Single-blinded randomized trial of mechanical bowel preparation for colon surgery with primary intraperitoneal anastomosis.

INTRODUCTION: We report the final analysis of a prospective single-blinded randomized trial designed to investigate whether omission of preoperative mechanical bowel preparation increases the rate of surgical-site infection and anastomotic failure after elective colon surgery with intraperitoneal anastomosis by a single surgeon. PATIENTS AND METHODS: Patients scheduled to undergo an elective colon or proximal rectal resection with a primary anastomosis by a single surgeon were randomized to receive either oral polyethylene glycol (Group A) or no mechanical bowel preparation (Group B). Patients were followed by an independent surgeon. RESULTS: One hundred and forty nine patients were enrolled. Three patients (2%) were preoperatively excluded because of active immunosuppression and 13 (9%) were excluded from the final analysis. Of the remaining 129 patients, 65 were assigned to Group A and 64 to Group B. Thirty patients (23.2%) developed wound infection, (Group A = 24.6% and Group B = 17.2%; NS). There were three cases of intra-abdominal sepsis a (Group A 4.6%). The anastomotic failure rate was 5.4% (n = 7), four patients in Group A (6.2%) vs. three patients in Group B (4.7%) (NS). When SSI and anastomotic failure were combined, the complication rate in Group A was 35.4% vs. 21.9% for Group B. The NNH was 7.4. CONCLUSION: Our final analysis shows that a single surgeon will not have a higher rate of either surgical-site infection or anastomotic failure if he/she routinely omits preoperative mechanical bowel preparation.

Mechanical bowel preparation for elective colorectal surgery with primary intraperitoneal anastomosis by a single surgeon: interim analysis of a prospective single-blinded randomized trial.

We report an interim analysis of a prospective single-blinded randomized trial designed to investigate whether preoperative mechanical bowel preparation influences the rate of surgical-site infection and anastomotic failure after elective colorectal surgery with primary intraperitoneal anastomosis performed by a single surgeon. Patients scheduled to undergo an elective colorectal procedure with a primary intraperitoneal anastomosis were randomized to receive either oral polyethylene glycol lavage solution and enemas (group A) or no preparation (group B). Surgical-site infection and anastomotic failure were investigated. Of 97 patients included, 48 were assigned to group A and 49 to group B. Twelve (12.4%) developed wound infections, six in each group (12.5 vs. 12.2%; NS). Intra-abdominal sepsis was only seen in group A (n = 3, 6.3%). Anastomotic failure occurred in four patients in group A (8.3%) vs. two patients in group B (4.1%) (NS). The overall complication rate in group A was 27.1%, vs. 16.3% in group B. The number needed to harm was 9.3. Our interim analysis of a prospective single-blinded randomized trial suggests that a surgeon may have the same or even worse outcomes when mechanical bowel preparation is routinely used for colorectal surgery with primary intraperitoneal anastomosis.

Luminal oxidants selectively modulate electrogenic ion transport in rat colon.

AIM: To investigate the effects of luminal exposure to H2O(2) and two related thiol oxidizing agents on basal and stimulated chloride secretion in native colon using electrophysiological and pharmacological approaches. METHODS: Unstripped rat distal colon segments were mounted in Ussing chambers. Potential difference, calculated resistance and short-circuit current across unstripped colon segments were monitored with a dual voltage/current clamp. Paracellular permeability was assessed by measuring the mucosa-to-serosa flux of a fluorescent probe (FITC). RESULTS: Luminal exposure to hydrogen peroxide transitorily stimulated chloride secretion without altering barrier function. This stimulatory effect could be blocked by basolateral atropine but not indomethacin. The cysteine and methionine oxidizing compounds, phenylarsine oxide and chloramine T respectively, mimicked the effect of H2O(2), except for a drop in transcolonic resistance after 30 min. In contrast to the observed stimulatory effect on basal secretion, cAMP-stimulated electrogenic ion transport was blunted by luminal H2O(2). However, the Ca(2+)-activated response remained unchanged. CONCLUSION: H2O(2) may be an important selective modulator of intestinal ion and water secretion in certain pathologic conditions such as inflammation or ischemia-reperfusion by multiple mechanisms.

Effects of luminal ATPase inhibitors on electrogenic ion transport in rat distal colon.

BACKGROUND: The involvement of transport proteins, other than chloride channels, expressed in the luminal membrane of epithelial cells in regulated chloride secretion in native colon remains poorly understood. There are at least two distinct ATPases expressed in the apical membrane of rat colonocytes. They can be distinguished by their different sensitivity to the vanadium-derived compound orthovanadate. The objective was to study the effects of luminal ATPase inhibitors on regulated chloride secretion using elecrophysiological and pharmacological approaches. MATERIALS AND METHODS: Unstripped rat distal colon segments were mounted in Ussing chambers. Potential difference, transepithelial resistance, and short-circuit current across unstripped colon segments were monitored with a dual voltage/current clamp. RESULTS: Luminal application of VO4(3-) did not alter baseline electrical values in rat distal colon but dose-dependently inhibited forskolin-stimulated Isc. Luminal ouabain (1 mm) did not blunt the response to the cAMP agonist. The inhibitory effect of luminal VO4(3-) occurred at a site distal to cAMP generation and was rather specific for the cyclic nucleotide-dependent signaling pathway, because the response to the Ca2+ agonist carbachol was largely preserved. CONCLUSION: VO4(3-) inhibits cAMP-stimulated Cl- secretion in rat distal colon at a site distal to cAMP generation without altering intestinal permeability. Ouabain-sensitive luminal K+-ATPases do not seem to contribute to forskolin-stimulated electrogenic ion transport. These findings may suggest new therapeutic targets for secretory diarrhea.

