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Liver failure following liver surgery is caused by an insufficient functioning remnant cell mass. This can be due to insufficient liver volume and can be aggravated by additional cell death during or after surgery. The aim of this study was to elucidate the causes of hepatocellular injury in patients undergoing liver resection. Markers of hepatocyte injury (AST, GSTα, and L-FABP) and inflammation (IL-6) were measured in plasma of patients undergoing liver resection with and without intermittent inflow occlusion. To study the separate involvement of the intestines and the liver in systemic L-FABP release, arteriovenous concentration differences for L-FABP were measured. During liver manipulation, liver injury markers increased significantly. Arterial plasma levels and transhepatic and transintestinal concentration gradients of L-FABP indicated that this increase was exclusively due to hepatic and not due to intestinal release. Intermittent hepatic inflow occlusion, anesthesia, and liver transection did not further enhance arterial L-FABP and GSTα levels. Hepatocyte injury was followed by an inflammatory response. This study shows that liver manipulation is a leading cause of hepatocyte injury during liver surgery. A potential causal relation between liver manipulation and systemic inflammation remains to be established; but since the inflammatory response is apparently initiated early during major abdominal surgery, interventions aimed at reducing postoperative inflammation and related complications should be started early during surgery or beforehand. [ABSTRACT FROM AUTHOR]

Background: For colorectal surgery, evidence suggests that optimal management includes: no pre-operative fasting, a thoracic epidural analgesia continued for 2 days post-operatively, and avoidance of fluid overload. In addition, no long-acting benzodiazepines on the day of surgery and use of short-acting anaesthetic medication may be beneficial. We examined whether these strategies have been adopted in five northern-European countries. Methods: In 2003, a questionnaire concerning peri-operative anaesthetic routines in elective, open colonic cancer resection was sent to the chief anaesthesiologist in 258 digestive surgical centres in Scotland, the Netherlands, Denmark, Sweden and Norway. Results: The response rate was 74% ( n = 191). Although periods of pre-operative fasting up to 48 h were reported, most (> 85%) responders in all countries declared to adhere to guidelines for pre-operative fasting and oral clear liquids were permitted until 2–3 h before anaesthesia. Solid food was permitted up to 6–8 h prior to anaesthesia. In all countries more than 85% of the responders indicated that epidural anaesthesia was routinely used. Except for Denmark, long-acting benzodiazepines were still widely used. Short-acting anaesthetics were used in all countries except Scotland where isoflurane is the anaesthetic of choice. With the exception of Denmark, intravenous fluids were used unrestrictedly. Conclusion: In northern Europe, most anaesthesiologists adhere to evidence-based optimal management strategies on pre-operative fasting, thoracic epidurals and short-acting anaesthetics. However, premedication with longer-acting agents is still common. Avoidance of fluid overload has not yet found its way into daily practice. This may leave patients undergoing elective colonic surgery at risk of oversedation and excessive fluid administration with potential adverse effects on surgical outcome. [ABSTRACT FROM AUTHOR]

Background: Recent developments in large bowel surgery are the introduction of laparoscopic surgery and the implementation of multimodal fast track recovery programs. Both focus on a faster recovery and shorter hospital stay. The randomized controlled multicenter LAFA-trial (LAparoscopy and/or FAst track multimodal management versus standard care) was conceived to determine whether laparoscopic surgery, fast track perioperative care or a combination of both is to be preferred over open surgery with standard care in patients having segmental colectomy for malignant disease. Methods/design: The LAFA-trial is a double blinded, multicenter trial with a 2 × 2 balanced factorial design. Patients eligible for segmental colectomy for malignant colorectal disease i.e. right and left colectomy and anterior resection will be randomized to either open or laparoscopic colectomy, and to either standard care or the fast track program. This factorial design produces four treatment groups; open colectomy with standard care (a), open colectomy with fast track program (b), laparoscopic colectomy with standard care (c), and laparoscopic surgery with fast track program (d). Primary outcome parameter is postoperative hospital length of stay including readmission within 30 days. Secondary outcome parameters are quality of life two and four weeks after surgery, overall hospital costs, morbidity, patient satisfaction and readmission rate. Based on a mean postoperative hospital stay of 9 +/- 2.5 days a group size of 400 patients (100 each arm) can reliably detect a minimum difference of 1 day between the four arms (alfa = 0.95, beta = 0.8). With 100 patients in each arm a difference of 10% in subscales of the Short Form 36 (SF-36) questionnaire and social functioning can be detected. Discussion: The LAFA-trial is a randomized controlled multicenter trial that will provide evidence on the merits of fast track perioperative care and laparoscopic colorectal surgery in patients having segmental colectomy for malignant disease. [ABSTRACT FROM AUTHOR]

Background: The initial treatment of acute necrotizing pancreatitis is conservative. Intervention is indicated in patients with (suspected) infected necrotizing pancreatitis. In the Netherlands, the standard intervention is necrosectomy by laparotomy followed by continuous postoperative lavage (CPL). In recent years several minimally invasive strategies have been introduced. So far, these strategies have never been compared in a randomised controlled trial. The PANTER study (PAncreatitis, Necrosectomy versus sTEp up appRoach) was conceived to yield the evidence needed for a considered policy decision. Methods/design: 88 patients with (suspected) infected necrotizing pancreatitis will be randomly allocated to either group A) minimally invasive 'step-up approach' starting with drainage followed, if necessary, by videoscopic assisted retroperitoneal debridement (VARD) or group B) maximal necrosectomy by laparotomy. Both procedures are followed by CPL. Patients will be recruited from 20 hospitals, including all Dutch university medical centres, over a 3-year period. The primary endpoint is the proportion of patients suffering from postoperative major morbidity and mortality. Secondary endpoints are complications, new onset sepsis, length of hospital and intensive care stay, quality of life and total (direct and indirect) costs. To demonstrate that the 'step-up approach' can reduce the major morbidity and mortality rate from 45 to 16%, with 80% power at 5% alpha, a total sample size of 88 patients was calculated. Discussion: The PANTER-study is a randomised controlled trial that will provide evidence on the merits of a minimally invasive 'step-up approach' in patients with (suspected) infected necrotizing pancreatitis. [ABSTRACT FROM AUTHOR]

Background: The disturbances leading to cancer cachexia remain to be unraveled. Preliminary evidence suggests that arginine availability in cancer is reduced. However, no valid data are available on plasma arginine concentrations in cancer patients. Objective: We aimed to determine whether there is evidence for disturbed arginine metabolism in cancer. Design: We measured plasma arginine concentrations postabsorptively in patients with various types of tumors, hypothesizing that arginine concentrations would be lower than those in age- and sex-matched control subjects. Patients with localized tumors with a range of metabolic implications were studied: breast cancer (no weight loss), colonic cancer (sometimes weight loss), and pancreatic cancer (usually weight loss). Plasma amino acid concentrations were measured by HPLC. Results: Plasma arginine concentrations were lower in patients with cancer (breast cancer: 80 ± 3 compared with 103 ± 9 μmol/L; colonic cancer: 80± 3 compared with 96 ± 7 μmol/L; pancreatic cancer: 76 ± 5 compared with 99 ± 7 μmol/L; P < 0.05 versus respective age- and sex-matched control subjects), irrespective of tumor type, weight loss, tumor stage, or body mass index (correlations with P > 0.05). Conclusions: Malignant tumors associated with various degrees of metabolic derangements are all associated with decreased plasma arginine concentrations, even without weight loss. This suggests that decreased arginine availability is a specific feature of the presence of cancer. These disturbances in arginine metabolism could contribute to the cascade of metabolic events leading to cancer cachexia. [ABSTRACT FROM AUTHOR]

