Search

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.

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., (Copyright © 2015 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.)

Purpose of Review: 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., Recent Findings: 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., Summary: 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., (© 2012 The Authors. Colorectal Disease © 2012 The Association of Coloproctology of Great Britain and Ireland.)

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 (P < 0.05) 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 (P < 0.05), rat α-defensin 5 (P < 0.01), and rat α-defensin 8 (P < 0.01). Finally, 14 d of TPN resulted in greater circulating ileal lipid-binding protein concentrations (P < 0.05) and greater leakage of horseradish peroxidase (P < 0.01), 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, P < 0.01). 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.

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.

Introduction: Arterial ammonia concentrations increase acutely during the anhepatic phase of a liver transplantation (LTx) and return to baseline within 1 h after reperfusion of a functioning liver graft. So far, this return to baseline has solely been attributed to hepatic ammonia clearance. No data exist on the potential contribution of altered renal ammonia handling to peritransplantation ammonia homoeostasis., Aim: The present study investigated the consequences of a hepatectomy and subsequent implantation of a partial liver graft on arterial ammonia concentrations and urinary ammonia excretion during a living donor liver transplantation (LDLTx)., Methods: Patients with end-stage liver disease undergoing LDLTx were selected. Samples of arterial blood and urine were taken before, during and 2 h after the anhepatic phase. Differences were tested using Wilcoxon's test. Results are given as median and range., Results: Eleven adult patients undergoing an LDLTx were included. Before hepatectomy, arterial ammonia concentrations were 89 μM (40-156 μM), increasing to 146 μM (102-229 μM) (P<0.001) during the anhepatic phase and returning to 79 μM (46-111 μM) (P<0.01) after reperfusion. Urinary ammonia excretion was initially 1.06 mmol/h (0.02-6.00 mmol/h), increasing to 3.81 mmol/h (0.32-12.55 mmol/h) (P=0.004) during the anhepatic phase and further increasing to 4.00 mmol/h (0.79-9.51 mmol/h) (P=0.013) after reperfusion., Conclusion: The kidney significantly increased urinary ammonia excretion during the anhepatic phase, which was sustained after reperfusion, contributing to the rapid decrease of ammonia concentrations. Accordingly, the plasma ammonia concentrations measured directly after LTx cannot simply be used as a read-out of initial liver graft function., (© 2011 John Wiley & Sons A/S.)

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.

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.

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<0.001) and mortality (p<0.001)., Conclusions: Application of the SOWATS guideline allowed a favorable outcome after a short convalescence period. Abdominal wall defects and preoperative hypoalbuminemia are important prognostic variables.