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Background: Laparoscopic surgery is increasingly used to repair paediatric inguinal hernias and can be divided into intra-or extra-corporeal closing techniques. No statement regarding the superiority of one of the two techniques can be made. This study aims to provide evidence supporting the superiority of intra-or extra-corporeal suturing technique. Methods: A systematic literature search was conducted using PubMed, Embase, MEDLINE, and Cochrane Library databases. Randomised controlled trials and prospective studies comparing different laparoscopic techniques were eligible for inclusion. Data were pooled using a random-effects model, com paring single -port extra-peritoneal closure to intra-peritoneal purse string suture closing. Primary outcome was recur-rence rate. Secondary outcomes were duration of surgery (min), peri- and post-operative complications (i.e. injury of spermatic vessels or spermatic cord, tuba lesions, bleeding and apnoea, haematoma/scrotal oedema, hydrocele, wound infection, iatrogenic ascent of the testis and testicular atrophy), contralateral patent processus vaginalis (CPPV) rate, post-operative pain, length of hospital stay and cosmetic appear-ance of the wound. Results: Fifteen studies ( n = 3680 patients, age range 0.5-12 years, follow-up range 3-10 months) were included is this systematic review. Intra-corporeal hernia repair was performed in 738 children and extra-corporeal repair was performed in 2942 children. A pooled data analysis could only be performed for the single port extra-corporeal closing technique and the three port intra-corporeal closing technique. We found that recurrence rate was lower in the single-port extra-corporeal closing technique compared to the intra-corporeal purse suture closing technique (0.6% vs 5.5%, 95% CI 0.107 (0.024-0.477); p < 0.001). Operation time was shorter for extra-corporeal unilateral and bilateral inguinal hernia repair compared with intra-corporeal approach, but no pooled data analysis could be performed. Due to the presence of substantial heterogeneity, it was not possible to assess other outcome measures. Conclusion: Single-port extra-corporeal closure seems to result in less recurrent hernias and a shorter operative time compared to intra-corporeal purse suture closing technique. No difference regarding peri- and post-operative complications could be found and no statements regarding the length of hospital ad -mission, post-operative pain and cosmetics could be made due to substantial heterogeneity. Level of Evidence: Level II (c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )

Inguinal hernia repair is one of the most frequently performed operations in the pediatric population and laparoscopic hernia repair is currently increasingly performed in Dutch academic and non-academic hospitals. The laparoscopic PIRS-technique is invented by Prof. Dr. D. Patkowski and is an extra-corporeal technique that uses one trocar for the camera and uses an subcutaneous knotted suture. Compared to the open technique, the PIRS-technique offers the possibility for contralateral inspection without making an extra incision and, in case of a contralateral patent processus vaginalis (CPPV), offers the possibility for the simultaneous repair of the CPPV. This prevents the development of a metachronous contralateral inguinal hernia (MCIH), one of the most frequent reason for re-operation after open inguinal hernia repair. This will result in less operations, less exposure to general anesthesia, less hospital admissions and less visits to the general practitioner and emergency department.

BACKGROUND: Time efficiency and hospital costs may influence the preferred method of groin hernia repair. Despite growing expertise in laparoscopic hernia repair, knowledge on the actual costs and the potential financial advantages over open hernia repair are limited.METHODS: A single-center retrospective cohort study comparing hospital costs and time-efficiency of open-mesh (Lichtenstein) and laparoscopic groin hernia repair between 2010 and 2015, including a comparison of surgeons and residents, was conducted. Secondary outcomes were length of hospital stay, complication and recurrence rates.RESULTS: Nine hundred forty-seven open and 449 laparoscopic groin hernia repairs were included. Unilateral open repair showed a shorter operation theatre occupancy (63.5 min +/- 17.2 vs. 71.9 min +/- 19.9, P