The kidneys play a role in the synthesis and interorgan exchange of several amino acids. The quantitative importance of renal amino acid metabolism in the body is not, however, clear. We review here the role of the kidney in the interorgan exchange of amino acids, with emphasis on quantitative aspects. We reviewed relevant literature by using a computerized literature search (PubMed) and checking relevant references from the identified articles. Our own data are discussed in the context of the literature. The kidney takes up glutamine and metabolizes it to ammonia. This process is sensitive to pH and serves to maintain acid-base homeostasis and to excrete nitrogen. In this way, the metabolism of renal glutamine and ammonia is complementary to hepatic urea synthesis. Citrulline, derived from intestinal glutamine breakdown, is converted to arginine by the kidney. Renal phenylalanine uptake is followed by stoichiometric tyrosine release, and glycine uptake is accompanied by serine release. Certain administered oligopeptides (eg, glutamine dipeptides) are converted by the kidneys to their constituent components before they can be used in metabolic processes. The kidneys play an important role in the interorgan exchange of amino acids. Quantitatively, for several important amino acids, the kidneys are as important as the gut in intermediary metabolism. The kidneys may be crucial "mediators" of the beneficial effects of specialized, disease-specific feeding solutions such as those enriched in glutamine dipeptides. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented about the rare complication of rectal injuries during barium enena, that was published in a previous issue.

The guidelines for metastatic colorectal cancer crudely state that the best local treatment should be selected from a 'toolbox' of techniques according to patient- and treatment-related factors. We created an interdisciplinary, consensus-based algorithm with specific resectability and ablatability criteria for the treatment of colorectal liver metastases (CRLM). To pursue consensus, members of the multidisciplinary COLLISION and COLDFIRE trial expert panel employed the RAND appropriateness method (RAM). Statements regarding patient, disease, tumor and treatment characteristics were categorized as appropriate, equipoise or inappropriate. Patients with ECOG≤2, ASA≤3 and Charlson comorbidity index ≤8 should be considered fit for curative-intent local therapy. When easily resectable and/or ablatable (stage IVa), (neo)adjuvant systemic therapy is not indicated. When requiring major hepatectomy (stage IVb), neo-adjuvant systemic therapy is appropriate for early metachronous disease and to reduce procedural risk. To downstage patients (stage IVc), downsizing induction systemic therapy and/or future remnant augmentation is advised. Disease can only be deemed permanently unsuitable for local therapy if downstaging failed (stage IVd). Liver resection remains the gold standard. Thermal ablation is reserved for unresectable CRLM, deep-seated resectable CRLM and can be considered when patients are in poor health. Irreversible electroporation and stereotactic body radiotherapy can be considered for unresectable perihilar and perivascular CRLM 0-5cm. This consensus document provides per-patient and per-tumor resectability and ablatability criteria for the treatment of CRLM. These criteria are intended to aid tumor board discussions, improve consistency when designing prospective trials and advance intersociety communications. Areas where consensus is lacking warrant future comparative studies. [ABSTRACT FROM AUTHOR]

The article offers information on the study regarding the enhanced recovery after elective colonic and upper gastrointestinal (GI) surgery. It highlights that enhancement in recovery from several surgical procedures can be reached with multimodal peri-operative care protocols. It adds that enhanced recovery program can be achieved through adequate pain control, avoidance of unnecessary fasting and negative postoperative effects of anesthesia.

Background: Liver surgery in perihilar cholangiocarcinoma (PHC) is associated with high postoperative morbidity because the tumor typically causes biliary obstruction. Preoperative biliary drainage is used to create a safer environment prior to liver surgery, but biliary drainage may be harmful when severe drainage-related complications deteriorate the patients' condition or increase the risk of postoperative morbidity. Biliary drainage can cause cholangitis/cholecystitis, pancreatitis, hemorrhage, portal vein thrombosis, bowel wall perforation, or dehydration. Two methods of preoperative biliary drainage are mostly applied: endoscopic biliary drainage, which is currently used in most regional centers before referring patients for surgical treatment, and percutaneous transhepatic biliary drainage. Both methods are associated with severe drainage-related complications, but two small retrospective series found a lower incidence in the number of preoperative complications after percutaneous drainage compared to endoscopic drainage (18-25% versus 38-60%, respectively). The present study randomizes patients with potentially resectable PHC and biliary obstruction between preoperative endoscopic or percutaneous transhepatic biliary drainage.Methods/design: The study is a multi-center trial with an "all-comers" design, randomizing patients between endoscopic or percutaneous transhepatic biliary drainage. All patients selected to potentially undergo a major liver resection for presumed PHC are eligible for inclusion in the study provided that the biliary system in the future liver remnant is obstructed (even if they underwent previous inadequate endoscopic drainage). Primary outcome measure is the total number of severe preoperative complications between randomization and exploratory laparotomy. The study is designed to detect superiority of percutaneous drainage: a provisional sample size of 106 patients is required to detect a relative decrease of 50% in the number of severe preoperative complications (alpha = 0.95; beta = 0.8). Interim analysis after inclusion of 53 patients (50%) will provide the definitive sample size. Secondary outcome measures encompass the success of biliary drainage, quality of life, and postoperative morbidity and mortality.Discussion: The DRAINAGE trial is designed to identify a difference in the number of severe drainage-related complications after endoscopic and percutaneous transhepatic biliary drainage in patients selected to undergo a major liver resection for perihilar cholangiocarcinoma.Trial Registration: Netherlands Trial Register [ NTR4243 , 11 October 2013]. [ABSTRACT FROM AUTHOR]

Background: Spread of evidence-based innovations beyond pioneering settings is essential to improve quality of care. This study aimed to evaluate the influence of a national project to implement ‘Enhanced Recovery After Surgery’ (ERAS) among colorectal teams on the spread of this innovation to gynaecological procedures.Methods: A retrospective observational multicentre study was performed of a consecutive sample of patients who underwent major elective gynaecological surgery in 2012-2013. Ten Dutch hospitals (294 patients) had participated in a colorectal breakthrough project implementing ERAS on a nationwide basis and were assigned to the intervention group. Thirteen hospitals (390 patients) that had not participated in this project acted as controls. Outcome measures were time to functional recovery and total length of postoperative hospital stay. Multilevel models adjusted for clustering and baseline demographics were used for analysis. The uptake of ten selected perioperative care elements was evaluated for each hospital.Results: The estimated mean difference (95% confidence interval) between the intervention and control hospitals was −0.3 (−0.9 to 0.3) days in the time to recovery and 0.2 (−0.8 to 1.3) days in the total length of hospital stay. The mean (± standard deviation) absolute rate of implemented perioperative care elements per hospital was 28.9 ± 14.9% in the control, versus 29.3 ± 11.1% in the intervention group (p = 0.934).Conclusion: Initial implementation effects seem to be restricted to the participating teams and do not automatically spread to other surgical teams in the same hospital. [ABSTRACT FROM AUTHOR]