Total mesorectal excision for rectal cancer: the truth lies underneath.

The surgical technique itself has emerged as a crucial factor for local recurrence since the popularization of total mesorectal excision for the treatment of rectal cancer. This procedure is associated with lower local recurrence rates after "curative" surgery compared to traditional dissection of the rectum. The aim is to remove an intact mesorectal envelope from the promontorium down to the pelvic floor by sharp dissection with tumor-free margins and without causing injury to the pelvic nerves. However, the description of total mesorectal excision has been confusing. Moreover, the implication that total excision of all the perirectal fat contained within the perirectal fascia en bloc in all patients with rectal cancer can minimize local recurrence remains contentious. Therefore a critical appraisal of the procedure is required. Nonrandomized clinical studies have shown that total mesorectal excision reduces the local recurrence rate and increases disease-free survival in patients with adenocarcinoma of the middle and distal third of the rectum. Circumferential resection margins of 2 mm or more are associated with a lower local recurrence rate. Additional benefits in local control can be obtained with neoadjuvant treatment. Thus the modern treatment of rectal cancer combining total mesorectal excision with neoadjuvant chemoradiation results in excellent local tumor control. However, it is achieved at the cost of significant functional sequelae and impaired quality of life. The development of therapeutic alternatives that can achieve similar rates of local and distant tumor control without the mortality, morbidity, and functional consequences of radical surgery is a major challenge for colorectal surgeons.

Electrogenic ion transport in mammalian colon involves an ammonia-sensitive apical membrane K+ conductance.

It is remarkable that high ammonia concentrations can be present within the colonic lumen without compromising normal epithelial function. We investigated the impact of luminal ammonia on Cl- secretion in native tissue. Stripped human colonic mucosa and unstripped rat distal colon were used. Paired samples were mounted in modified Ussing chambers for electrophysiological studies. In rat distal colon, apical ammonia dose-dependently blocked forskolin-activated short-circuit current with an IC50 to approximately 5 mM. Basolateral NH4Cl was less effective. Luminal methylamine (50 mM), chromanol 293B (10-50 microM), and Ba2+ (5 mM) blocked cAMP-activated short-circuit current but apical clotrimazole (100 microM) was without effect. In stripped human colonic mucosa, luminal but not basolateral NH4Cl (10 mM) and luminal Ba2+ (5 mM) suppressed forskolin-activated short-circuit current. Ammonia may be an endogenous regulator of colonic water and salt secretion. Apical K+ channels may be involved in the regulation of cAMP-stimulated Cl- secretion in mammalian colon.

Progesterone inhibits chloride transport in human intestinal epithelial cells.

Several pieces of evidence suggest that female sex hormones may play a role in the regulation of electrolyte transport. We therefore hypothesized that female sex hormones might impair regulated transcellular chloride transport in human intestinal epithelial cells. The T84 cell line was used for electrophysiological studies. Changes in transepithelial resistance and short-circuit current (Isc) were measured via a dual voltage/current clamp in epithelial monolayers. Short-circuit current is equivalent to chloride secretion in T84 cells. Forskolin and 8-Br-cyclic adenosine monophosphate (cAMP) were used to activate cAMP-dependent Cl? transport. Ca2+-dependent secretion was stimulated by the receptor-mediated Ca2+ agonist carbachol. Acute exposure (30 minutes) to either progesterone or estradiol did not affect monolayer viability as reflected by transepithelial resistance. Moreover, the secretory response to both cAMP and Ca2+ agonists remained unaffected. In contrast, long-term exposure (24 hours) to physiological concentrations of progesterone (100 nM), but not estradiol, dose-dependently reduced the peak Isc induced by the cAMP-agonist forskolin from 125 +/- 2.7 mA. cm(2) in the control group to 96 +/- 2.5 mA. cm(2) in monolayers exposed to progesterone (n = 6 for each group; p <0.001). When the cAMP-analogue 8-Br-cAMP was used, the same behavior was observed (peak Isc = 112 +/- 1.6 mA. cm(2) vs 88 +/- 1.7 mA. cm(2) for control vs. progesterone-treated monolayers; n = 6 for each group; p <0.001). Taken together, our results suggest that progesterone but not estradiol inhibits cAMP-stimulated Cl- secretion in intestinal epithelial cells at a site distal to cyclic nucleotide generation.