Purpose Patients with Hirschsprung disease (HD) can have persistent obstructive symptoms after resection of the aganglionic segment. If obstructive symptoms are treated inadequately, this may lead to recurrent faecal stasis and impaction, and may result in severe distension of the bowel. A permanently distended bowel which not responds to conservative treatment may be an indication for redo surgery. The aim of this study is to describe our experiences and the short-term results of a novel technique: longitudinal antimesenteric resection with a longitudinal anastomosis. Methods We reviewed the medical records of our three patients who underwent longitudinal resection of severe distended bowel. This technique aims to improve defecation by improving faecal passage and is characterized by resection of the antimesenteric side of the distended intestinal segment, followed by plication with a longitudinal anastomosis. In this paper, this novel technique is described in detail, as well as short-term outcomes. Results All patients had an uneventful recovery after longitudinal antimesenteric resection. During follow-up, the functional outcomes were excellent, with a large improvement of bowel function. All patients were continent for faeces, and treated with low-dose laxatives or occasional preventive irrigation in one patient. There were no more complaints of persistent constipation or soiling. Conclusion Longitudinal resection is a surgical redo-procedure offering large benefits for patients with Hirschsprung disease with distended bowel after primary surgery.

Mitochondria are critical cellular organelles for energy generation and are now also recognized as playing important roles in cellular signaling. Their central role in energy metabolism, as well as their high abundance in hepatocytes, make them important targets for drug-induced hepatotoxicity. This review summarizes the current mechanistic understanding of the role of mitochondria in drug-induced hepatotoxicity caused by acetaminophen, diclofenac, anti-tuberculosis drugs such as rifampin and isoniazid, anti-epileptic drugs such as valproic acid and constituents of herbal supplements such as pyrrolizidine alkaloids. The utilization of circulating mitochondrial-specific biomarkers in understanding mechanisms of toxicity in humans will also be examined. In summary, it is well-established that mitochondria are central to acetaminophen-induced cell death. However, the most promising areas for clinically useful therapeutic interventions after acetaminophen toxicity may involve the promotion of adaptive responses and repair processes including mitophagy and mitochondrial biogenesis, In contrast, the limited understanding of the role of mitochondria in various aspects of hepatotoxicity by most other drugs and herbs requires more detailed mechanistic investigations in both animals and humans. Development of clinically relevant animal models and more translational studies using mechanistic biomarkers are critical for progress in this area. Relevance for patients:This review focuses on the role of mitochondrial dysfunction in liver injury mechanisms of clinically important drugs like acetaminophen, diclofenac, rifampicin, isoniazid, amiodarone and others. A better understanding ofthe mechanisms in animal models and their translation to patients will be critical for the identification of new therapeutic targets.

Background & aims: Parenteral nutrition (PN), a lifesaving therapy in patients with intestinal failure, has been associated with hepatobiliary complications including steatosis, cholestasis and fibrosis, collectively known as parenteral nutrition-associated liver disease (PNALD). To date, the pathogenesis of PNALD is poorly understood and therapeutic options are limited. Impaired bile salt homeostasis has been proposed to contribute PNALD. The objective of this study was to establish a PNALD model in rats and to evaluate the effects of continuous parenteral nutrition (PN) on bile salt homeostasis.Methods: Rats received either PN via the jugular vein or received normal diet for 3, 7 or 14 days. Serum biochemistry, hepatic triglycerides, circulating bile salts and C4, IL-6 and TNF-alpha, and lipogenic and bile salt homeostatic gene expression in liver and ileum were assessed.Results: PN increased hepatic triglycerides already after 3 days of administration, and resulted in conjugated bilirubin elevation after 7 or more days. This indicates PN-induced steatosis and impaired canalicular secretion of bilirubin, the latter which is in line with reduced hepatic expression of Mrp2 mRNA. There was no histological evidence for liver inflammation after PN administration, and circulating levels of pro-inflammatory cytokines IL-6 and TNF-alpha, were comparable in all groups. Hepatic expression of Fxr mRNA was decreased after 7 days of PN, without apparent effect on expression of Fxr targets Bsep and Shp. Nonetheless, Cyp7a1 expression was reduced after 7 days of PN, indicative for lowered bile salt synthesis. Circulating levels of C4 (marker of bile salt synthesis) were also decreased after 3, 7 and 14 days of PN. Levels of circulating bile salts were not affected by PN.Conclusions: This study showed that PN in rats caused early mild steatosis and cholestasis, while hepatic and systemic inflammation were not present. The onset of these abnormalities was associated with alterations in bile salt synthesis and transport. This animal model serves as an experimental model to further investigate the pathogenesis of PNALD inflicted by steatosis and cholestasis. (C) 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Introduction Low rectal surgery remains challenging. New surgical stapler devices have been developed to counteract problems of impaired visibility and inability to get low into the pelvis. One of them is the Radial Reload (RR) with Tri-staple ™ Technology (Covidien, New Haven, CT, USA). The aim of this study was to assess the first impressions and experiences regarding handling of this new stapler device in low anterior resection procedures in living humans. Methods A questionnaire, consisting of 27 statements concerning accessibility, maneuverability and visibility, was sent to 35 surgeons worldwide. Results A total of 85 rectal surgical procedures, both open and laparoscopic, were assessed by 31 surgeons. In 97% of the procedures the surgeons agreed that the RR stapler device facilitated access in the low pelvis. The first stapler device firing achieved complete transection in 54% of the procedures. According to the surgeons' assessments, in 91% percent of the procedures the RR stapler device enabled creation of adequate margins. Visualization of the pelvic floor was reported in 93% of the procedures. In the surgeons' opinion, the RR stapler device was considered clinically acceptable in 93% of the procedures. In 79% of the procedures the surgeon preferred the RR stapler device over the stapler device they normally used. Conclusion This study showed that the first experiences with the RR stapler device of 33 surgeons in 85 low rectal procedures are positive. It facilitates low stapling in both open and laparoscopic procedures. Good visibility, maneuverability and the possibility to create adequate distal margins were reported.