Large differences in toxicity responses occur within the human population. In this study we evaluate whether interindividual variation in baseline enzyme activity (EA)/gene expression (GE) levels in liver predispose for the variation in toxicity responses by assessing dose-response relationships for several prototypical hepatotoxicants. Baseline levels of cytochrome-P450 (CYP) GE/EA were measured in precision-cut human liver slices. Slices (n = 4-5/compound) were exposed to a dose-range of acetaminophen, aflatoxin B1, benzo(α) pyrene or 2-nitrofluorene. Interindividual variation in induced genotoxicity (COMET-assay and CDKN1A/p21 GE) and cytotoxicity (lactate dehydrogenase-leakage), combined with NQO1- and GSTM1-induced GE-responses for oxidative stress and GE-responses of several CYPs was evaluated. The benchmark dose-approach was applied as a tool to model exposure responses on an individual level. Variation in baseline CYP levels, both GE and EA, can explain variation in compound exposure-responses on an individual level. Network analyses enable the definition of key parameters influencing interindividual variation after compound exposure. For 2-nitrofluorene, this analysis suggests involvement of CYP1B1 in the metabolism of this compound, which represents a novel finding. In this study, GSTM1 which is known to be highly polymorphic within the human population, but so far could not be linked to toxicity in acetaminophen-poisoned patients, is suggested to cause interindividual variability in acetaminophen-metabolism, dependent on the individual's gene expression-responses of CYP-enzymes. This study demonstrates that using interindividual variation within network modelling provides a source for the definition of essential and even new parameters involved in compound-related metabolism. This information might enable ways to make more quantitative estimates of human risks. [ABSTRACT FROM AUTHOR]

Liver failure is a dreaded and often fatal complication that sometimes follows a partial hepatic resection. This article reviews the definition, incidence, pathogenesis, risk factors, risk assessment, prevention, clinical features and treatment of post-resectional liver failure (PLF). A systematic, computerized search was performed using key words related to ‘partial hepatic resection’ and ‘liver failure’ to review most relevant literature about PLF published in the last 20 years. The reported incidence of PLF ranges between 0.7 and 9.1%. An inadequate quantity or quality of residual liver mass are key events in its pathogenesis. Major risk factors are the presence of comorbid conditions, pre-existent liver disease and small remnant liver volume (RLV). It is essential to identify these risk factors during the pre-operative assessment that includes evaluation of liver volume, anatomy and function. Preventive measures should be applied whenever possible as curative treatment options for PLF are limited. These preventive measures intend to increase RLV and protect remnant liver function. Management principles focus on support of end-organ and liver function. Further research is needed to elucidate the exact pathogenesis of PLF and to develop and validate adequate treatment options. [ABSTRACT FROM AUTHOR]

Background: We developed a jejunal and colonic experimental human ischemia-reperfusion (IR) model to study pathophysiological intestinal IR mechanisms and potential new intestinal ischemia biomarkers. Our objective was to evaluate the safety of these IR models by comparing patients undergoing surgery with and without in vivo intestinal IR. Methods: A retrospective study was performed comparing complication rates and severity, based on the Clavien-Dindo classification system, in patients undergoing pancreatoduodenectomy with (n = 10) and without (n = 20 matched controls) jejunal IR or colorectal surgery with (n = 10) and without (n = 20 matched controls) colon IR. Secondary outcome parameters were operative time, blood loss, 90-day mortality and length of hospital stay. Results: Following pancreatic surgery, 63% of the patients experienced one or more postoperative complications. There was no significant difference in incidence or severity of complications between patients undergoing pancreatic surgery with (70%) or without (60%, P = 0.7) jejunal IR. Following colorectal surgery, 60% of the patients experienced one or more postoperative complication. Complication rate and severity were similar in patients with (50%) and without (65%, P = 0.46) colonic IR. Operative time, amount of blood loss, postoperative C-reactive protein, length of hospital stay or mortality were equal in both intervention and control groups for jejunal and colon IR. Conclusion: This study showed that human experimental intestinal IR models are safe in patients undergoing pancreatic or colorectal surgery. [ABSTRACT FROM AUTHOR]

Background: Enhanced recovery after surgery (ERAS) pathways are now implemented worldwide with strong evidence that adhesion to such protocol reduces medical complications, costs and hospital stay. This concept has been applied for pancreatic surgery since the first published guidelines in 2012. This study presents the updated ERAS recommendations for pancreatoduodenectomy (PD) based on the best available evidence and on expert consensus. Methods: A systematic literature search was conducted in three databases (Embase, Medline Ovid and Cochrane Library Wiley) for the 27 developed ERAS items. Quality of randomized trials was assessed using the Consolidated Standards of Reporting Trials statement checklist. The level of evidence for each item was determined using the Grading of Recommendations Assessment Development and Evaluation system. The Delphi method was used to validate the final recommendations. Results: A total of 314 articles were included in the systematic review. Consensus among experts was reached after three rounds. A well-implemented ERAS protocol with good compliance is associated with a reduction in medical complications and length of hospital stay. The highest level of evidence was available for five items: avoiding hypothermia, use of wound catheters as an alternative to epidural analgesia, antimicrobial and thromboprophylaxis protocols and preoperative nutritional interventions for patients with severe weight loss (> 15%). Conclusions: The current updated ERAS recommendations for PD are based on the best available evidence and processed by the Delphi method. Prospective studies of high quality are encouraged to confirm the benefit of current updated recommendations. [ABSTRACT FROM AUTHOR]

Introduction: Postoperative liver failure (PLF) is a dreaded complication after partial hepatectomy. The peak bilirubin criterion (>7.0 mg/dL or ≥120 μmol/L) is used to define PLF. This study aimed to validate the peak bilirubin criterion as postoperative risk indicator for 90-day liver-related mortality. Methods: Characteristics of 956 consecutive patients who underwent partial hepatectomy at the Maastricht University Medical Centre or Royal Free London between 2005 and 2012 were analyzed by uni- and multivariable analyses with odds ratios (OR) and 95% confidence intervals (95%CI). Results: Thirty-five patients (3.7%) met the postoperative peak bilirubin criterion at median day 19 with a median bilirubin level of 183 [121-588] mmol/L. Sensitivity and specificity for liver-related mortality after major hepatectomy were 41.2% and 94.6%, respectively. The positive predictive value was 22.6%. Predictors of liver-related mortality were the peak bilirubin criterion (p < 0.001, OR = 15.9 [95%CI 5.2-48.7]), moderate-severe steatosis and fibrosis (p = 0.013, OR = 8.5 [95%CI 1.6-46.6]), ASA 3-4 (p = 0.047, OR = 3.0 [95%CI 1.0-8.8]) and age (p = 0.044, OR = 1.1 [95%CI 1.0-1.1]). Conclusion: The peak bilirubin criterion has a low sensitivity and positive predictive value for 90-day liver-related mortality after major hepatectomy. [ABSTRACT FROM AUTHOR]

