Treatment strategies and overall survival for incurable metastatic colorectal cancer - A EURECCA international comparison including 21,196 patients from the Netherlands and Norway.

BACKGROUND: The potential benefit of surgery of the primary tumour in patients with asymptomatic metastatic colorectal cancer is debated. This EURECCA international comparison analyses treatment strategies and overall survival in the Netherlands and Norway in patients with incurable metastatic colorectal cancer. METHODS: National cohorts (2007-2013) from the Netherlands and Norway including all patients with synchronous metastatic colorectal cancer were compared on treatment strategy and overall survival. Using country as an instrumental variable, we assessed the effect of different treatment strategies on mortality in the first year. RESULTS: Of 21,196 patients (16,144 Dutch and 5052 Norwegian), 38.6% Dutch and 51.5% (p < 0.001) Norwegian patients underwent resection of the primary tumour. In the Netherlands, 58.2% received chemotherapy compared with 21.4% in Norway. Radiotherapy was given in 9.5% of Dutch patients and 7.2% of Norwegian patients. Using the Netherlands as reference, the adjusted HR for overall survival was 0.96 (95% CI 0.93-0.99; p = 0.024). Instrumental variable analysis showed an adjusted OR of 1.00 (95% CI 0.99-1.02; p = 0.741). CONCLUSIONS: Treatment strategies varied significantly between the Netherlands and Norway, with more surgery and less radiotherapy in Norway. Adjusted overall survival was better in Norway for all patients and patients <75 years, but not for patients ≥75 years. Instrumental variable analysis showed no benefit in one-year mortality for a treatment strategy with a higher proportion of surgery and a lower proportion of radiotherapy. Our findings emphasise the need for further research to select patients with incurable metastatic colorectal cancer for different treatment options.

Patterns of axillary staging and management in clinically node positive breast cancer patients treated with neoadjuvant systemic therapy: Results of a survey amongst breast cancer specialists.

INTRODUCTION: Various options for axillary staging after neoadjuvant systemic therapy (NST) are available for breast cancer patients with a clinically positive axillary node (cN+). This survey assessed current practices amongst breast cancer specialists. MATERIALS AND METHODS: A survey was performed amongst members of the European Society of Surgical Oncology and two UK-based Associations: the Association of Breast Surgery and the British Association of Surgical Oncology. The survey included 3 parts: 1. general information, 2. diagnostic work-up and 3. axillary staging after NST. RESULTS: A total of 310 responses were collected: parts 1, 2 and 3 were fully completed by 282 (91%), 270 (87.1%) and 225 (72.6%) respondents respectively. After NST, 153/267 (57.3%) respondents currently perform ALND routinely and 114 (42.7%) respondents perform less invasive restaging of the axilla with possible omission of ALND. In the latter group, 85% does and 15% does not use nodal response seen on imaging to guide the axillary restaging procedure. Regarding respondents that do use imaging: 95% would perform a less invasive staging procedure in case of complete nodal response on imaging (63% sentinel lymph node biopsy (SLNB), excision of a previously marked positive node with SLNB (21%) and without SLNB (11%)). In case of no nodal response on imaging 77% would perform ALND. CONCLUSION: Current axillary staging and management practices in cN + patients after NST vary widely. To determine optimal axillary staging and management in terms of quality of life and oncologic safety, breast specialists are encouraged to include patients in clinical trials/prospective registries.

Oncologic treatment strategies and relative survival of patients with stage I-III rectal cancer - A EURECCA international comparison between the Netherlands, Belgium, Denmark, Sweden, England, Ireland, Spain, and Lithuania.

INTRODUCTION: The aim of this EURECCA international comparison is to compare oncologic treatment strategies and relative survival of patients with stage I-III rectal cancer between European countries. MATERIAL AND METHODS: Population-based national cohort data from the Netherlands (NL), Belgium (BE), Denmark (DK), Sweden (SE), England (ENG), Ireland (IE), Spain (ES), and single-centre data from Lithuania (LT) were obtained. All operated patients with (y)pTNM stage I-III rectal cancer diagnosed between 2004 and 2009 were included. Oncologic treatment strategies and relative survival were calculated and compared between neighbouring countries. RESULTS: We included 57,120 patients. Treatment strategies differed between NL and BE (p < 0.001), DK and SE (p < 0.001), and ENG and IE (p < 0.001). More preoperative radiotherapy as single treatment before surgery was administered in NL compared with BE (59.7% vs. 13.1%), in SE compared with DK (55.1% vs. 10.4%), and in ENG compared with IE (15.2% vs. 9.6%). Less postoperative chemotherapy was given in NL (9.6% vs. 39.1%), in SE (7.9% vs. 14.1%), and in IE (12.6% vs. 18.5%) compared with their neighbouring country. In ES, 55.1% of patients received preoperative chemoradiation and 62.3% postoperative chemotherapy. There were no significant differences in relative survival between neighbouring countries. CONCLUSION: Large differences in oncologic treatment strategies for patients with (y)pTNM I-III rectal cancer were observed across European countries. No clear relation between oncologic treatment strategies and relative survival was observed. Further research into selection criteria for specific treatments could eventually lead to individualised and optimal treatment for patients with non-metastasised rectal cancer.