The liver adaptively responds to extra-intestinal and intestinal inflammation. In recent years, the role of the autonomic nervous system, intestinal failure and gut microbiota has been investigated in the development of hepatic, intestinal and extra-intestinal disease. The autonomic nervous system can be stimulated via enteral fat leading to cholecystokinin release, stimulating receptors in the gut and in the brain. This promotes bowel integrity, dampening the inflammatory response to food antigens. Consensus exists that intravenously administered long-chain fatty acids can cause liver damage but randomized-controlled trials are lacking. Disruption of the enterohepatic circulation of bile salts can give rise to cholestasis and nonalcoholic fatty liver disease, which may progress to fibrosis and cirrhosis. Reduced intestinal availability of bile salts reduces stimulation of the farnesoid X receptor. This may induce hepatic bile salt overload and associated hepatotoxicity through reduced action of intestinal fibroblast growth factor 19. Evidence is put forward to suggest that the intestinal microbiota is associated with liver abnormalities. Enteral lipids reduce inflammation and liver damage during stress or systemic inflammation, whereas parenteral lipid is associated with liver damage. Maintaining the enterohepatic circulation of bile salts limits hepatic cholestasis through an farnesoid X receptor feedback pathway. Changes in gut microbiota composition may induce liver disease

Aim Sacral neuromodulation (SNM) plays a major part in the algorithm of management of faecal incontinence, but there are limited data on its cost-effectiveness. This study aimed to analyse this and the quality-adjusted life-years (QALYs) associated with two different treatment algorithms. The first (SNM−) included use of an artificial sphincter [dynamic graciloplasty (DGP) (50%) and artificial bowel sphincter (ABS) (50%)]. The second (SNM+) included SNM (80% of cases) and artificial sphincter (DGP 10%; ABS 10%) The incidence of sphincteroplasty was assumed to be equal in both algorithms. Method A Markov model was developed. A hypothetical cohort of patients was run through both strategies of the model. A mailed EuroQoL-5D questionnaire was used to determine health-related quality of life. Costs were reproduced from the Maastricht University Medical Centre prospective faecal incontinence database. The time scale of the analysis was 5 years. Results The former treatment protocol cost €22 651 per patient and the latter, after the introduction of SNM, cost €16 473 per patient. The former treatment protocol resulted in a success rate of 0.59 after 5 years, whereas with the introduction of SNM this was 0.82. Adhering to the former treatment protocol yielded 4.14 QALYs and implementing the latter produced 4.21 QALYs. Conclusion The study demonstrated that introducing SNM in the surgical management algorithm for faecal incontinence was both more effective and less costly than DGP or ABS without SNM. This justifies adequate funding for SNM for patients with faecal incontinence.

