization are mandatory to block enzymatic degradation.
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 06/2012; 903:1-6. · 2.78 Impact Factor
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ABSTRACT: 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.
HPB 06/2012; · 1.60 Impact Factor
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ABSTRACT: Sinusoidal obstruction syndrome (SOS) occurs in 50-70% of patients after oxaliplatin treatment for hepatic colorectal metastasis. SOS is associated with portal hypertension and is caused by oxidative damage to endothelial cells and matrix metalloproteinase (MMP) induction. We studied the effect of a flavonoid (monoHER) on SOS prevention.
A monocrotaline (MTC) SOS model was used in rats, with pre-treatment of monoHER. We studied hepatocellular damage and MMP expression. The potential inhibition of oxaliplatin cytotoxicity by monoHER was tested in vitro in colorectal cancer cell lines.
MonoHER ameliorated the increase in portal pressure after MCT (72 hr: 7.3 ± 2.7 mmHg vs. 11.4 ± 3.0 mmHg, P = 0.016 MCT + monoHER vs. MCT, P < 0.01). MonoHER prevented hepatocellular damage (ALT: 48 hr 42.2 ± 3.1 IU/L vs. 253.4 ± 171.7 IU/L, P = 0.034; 72 hr: 46.2 ± 4.3 IU/L vs. 311.9 ± 163.6 IU/L, MCT + monoHER vs. MCT, P < 0.01). The liver damage score was lower in the monoHER group (72 hr: 4.8 ± 3.6 vs. 10.3 ± 0.5, MCT-monoHER vs. MCT, P < 0.01) associated with less inflammatory cell infiltration. Livers of MCT treated rats had higher expression of MMP-9 when compared to monoHER pairs at 24 hr (P = 0.016) and 72 hr (P < 0.001). MonoHER had no effect on in vitro proliferation of colorectal cancer cells when used either alone or in combination with oxaliplatin.
MonoHER prevented MCT induced portal hypertension and hepatic injury in rats.
Journal of Surgical Oncology 01/2012; 106(1):72-8. · 2.10 Impact Factor
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ABSTRACT: 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.
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.
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.
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.
ClinicalTrials.gov NCT01099475.
PLoS ONE 01/2012; 7(1):e30539. · 4.09 Impact Factor
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ABSTRACT: Small intestinal ischemia-reperfusion (IR) is a frequent, potentially life threatening phenomenon. There is a lack of non-invasive diagnostic modalities. For many intestinal diseases, visualizing the intestinal mucosa using endoscopy is gold standard. However, limited knowledge exists on small intestinal IR-induced, early mucosal changes. The aims of this study were to investigate endoscopic changes in human jejunum exposed to IR, and to study concordance between endoscopic appearance and histology.
In 23 patients a part of jejunum, to be removed for surgical reasons, was isolated and selectively exposed to ischemia with 0, 30 or 120 minutes of reperfusion. In 3 patients, a videocapsule was inserted in the isolated segment before exposure to IR, to visualize the mucosa. Endoscopic view at several time points was related to histology (Heamatoxylin & Eosin) obtained from 20 patients.
Ischemia was characterized by loss of villous structure, mucosal whitening and appearance of punctate lesions. This was related to appearance of subepithelial spaces and breaches in the epithelial lining in the histological view. Early during reperfusion, the lumen filled with IR-damaged, shed cells and VCE showed mucosal erosions, hemorrhage and intraluminal debris. At 60 minutes of reperfusion, the only remaining signs of IR were loss of villous structure and small erosions, indicating rapid mucosal healing.
This study shows a unique, real-time in vivo endoscopic view of early mucosal changes during IR of the human small intestine. Future studies should evaluate its usefulness in diagnosis of patients suspected of IR.
PLoS ONE 01/2012; 7(6):e39638. · 4.09 Impact Factor
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Jan H M B Stoot,
Edgar M Wong-Lun-Hing,
Ione Limantoro,
Ruben Visschers,
Olivier R Busch,
Richard Van Hillegersberg,
Koert M De Jong,
Arjen M Rijken,
Geert Kazemier,
Steven W M Olde Damink,
Toine M Lodewick,
Marc H A Bemelmans,
Ronald M van Dam, Cornelis H C Dejong
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ABSTRACT: The objective of this study was to provide a systematic review on the introduction of laparoscopic liver surgery in the Netherlands, to investigate the initial experience with laparoscopic liver resections and to report on the current status of laparoscopic liver surgery in the Netherlands.
