Surgical techniques for mesenteric lengthening in ileoanal pouch surgery: a systematic review.

AIM: The key to successful construction of an ileal pouch-anal anastomosis (IPAA) following proctocolectomy in patients with ulcerative colitis or familial adenomatous polyposis is the ability of the pouch reservoir to reach the anus well vascularized and without tension. The aim of this systematic review was to provide an overview of previously described different surgical lengthening techniques to achieve adequate length for a tension-free IPAA. METHOD: Pubmed, Embase and Cochrane Library databases were systematically searched. Two reviewers conducted a systematic search with combinations of keywords for the surgical procedure and surgical lengthening techniques. All publications that reported one or more surgical lengthening techniques during IPAA surgery in adult patients were selected, consisting of reviews, cohort studies, case reports, human cadaver studies and expert opinions. The primary outcomes measured were the different surgical lengthening techniques and the step-by-step approach they involve that can be used during surgery to achieve adequate length for an IPAA. RESULTS: Of 1577 records reviewed, 19 articles were included in this systematic review describing at least 1181 patients (i.e. one review, four retrospective studies, five human cadaver studies, two case reports and seven expert opinions). A total of six different surgical lengthening techniques with various subtechniques were found and described, consisting of pouch folding, construction of different types of pouches, stepladder incisions, skeletonization of vessels, division and ligation of mesenteric vessels and using an interposition vein graft. No prospective or randomized controlled trials were performed regarding this topic. Quality assessment showed a medium quality of the included studies. CONCLUSION: Different surgical lengthening techniques are described in a step-by-step approach to create adequate mesenteric length during IPAA surgery, in patients in whom the ileal pouch cannot reach the dentate line.

Hypothermic Machine Perfusion as a National Standard Preservation Method for Deceased Donor Kidneys.

BACKGROUND: Recently, continuous nonoxygenated hypothermic machine perfusion (HMP) has been implemented as standard preservation method for deceased donor kidneys in the Netherlands. This study was designed to assess the effect of the implementation of HMP on early outcomes after transplantation. METHODS: Kidneys donated in the Netherlands in 2016 and 2017 were intended to be preserved by HMP. A historical cohort (2010-2014) preserved by static cold storage was chosen as the control group. Primary outcome was delayed graft function (DGF). Additional analyses were performed on safety, graft function, and survival up until 2 y after transplantation. RESULTS: Data were collected on 2493 kidneys. Analyses showed significantly more donation after circulatory death, preemptive transplantation, and retransplants in the project cohort. Of the 681 kidneys that were transplanted during the project, 81% were preserved by HMP. No kidneys were discarded due to HMP-related complications. DGF occurred in 38.2% of the project cohort versus 43.7% of the historical cohort (P < 0.001), with a significantly shorter duration within the project cohort (7 versus 9 d, P = 0.003). Multivariate regression analysis showed an odds ratio of 0.69 (95% confidence interval, 0.553-0.855) for the risk of DGF when using HMP compared with cold storage (P = 0.001). There was no significant difference in kidney function, graft survival, and recipient survival up until 2 y posttransplantation. CONCLUSIONS: This study showed that HMP as a standard preservation method for deceased donor kidneys is safe and feasible. HMP was associated with a significant reduction of DGF.

How Should the Low Anterior Resection Syndrome Score Be Interpreted?

