Background
Previous work has demonstrated that anastomotic leak can be caused by collagenolytic bacteria such as Enterococcus faecalis via an effect on wound collagen. In humans, E. faecalis is the ...organism cultured most commonly from a leaking anastomosis, and is not routinely eliminated by standard oral or intravenous antibiotics. Novel strategies are needed to contain the virulence of this pathogen when present on anastomotic tissues.
Methods
Polyphosphorylated polymer ABA‐PEG20k‐Pi20 was tested in mice for its ability to prevent anastomotic leak caused by collagenolytic E. faecalis. The study design included a distal colonic resection and anastomosis followed by introduction of E. faecalis to anastomotic tissues via enema. Mice were assigned randomly to receive either ABA‐PEG20‐Pi20 or its unphosphorylated precursor ABA‐PEG20k in their drinking water. The development of anastomotic leak was determined after the animals had been killed.
Results
Overnight incubation of two different E. faecalis collagenolytic strains with 2 mmol/l of ABA‐PEG20k‐Pi20 led to near complete inhibition of collagenase production (from 21 000 to 1000 and from 68 000 to 5000 units; P < 0·001; 6 samples per group) without suppressing bacterial growth. In mice drinking 1 per cent ABA‐PEG20k‐Pi20, the phosphate concentration in the distal colonic mucosa increased twofold and leak rates decreased from eight of 15 to three of 15 animals (P < 0·001). In mice drinking ABA‐PEG20k‐Pi20, the percentage of collagenolytic colonies among E. faecalis populations present at anastomotic tissue sites was decreased by 6–4800‐fold (P = 0·008; 5 animals).
Conclusion
These data indicate that oral intake of ABA‐PEG20k‐Pi20 may be an effective agent to contain the virulence of E. faecalis and may prevent anastomotic leak caused by this organism.
Clinical relevance
Progress in understanding the pathogenesis of anastomotic leak continues to point to intestinal bacteria as key causative agents. The presence of pathogens such as Enterococcus faecalis that predominate on anastomotic tissues despite antibiotic use, coupled with their ability to produce collagenase, appears to alter the process of healing that leads to leakage. Further antibiotic administration may seem logical, but carries the unwanted risk of eliminating the normal microbiome, which functions competitively to exclude and suppress the virulence of pathogens such as E. faecalis. Therefore, non‐antibiotic strategies that can suppress the production of collagenase by E. faecalis without affecting its growth, or potentially normal beneficial microbiota, may have unique advantages. The findings of this study demonstrate that drinking a phosphate‐based polymer can achieve the goal of preventing anastomotic leak by suppressing collagenase production in E. faecalis without affecting its growth.
Further evidence the microbiome may be important
Postoperative ileus presents significant clinical challenges that potentially prolong hospital stay, contribute to readmission, and increase morbidity. There is no approved treatment for ...postoperative ileus. Alvimopan is a novel, peripherally acting, mu opioid receptor antagonist currently in development for the management of postoperative ileus.
Patients undergoing partial colectomy or simple or radical hysterectomy were randomized to receive alvimopan 6 mg (n = 152), alvimopan 12 mg (n = 146), or placebo (n = 153) orally 2 hours before surgery and twice daily thereafter until discharge or for up to seven days. The primary efficacy end point, time to return of gastrointestinal function, was a composite measure of passage of flatus or stool and tolerating solid food. Secondary end points included time to the hospital discharge order written. Adverse events were monitored throughout the study.
Mean time to gastrointestinal recovery was significantly reduced in patients treated with alvimopan 6 mg vs. placebo (hazard ratio = 1.45; P = 0.003), with a smaller reduction seen with alvimopan 12 mg (hazard ratio = 1.28; P = 0.059). Mean time to the hospital discharge order written was significantly accelerated in patients treated with alvimopan 6 mg (hazard ratio = 1.50; P < 0.001). The most common treatment-emergent adverse events across all treatment groups were nausea, vomiting, and hypotension; the incidence of nausea and vomiting was reduced by 53 percent in the alvimopan 12-mg group.