Summary background data: Hepatic sinusoidal dilatation (SD) is a histopathological entity that occurs in up to 75% of patients undergoing oxaliplatin-based chemotherapy for colorectal liver metastases (CRLM). Objective: To study the influence of SD on outcome after partial hepatectomy in patients with CRLM. Methods: Medline, Embase, CENTRAL, LILACS and C1NAHL were searched for studies published between 01.01.2004 and 09.06.2015 with keywords: "sinusoidal obstruction syndrome", "hepatic veno-occlusive disease", and "Stuart-Bras syndrome". Studies comprising adults who underwent partial hepatectomy for CRLM with grading of SD and registration of postoperative morbidity and/or mortality were included. Risk of bias and quality of studies were evaluated with the Quality In Prognosis Studies Instrument (QUIPS) and modified GRADE framework. Results: Search strategies produced 2007 hits from which 23 and 13 articles were extracted for qualitative and quantitative analyses, respectively. Meta-analysis on the influence of SD grade 2 -3 vs. SD grade 0-1 on postoperative overall morbidity showed an odds ratio (OR) of 1.26 [95% Cl 0.74, 2.15](p = 0.40), an OR of 1.03 [0.15, 6.89l(p = 0.98) for liver failure, an OR of 1.21 [0.23,6.35](p = 0.82) for overall mortality, and an OR of 3.52 [0.31, 39.91 ](p = 0.31) for liver-related morbidity. QUIPS showed a low to high risk of bias for studies, and GRADE showed very low quality of evidence per outcome. Conclusions: No significant effect of SD grade 2 -3 on short-term outcome after partial hepatectomy was found. However, the data on which this conclusion was based were not very robust and therefore no solid conclusions could be drawn. [ABSTRACT FROM AUTHOR]

Background: Volumetric assessment of the liver is essential in the prevention of postresectional liver failure after partial hepatectomy. Currently used methods are accurate but time-consuming. This study aimed to test a new automated method for preoperative volumetric liver assessment. Methods: Patients who underwent a contrast enhanced portovenous phase CT-scan prior to hepatectomy in 2012 were included. Total liver volume (TLV) and future remnant liver volume (FRLV) were measured using TeraRecon Aquarius iNtuition® (autosegmentation) and OsiriX® (manual segmentation) software by two observers for each software package. Remnant liver volume percentage (RLV%) was calculated. Time needed to determine TLV and FRLV was measured. Inter-observer variability was assessed using Bland-Altman plots. Results: Twenty-seven patients were included. There were no significant differences in measured volumes between OsiriX® and iNtuition®. Moreover, there were significant correlations between the OsiriX® observers, the iNtuition® observers and between OsiriX® and iNtuition® post-processing systems (all R2 > 0.97). The median time needed for complete liver volumetric analysis was 18.4 ± 4.9 min with OsiriX® and 5.8 ± 1.7 min using iNtuition® (p < 0.001). Conclusion: Both OsiriX® and iNtuition® liver volumetry are accurate and easily applicable. However, volumetric assessment of the liver with iNtuition® auto-segmentation is three times faster compared to manual OsiriX® volumetry. [ABSTRACT FROM AUTHOR]

Background The impact of body composition on outcomes after surgery for colorectal liver metastases ( CRLM) remains unclear. The aim of the present study was to determine the influence of sarcopenia, obesity and sarcopenic obesity on morbidity, disease-free ( DFS) and overall survival ( OS). Method Between 2005 and 2012, all patients undergoing a partial liver resection for CRLM in the Maastricht University Medical Centre, and who underwent computed tomography ( CT) imaging within 3 months before liver surgery, were included. Body composition was primarily based on pre-operative CT measurements. Sarcopenia was based on total muscle area at the level of the third lumbar vertebra and predefined body mass index ( BMI)- and gender-specific cut-off values for sarcopenia were used. Body fat percentages were calculated and the top 40% for men and women were considered obese. Results Of the 171 included patients undergoing liver surgery for CRLM, 80 (46.8%) patients were sarcopenic, 69 (40.4%) obese and 49 (28.7%) sarcopenic obese. The presence of sarcopenia, obesity or sarcopenic obesity did not affect the complication rates. However, readmission rates were significantly increased in patients with (sarcopenic) obesity ( P < 0.05). Surprisingly, obesity seemed to prolong OS ( P = 0.021) and was identified as an independent predictor [hazard ratio ( HR):0.58 and P = 0.046] for better OS. Sarcopenia and sarcopenic obesity did not affect DFS or OS. Conclusion Sarcopenia, obesity and sarcopenic obesity did not worsen DFS, OS and complication rates after a partial liver resection for CRLM. [ABSTRACT FROM AUTHOR]

Purpose: Splanchnic hypoperfusion is a physiological phenomenon during strenuous exercise. It has been associated with gastrointestinal symptoms and intestinal injury and may hamper athletic performance. We hypothesized that L-citrulline supplementation improves splanchnic perfusion and decreases intestinal injury by enhancing arginine availability. The aim of this study was to determine the effect of L-citrulline intake on splanchnic perfusion, intestinal injury, and barrier function during exercise. Methods: In this randomized, double-blind crossover study, 10 men cycled for 60 min at 70% of their maximum workload after L-citrulline (10 g) or placebo (L-alanine) intake. Splanchnic perfusion was assessed using gastric air tonometry. Sublingual microcirculation was evaluated by sidestream dark field imaging. Plasma amino acid levels and intestinal fatty acid binding protein concentrations, reflecting enterocyte damage, were assessed every 10 min. Urinary excretion of sugar probes was measured to evaluate intestinal permeability changes. Results: Oral L-citrulline supplementation enhanced plasma citrulline (1840.3 ± 142.3 µM) and arginine levels (238.5 ± 9.1 µM) compared with that in placebo (45.7 ± 4.8 µM and 101.5 + 6.1 µM, respectively, P < 0.0001), resulting in increased arginine availability. Splanchnic hypoperfusion was prevented during exercise after L-citrulline ingestion (reflected by unaltered gapg-apCO2 levels), whereas gapg-apCO2 increased with placebo treatment (P < 0.01). Accordingly, L-citrulline intake resulted in an increased number of perfused small sublingual vessels compared with that in placebo (7.8 ± 6.0 vs —2.0 ± 2.4, P = 0.06). Furthermore, plasma intestinal fatty acid binding protein levels were attenuated during exercise after L-citrulline supplementation compared with that in placebo (AUC0-60 min, 185% ± 506% vs 1318% ± 553%, P < 0.01). No significant differences were observed for intestinal permeability. Conclusions: Pre-exercise L-citrulline intake preserves splanchnic perfusion and attenuates intestinal injury during exercise in athletes compared with placebo, probably by enhancing arginine availability. These results suggest that oral L-citrulline supplementation is a promising intervention to combat splanchnic hypoperfusion-induced intestinal compromise. [ABSTRACT FROM AUTHOR]