BACKGROUND: Bowel dysfunction after low anterior resection is often assessed by determining the low anterior resection syndrome score. What is unknown, however, is whether this syndrome is already present in the general population and which nonsurgical factors are associated. OBJECTIVE: The purpose of this study was to determine the prevalence of minor and major low anterior resection syndrome in the general Dutch population and which other factors are associated with this syndrome. DESIGN: This was a cross-sectional study. SETTINGS: The study was conducted within the general Dutch population. PATIENTS: The Groningen Defecation and Fecal Continence Questionnaire was distributed among a general Dutch population-based sample (N = 1259). MAIN OUTCOME MEASURES: Minor and major low anterior resection syndrome were classified according to the scores obtained. RESULTS: The median, overall score was 16 (range, 0-42). Minor low anterior resection syndrome was more prevalent than the major form (24.3% vs 12.2%; p < 0.001). Bowel disorders, including fecal incontinence, constipation, and irritable bowel syndrome were associated with the syndrome, whereas sex, age, BMI, and vaginal delivery were not. Remarkably, patients with diabetes mellitus were significantly more prone to experience minor or major low anterior resection syndrome. The ORs were 2.8 (95% CI, 1.8-4.4) and 3.7 (95% CI, 2.2-6.2). LIMITATIONS: We selected frequent comorbidities and other patient-related factors that possibly influence the syndrome. Additional important factors do exist and require future research. CONCLUSIONS: Minor and major low anterior resection syndrome occur in a large portion of the general Dutch population and even in a healthy subgroup. This implies that the low anterior resection syndrome score can only be used to interpret the functional result of the low anterior resection provided that a baseline measurement of each individual is available. Furthermore, because people with low anterior resection syndrome often experience constipation and/or fecal incontinence, direct examination and diagnosis of these conditions might be a more efficient approach to treating patient bowel dysfunctions. See Video Abstract at http://links.lww.com/DCR/B110. ¿CÓMO DEBE INTERPRETARSE LA PUNTUACIÓN DEL SÍNDROME DE RESECCIÓN ANTERIOR BAJA?: La disfunción intestinal después de la resección anterior baja a menudo se evalúa determinando la puntuación del síndrome de resección anterior baja. Sin embargo, lo que se desconoce es si este síndrome ya está presente en la población general y qué factores no quirúrgicos están asociados.Determinar la prevalencia del síndrome de resección anterior baja menor y mayor en la población holandesa general y qué otros factores están asociados con este síndrome.Estudio transversal.Población holandesa general.El cuestionario de defecación y continencia fecal de Groningen se distribuyó entre una muestra general de población holandesa (N = 1259).El síndrome de resección anterior baja menor y mayor se clasificó de acuerdo con las puntuaciones obtenidas.La mediana de la puntuación general fue de 16.0 (rango 0-42). El síndrome de resección anterior baja menor fue más frecuente que la forma principal (24.3% versus 12.2%, (P <0.001). Los trastornos intestinales, incluyendo incontinencia fecal, estreñimiento y síndrome del intestino irritable se asociaron con el síndrome, mientras que el sexo, la edad y el cuerpo el índice de masa y el parto vaginal no lo hicieron. Notablemente, los pacientes con diabetes mellitus fueron significativamente más propensos a experimentar el síndrome de resección anterior baja menor o mayor. Las razones de probabilidad fueron 2.8 (IC 95%, 1.8-4.4) y 3.7 (IC 95%, 2.2 -6.2), respectivamente.Se seleccionaron las comorbilidades frecuentes y otros factores relacionados con el paciente que posiblemente influyen en el síndrome. Existen otros factores importantes que requieren investigación en el futuro.El síndrome de resección anterior baja menor y mayor ocurre en una gran parte de la población holandesa general e incluso en un subgrupo sano. Esto implica que la puntuación del síndrome de resección anterior baja solo se puede utilizar para interpretar el resultado funcional de la resección anterior baja, siempre que esté disponible una medición inicial de cada individuo. Además, dado que las personas con síndrome de resección anterior baja a menudo experimentan estreñimiento y/o incontinencia fecal, el examen directo y el diagnóstico de estas afecciones pueden ser un enfoque más eficiente para tratar las disfunciones intestinales de los pacientes. Consulte Video Resumen en http://links.lww.com/DCR/B110.

Hydrogen sulphide-induced hypometabolism in human-sized porcine kidneys.

BACKGROUND: Since the start of organ transplantation, hypothermia-forced hypometabolism has been the cornerstone in organ preservation. Cold preservation showed to protect against ischemia, although post-transplant injury still occurs and further improvement in preservation techniques is needed. We hypothesize that hydrogen sulphide can be used as such a new preservation method, by inducing a reversible hypometabolic state in human sized kidneys during normothermic machine perfusion. METHODS: Porcine kidneys were connected to an ex-vivo isolated, oxygen supplemented, normothermic blood perfusion set-up. Experimental kidneys (n = 5) received a 85mg NaHS infusion of 100 ppm and were compared to controls (n = 5). As a reflection of the cellular metabolism, oxygen consumption, mitochondrial activity and tissue ATP levels were measured. Kidney function was assessed by creatinine clearance and fractional excretion of sodium. To rule out potential structural and functional deterioration, kidneys were studied for biochemical markers and histology. RESULTS: Hydrogen sulphide strongly decreased oxygen consumption by 61%, which was associated with a marked decrease in mitochondrial activity/function, without directly affecting ATP levels. Renal biological markers, renal function and histology did not change after hydrogen sulphide treatment. CONCLUSION: In conclusion, we showed that hydrogen sulphide can induce a controllable hypometabolic state in a human sized organ, without damaging the organ itself and could thereby be a promising therapeutic alternative for cold preservation under normothermic conditions in renal transplantation.