In patients undergoing major abdominal surgery, alvimopan accelerated gastrointestinal recovery and time to the hospital discharge order written compared with placebo and was well tolerated.
A leaking intestinal anastomosis is typically regarded as a devastating post-operative complication. The reported incidence of anastomotic leakage is highly variable and depends on the definitions ...used and the anatomical location involved. Early leaks are usually readily diagnosed and aggressive management is warranted. Late leaks may be unrecognised and are likely to be underreported in the literature; diagnosis and treatment in this setting requires a thoughtful, individualised approach.
Hyperplastic polyps are usually considered to be an innocent finding with little or no potential to progress to colorectal cancer. However, recent literature suggests that some of these polyps may be ...morphologically and genetically distinct and lead to microsatellite unstable colorectal cancers. The purpose of this study was to define the cancer risk associated with hyperplastic polyposis.
All patients with hyperplastic polyposis diagnosed by a single colorectal surgeon at a university hospital were followed prospectively. The diagnosis of hyperplastic polyposis was made by the presence of more than 20 hyperplastic polyps distributed throughout the colon and/or a hyperplastic polyp at least 1 cm in size in diameter in the right colon. Patient demographics, family history, size, location, and distribution of polyps and the development of colorectal cancer were noted.
Thirteen patients who met the criteria for hyperplastic polyposis were identified and followed prospectively. All of these patients had at least 30 polyps distributed throughout the colon, often > 100. Nine of 13 also had a hyperplastic polyp at least 1 cm in size, usually in the right colon. Of particular note, 7 of 13 patients (54 percent) were diagnosed with colorectal cancer during the study period. Four had cancer on initial diagnosis and three patients developed cancer despite frequent colonoscopic surveillance. Five of seven colorectal cancers were located in the right colon.
Patients with hyperplastic polyposis are at high risk for colorectal cancer. Failure to identify this subset of patients could have dire consequences.
Topical nitrates have been shown to cause nitric oxide-mediated relaxation of the internal anal sphincter. Previous reports have suggested initial efficacy in the treatment of anal fissures. The aim ...of this study was to assess the longer-term usefulness of this treatment.
Thirty-three patients with an anal fissure were treated with topical 0.3% nitroglycerin ointment, applied to the anoderm three times per day and after bowel movements. Patients were followed up by office visits and telephone calls until symptoms were completely resolved or treatment was noted to be ineffective or intolerable.
Thirty-three patients were treated, 16 with acute fissures, and 17 with chronic fissures. Nitroglycerin was effective in 9 of 16 acute fissures (56%), and 7 of 17 chronic fissures (41%). Even when effective, 75% of patients reported an adverse reaction.
Topical nitroglycerin was only effective in approximately one-half of patients with an anal fissure. There was a very high incidence of adverse reactions. In our experience nitroglycerin more often causes a headache than treats the symptoms of anal fissure.
Ileal pouch-anal anastomosis is widely claimed to have replaced total proctocolectomy with ileostomy as the "procedure of choice" for ulcerative colitis, largely on the basis of a perceived improved ...quality of life. There exists relatively little support for this assertion in the literature. Our aim was to determine if educated patients choosing total proctocolectomy with ileostomy have a similar quality of life as with ileal pouch-anal anastomosis.
All patients with ulcerative colitis referred to a single surgeon and deemed an appropriate surgical candidate were educated and then offered ileal pouch-anal anastomosis or total proctocolectomy with ileostomy. Age, gender, and complications (including pouchitis) were recorded prospectively, and all patients were questioned regarding functional outcome and level of satisfaction. They were then asked to complete a slightly modified Inflammatory Bowel Disease Questionnaire, which was analyzed by categoric and overall scores.