Adjuvant chemotherapy and relative survival of patients with stage II colon cancer - A EURECCA international comparison between the Netherlands, Denmark, Sweden, England, Ireland, Belgium, and Lithuania.

BACKGROUND: The aim of the present EURECCA international comparison is to compare adjuvant chemotherapy and relative survival of patients with stage II colon cancer between European countries. METHODS: Population-based national cohort data (2004-2009) from the Netherlands (NL), Denmark (DK), Sweden (SE), England (ENG), Ireland (IE), and Belgium (BE) were obtained, as well as single-centre data from Lithuania. All surgically treated patients with stage II colon cancer were included. The proportion of patients receiving adjuvant chemotherapy was calculated and compared between countries. Besides, relative survival was calculated and compared between countries. RESULTS: Overall, 59,154 patients were included. The proportion of patients receiving adjuvant chemotherapy ranged from 7.1% to 29.0% (p < 0.001). Compared with NL, a better adjusted relative survival was observed in SE (stage II: relative excess risks (RER) 0.53, 95% confidence interval (CI) 0.44-0.64; p < 0.001), and BE (stage II: RER 0.84, 95% CI 0.76-0.92; p < 0.001), and in IE for patients with stage IIA disease (RER 0.80, 95% CI 0.65-0.98; p = 0.03). CONCLUSION: The proportion of patients with stage II colon cancer receiving adjuvant chemotherapy varied largely between seven European countries. No clear linear pattern between adjuvant chemotherapy and adjusted relative survival was observed. Compared with NL, SE and BE showed an improved adjusted relative survival for stage II disease, and IE for patients with stage IIA disease only. Further research into selection criteria for adjuvant chemotherapy could eventually lead to individually tailored, optimal treatment of patients with stage II colon cancer.

Common variables in European pancreatic cancer registries: The introduction of the EURECCA pancreatic cancer project.

BACKGROUND: Quality assurance of cancer care is of utmost importance to detect and avoid under and over treatment. Most cancer data are collected by different procedures in different countries, and are poorly comparable at an international level. EURECCA, acronym for European Registration of Cancer Care, is a platform aiming to harmonize cancer data collection and improve cancer care by feedback. After the prior launch of the projects on colorectal, breast and upper GI cancer, EURECCA's newest project is collecting data on pancreatic cancer in several European countries. METHODS: National cancer registries, as well as specific pancreatic cancer audits/registries, were invited to participate in EURECCA Pancreas. Participating countries were requested to share an overview of their collected data items. Of the received datasets, a shared items list was made which creates insight in similarities between different national registries and will enable data comparison on a larger scale. Additionally, first data was requested from the participating countries. RESULTS: Over 24 countries have been approached and 11 confirmed participation: Austria, Belgium, Bulgaria, Denmark, Germany, The Netherlands, Slovenia, Spain, Sweden, Ukraine and United Kingdom. The number of collected data items varied between 16 and 285. This led to a shared items list of 25 variables divided into five categories: patient characteristics, preoperative diagnostics, treatment, staging and survival. Eight countries shared their first data. CONCLUSIONS: A list of 25 shared items on pancreatic cancer coming from eleven participating registries was created, providing a basis for future prospective data collection in pancreatic cancer treatment internationally.

Description and analysis of clinical pathways for oesophago-gastric adenocarcinoma, in 10 European countries (the EURECCA upper gastro intestinal group - European Registration of Cancer Care).