[Diaphragm pacemaker: alternative for long-term ventilatory support; 5 years later]. / Diafragmapacemaker: alternatief voor chronische beademing.

Currently, more than 3000 patients in the Netherlands receive long-term ventilatory support. In the majority of patients, long-term ventilatory support leads to increased survival without any complications. Diaphragm pacing with an external pacemaker (diaphragm pacing system, DPS) seems an attractive alternative for long-term ventilatory support by mask or tracheostomy. Scientific research has since shown that DPS is effective in patients with high cervical paraplegia. In addition, patients with congenital central hypoventilation syndrome are also eligible for DPS. Patients with diaphragm paralysis are a new group of patients who may be eligible for DPS. Two European studies have shown that DPS should not be used in patients with amyotrophic lateral sclerosis. In our experience, patients are no longer completely dependent on a ventilator or may even be able to discontinue using one if the procedure was successful. In the Netherlands, as far as we know, the technique is only used at the University Medical Center Groningen.

Superiority of Step-up Approach vs Open Necrosectomy in Long-term Follow-up of Patients With Necrotizing Pancreatitis.

BACKGROUND & AIMS: In a 2010 randomized trial (the PANTER trial), a surgical step-up approach for infected necrotizing pancreatitis was found to reduce the composite endpoint of death or major complications compared with open necrosectomy; 35% of patients were successfully treated with simple catheter drainage only. There is concern, however, that minimally invasive treatment increases the need for reinterventions for residual peripancreatic necrotic collections and other complications during the long term. We therefore performed a long-term follow-up study. METHODS: We reevaluated all the 73 patients (of the 88 patients randomly assigned to groups) who were still alive after the index admission, at a mean 86 months (±11 months) of follow-up. We collected data on all clinical and health care resource utilization endpoints through this follow-up period. The primary endpoint was death or major complications (the same as for the PANTER trial). We also measured exocrine insufficiency, quality of life (using the Short Form-36 and EuroQol 5 dimensions forms), and Izbicki pain scores. RESULTS: From index admission to long-term follow-up, 19 patients (44%) died or had major complications in the step-up group compared with 33 patients (73%) in the open-necrosectomy group (P = .005). Significantly lower proportions of patients in the step-up group had incisional hernias (23% vs 53%; P = .004), pancreatic exocrine insufficiency (29% vs 56%; P = .03), or endocrine insufficiency (40% vs 64%; P = .05). There were no significant differences between groups in proportions of patients requiring additional drainage procedures (11% vs 13%; P = .99) or pancreatic surgery (11% vs 5%; P = .43), or in recurrent acute pancreatitis, chronic pancreatitis, Izbicki pain scores, or medical costs. Quality of life increased during follow-up without a significant difference between groups. CONCLUSIONS: In an analysis of long-term outcomes of trial participants, we found the step-up approach for necrotizing pancreatitis to be superior to open necrosectomy, without increased risk of reinterventions.

Predicting a 'difficult cholecystectomy' after mild gallstone pancreatitis.

