Prophylactic mesh placement to prevent parastomal hernia, early results of a prospective multicentre randomized trial.

PURPOSE: Parastomal hernia (PSH) is a common complication after colostomy formation. Recent studies indicate that mesh implantation during formation of a colostomy might prevent a PSH. To determine if placement of a retromuscular mesh at the colostomy site is a feasible, safe and effective procedure in preventing a parastomal hernia, we performed a multicentre randomized controlled trial in 11 large teaching hospitals and three university centres in The Netherlands. METHODS: Augmentation of the abdominal wall with a retromuscular light-weight polypropylene mesh (Parietene Light™, Covidien) around the trephine was compared with traditional colostomy formation. Patients undergoing elective open formation of a permanent end-colostomy were eligible. 150 patients were randomized between 2010 and 2012. Primary endpoint of the PREVENT trial is the incidence of parastomal hernia. Secondary endpoints are morbidity, pain, quality of life, mortality and cost-effectiveness. This article focussed on the early results of the PREVENT trial and, therefore, operation time, postoperative morbidity, pain, and quality of life were measured. RESULTS: Outcomes represent results after 3 months of follow-up. A total of 150 patients were randomized. Mean operation time of the mesh group (N = 72) was significantly longer than in the control group (N = 78) (182.6 vs. 156.8 min; P = 0.018). Four (2.7 %) peristomal infections occurred of which one (1.4 %) in the mesh group. No infection of the mesh occurred. Most of the other infections were infections of the perineal wound, equally distributed over both groups. No statistical differences were discovered in stoma or mesh-related complications, fistula or stricture formation, pain, or quality of life. CONCLUSIONS: During open and elective formation of an end-colostomy, primary placement of a retromuscular light-weight polypropylene mesh for prevention of a parastomal hernia is a safe and feasible procedure. The PREVENT trial is registered at: http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2018 .

Feeding elicited by cholinergic and adrenergic hypothalamic stimulation of anorectic tumor-bearing rats.

Injection of norepinephrine into the hypothalamus of methylcholanthrene sarcoma-bearing rats elicited a normal feeding response both prior to and following the development of anorexia. Feeding elicited by cholinergic stimulation of the hypothalamus of tumor-bearing rats with carbachol was normal prior to the onset of anorexia, but decreased in magnitude as the anorexia became more severe. These data indicate that noradrenergic feeding mechanisms in the hypothalamus of tumor-bearing rats are functioning normally during anorexia. However, cholinergic feeding mechanisms in the hypothalamus of tumor-bearing rats appear to be depressed to the same degree as ad lib intake, possibly through adaptation or depletion of endorphin systems that mediate stress-induced feeding.

Plasma and brain cholecystokinin levels in cancer anorexia.

The syndrome of cancer anorexia includes early satiety in man and a reduction in the duration of feeding in experimental animals. These aberrations suggest dysfunction of peripheral and/or central nervous system satiety mechanisms in tumor-bearing individuals. Since the gut peptide, cholecystokinin (CCK), has been implicated as a potent satiety cue in man and animals, plasma and brain concentrations of CCK were measured by radioimmunoassay in anorectic tumor-bearing rats. Plasma concentrations of immunoreactive CCK were not significantly altered in either an acute Walker 256 carcinosarcoma or more chronic methylcholanthrene-induced sarcoma animal model of cancer anorexia. However, levels of immunoreactive CCK were significantly reduced in the hypothalamus and cerebral cortex of animals bearing the methylcholanthrene sarcoma during both mild and severe anorexia. These data demonstrate that elevations in immunoreactive CCK are not a major factor in the etiology of cancer anorexia. If brain CCK is involved in satiety, tumor-bearing rats may be attempting to compensate for their anorexia by down-regulating CCK production.

Cholecystokinin-induced hypophagia is not potentiated by cancer anorexia.

The interaction of cholecystokinin-induced hypophagia with cancer anorexia was investigated within both acute (Walker 256 carcinosarcoma) and chronic (methylcholanthrene-induced sarcoma) animal models of cancer anorexia. Cholecystokinin octapeptide (CCK8) effectively reduced feeding for at least one hour in both groups of rats. However, this peptide was no more effective in inducing hypophagia in tumor-bearing rats than in nontumor-bearing control rats when tested at a variety of doses (0.5, 5.0 and 50.0 microgram/kg; IP) both prior to and after the development of anorexia. Therefore, these data do not support a role of cholecystokinin in the mediation of experimental cancer anorexia, since no synergism of CCK8-induced hypophagia with the anorexia was observed.

Analysis of the interaction of naltrexone with eating following adrenergic and cholinergic stimulation of the hypothalamus.

The anoretic potency of the narcotic antagonist drug nalthrexone, was investigated against eating elicited by the perifornical hypothalamic injection of 24.0 nmol of norepinephrine or 6.0 nmol of carbachol. Although eating following administration of norepinephrine was not significantly affected by pretreatment with naltrexone, carbachol-induced eating and drinking were dramatically attenuated by doses of naltrexone as small as 0.25 mg/kg. These data suggest the existence of an opiate link in these cholinergically-mediated behaviors.