Ruben G.J. Visschers

Long-Term Quality of Life in Patients with Rectal Cancer: Association with Severe Postoperative Complications and Presence of a Stoma

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.

Total Parenteral Nutrition Induces a Shift in the Firmicutes to Bacteroidetes Ratio in Association with Paneth Cell Activation in Rats

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.

The gut-liver axis.

Purpose of reviewThe 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 findingsThe 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. SummaryEnteral 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.

Long-term results after restorative proctocolectomy with ileal pouch-anal anastomosis at a young age

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.

Management of acute intestinal failure: A position paper from the European Society for Clinical Nutrition and Metabolism (ESPEN) Special Interest Group

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.

Treatment of Hypertriglyceridemia in Patients Receiving Parenteral Nutrition

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.

Health-related quality of life in patients treated for enterocutaneous fistula

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.

Citrulline Supplementation Improves Organ Perfusion and Arginine Availability under Conditions with Enhanced Arginase Activity

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.

Development of hypertriglyceridemia in patients with enterocutaneous fistulas.

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.

Cost-effectiveness analysis of sacral neuromodulation for faecal incontinence in The Netherlands.

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.