Contains fulltext : 165702.pdf (Publisher’s version ) (Closed access) Intestinal failure (IF) is the consequence of a reduction of gut function below the minimum necessary for the absorption of nutrients from the gastrointestinal tract. Types I and II comprise acute intestinal failure (AIF). Although its prevalence is relatively low, type II AIF is serious and requires specialist multidisciplinary care, often for prolonged periods before its resolution. The key aspects are: sepsis control, fluid and electrolyte resuscitation, optimization of nutritional status, wound care, appropriate surgery and active rehabilitation. The ESPEN Acute Intestinal Failure Special Interest Group (AIF SIG) has devised this position paper to provide a state-of-the-art overview of the management of type II AIF and to point out areas for future research.

BACKGROUND: The present study was designed to evaluate the effects of guided treatment of patients with an enterocutaneous fistula and to evaluate the effect of prolonged period of convalescence on outcome. METHODS: All consecutive patients with an enterocutaneous fistula treated between 2006 and 2010 were included in this study. Patient information was gathered prospectively. Treatment of patients focused on sepsis control, optimization of nutritional status, wound care, establishing the anatomy of the fistula, timing of surgery, and surgical principles. Outcome included spontaneous and surgical closure, mortality, and postoperative recurrence. The relationship between period of convalescence and recurrence rate was determined by combining the present prospective cohort with a historical cohort from our group. RESULTS: Between 2006 and 2010, 79 patients underwent focused treatment for enterocutaneous fistula. Cox regression analysis showed that period of convalescence related significantly with recurrence of the fistula (hazard ratio 0.99; 95 % confidence interval 0.98-0.999; p = 0.04). Spontaneous closure occurred in 23 (29 %) patients after a median period of convalescence of 39 (range 7-163) days. Forty-nine patients underwent operative repair after median period of 101 (range 7-374) days and achieved closure in 47 (96 %). Overall, eight patients (10 %) died. CONCLUSIONS: Prolonging period of convalescence for patients with enterocutaneous fistulas improves spontaneous closure and reduces recurrence rate.

Background Restorative proctocolectomy with IPAA is an optimal surgical treatment for patients with familial adenomatous polyposis and therapy resistant ulcerative colitis, few data are available on long-term results in patients who have undergone this operation at a young age. Objective The aim of this study was to investigate long-term functional outcome, quality of life, body image, and sexual function after restorative proctocolectomy with IPAA in young patients with familial adenomatous polyposis or ulcerative colitis. Design, settings, and patients The study consisted of a retrospective review of medical records and questionnaire follow-up of 26 consecutive patients with familial adenomatous polyposis or ulcerative colitis who had undergone surgery between January 1992 and October 2008 at the Maastricht University Medical Center, were aged 10 to 24 years at the time of surgery, and had at least 1 year of follow-up after surgery. Main outcome measures We reviewed medical records from an institutional database regarding surgical procedures and short- and long-term complications. At the end of 2009, validated questionnaires covering bowel function (Colorectal Functional Outcome Questionnaire), quality of life (Short Form-36 and Gastrointestinal Quality of Life Index), body image and cosmesis (Body Image Questionnaire), and sexual function (International Index of Erectile Function for men and Female Sexual Function Index for women) were mailed to patients. Results Median age at surgery was 18 years, and median follow-up was 12.5 (range, 2-18) years. Long-term colorectal complications occurred in 23 patients (88%), and were directly related to the surgery in 20 patients (77%). Five patients needed pouch excision. The questionnaire response rate was 88%. Bowel function, quality-of-life, and body image and cosmesis scores were all lower in patients than in historical normal control populations. Men did not report impotence or retrograde ejaculation, but 50% of women reported sexual dysfunction. Limitations This was a retrospective study in a small number of patients from a single institution with no comparison groups. Conclusions Restorative proctocolectomy with IPAA can be performed in young patients with an acceptable functional outcome, but at the cost of relatively high complication rates, poor body image and cosmesis, and a high rate of sexual dysfunction in women. Because young patients undergoing this surgical procedure may experience negative long-term effects, surgeons should be aware of all potential consequences, inform patients as to what to expect, and ensure long-term follow-up to deal with long-term complications.