A systematic literature search of laparoscopic liver resections in the Netherlands was conducted using PubMed/MEDLINE. Analysis of initial experience with laparoscopic liver surgery was performed by case-control comparison of patients undergoing laparoscopic left lateral sectionectomy matched with patients undergoing the open procedure in the Netherlands between the years 2000 and 2008. Furthermore, a nationwide survey was conducted in 2011 on the current status of laparoscopic liver surgery.
The systematic review revealed only 6 Dutch reports on actual laparoscopic liver surgery. Matched case-control comparison showed significant differences in the length of hospital stay, blood loss and operation time. Complications did not differ significantly between the two groups (26 vs. 21%). The 2011 survey showed that 21 centers in the Netherlands performed formal liver resections and that 49 (5% of total) laparoscopic liver resections were performed in 2010.
The systematic review revealed that very few laparoscopic liver resections were performed in the Netherlands in the previous millennium. The matched case-control comparison of laparoscopic and open left lateral resection showed a reduction in hospital length of stay with comparable morbidity. The laparoscopic technique has been slowly adopted in the Netherlands, but its popularity seems to increase in recent years.
Digestive surgery 01/2012; 29(1):70-8. · 1.37 Impact Factor
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ABSTRACT: For patients who present with synchronous colorectal carcinoma and colorectal liver metastasis (CRLM), a reversed treatment sequence in which the CRLM are resected before the primary carcinoma has been proposed (liver-first approach). The aim of the present study was to assess the feasibility and outcome of this approach for synchronous CRLM.
Between 2005 and 2010, 22 patients were planned to undergo the liver-first approach. Feasibility and outcomes were prospectively evaluated.
Of the 22 patients planned to undergo the liver-first strategy, the approach was completed in 18 patients (81.8%). The main reason for treatment failure was disease progression. Patients who completed treatment and patients who deviated from the protocol had a similar location of the primary tumour, as well as comparable size, number and distribution of CRLM (all P > 0.05). Post-operative morbidity and mortality were 27.3% and 0% following liver resection and 44.4% and 5.6% after colorectal surgery, respectively. On an intention-to-treat-basis, overall 3-year survival was 41.1%. However, 37.5% of patients who completed the treatment had developed recurrent disease at the time of the last follow-up.
The liver-first approach is feasible in approximately four-fifths of patients and can be performed with peri-operative mortality and morbidity similar to the traditional treatment paradigm. Patients treated with this novel strategy derive a considerable overall-survival-benefit, although disease-recurrence-rates remain relatively high, necessitating a multidisciplinary approach.
HPB 10/2011; 13(10):745-52. · 1.60 Impact Factor
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ABSTRACT: Many pathophysiological conditions are associated with increased gastrointestinal permeability, reflecting an elevated risk of endotoxaemia, inflammation, and sepsis. Permeability tests are increasingly used in clinical practice to obtain information on gastrointestinal functioning, but tests are often restricted to the small intestine, and require large oral sugar doses. Therefore, a novel multi-sugar assay was developed, allowing assessment of whole gut permeability changes in urinary and plasma samples collected at regular intervals from 10 healthy volunteers at baseline and after intake of monosaccharides (rhamnose and erythritol) and disaccharides (sucrose, lactulose, and sucralose). Samples were analyzed by isocratic cation-exchange LC-MS. Sample preparation and detection conditions were optimized. After centrifugation, chromatographic separation was achieved on an IOA-1000 column set at 30°C. Column effluent was mixed with ammonia for sugar-ammonium adduct formation. The lower limit of detection was 0.05 μmol/L for disaccharides and 0.1 μmol/L for monosaccharides. Linearity for each probe was between 1 and 1000 μmol/L (R(2): 0.9987-0.9999). Coefficients of variation were <5% in urine, and <9% in plasma. Recovery data were within the 90% to 110% range at all spiked concentrations. This highly sensitive novel LC-MS approach resulted in a significant decrease of the detection limit for all sugar probes, allowing a 5-fold reduction of the commonly used lactulose dose and the addition of sugar probes to also assess the gastroduodenal and colon permeability. In combination with its extended application in plasma, these features make the novel assay a promising tool in the assessment of site-specific changes in gastrointestinal permeability in clinical practice.
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 08/2011; 879(26):2794-801. · 2.78 Impact Factor
