Timing of colonoscopy after resection for colorectal cancer: are we looking too soon?

BACKGROUND: Based on current National Comprehensive Cancer Network guidelines, colonoscopic surveillance after colorectal cancer resection should begin at 1 year. OBJECTIVE: The aim of this study was to determine whether the incidence of cancer or advanced polyp detection rate was high enough to justify colonoscopy at 1 year. DESIGN: The Ochsner Clinic Tumor Registry Database was queried for patients who underwent a segmental colectomy or proctectomy between 2002 and 2010. Patients who had a preoperative colonoscopy and at least 1 documented postoperative colonoscopy were included. We considered new cancer or polyps of ≥1 cm as missed on the preoperative colonoscopy. Patients with an identified genetic trait causing a predisposition to colorectal cancer were excluded. RESULTS: Five hundred twelve patients underwent resection, and 155 met our inclusion criteria. The average age was 64 years, and 53% patients were male. There were 32.9% with stage I disease, 35% with stage II disease, 27.1% with stage III disease, and 5.2% with stage IV disease. Of these patients, 52.2% had a right colectomy, 7.1% had a left colectomy, 16.8% had a sigmoid colectomy, 22% had a low anterior resection, and 1.3% had a transanal resection. The average time to first postoperative colonoscopy was 478 days (SD ±283 days). Twenty-four patients had adenomatous polyps detected on their first surveillance colonoscopy, but only 5 (3.2%) polyps were ≥1 cm, and there was no correlation between stage of cancer and finding a polyp. No new cancers were detected, but 3 (1.9%) had an anastomotic recurrence. CONCLUSIONS: The performance of surveillance colonoscopy at 1 year resulted in the detection of only 5 missed polyps ≥1 cm and no metachronous cancers. Anastomotic recurrences were rare, and the majority were in patients who had rectal cancer that could be evaluated by in-office flexible sigmoidoscopy. Extending the time to first colonoscopy appears to be safe and would help conserve valuable resources, including physician and facility time, which is imperative in the current health care climate.

Calculation of the effect of pressurizing gases on the resonant modes of single-crystal parallelepiped.

Resonant ultrasound spectroscopy provides for an experimental determination of the elastic moduli of a solid sample. The moduli are extracted by matching a theoretically computed resonant spectrum to the experimental vibrational spectrum. To determine the pressure dependence of the moduli, the vibrational spectrum can be taken with the sample in a pressurizing gas. Then the extraction of the intrinsic, pressure dependent moduli requires a theoretical treatment which permits removal of the perturbation of the spectrum due to the surface loading by the pressure and shear waves in the gas. In order to illustrate a treatment which accomplishes this removal, the theoretically computed frequency shifts and the quality factors are reported for two single-crystal parallelepiped pressurized by noble gases.

Rayleigh-ritz calculation of the resonant modes of a solid parallelepiped in a pressurizing fluid.

Resonant ultrasound spectroscopy relies on comparisons of experimentally determined vibrational spectra to theoretically computed spectra for the extraction of the elastic moduli of the solid samples. To determine the pressure dependence of these moduli, resonant spectra are taken for samples pressurized by a surrounding gas and knowledge of the contribution of the surface loading of the sample by the gas is needed in order to extract the intrinsic pressure dependence of the moduli. To facilitate the required comparisons, a Rayleigh-Ritz variational calculation of the vibrational spectrum is formulated which includes the loading of the solid by the pressurizing fluid. This formalism is used to compute the effect of gas loading on the vibrational spectrum of an isotropic, solid parallelepiped.

Colonoscopy in the patient requiring anticoagulation.

PURPOSE: The aim of this study was to assess perioperative warfarin management and complications in patients requiring colonoscopy. METHODS: We retrospectively reviewed 109 cases of colonoscopies performed on 94 patients requiring anticoagulation with warfarin. Patients stopped their warfarin three days before colonoscopy. Coagulation profiles obtained just before the colonoscopy showed a median prothrombin time of 13.4 seconds with a range of 11.1 to 29.1 (normal range, 10.9-13) and a median international normalized ratio of 1.2 with a range of 0.9 to 2.6. Patients restarted warfarin the day after the examination. RESULTS: During the 109 colonoscopies, 47 percent of the patients underwent either hot biopsy or snare polypectomy. One examination that included several biopsies was associated with a hemorrhagic complication (0.92 percent) requiring hospitalization and transfusion. Subset analysis of the therapeutic (biopsy and snare polypectomy) group indicated a slightly higher complication rate (1.96 percent) with a median international normalized ratio of 1.3 (range, 1-2.3) and a median prothrombin time of 13.7 (range, 11.6-25.9). CONCLUSION: Patients taking warfarin for anticoagulation may safely undergo colonoscopy. The risk of hemorrhagic complications increases slightly with hot biopsy or snare procedures. Further studies are needed to refine guidelines for colonoscopy in the patient requiring anticoagulation.