Sixty-seven patients underwent elective surgery for ulcerative colitis during the study period. Fifty-five patients chose ileal pouch-anal anastomosis, and 12 had total proctocolectomy with ileostomy. The groups were similar except for younger age and longer follow-up in the ileal pouch-anal anastomosis group. Patients undergoing ileal pouch-anal anastomosis had significantly more short-term or long-term complications (49 vs. 8 percent), with pouchitis being the most frequent complication. There was no difference in level of satisfaction between the two groups, and no patient in either group wishes they had undergone the other procedure. There was no difference in the overall or any categoric Inflammatory Bowel Disease Questionnaire score.
Patient satisfaction with both procedures was similarly high. Patients who undergo ileal pouch-anal anastomosis can expect a high level of satisfaction, with a good quality of life. However, educated patients choosing an ileostomy can achieve the same quality of life, without the higher complication rate associated with a pelvic pouch.
Ogilvie's syndrome, or acute colonic pseudo-obstruction, is a common and relatively dangerous condition. If left untreated, it may cause ischemic necrosis and colonic perforation, with a mortality ...rate as high as 50 percent. Neostigmine enhances excitatory parasympathetic activity by competing with acetylcholine for attachment to acetylcholinesterase at sites of cholinergic transmission and enhancing cholinergic action. We hypothesized that neostigmine would restore peristalsis in patients with acute colonic pseudo-obstruction.
Twenty-eight patients at Fletcher Allen Health Care and The Cleveland Clinic Foundation were treated for acute colonic pseudo-obstruction with neostigmine 2.5 mg IV over 3 minutes while being monitored with telemetry. Mechanical obstruction had been excluded.
Complete clinical resolution of large bowel distention occurred in 26 of the 28 patients. Time to pass flatus varied from 30 seconds to 10 minutes after administration of neostigmine. No adverse effects or complications were noted. Of the two patients who did not resolve, one had a sigmoid cancer that required resection and one patient died from multiorgan failure.
This study supports the theory that acute colonic pseudo-obstruction is the result of excessive parasympathetic suppression rather than sympathetic overactivity. We have shown that neostigmine is a safe and effective treatment for acute colonic pseudo-obstruction.
The purpose of this study was to assess the safety of subtotal colectomy and outcomes after this procedure in the modern era of immunosuppressive agents and primary pelvic pouch surgery.
All patients ...undergoing subtotal colectomy with ileostomy for ulcerative colitis or Crohn's colitis from July 1, 1990 to June 30, 2003 were identified from a prospective database. Only patients who were operated on while hospitalized for disease exacerbation were included in the analysis. Age at colectomy, preoperative days in the hospital, postoperative length of stay, and complications were recorded. The medical records were then reviewed for duration of disease, preoperative diagnosis, use of steroids and immunomodulators, parenteral nutrition, endoscopy findings, albumin level, postoperative diagnosis, and ultimate disposition.
One hundred one patients underwent subtotal colectomy for inflammatory bowel disease during the study period. Seventy-four patients met all the inclusion criteria. The mean age was 35.9 (range, 18-86) years. Median duration of disease was 36 (0-240) months, but 28 patients had colitis for less than 1 year, whereas 10 patients had disease of greater than 10 years duration at the time of colectomy. Median preoperative hospital stay was 7 (range, 0-43) days and median postoperative length of stay was 6.5 (range, 4-37) days. Sixty-six patients underwent surgery for refractory exacerbation, 5 for free perforation, 2 for abscess, and 1 patient for hemorrhage. Twenty-seven patients (36.5 percent) had a change in diagnosis after surgery. Complications occurred in 17 patients (23 percent), including 8 cases of central venous catheter-associated thrombosis; 7 of these occurred in patients who had been hospitalized for more than a week before surgery. In the ulcerative colitis patients, 31 of 52 ultimately underwent ileal pouch-anal anastomosis, but 20 (39 percent) chose either completion proctectomy or no further surgery.
Subtotal colectomy with ileostomy remains a safe and effective treatment for patients requiring urgent surgery for severe inflammatory bowel disease. Because of the substantial incidence of change in diagnosis and satisfaction in many patients with an ileostomy, subtotal colectomy with ileostomy may be preferable to primary ileal pouch-anal anastomosis, even when a pouch is considered safe.
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