Objectives There is debate concerning the best mode of delivery of analgesia following liver resection, with continuous i.m. infusion of bupivacaine (CIB) plus patient-controlled i.v. analgesia ( PCA) suggested as an alternative to continuous epidural analgesia ( CEA). This study compares these two modalities. Methods A total of 498 patients undergoing major hepatectomy between July 2004 and July 2011 were included. Group 1 received CIB + PCA ( n = 429) and Group 2 received CEA ( n = 69). Groups were analysed on baseline patient and surgical characteristics. Primary endpoints were pain severity scores and total opioid consumption. Secondary endpoints were pain management failures, need for rescue medication, postoperative (opioid-related) morbidity and hospital length of stay (LoS). Results In both groups pain was well controlled and >70% of patients had no or minimal pain on PoDs 1 and 2. The numbers of patients experiencing severe pain were similar in both groups: PoD 1 at rest: 0.3% in Group 1 and 0% in Group 2 ( P = 1.000); PoD 1 on movement: 8% in Group 1 and 2% in Group 2 ( P = 0.338); PoD 2 at rest: 0% in Group 1 and 2% in Group 2 ( P = 0.126), and PoD 2 on movement: 5% in Group 1 and 5% in Group 2 ( P = 1.000). Although the CIB + PCA group required more opioid rescue medication on PoD 0 (53% versus 22%; P < 0.001), they used less opioids on PoDs 0-3 ( P ≤ 0.001), had lower morbidity (26% versus 39%; P = 0.018), and a shorter LoS (7 days versus 8 days; P = 0.005). Conclusions The combination of CIB + PCA provides pain control similar to that provided by CEA, but facilitates lower opioid consumption after major hepatectomy. It has the potential to replace epidural analgesia, thereby avoiding the occurrence of rare but serious complications. [ABSTRACT FROM AUTHOR]

Background: Bile duct injury in patients undergoing laparoscopic cholecystectomy is a rare but serious complication. Concomitant vascular injury worsens the outcome of bile duct injury repair. Near-infrared fluorescence imaging using indocyanine green (ICG) is a promising, innovative, and noninvasive method for the intraoperative identification of biliary and vascular anatomy during cholecystectomy. This study assessed the practical application of combined vascular and biliary fluorescence imaging in laparoscopic gallbladder surgery for early biliary tract delineation and arterial anatomy confirmation. Methods: Patients undergoing elective laparoscopic cholecystectomy were enrolled in this prospective, single-institutional study. To delineate the major bile ducts and arteries, a dedicated laparoscope, offering both conventional and fluorescence imaging, was used. ICG (2.5 mg) was administered intravenously immediately after induction of anesthesia and in half of the patients repeated at establishment of critical view of safety for concomitant arterial imaging. During dissection of the base of the gallbladder and the cystic duct, the extrahepatic bile ducts were visualized. Intraoperative recognition of the biliary structures was registered at set time points, as well as visualization of the cystic artery after repeat ICG administration. Results: Thirty patients were included. ICG was visible in the liver and bile ducts within 20 minutes after injection and remained up to approximately 2 h, using the ICG-filter of the laparoscope. In most cases, the common bile duct (83 %) and cystic duct (97 %) could be identified significantly earlier than with conventional camera mode. In 13 of 15 patients (87 %), confirmation of the cystic artery was obtained successfully after repeat ICG injection. No per- or postoperative complications occurred as a consequence of ICG use. Conclusion: Biliary and vascular fluorescence imaging in laparoscopic cholecystectomy is easily applicable in clinical practice, can be helpful for earlier visualization of the biliary tree, and is useful for the confirmation of the arterial anatomy. [ABSTRACT FROM AUTHOR]

Background 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. Methods 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. Results 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). Conclusions The routine use of abdominal drains after pancreatic resection may result in a higher risk for major complications, but the evidence is inconclusive. [ABSTRACT FROM AUTHOR]

Objectives 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. Methods The MEDLINE, EMBASE, Pub Med 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. Results 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. Conclusions 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 (cm2/m2) 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. [ABSTRACT FROM AUTHOR]

Objectives 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. Methods 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. Results 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. Conclusions 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. [ABSTRACT FROM AUTHOR]

Introduction: Arterial ammonia concentrations increase acutely during the anhepatic phase of a liver transplantation (LTx) and return to baseline within 1 h after reperfusion of a functioning liver graft. So far, this return to baseline has solely been attributed to hepatic ammonia clearance. No data exist on the potential contribution of altered renal ammonia handling to peritransplantation ammonia homoeostasis. Aim: The present study investigated the consequences of a hepatectomy and subsequent implantation of a partial liver graft on arterial ammonia concentrations and urinary ammonia excretion during a living donor liver transplantation (LDLTx). Methods: Patients with end-stage liver disease undergoing LDLTx were selected. Samples of arterial blood and urine were taken before, during and 2 h after the anhepatic phase. Differences were tested using Wilcoxon's test. Results are given as median and range. Results: Eleven adult patients undergoing an LDLTx were included. Before hepatectomy, arterial ammonia concentrations were 89 μM (40-156 μM), increasing to 146 μM (102-229 μM) ( P<0.001) during the anhepatic phase and returning to 79 μM (46-111 μM) ( P<0.01) after reperfusion. Urinary ammonia excretion was initially 1.06 mmol/h (0.02-6.00 mmol/h), increasing to 3.81 mmol/h (0.32-12.55 mmol/h) ( P=0.004) during the anhepatic phase and further increasing to 4.00 mmol/h (0.79-9.51 mmol/h) ( P=0.013) after reperfusion. Conclusion: The kidney significantly increased urinary ammonia excretion during the anhepatic phase, which was sustained after reperfusion, contributing to the rapid decrease of ammonia concentrations. Accordingly, the plasma ammonia concentrations measured directly after LTx cannot simply be used as a read-out of initial liver graft function. [ABSTRACT FROM AUTHOR]