Background: The objective of this study was to provide a systematic review on the introduction of laparoscopic liver surgery in the Netherlands, to investigate the initial experience with laparoscopic liver resections and to report on the current status of laparoscopic liver surgery in the Netherlands. Methods: A systematic literature search of laparoscopic liver resections in the Netherlands was conducted using PubMed/MEDLINE. Analysis of initial experience with laparoscopic liver surgery was performed by case-control comparison of patients undergoing laparoscopic left lateral sectionectomy matched with patients undergoing the open procedure in the Netherlands between the years 2000 and 2008. Furthermore, a nationwide survey was conducted in 2011 on the current status of laparoscopic liver surgery. Results: The systematic review revealed only 6 Dutch reports on actual laparoscopic liver surgery. Matched case-control comparison showed significant differences in the length of hospital stay, blood loss and operation time. Complications did not differ significantly between the two groups (26 vs. 21%). The 2011 survey showed that 21 centers in the Netherlands performed formal liver resections and that 49 (5% of total) laparoscopic liver resections were performed in 2010. Conclusion: The systematic review revealed that very few laparoscopic liver resections were performed in the Netherlands in the previous millennium. The matched case-control comparison of laparoscopic and open left lateral resection showed a reduction in hospital length of stay with comparable morbidity. The laparoscopic technique has been slowly adopted in the Netherlands, but its popularity seems to increase in recent years.

BACKGROUND: This study aims to evaluate whether withdrawal of a soy oil-based lipid emulsion from the parenteral nutrition (PN) regimen in humans is associated with improved triglyceride and liver enzyme concentrations. METHODS: In this retrospective study, patients with hypertriglyceridemia (>4.50 mmol/L) while receiving PN were retrieved from a prospective complication registration database. Patients received Intralipid 20% as part of an all-in-one system containing all necessary macro- and micronutrients, electrolytes, trace elements, and vitamins. RESULTS: Forty patients with hypertriglyceridemia were included. Lipid emulsions were withdrawn from the all-in-one mixture for a median of 5 (range, 1-23) days, after which triglyceride concentrations decreased significantly (mean difference -2.5 +/- 0.30 mmol/L, P < .001). Aspartate aminotransaminase and leukocyte count decreased significantly (mean difference -35 +/- 17 U/L, P = .049 and -3.8 +/- 1.7*10E9/L, P = .028, respectively), whereas albumin level increased significantly (mean difference 2.1 +/- 0.9 g/L, P = .027). Alanine aminotransaminase showed a nonsignificant reduction (mean difference -30 +/- 22 U/L, P = .194). In 11 patients, the lipid emulsion was reintroduced, after which triglyceride levels showed a significant increase (mean difference 1.5 +/- 0.30 mmol/L, P = .001). CONCLUSIONS: Short-term withdrawal of the lipid fraction in the PN mixture is associated with a significant reduction of plasma triglyceride concentration. Reintroduction was related to an increase of triglyceride concentration. In addition, liver enzyme abnormalities and leukocyte count reduced, whereas albumin levels increased, suggesting that even short withdrawal of the lipid emulsion diminished hepatocellular damage and systemic inflammation. (JPEN J Parenter Enteral Nutr. XXXX;xx:xx-xx).