BACKGROUND: Cholecystectomy after gallstone pancreatitis may be technically demanding. The aim of this study was to investigate risk factors for a difficult cholecystectomy after mild pancreatitis. METHODS: This was a prospective study within a randomized controlled trial on the timing of cholecystectomy after mild gallstone pancreatitis. Difficulty of cholecystectomy was scored on a 0 to 10 visual analogue scale (VAS) by the senior attending surgeon. The primary outcome 'difficult cholecystectomy' was defined by presence of one or more of the following features: a VAS score ≥ 8, duration of surgery > 75 minutes, conversion or subtotal cholecystectomy. RESULTS: 249 patients were included in the primary analysis. A difficult cholecystectomy occurred in 82 patients (33%). In the 'same-admission cholecystectomy' group 29 of 112 cholecystectomies were difficult (26%) versus 49 of 127 patients (39%) who underwent surgery after 2 weeks (p = 0.037). After multivariable analysis, male sex (OR 1.80, 95% confidence interval [CI] 1.04-3.13; p = 0.037), prior sphincterotomy (OR 1.79, 95% CI 1.01-3.16; p = 0.046), and delaying cholecystectomy for at least two weeks (OR 1.81, 95% CI 1.04-3.16; p = 0.036) were independent predictors of a difficult cholecystectomy. CONCLUSION: Surgeons should anticipate a difficult cholecystectomy after mild gallstone pancreatitis in case of male sex, prior sphincterotomy and delayed cholecystectomy.

Endoscopic or surgical step-up approach for infected necrotising pancreatitis: a multicentre randomised trial.

BACKGROUND: Infected necrotising pancreatitis is a potentially lethal disease and an indication for invasive intervention. The surgical step-up approach is the standard treatment. A promising alternative is the endoscopic step-up approach. We compared both approaches to see whether the endoscopic step-up approach was superior to the surgical step-up approach in terms of clinical and economic outcomes. METHODS: In this multicentre, randomised, superiority trial, we recruited adult patients with infected necrotising pancreatitis and an indication for invasive intervention from 19 hospitals in the Netherlands. Patients were randomly assigned to either the endoscopic or the surgical step-up approach. The endoscopic approach consisted of endoscopic ultrasound-guided transluminal drainage followed, if necessary, by endoscopic necrosectomy. The surgical approach consisted of percutaneous catheter drainage followed, if necessary, by video-assisted retroperitoneal debridement. The primary endpoint was a composite of major complications or death during 6-month follow-up. Analyses were by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN09186711. FINDINGS: Between Sept 20, 2011, and Jan 29, 2015, we screened 418 patients with pancreatic or extrapancreatic necrosis, of which 98 patients were enrolled and randomly assigned to the endoscopic step-up approach (n=51) or the surgical step-up approach (n=47). The primary endpoint occurred in 22 (43%) of 51 patients in the endoscopy group and in 21 (45%) of 47 patients in the surgery group (risk ratio [RR] 0·97, 95% CI 0·62-1·51; p=0·88). Mortality did not differ between groups (nine [18%] patients in the endoscopy group vs six [13%] patients in the surgery group; RR 1·38, 95% CI 0·53-3·59, p=0·50), nor did any of the major complications included in the primary endpoint. INTERPRETATION: In patients with infected necrotising pancreatitis, the endoscopic step-up approach was not superior to the surgical step-up approach in reducing major complications or death. The rate of pancreatic fistulas and length of hospital stay were lower in the endoscopy group. The outcome of this trial will probably result in a shift to the endoscopic step-up approach as treatment preference. FUNDING: The Dutch Digestive Disease Foundation, Fonds NutsOhra, and the Netherlands Organization for Health Research and Development.

Abdominal compartment syndrome in acute pancreatitis: a systematic review.

Abdominal compartment syndrome (ACS) is a lethal complication of acute pancreatitis. We performed a systematic review to assess the treatment and outcome of these patients.A systematic literature search for cohorts of patients with acute pancreatitis and ACS was performed. The main outcomes were number of patients with ACS, radiologic and surgical interventions, morbidity, mortality, and methodological quality.After screening 169 articles, 7 studies were included. Three studies were prospective and 4 studies were retrospective. The overall methodological quality of the studies was moderate to low. The pooled data consisted of 271 patients, of whom 103 (38%) developed ACS. Percutaneous drainage of intraabdominal fluid was reported as first intervention in 11 (11%) patients. Additional decompressive laparotomy was performed in 8 patients. Decompressive laparotomy was performed in a total of 76 (74%) patients. The median decrease in intraabdominal pressure was 15 mm Hg (range, 33-18 mm Hg). Mortality in acute pancreatitis patients with ACS was 49% versus 11% without ACS. Morbidity ranged from 17% to 90%.Abdominal compartment syndrome during acute pancreatitis is associated with high mortality and morbidity. Studies are relatively small and have methodological shortcomings. The optimal timing and method of invasive interventions, as well as their effect on clinical outcomes, should be further evaluated.