Background: A small remnant liver volume is an important risk factor for posthepatectomy liver failure. ImageJ and OsiriX are both free, open-source image processing software packages. The aim of the present study was to compare ImageJ and OsiriX in performing prospective computed tomography (CT) volumetric analysis of the liver on a personal computer (PC) in patients undergoing major liver resection. Methods: Patients scheduled for a right hemihepatectomy were eligible for inclusion. Two surgeons and one surgical trainee measured volumes of total liver, tumor, and future resection specimen prospectively with ImageJ and OsiriX. A radiologist also measured these volumes with CT scanner-linked Aquarius iNtuition software. Resection volumes were compared with the actual weights of the liver specimens removed during surgery, and differences between the measured liver volumes were analyzed. Results: A total of 15 patients (8 men, 7 women) with a median age of 63 years (48-79 years) were included. There was a significant correlation between the measured weights of resection specimens and the volumes calculated prospectively with ImageJ and OsiriX ( r = 0.89; r = 0.83, respectively). There was also a significant correlation between the volumes measured with radiological software iNtuition and the volumes measured with ImageJ and OsiriX ( r = 0.93; r = 0.95, respectively). Conclusions: There were no major differences in total liver volumes, resection volumes, or tumour volumes for these three software packages. Prospective hepatic CT volumetry with ImageJ or OsiriX is reliable and can be accurately used on a PC by nonradiologists. ImageJ and OsiriX yield results comparable to the radiological software iNtuition. [ABSTRACT FROM AUTHOR]

Background: Malignant transformation of hepatocellular adenomas (HCAs) into hepatocellular carcinomas (HCCs) has been reported repeatedly and is considered to be one of the main reasons for surgical treatment. However, its actual risk is currently unknown. Objective: To provide an estimation of the frequency of malignant transformation of HCAs and to discuss its clinical implications. Methods: A systematic literature search was conducted using the following databases: The Cochrane Hepatobiliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, MEDLINE and EMBASE. Results: One hundred and fifty-seven relevant series and 17 case reports (a total of 1635 HCAs) were retrieved, reporting an overall frequency of malignant transformation of 4.2%. Only three cases (4.4%) of malignant alteration were reported in a tumour smaller than 5 cm in diameter. Discussion: Malignant transformation of HCAs into HCCs remains a rare phenomenon with a reported frequency of 4.2%. A better selection of exactly those patients presenting with an HCA with an amplified risk of malignant degeneration is advocated in order to reduce the number of liver resections and thus reducing the operative risk for these predominantly young patients. The Bordeaux adenoma tumour markers are a promising method of identifying these high-risk adenomas. [ABSTRACT FROM AUTHOR]

Background: After extended liver resection, a remnant liver that is too small can lead to postresection liver failure. To reduce this risk, preoperative evaluation of the future liver remnant volume (FLRV) is critical. The open-source OsiriX PAC software system can be downloaded for free and used by nonradiologists to calculate liver volume using a stand-alone Apple computer. The purpose of this study was to assess the accuracy of OsiriX CT volumetry for predicting liver resection volume and FLVR in patients undergoing partial hepatectomy. Methods: Preoperative contrast-enhanced liver CT scans of patients who underwent partial hepatectomy were analyzed by three observers. Two surgical trainees measured the total liver volume, resection volume, and tumor volume using OsiriX, and a radiologist measured these volumes using CT scanner-linked Aquarius iNtuition software. Resection volume was correlated with prospectively determined resection weight, and differences in the measured liver volumes were analyzed. Interobserver variability was assessed using Bland–Altman plots. Results: 25 patients (M/F ratio: 13/12) with a median age of 61 (range, 34–77) years were included. There were significant correlations between the weight and volume of the resected specimens (Pearson’s correlation coefficient: R = 0.95). There were no major differences in total liver volumes, resection volumes, or tumor volumes for observers 1, 2, and 3. Bland–Altman plots showed a small interobserver variability. The mean time to complete liver volumetry for one patient using OsiriX was 19 ± 3 min. Conclusions: OsiriX liver volumetry performed by surgeons is an accurate and time-efficient method for predicting resection volume and FLRV. [ABSTRACT FROM AUTHOR]

Objectives: This study was conducted to evaluate the added value of an enhanced recovery after surgery (ERAS) programme in laparoscopic liver resections for solid tumours. Methods: Patients undergoing laparoscopic liver resection between July 2005 and July 2008 were included. Indications for resections included presumed benign and malignant liver lesions. Primary outcome was total length of hospital stay (LOS). Secondary outcomes were functional recovery, complications, conversions, blood loss and duration of operation. Results: Thirteen patients were treated by laparoscopic liver resections in the ERAS programme in one centre (group 1). Their outcomes were compared with outcomes of 13 laparoscopic procedures performed either before the introduction of the ERAS programme during 2003-2005 in the same centre or during the same period in other centres using traditional care (group 2). Median total LOS was 5.0 days (range 3-10 days) in group 1 and 7.0 days (3-12 days) in group 2. This difference was not statistically significant. Functional recovery occurred 2 days earlier in group 1 (median 3.0 days [range 1-7 days] vs. median 5.0 days [range 2-8 days]; P < 0.044). There were no significant differences in complications, conversions or duration of operation. Blood loss was significantly less in the ERAS group (median 50 ml [range 50-200 ml] vs. median 250 ml [range 50-800 ml]; P < 0.002). Conclusions: This exploratory, multicentre, fast-track laparoscopic liver resection study is the first such study conducted. Although small, the study suggests that a multimodal enhanced recovery programme in laparoscopic liver surgery is feasible, safe and may lead to accelerated functional recovery and reductions in LOS. [ABSTRACT FROM AUTHOR]

The article focuses on research which examined probiotic prophylaxis in predicted severe acute pancreatitis. In the research 298 patients with predicted severe acute pancreatitis were studied. researchers found that in patients with predicted severe acute pancreatitis, probiotic prophylaxis with a combination of probiotic strains did not reduce the risk of infectious complications and was also associated with an increased risk of mortality. Researchers suggested that probiotic prophylaxis should not be administered in patients with predicted severe acute pancreatitis.

A small remnant liver volume is an important risk factor for posthepatectomy liver failure and can be predicted accurately by computed tomography (CT) volumetry using radiologic image analysis software. Unfortunately, this software is expensive and usually requires support by a radiologist. ImageJ is a freely downloadable image analysis software package developed by the National Institute of Health (NIH) and brings liver volumetry to the surgeon’s desktop. We aimed to assess the accuracy of ImageJ for hepatic CT volumetry. ImageJ was downloaded from . Preoperative CT scans of 15 patients who underwent liver resection for colorectal cancer liver metastases were retrospectively analyzed. Scans were opened in ImageJ; and the liver, all metastases, and the intended parenchymal transection line were manually outlined on each slice. The area of each selected region, metastasis, resection specimen, and remnant liver was multiplied by the slice thickness to calculate volume. Volumes of virtual liver resection specimens measured with ImageJ were compared with specimen weights and calculated volumes obtained during pathology examination after resection. There was an excellent correlation between the volumes calculated with ImageJ and the actual measured weights of the resection specimens ( r² = 0.98, p < 0.0001). The weight/volume ratio amounted to 0.88 ± 0.04 (standard error) and was in agreement with our earlier findings using CT-linked radiologic software. ImageJ can be used for accurate hepatic CT volumetry on a personal computer. This application brings CT volumetry to the surgeon’s desktop at no expense and is particularly useful in cases of tertiary referred patients, who already have a proper CT scan on CD-ROM from the referring institution. Most likely the discrepancy between volume and weight results from exsanguination of the liver after resection. [ABSTRACT FROM AUTHOR]