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

PURPOSE: The purpose of this study was to evaluate the impact of postoperative complications and the presence of a stoma on long-term quality of life in patients with rectal cancer. METHODS: Consecutive patients with an adenocarcinoma of the rectum who underwent surgery at Maastricht University Medical Center or VieCuri Medical Center between 2003 and 2005 were included in this study. Data on surgical treatment and complications were collected. Severe postoperative complications were classified according to a standardized complication severity score. Quality of life was assessed by use of the European Organization for Research and Treatment of Cancer core and colorectal cancer-specific quality-of-life questionnaires. RESULTS: One hundred seventy patients received a questionnaire, and 121 (71%) responded. Of the responders, 33 (27.3%) patients suffered from severe postoperative complications. The median follow-up was 36 months. In the univariate analysis, patients with severe postoperative complications had a lower score on physical functioning (73 vs. 85, P = 0.031) and higher scores on pain (17 vs. 0, P = 0.025) and fatigue (33 vs. 22, P = 0.036). Stoma construction (n = 51) was associated with a higher global health status (83 vs. 75, P = 0.019), and these patients reported fewer gastrointestinal problems (P = 0.001). CONCLUSION: Severe postoperative complications seem to be associated with several lower quality-of-life subscores over the long term. In contrast, a stoma is associated with improved global health status and leads to fewer gastrointestinal complaints. In patients prone to complications, it may be sensible to avoid creating a low anastomosis and to construct a permanent stoma immediately.

Summary Background & aims Hypertriglyceridemia is commonly observed in patients with enterocutaneous fistulas, compromising their health status. In this study potential causes for hypertriglyceridemia in patients with an enterocutaneous fistula are explored and treatment options discussed accordingly. Methods A database was created consisting of all consecutively treated patients with an enterocutaneous fistula from 1991 until 2007. Two successive measures of serum triglyceride concentrations of more than 3.0 mmol/L (266 mg/dL) were regarded as hypertriglyceridemia. The relation between fistula specific characteristics and hypertriglyceridemia was analyzed using a multivariable Cox proportional hazard model with time-dependent covariates. Results A total 102 patients were eligible for this study of whom 25 had hypertriglyceridemia. Multivariable analysis showed that sepsis (HR 4.503, CI 1.778–11.401, P = 0.002), high output small bowel fistula (HR 3.534, CI 1.260–9.916, P = 0.016), parenteral nutrition (HR 5.689, CI 1.234–26.216, P = 0.026) and inflammatory diseases (inflammatory bowel disease vs. malignancy HR 6.211, CI 1.081–35.696, P = 0.041) were independent predictors of hypertriglyceridemia. Conclusions High triglyceride concentrations in patients with an enterocutaneous fistula were mainly associated with sepsis, a high output small bowel fistula, nutrition by the parenteral route and primary diseases with inflammatory aetiology. This should direct a treatment strategy that focuses on these aspects.

Background Patients with enterocutaneous fistulas undergo long intensive treatment. The aim of this study was to investigate the long-term health-related quality of life (HRQL) of these patients. Methods Consecutive patients treated for enterocutaneous fistula between 1990 and 2005 were eligible for this retrospective study. The Karnofsky Performance Scale (KPS), Short Form 36 (SF-36®) and the Inflammatory Bowel Disease Questionnaire were used to measure HRQL. The SF-36® was matched with results from healthy controls. Patients also gave information on concurrent medical illnesses. Results Of 135 patients, 44 died, 14 were lost to follow-up and 12 refused to participate; of the remaining 65, 62 participated (response rate 81 per cent). HRQL was independent of patient characteristics during treatment. Scores for SF-36® domains were lower than in their matched controls (P < 0·050). Concurrent medical illness (cancer, depression and gastrointestinal disease) significantly reduced HRQL (for example with a 40 per cent reduction in vitality). The median KPS score was 80, indicating that activities could be performed with effort and patients had some signs of disease. Conclusion HRQL is lower in patients treated for enterocutaneous fistula than in matched controls, particularly in those with concurrent medical illnesses. Patients treated successfully have normal independence in daily functioning.

Enhanced arginase-induced arginine consumption is believed to play a key role in the pathogenesis of sickle cell disease-induced end organ failure. Enhancement of arginine availability with l-arginine supplementation exhibited less consistent results, however, l-citrulline, the precursor of l-arginine, may be a promising alternative. In this study, we determined the effects of l-citrulline compared to l-arginine supplementation on arginine-nitric oxide (NO) metabolism, arginine availability and microcirculation in a murine model with acutely-enhanced arginase activity. The effects were measured in six groups of mice (n = 8 each) injected intraperitoneally with sterile saline or arginase (1000 IE/mouse) with or without being separately injected with l-citrulline or l-arginine 1 h prior to assessment of the microcirculation with side stream dark-field (SDF)-imaging or in vivo NO-production with electron spin resonance (ESR) spectroscopy. Arginase injection caused a decrease in plasma and tissue arginine concentrations. l-arginine and l-citrulline supplementation both enhanced plasma and tissue arginine concentrations in arginase-injected mice. However, only the citrulline supplementation increased NO production and improved microcirculatory flow in arginase-injected mice. In conclusion, the present study provides for the first time in vivo experimental evidence that l-citrulline, and not l-arginine supplementation, improves the end organ microcirculation during conditions with acute arginase-induced arginine deficiency by increasing the NO concentration in tissues.