Transluminal endoscopic step-up approach versus minimally invasive surgical step-up approach in patients with infected necrotising pancreatitis (TENSION trial): design and rationale of a randomised controlled multicenter trial [ISRCTN09186711].

BACKGROUND: Infected necrotising pancreatitis is a potentially lethal disease that nearly always requires intervention. Traditionally, primary open necrosectomy has been the treatment of choice. In recent years, the surgical step-up approach, consisting of percutaneous catheter drainage followed, if necessary, by (minimally invasive) surgical necrosectomy has become the standard of care. A promising minimally invasive alternative is the endoscopic transluminal step-up approach. This approach consists of endoscopic transluminal drainage followed, if necessary, by endoscopic transluminal necrosectomy. We hypothesise that the less invasive endoscopic step-up approach is superior to the surgical step-up approach in terms of clinical and economic outcomes. METHODS/DESIGN: The TENSION trial is a randomised controlled, parallel-group superiority multicenter trial. Patients with (suspected) infected necrotising pancreatitis with an indication for intervention and in whom both treatment modalities are deemed possible, will be randomised to either an endoscopic transluminal or a surgical step-up approach. During a 4 year study period, 98 patients will be enrolled from 24 hospitals of the Dutch Pancreatitis Study Group. The primary endpoint is a composite of death and major complications within 6 months following randomisation. Secondary endpoints include complications such as pancreaticocutaneous fistula, exocrine or endocrine pancreatic insufficiency, need for additional radiological, endoscopic or surgical intervention, the need for necrosectomy after drainage, the number of (re-)interventions, quality of life, and total direct and indirect costs. DISCUSSION: The TENSION trial will answer the question whether an endoscopic step-up approach reduces the combined primary endpoint of death and major complications, as well as hospital stay and related costs compared with a surgical step-up approach in patients with infected necrotising pancreatitis.

[Diaphragm pacemaker: alternative for chronic ventilatory support]. / Diafragmapacemaker: alternatief voor chronische beademing.

Currently, more than 2200 patients in the Netherlands receive chronic ventilatory support. In the majority of patients this leads to increased survival without any complications. Nevertheless, in case of ventilatory support via a mask, problems such as skin irritation, leakage and claustrophobia can occur. In case of tracheostomy, it can lead to increased pulmonary secretion. Diaphragm pacing with an external pacemaker might be an attractive alternative to prevent these symptoms as it can replace ventilatory support by mask or tracheostomy. Current indications are patients with spinal cord injury or with congenital central hypoventilation syndrome who are chronically respiratory insufficient. In our experience, patients can be completely or partially weaned from mechanical ventilation when using the diaphragm pacer. In the Netherlands, the technique is only performed at the University Medical Center Groningen.

Extrapancreatic necrosis without pancreatic parenchymal necrosis: a separate entity in necrotising pancreatitis?

OBJECTIVE: In the revised Atlanta classification of acute pancreatitis, the term necrotising pancreatitis also refers to patients with only extrapancreatic fat necrosis without pancreatic parenchymal necrosis (EXPN), as determined on contrast-enhanced CT (CECT). Patients with EXPN are thought to have a better clinical outcome, although robust data are lacking. METHODS: A post hoc analysis was performed of a prospective multicentre database including 639 patients with necrotising pancreatitis on contrast-enhanced CT. All CECT scans were reviewed by a single radiologist blinded to the clinical outcome. Patients with EXPN were compared with patients with pancreatic parenchymal necrosis (with or without extrapancreatic necrosis). Outcomes were persistent organ failure, need for intervention and mortality. A predefined subgroup analysis was performed on patients who developed infected necrosis. RESULTS: 315 patients with EXPN were compared with 324 patients with pancreatic parenchymal necrosis. Patients with EXPN less often suffered from complications: persistent organ failure (21% vs 45%, p<0.001), persistent multiple organ failure (15% vs 36%, p<0.001), infected necrosis (16% vs 47%, p<0.001), intervention (18% vs 57%, p<0.001) and mortality (9% vs 20%, p<0.001). When infection of extrapancreatic necrosis developed, outcomes between groups were equal (mortality with infected necrosis: EXPN 28% vs pancreatic necrosis 18%, p=0.16). CONCLUSION: EXPN causes fewer complications than pancreatic parenchymal necrosis. It should therefore be considered a separate entity in acute pancreatitis. Outcome in cases of infected necrosis is similar.