High-fat enteral nutrition reduces the inflammatory response following hemorrhagic shock in the rat. We hypothesized that this intervention might also ameliorate the remote organ injury to the liver associated with this model. Male Sprague-Dawley rats were either starved or fed low-fat or high-fat isocaloric isonitrogenous feed prior to nonlethal hemorrhagic shock induced by a 40% reduction in the blood volume. Animals were sacrificed at 90 minutes or 24 hours after injury. Liver cell damage was assessed by histology and long polymerase chain reaction (PCR) to detect mitochondrial DNA damage. Stress protein expression was measured by Western blot and mRNA expression by real-time PCR and immunohistochemistry. Animals fed a low-fat diet had the same severity of liver injury as starved animals and increased expression of stress proteins. Animals fed a high-fat diet had minimal liver injury, no evidence of mitochondrial DNA damage, and significantly lower expression of stress proteins. This effect is associated with preservation of hepatocellular morphology, attenuation of mitochondrial DNA damage, and a reduced stress protein response to injury. High-fat enteral nutrition protects the liver from the remote effects of hemorrhagic shock, but the mechanism of this effect is not yet known. [ABSTRACT FROM AUTHOR]

Glutamine plays an important role in nitrogen homeostasis and intestinal substrate supply. It has been suggested that glutamine is a precursor for arginine through an intestinal–renal pathway involving inter-organ transport of citrulline. The importance of intestinal glutamine metabolism for endogenous arginine synthesis in humans, however, has remained unaddressed. The aim of this study was to investigate the intestinal conversion of glutamine to citrulline and the effect of the liver on splanchnic citrulline metabolism in humans. Eight patients undergoing upper gastrointestinal surgery received a primed continuous intravenous infusion of [2-15N]glutamine and [ureido-13C–2H2]citrulline. Arterial, portal venous and hepatic venous blood were sampled and portal and hepatic blood flows were measured. Organ specific amino acid uptake (disposal), production and net balance, as well as whole body rates of plasma appearance were calculated according to established methods. The intestines consumed glutamine at a rate that was dependent on glutamine supply. Approximately 13% of glutamine taken up by the intestines was converted to citrulline. Quantitatively glutamine was the only important precursor for intestinal citrulline release. Both glutamine and citrulline were consumed and produced by the liver, but net hepatic flux of both amino acids was not significantly different from zero. Plasma glutamine was the precursor of 80% of plasma citrulline and plasma citrulline in turn was the precursor of 10% of plasma arginine. In conclusion, glutamine is an important precursor for the synthesis of arginine after intestinal conversion to citrulline in humans. [ABSTRACT FROM AUTHOR]

Purpose: To compare outcomes after laparoscopic versus open major liver resection (hemihepatectomy) mainly for primary or metastatic cancer. The primary outcome measure was time to functional recovery. Secondary outcomes included morbidity, quality of life (QoL), and for those with cancer, resection margin status and time to adjuvant systemic therapy., Patients and Methods: This was a multicenter, randomized controlled, patient-blinded, superiority trial on adult patients undergoing hemihepatectomy. Patients were recruited from 16 hospitals in Europe between November 2013 and December 2018., Results: Of the 352 randomly assigned patients, 332 patients (94.3%) underwent surgery (laparoscopic, n = 166 and open, n = 166) and comprised the analysis population. The median time to functional recovery was 4 days (IQR, 3-5; range, 1-30) for laparoscopic hemihepatectomy versus 5 days (IQR, 4-6; range, 1-33) for open hemihepatectomy (difference, -17.5% [96% CI, -25.6 to -8.4]; P < .001). There was no difference in major complications (laparoscopic 24/166 [14.5%] v open 28/166 [16.9%]; odds ratio [OR], 0.84; P = .58). Regarding QoL, both global health status (difference, 3.2 points; P < .001) and body image (difference, 0.9 points; P < .001) scored significantly higher in the laparoscopic group. For the 281 (84.6%) patients with cancer, R0 resection margin status was similar (laparoscopic 106 [77.9%] v open 122 patients [84.1%], OR, 0.60; P = .14) with a shorter time to adjuvant systemic therapy in the laparoscopic group (46.5 days v 62.8 days, hazard ratio, 2.20; P = .009)., Conclusion: Among patients undergoing hemihepatectomy, the laparoscopic approach resulted in a shorter time to functional recovery compared with open surgery. In addition, it was associated with a better QoL, and in patients with cancer, a shorter time to adjuvant systemic therapy with no adverse impact on cancer outcomes observed.

Background: Consensus on resectability criteria for colorectal cancer liver metastases (CRLM) is lacking, resulting in differences in therapeutic strategies. This study evaluated variability of resectability assessments and local treatment plans for patients with initially unresectable CRLM by the liver expert panel from the randomised phase III CAIRO5 study., Methods: The liver panel, comprising surgeons and radiologists, evaluated resectability by predefined criteria at baseline and 2-monthly thereafter. If surgeons judged CRLM as resectable, detailed local treatment plans were provided. The panel chair determined the conclusion of resectability status and local treatment advice, and forwarded it to local surgeons., Results: A total of 1149 panel evaluations of 496 patients were included. Intersurgeon disagreement was observed in 50% of evaluations and was lower at baseline than follow-up (36% vs. 60%, p < 0.001). Among surgeons in general, votes for resectable CRLM at baseline and follow-up ranged between 0-12% and 27-62%, and for permanently unresectable CRLM between 3-40% and 6-47%, respectively. Surgeons proposed different local treatment plans in 77% of patients. The most pronounced intersurgeon differences concerned the advice to proceed with hemihepatectomy versus parenchymal-preserving approaches. Eighty-four percent of patients judged by the panel as having resectable CRLM indeed received local treatment. Local surgeons followed the technical plan proposed by the panel in 40% of patients., Conclusion: Considerable variability exists among expert liver surgeons in assessing resectability and local treatment planning of initially unresectable CRLM. This stresses the value of panel-based decisions, and the need for consensus guidelines on resectability criteria and technical approach to prevent unwarranted variability in clinical practice., (© 2023. The Author(s).)