AIMS: Outcomes for patients with oesophago-gastric cancer are variable across Europe. The reasons for this variability are not clear. The aim of this study was to describe and analyse clinical pathways to understand differences in service provision for oesophageal and gastric cancer in the countries participating in the EURECCA Upper GI group. METHODS: A questionnaire was devised to assess clinical presentation, diagnosis, staging, treatment, pathology, follow-up and service frameworks across Europe for patients with oesophageal and gastric cancer. The questionnaire was issued to experts from 14 countries. The responses were analysed quantitatively and qualitatively and compared. RESULTS: The response rate was (10/14) 71.4%. The approach to diagnosis was similar. Most countries established a diagnosis within 3 weeks of presentation. However, there were different approaches to staging with variable use of endoscopic ultrasound reflecting availability. There has been centralisation of treatments in most countries for oesophageal surgery. The most consistent area was the approach to pathology. There were variations in access to specialist nurse and dietitian support. Although most countries have multidisciplinary teams, their composition and frequency of meetings varied. The two main areas of significant difference were research and audit and overall service provision. Observations on service framework indicated that limited resources restricted many of the services. CONCLUSION: The principle approaches to diagnosis, treatment and pathology were similar. Factors affecting the quality of patient experience were variable. This may reflect availability of resources. Standard pathways of care may enhance both the quality of treatment and patient experience.

Variations among 5 European countries for curative treatment of resectable oesophageal and gastric cancer: A survey from the EURECCA Upper GI Group (EUropean REgistration of Cancer CAre).

INTRODUCTION: EURECCA (EUropean REgistration of Cancer CAre) is a network aiming to improve cancer care by auditing outcome. EURECCA initiated an international survey to share and compare patient outcome for oesophagogastric cancer. The present study assessed how a uniform dataset could be introduced for oesophagogastric cancer in Europe. METHODS: Participating countries presented data using common data items describing patients', disease, strategies, and outcome characteristics. Patients treated with curative surgery for squamous cell carcinoma (SCC) or adenocarcinoma (ACA) were included. RESULTS: United Kingdom, the Netherlands, France, Spain and Ireland participated. There were differences in data source ranging from national registries to large collaborative groups. 4668 oesophagogastric cancer cases over a 12 months period were included. The predominant histological type was ACA. Disease stage tended to be earlier in France and Ireland. In oesophageal and junctional cancers neoadjuvant chemoradiotherapy was preferred in the Netherlands and Ireland contrasting with chemotherapy in the UK and France. All countries used perioperative chemotherapy in gastric cancer but 1/3 of patients received this treatment. The mean R0 resection rate was 86% for oesophageal and junctional resections and 88% for gastric resections. Postoperative mortality varied from 1% to 7%. CONCLUSION: This European survey shown that implementing a uniform treatment and outcome data format of oesophagogastric cancer is feasible. It identified differences in disease presentation, treatment approaches and outcome, which need to be investigated, especially by increasing the number of participating countries. Future comparisons will facilitate developments in treatment for the benefit of patient outcomes.

Quality assurance in the treatment of colorectal cancer: the EURECCA initiative.

Colorectal cancer is one of the most common cancers in Europe. Over the past few decades, important advances have been made in screening, staging and treatment of colorectal cancer. However, considerable variation between and within European countries remains, which implies that further improvements are possible. The most important remaining question now is: when are we, health care professionals, delivering the best available care to patients with colon or rectal cancer? Currently, quality assurance is a major issue in colorectal cancer care and quality assurance awareness is developing in almost all disciplines involved in the treatment of colorectal cancer patients. Quality assurance has shown to be effective in clinical trials. For example, standardisation and quality control were introduced in the Dutch TME trial and led to marked improvements of local control and survival in rectal cancer patients. Besides, audit structures can also be very effective in monitoring cancer management and national audits showed to further improve outcome in colorectal cancer patients. To reduce the differences between European countries, an international, multidisciplinary, outcome-based quality improvement programme, European Registration of Cancer Care (EURECCA), has been initiated. In the near future, the EURECCA dataset will perform research on subgroups as elderly patients or patients with comorbidities, which are often excluded from trials. For optimal colorectal cancer care, quality assurance in guideline formation and in multidisciplinary team management is also of great importance. The aim of this review was to create greater awareness and to give an overview of quality assurance in the management of colorectal cancer.

EURECCA consensus conference highlights about colon & rectal cancer multidisciplinary management: the radiology experts review.