A conservative and minimally invasive approach to necrotizing pancreatitis improves outcome.

BACKGROUND & AIMS: Treatment of patients with necrotizing pancreatitis has become more conservative and less invasive, but there are few data from prospective studies to support the efficacy of this change. We performed a prospective multicenter study of treatment outcomes among patients with necrotizing pancreatitis. METHODS: We collected data from 639 consecutive patients with necrotizing pancreatitis, from 2004 to 2008, treated at 21 Dutch hospitals. Data were analyzed for disease severity, interventions (radiologic, endoscopic, surgical), and outcome. RESULTS: Overall mortality was 15% (n=93). Organ failure occurred in 240 patients (38%), with 35% mortality. Treatment was conservative in 397 patients (62%), with 7% mortality. An intervention was performed in 242 patients (38%), with 27% mortality; this included early emergency laparotomy in 32 patients (5%), with 78% mortality. Patients with longer times between admission and intervention had lower mortality: 0 to 14 days, 56%; 14 to 29 days, 26%; and >29 days, 15% (P<.001). A total of 208 patients (33%) received interventions for infected necrosis, with 19% mortality. Catheter drainage was most often performed as the first intervention (63% of cases), without additional necrosectomy in 35% of patients. Primary catheter drainage had fewer complications than primary necrosectomy (42% vs 64%, P=.003). Patients with pancreatic parenchymal necrosis (n=324), compared with patients with only peripancreatic necrosis (n=315), had a higher risk of organ failure (50% vs 24%, P<.001) and mortality (20% vs 9%, P<.001). CONCLUSIONS: Approximately 62% of patients with necrotizing pancreatitis can be treated without an intervention and with low mortality. In patients with infected necrosis, delayed intervention and catheter drainage as first treatment improves outcome.

Minimally invasive 'step-up approach' versus maximal necrosectomy in patients with acute necrotising pancreatitis (PANTER trial): design and rationale of a randomised controlled multicenter trial [ISRCTN13975868].

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.

Effect of brain death on gene expression and tissue activation in human donor kidneys.

BACKGROUND: After kidney transplantation, decreased graft survival is seen in grafts from brain dead (BD) donors compared with living donors. This might result partly from a progressive nonspecific inflammation in the graft. In this study, we focused on the effects of BD on inflammatory response (adhesion molecules, leukocyte invasion, gene expression) and stress-related heat shock proteins in the human kidney. Research outcomes and clinical donor parameters were then linked to outcome data after transplantation. METHODS: Kidney biopsy specimens and serum were obtained during organ retrieval from BD and living organ donor controls. Immunohistochemistry and semiquantitative reverse transcriptase-polymerase chain reaction were performed on the biopsy specimens. Clinical and laboratory parameters from BD donors were recorded and connected to outcome data of the recipients of the kidneys studied. RESULTS: After brain death, immunohistochemistry showed an increase of E-selectin (P<0.01) and interstitial leukocyte invasion (P<0.05) compared with controls. Also, reverse transcriptase-polymerase chain reaction showed a threefold increased heme oxygenase-1 (P<0.05) and Hsp70 (P<0.01) gene expression after BD. Levels of monocyte chemotactic protein-1 and transforming growth factor-beta were twice as high after brain death but did not reach significance. Transplantation outcome was influenced by several donor variables: positively most notably by donor treatment with desmopressin and negatively by high serum urea levels during brain death and by high intercellular adhesion molecule and vascular cell adhesion molecule expression in the kidney. Heme oxygenase-1 proved to have a protective function, but only in kidneys from living donors. CONCLUSIONS: The presence of interstitial leukocytes and the early adhesion molecule E-selectin in BD donor kidneys indicates an early-phase inflammatory process during organ retrieval. Elevated levels of monocyte chemotactic protein-1 and transforming growth factor-beta suggest a role for monocytes/macrophages in this phase. We suggest that BD causes a stress-related response against which protective heat shock proteins are formed in the future graft. This stress response may be too severe to be fully counteracted by elevated heat shock proteins. Which systemic and/or local factors trigger brain death-related graft injury is currently under investigation.