Background: Large inter-surgeon variability exists in technical anatomical resectability assessment of colorectal cancer liver-only metastases (CRLM) following induction systemic therapy. We evaluated the role of tumour biological factors in predicting resectability and (early) recurrence after surgery for initially unresectable CRLM., Methods: 482 patients with initially unresectable CRLM from the phase 3 CAIRO5 trial were selected, with two-monthly resectability assessments by a liver expert panel. If no consensus existed among panel surgeons (i.e. same vote for (un)resectability of CRLM), conclusion was based on majority. The association of tumour biological (sidedness, synchronous CRLM, carcinoembryonic antigen and RAS/BRAF V600E mutation status) and technical anatomical factors with consensus among panel surgeons, secondary resectability and early recurrence (<6 months) without curative-intent repeat local treatment was analysed by uni- and pre-specified multivariable logistic regression., Results: After systemic treatment, 240 (50%) patients received complete local treatment of CRLM of which 75 (31%) patients experienced early recurrence without repeat local treatment. Higher number of CRLM (odds ratio 1.09 [95% confidence interval 1.03-1.15]) and age (odds ratio 1.03 [95% confidence interval 1.00-1.07]) were independently associated with early recurrence without repeat local treatment. In 138 (52%) patients, no consensus among panel surgeons was present prior to local treatment. Postoperative outcomes in patients with and without consensus were comparable., Conclusions: Almost a third of patients selected by an expert panel for secondary CRLM surgery following induction systemic treatment experience an early recurrence only amenable to palliative treatment. Number of CRLM and age, but no tumour biological factors are predictive, suggesting that until there are better biomarkers; resectability assessment remains primarily a technical anatomical decision., Competing Interests: Conflict of interest statement C.J.A.P. has an advisory role for Nordic Pharma. This funding is not related to the current research. The remaining authors declare no potential conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background and Aims: The DRAINAGE trial was a randomized controlled trial comparing preoperative endoscopic (EBD) and percutaneous biliary drainage (PTBD) in patients with potentially resectable, perihilar cholangiocarcinoma (pCCA). The aim of this study was to compare the long-term outcomes., Methods: Patients were randomized in four tertiary referral centers. Follow-up data were available for all included patients. Primary outcome was overall survival (OS). Secondary outcomes were readmissions, and re-interventions not including in-trial interventions., Results: A total of 54 patients were randomized; 27 in both groups. Median follow-up for both groups was 62 months (95% CI 54-70). The median OS was 13 months (95% CI 7.9-18.1) in the EBD and 7 months (95% CI 0.0-17.2) in the PTBD group (P = 0.28). Twenty (37%, n = 8 EBD vs n = 12 PTBD, P = 0.43) of 54 patients were readmitted at least once, mostly due to drainage-related complications (n = 13, 24%). Of note, 14 out of the 54 patients died within the trial. A total of 76 drainage procedures (32 EBD and 44 PTBD) were performed in 28 patients. The median number of stent or drain placements was 2 (2-4) for the EBD group and 2 (1-3) for the PTBD group (P = 0.77)., Discussion: Although this follow-up study represented a small cohort, no long-term differences in survival, readmissions, and drainage procedures for EBD and PTBD were found, even when comparing the resected and unresected group. However, this study demonstrates the complexity of biliary drainage for patients with potentially resectable pCCA, even in tertiary referral centers., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Textbook outcome (TO) is a composite outcome measure covering the surgical care process in a single outcome measure. TO has an advantage over single outcome parameters with low event rates, which have less discriminating impact to detect differences between hospitals. This study aimed to assess factors associated with TO, and evaluate hospital and network variation after case-mix correction in TO rates for liver surgery., Methods: This was a population-based retrospective study of all patients who underwent liver resection for malignancy in the Netherlands in 2019 and 2020. TO was defined as absence of severe postoperative complications, mortality, prolonged length of hospital stay, and readmission, and obtaining adequate resection margins. Multivariable logistic regression was used for case-mix adjustment., Results: 2376 patients were included. TO was accomplished in 1380 (80%) patients with colorectal liver metastases, in 192 (76%) patients with other liver metastases, in 183 (74%) patients with hepatocellular carcinoma and 86 (51%) patients with biliary cancers. Factors associated with lower TO rates for CRLM included ASA score ≥3 (aOR 0.70, CI 0.51-0.95 p = 0.02), extrahepatic disease (aOR 0.64, CI 0.44-0.95, p = 0.02), tumour size >55 mm on preoperative imaging (aOR 0.56, CI 0.34-0.94, p = 0.02), Charlson Comorbidity Index ≥2 (aOR 0.73, CI 0.54-0.98, p = 0.04), and major liver resection (aOR 0.50, CI 0.36-0.69, p < 0.001). After case-mix correction, no significant hospital or oncological network variation was observed., Conclusion: TO differs between indications for liver resection and can be used to assess between hospital and network differences., Competing Interests: Declaration of competing interest All authors declare no conflict of interest., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: This study evaluates the effect of preoperative macrogol on gastrointestinal recovery and functional recovery after liver surgery combined with an enhanced recovery programme in a randomized controlled setting., Methods: Patients were randomized to either 1 sachet of macrogol a day, one week prior to surgery versus no preoperative laxatives. Postoperative management for all patients was within an enhanced recovery programme. The primary outcome was recovery of gastrointestinal function, defined as Time to First Defecation. Secondary outcomes included Time to Functional Recovery., Results: Between August 2012 and September 2016, 82 patients planned for liver resection were included in the study, 39 in the intervention group and 43 in the control group. Median Time to First Defecation was 4.0 days in the intervention group (IQR 2.8-5.0) and 4.0 days in the control group (IQR 2.9-5.0), P = 0.487. Median Time to Functional Recovery was day 6 (IQR 4.0-8.0) in the intervention group and day 5 (IQR 4.0-7.5) in the control group, P = 0.752. No significant differences were seen in complication rate, reinterventions or mortality., Conclusion: This randomized controlled trial showed no advantages of 1 sachet of macrogol preoperatively combined with an enhanced recovery programme, for patients undergoing liver surgery., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose To evaluate interobserver variability in the morphologic tumor response assessment of colorectal liver metastases (CRLM) managed with systemic therapy and to assess the relation of morphologic response with gene mutation status, targeted therapy, and Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 measurements. Materials and Methods Participants with initially unresectable CRLM receiving different systemic therapy regimens from the randomized, controlled CAIRO5 trial (NCT02162563) were included in this prospective imaging study. Three radiologists independently assessed morphologic tumor response on baseline and first follow-up CT scans according to previously published criteria. Two additional radiologists evaluated disagreement cases. Interobserver agreement was calculated by using Fleiss κ. On the basis of the majority of individual radiologic assessments, the final morphologic tumor response was determined. Finally, the relation of morphologic tumor response and clinical prognostic parameters was assessed. Results In total, 153 participants (median age, 63 years [IQR, 56-71]; 101 men) with 306 CT scans comprising 2192 CRLM were included. Morphologic assessment performed by the three radiologists yielded 86 (56%) agreement cases and 67 (44%) disagreement cases (including four major disagreement cases). Overall interobserver agreement between the panel radiologists on morphology groups and morphologic response categories was moderate (κ = 0.53, 95% CI: 0.48, 0.58 and κ = 0.54, 95% CI: 0.47, 0.60). Optimal morphologic response was particularly observed in patients treated with bevacizumab ( P = .001) and in patients with RAS/BRAF mutation ( P = .04). No evidence of a relationship between RECIST 1.1 and morphologic response was found ( P = .61). Conclusion Morphologic tumor response assessment following systemic therapy in participants with CRLM demonstrated considerable interobserver variability. Keywords: Tumor Response, Observer Performance, CT, Liver, Metastases, Oncology, Abdomen/Gastrointestinal Clinical trial registration no. NCT02162563 Supplemental material is available for this article. © RSNA, 2022.