Some interesting shifts have taken place in the diagnostic approach for detection of colorectal lesions over the past decade. This article accompanies the recent EURECCA consensus group reccomendations for optimal management of colon and rectal cancers. In summary, imaging has a crucial role to play in the diagnosis, staging assessment and follow up of patients with colon and rectal cancer. Recent advances include the use of CT colonography instead of Barium Enema in the diagnosis of colonoic cancer and as an alternative to colonoscopy. Modern mutlidetector CT scanning techniques have also shown improvements in prognostic stratification of patients with colonic cancer and clinical trials are underway testing the selective use of neoadjuvant therapy for imaging identified high risk colon cancers. In rectal cancer, high resolution MRI with a voxel size less or equal to 3 × 1 × 1 mm3 on T2-weighted images has a proven ability to accurately stage patients with rectal cancer. Moreover, preoperative identification of prognostic features allows stratification of patients into different prognostic groups based on assessment of depth of extramural spread, relationship of the tumour edge to the mesorectal fascia (MRF) and extramural venous invasion (EMVI). These poor prognostic features predict an increased risk of local recurrence and/or metastatic disease and should form the basis for preoperative local staging and multidisciplinary preoperative discussion of patient treatment options.

Experts reviews of the multidisciplinary consensus conference colon and rectal cancer 2012: science, opinions and experiences from the experts of surgery.

The first multidisciplinary consensus conference on colon and rectal cancer was held in December 2012, achieving a majority of consensus for diagnostic and treatment decisions using the Delphi Method. This article will give a critical appraisal of the topics discussed during the meeting and in the consensus document by well-known leaders in surgery that were involved in this multidisciplinary consensus process. Scientific evidence, experience and opinions are collected to support multidisciplinary teams (MDT) with arguments for medical decision-making in diagnosis, staging and treatment strategies for patients with colon or rectal cancer. Surgery is the cornerstone of curative treatment for colon and rectal cancer. Standardizing treatment is an effective instrument to improve outcome of multidisciplinary cancer care for patients with colon and rectal cancer. In this article, a review of the following focuses; Perioperative care, age and colorectal surgery, obstructive colorectal cancer, stenting, surgical anatomical considerations, total mesorectal excision (TME) surgery and training, surgical considerations for locally advanced rectal cancer (LARC) and local recurrent rectal cancer (LRRC), surgery in stage IV colorectal cancer, definitions of quality of surgery, transanal endoscopic microsurgery (TEM), laparoscopic colon and rectal surgery, preoperative radiotherapy and chemoradiotherapy, and how about functional outcome after surgery?

Immunological consequences of laparoscopic versus open transhiatal resection for malignancies of the distal esophagus and gastroesophageal junction.

BACKGROUND/AIM: Surgery remains the only curative therapy for esophageal cancer. The objective of the current study was to evaluate the impact of laparoscopic transhiatal esophagectomy versus open transhiatal esophagectomy on both inflammatory and immunological responses. METHODS: Seventeen patients undergoing laparoscopic or open surgery were included in the study. The postoperative inflammatory response was assessed by measuring WBC count and CRP, IL-6, IL-8, soluble TNF I and II receptor, and elastase levels. The postoperative immune function was assessed by measuring the monocyte HLA-DR expression. LPS-binding protein (LBP) and bactericidal/permeability-increasing protein (BPI) were measured to evaluate bacterial translocation. RESULTS: The IL-6 level increased significantly more in the patients who received open surgery as compared with the laparoscopic group. Both LBP and BPI increased predominantly in the laparoscopic group as compared with the group who received open surgery. No difference was found in HLA-DR expression between the two groups. CONCLUSION: Although both laparoscopic and conventional esophageal resections result in an activation of the inflammatory response, this study suggests that this response could be less pronounced after the laparoscopic approach. However, in the laparoscopic group higher LBP and BPI levels were seen, suggesting an increased endotoxemia. We postulate that the persistently elevated abdominal pressure results in a loss of mucosal barrier function, resulting in bacterial translocation. The cellular acidification of the cells of the peritoneum induced by CO(2) insufflation, however, blunts the expected inflammatory response.

[Perioperative nutrition]. / Perioperatieve voeding.