Costs of healthcare are high and an important topic of debate in many countries, necessitating careful evaluation of future governmental spending. Patients with rare diseases, so called orphan diseases, are often severely ill, depending on expensive medical care. It is generally agreed upon that they benefit from centralised treatment. At present, Dutch healthcare regulations and reimbursement fail to cover the costs of this specific patient population and it can be expected that this becomes more difficult during the current financial crisis. Consequently, it blocks the establishment of centres of expertise. When patients with an orphan disease will not be fully recognised, erroneous decisions will lead to poor patient outcome and loss of clinical expertise. Therefore, it is imperative to keep the debate alive and this subject on the political agenda preventing orphan diseases from becoming a neglected disease again.

The use of total parenteral nutrition (TPN) in the treatment of critically ill patients has been the subject of debate because it has been associated with disturbances in intestinal homeostasis. Important factors in maintaining intestinal homeostasis are the intestinal microbiota and Paneth cells, which exist in a mutually amendable relationship. We hypothesized that the disturbed intestinal homeostasis in TPN-fed individuals results from an interplay between a shift in microbiota composition and alterations in Paneth cells. We studied the microbiota composition and expression of Paneth cell antimicrobial proteins in rats receiving TPN or a control diet for 3, 7, or 14 d. qPCR analysis of DNA extracts from small intestinal luminal contents of TPN-fed rats showed a shift in the Firmicutes:Bacteroidetes ratio in favor of Bacteroidetes after 14 d (P0.05) compared with the control group. This finding coincided with greater staining intensity for lysozyme and significantly greater mRNA expression of the Paneth cell antimicrobial proteins lysozyme (P0.05), rat α-defensin 5 (P0.01), and rat α-defensin 8 (P0.01). Finally, 14 d of TPN resulted in greater circulating ileal lipid-binding protein concentrations (P0.05) and greater leakage of horseradish peroxidase (P0.01), which is indicative of enterocyte damage and a breached intestinal barrier. Our findings show a shift in intestinal microbiota in TPN-fed rats that correlated with changes in Paneth cell lysozyme expression (r(s) = -0.75, P0.01). Further studies that include interventions with microbiota or nutrients that modulate them may yield information on the involvement of the microbiota and Paneth cells in TPN-associated intestinal compromise.

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.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).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.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) (P0.001) during the anhepatic phase and returning to 79 μM (46-111 μM) (P0.01) 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.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.

BACKGROUND: Enterocutaneous fistulas (ECF) pose a major challenge to every gastrointestinal (GI) surgeon. Based on earlier studies, a standardized treatment guideline was implemented. The focus of the present study was to assess that guideline and determine prognostic factors for outcome of patients with ECF, and to define a more detailed therapeutic approach including the convalescence time before restorative surgery. METHODS: All patients with ECF treated between 1990 and 2005 were included. Management consisted of controlling Sepsis, Optimization of nutritional state, Wound care, assessment of fistula Anatomy, Timing of surgery, and Surgical strategy (the SOWATS guideline). Prognostic factors were assessed by way of multiple logistic regression analysis. RESULTS: A total of 135 patients were treated at our unit. Overall closure was achieved in 118 patients (87.4%). Restorative operations for fistula closure were performed after a median of 53 days (range: 4-270 days). Restorative operations were successful in 97/107 patients (90.7%). Thirteen patients (9.6%) died. An abdominal wall defect was the most predominant negative prognostic factor for spontaneous closure (odds ratio [OR]=0.195, confidence interval [CI] 0.052-0.726, p=0.015). A strong relation was found between preoperative albumin level and surgical closure (p