Illness is associated with involuntary weight loss, which is often the result of malnutrition. The undernourished surgical patient runs a higher risk of postoperative morbidity and mortality. For this reason, perioperative nutrition is an important part of a patient's therapy. Supplying substrates for wound healing and maintaining existing organic structures are the major goals of nutrition. It is recommended that extremely malnourished patients be fed at least 7 days prior to surgery. It would seem sensible to give a carbohydrate-rich beverage up to 2 hours before surgery, both to decrease preoperative anxiety and to reduce postoperative insulin resistance. The Dutch tradition of fasting patients before surgery is difficult to defend any longer because this policy impairs patients' state of health as a result of which they are not optimally prepared for the surgical induced stress response. The postoperative recovery of all surgical patients can be improved by an early postoperative start of enteric nutrition. When the enteric administration of food turns out to be impossible, total parenteral nutrition can be given to bridge a long period without food.

Preoperative fasting: an outdated concept?

Recent studies have shown that fasting during the preoperative period for elective surgery induces a metabolic state that seems unfavorable for patients. Results from animal studies indicate that rapid depletion of liver glycogen before surgery leads to mobilization of muscle glycogen after surgery, in turn leading to reduced muscle strength. Depletion of liver glycogen also influences the function of the mononuclear phagocytic system (MPS), which is located predominantly in the liver. The MPS is essential in restricting endotoxin, which may translocate from the gut. In addition, surgery per se puts a substantial physical strain on the patient, and fasting may adversely affect the metabolic response to surgery. This paper presents experimental and clinical data that, when combined together, prove that fasting before surgery has adverse consequences for the patient.

Aortic aneurysm repair is associated with a lower inflammatory response compared with surgery for inflammatory bowel disease.

BACKGROUND: Since the plasma cytokine profile reflects the body's inflammatory response to injury, this study was designed to prospectively observe the plasma cytokine levels in response to the degree of different sorts of abdominal surgical trauma. METHODS: Plasma levels of TNF-alpha, type I TNF receptor (p55), type II TNF receptor (p75), IL-6, IL-8, IL-10, phospholipase A(2) (PLA(2)), and haptoglobin were measured peri-operatively in patients undergoing bowel resection for inflammatory bowel disease or diverticulitis (IBD) (n = 9), elective repair of abdominal aortic aneurysm (AAA) (n = 9), or laparoscopic cholecystectomy (lap chole) (n = 9). RESULTS: The IBD patients showed a significant (p < 0.05) post-operative elevation in plasma IL-6, p55, p75, and PLA(2) levels, but no significant change in TNF-alpha, IL-8, IL-10 or haptoglobin levels. The AAA patients had a significant post-operative rise in IL-10 levels and a significant decrease in plasma haptoglobin levels, but no significant change of TNF-alpha, IL-6, IL-8, p55, p75, or PLA(2) concentrations. The lap chole patients demonstrated no significant change in any of these parameters. CONCLUSION: These data show that IL-6, IL-10, p55, and p75 are markers to measure the degree of inflammatory stress associated with abdominal operative procedures and demonstrate the relative lack of a cytokine response to laparoscopic cholecystectomy.

Primary immune response to keyhole limpet haemocyanin following trauma in relation to low plasma glutamine.

Severe trauma can lead to a compromised immune response, thereby increasing susceptibility to infections. Here we will study to what extent these early changes in the immune status upon trauma affect a primary immune response to keyhole limpet haemocyanin (KLH). Because glutamine is the preferred respiratory substrate for immune competent cells and known to be depleted after trauma, we studied the immune status and the primary sensitization in relation to the glutamine plasma concentration in a group of severe trauma patients [injury severity score (ISS) >17]. Trauma patients (n = 31) were sensitized with KLH within 12 h after trauma; plasma glutamine concentrations and immune parameters were determined, after which KLH-specific immune responsiveness was evaluated on days 9 and 14. Low plasma glutamine concentrations were found after trauma. Significantly elevated numbers of granulocytes and CD14-positive leucocytes were found, whereas the HLA-DR expression on CD14-positive cells was significantly lower in trauma patients than in healthy controls. Trauma did not change the in vitro proliferative capacity of lymphocytes when cultured with glutamine; however, when lymphocytes were cultured without glutamine, trauma resulted in lower proliferation than healthy controls. Phytohaemagglutinin-(PHA)-induced interferon (IFN)-gamma and interleukin (IL)-10 production was significantly lower after trauma, whereas IL-4 production was not affected. KLH sensitization following trauma resulted in poor skin test reactivity and low in vitro KLH-induced lymphocyte proliferation compared to controls. In contrast, the development of anti-KLH IgM, IgG, IgA, IgG1, IgG2, IgG3 and IgG4 production on days 9 and 14 following trauma was not different from that in healthy controls. Major trauma was associated with a reduced cell-mediated immune response, correlating with low plasma glutamine concentrations, while no effects of trauma were found on the development of a primary humoral immune response.

Glutamine alimentation in catabolic state.

Glutamine should be reclassified as a conditionally essential amino acid in the catabolic state because the body's glutamine expenditures exceed synthesis and low glutamine levels in plasma are associated with poor clinical outcome. After severe stress, several amino acids are mobilized from muscle tissue to supply energy and substrate to the host. Glutamine is one of the most important amino acids that provide this function. Glutamine acts as the preferred respiratory fuel for lymphocytes, hepatocytes and intestinal mucosal cells and is metabolized in the gut to citrulline, ammonium and other amino acids. Low concentrations of glutamine in plasma reflect reduced stores in muscle and this reduced availability of glutamine in the catabolic state seems to correlate with increased morbidity and mortality. Adding glutamine to the nutrition of clinical patients, enterally or parenterally, may reduce morbidity. Several excellent clinical trials have been performed to prove efficacy and feasibility of the use of glutamine supplementation in parenteral and enteral nutrition. The increased intake of glutamine has resulted in lower septic morbidity in certain critically ill patient populations. This review will focus on the efficacy and the importance of glutamine supplementation in diverse catabolic states.

Flavonoids: a review of probable mechanisms of action and potential applications.

The aim of this review, a summary of the putative biological actions of flavonoids, was to obtain a further understanding of the reported beneficial health effects of these substances. Flavonoids occur naturally in fruit, vegetables, and beverages such as tea and wine. Research in the field of flavonoids has increased since the discovery of the French paradox,ie, the low cardiovascular mortality rate observed in Mediterranean populations in association with red wine consumption and a high saturated fat intake. Several other potential beneficial properties of flavonoids have since been ascertained. We review the different groups of known flavonoids, the probable mechanisms by which they act, and the potential clinical applications of these fascinating natural substances.

Low arginine plasma levels do not aggravate renal blood flow after experimental renal ischaemia/reperfusion.

BACKGROUND: Ischaemic renal dysfunction is present in many clinical settings, including cardiovascular surgery. Renal hypoperfusion seems to be the most important pathophysiologic mechanism. Arginine plasma levels are rate limiting for NO synthesis, and low arginine plasma levels are seen after major vascular surgery. OBJECTIVE: to establish the effects of low arginine plasma levels on renal blood flow after renal ischaemia/reperfusion. DESIGN: Wistar rats were used in this unilateral renal ischaemia/reperfusion model. After 70 min of ischaemia, the kidney was reperfused for 150 min. Arginase infusion was used to lower arginine plasma levels. Blood flow measurement was performed at the end of the experiment using radiolabelled microspheres. Additional experiments were performed for histopathology. RESULTS: Arginase efficiently decreased arginine plasma levels to about 50% of normal. There was a lower blood flow in the ischaemic kidney than the contralateral (non-ischaemic) kidney. Lowering arginine plasma levels did not reduce renal blood flow in the ischaemic kidney. Renal histopathology was not influenced by lowered arginine plasma levels. CONCLUSIONS: Lowering arginine plasma levels did not affect blood flow or histology following renal ischaemia and reperfusion.

Perioperative treatment with bactericidal/permeability-increasing protein (rBPI21) in major liver surgery: a concise summary.

INTRODUCTION: Major hepatic resections are still associated with considerable morbidity. Gut-derived bacteria and bacterial endotoxin are considered to play a central role in the pathophysiology of complications. Experimental studies suggest that bactericidal/permeability-increasing protein (BPI), which has both antibacterial and endotoxin-neutralising properties, can reduce postoperative complications. MATERIAL AND METHODS: A phase II, double-blind, placebo-controlled, multicentre, dose escalation trial was conducted in patients undergoing major liver resection, and clinical outcome, infectious complications, plasma amino acid patterns, coagulation and fibrinolytic cascade systems and neutrophil functions were compared between the two treatment groups and an extra group of patients undergoing major abdominal non-hepatic surgery. RESULTS: Drug administration in this patient group was safe, and resulted in a significant reduction of infectious complications. Furthermore, beneficial effects were found in the postoperative amino acid ratio and fibrinolytic cascades, and rBPI21 preserved leukocyte functions. CONCLUSION: Administration of rBPI21 in patients undergoing major liver resection is well tolerated and results in improvement of both clinical and biochemical parameters.