Colonoscopic perforations.

PURPOSE: This study was designed to assess the medical and surgical treatment of colonoscopic perforations. METHODS: A retrospective review of colonoscopic perforations from 1970 to 1999 was performed. RESULTS: In 30 years, 34,620 colonoscopies resulted in 31 (0.09 percent) perforations. Eighteen (58 percent) resulted from therapeutic colonoscopies, whereas 13 (42 percent) occurred after diagnostic colonoscopies. Sixteen perforations (52 percent) were identified during the procedure, 13 (42 percent) within 24 hours, and two (6 percent) within 48 hours. Twenty patients (65 percent) underwent surgical therapy, and 11 (35 percent) were treated medically with intestinal rest and intravenous antibiotics. In the medically treated group, one patient required rehospitalization for percutaneous drainage of an intra-abdominal abscess, and one patient died after requesting no further treatment because of an underlying terminal medical condition. Three patients failed medical treatment and required surgical intervention. One underwent repair with proximal diversion, whereas the remaining two received a colorrhaphy without resection or diversion. In the surgical treatment group, nine patients received colorrhaphy without diversion, seven underwent resection with primary anastomosis, and four had resection with diversion. CONCLUSION: Selected patients with colonoscopic perforation may be safely treated nonoperatively. Surgical treatment is reserved for patients with a large perforation or diffuse peritonitis.

Restorative proctocolectomy: Ochsner Clinic experience.

BACKGROUND: Restorative proctocolectomy, a standard operation for ulcerative colitis and familial adenomatous polyposis has significant complications, even in experienced hands. METHODS: We studied surgical outcome by retrospectively reviewing cases of restorative proctocolectomy done at Ochsner Foundation Hospital from 1982 to 1995. Demographic and clinical data from two periods (1982 to 1989 and 1989 to 1995) were compared to determine factors associated with improved outcome. RESULTS: We performed 145 ileal pouch-anal procedures. In 56 patients, 104 complications occurred. The more recent group had a greater incidence of inflammatory bowel disease, steroid use, and staged operations; reduced operative times and hospital stays; more general but fewer pouch-related complications. Pouch failures were similar for both groups. CONCLUSIONS: Perioperative outcome appeared to be associated with technical experience, improved perioperative care, exclusion of patients with Crohn's disease,judicious surgical reoperation for pouch complications, and use of a 3-stage procedure in malnourished patients or those with acute or toxic colitis.

Outcomes and experiential education.

Outcomes-based assessment in education involves continuous use of assessment measures to provide feedback about the efficacy of the curricular structure, content, and teaching methods. This process is initiated by establishing educational outcome statements for the Doctor of Pharmacy curriculum, selecting assessment methods that most appropriately measure the educational outcomes, and establishing a learning environment that is congruent with both the outcomes and assessment methods. To ensure a successful continuous outcomes-based assessment process, a systematic assessment plan should be prepared that focuses the process by identifying only the most essential hypotheses, uses a practical yet appropriate methodology, ensures efficient data collection, includes data analyses that link the educational outcomes to the learning environment, and promotes timely development and implementation of an action plan. An overview of outcomes-based education and the use of outcomes-based practice experiences in pharmacy education is presented.

Significance of a normal surveillance colonoscopy in patients with a history of adenomatous polyps.

PURPOSE: The aim of this study was to determine the appropriate surveillance for patients with a history of adenomatous polyps whose last colonoscopic examination was normal. METHODS: This was a retrospective review of a database of 7,677 colonoscopies (1990 to 1996). In patients under colonoscopic surveillance, we reviewed cases of patients who had received three colonoscopies (an index (initial) colonoscopy positive for adenomas and 2 follow-up colonoscopies (interim and final)). The risk of adenomas and cancers at final follow-up colonoscopy was compared between patients having a normal interim colonoscopy and those with a positive interim colonoscopy. The risk at final colonoscopy was also stratified by time interval and the size and number of adenomas at the initial index colonoscopy. RESULTS: Two hundred four patients undergoing surveillance for adenomas met inclusion criteria. At index colonoscopy the median polyp size was 1 cm and median frequency was three polyps. At all follow-up colonoscopies, we detected 493 adenomas and one cancer (median follow-up, 55 months). At 36 months patients with a normal interim colonoscopy (n = 91) had significantly fewer polyps than patients with a positive interim colonoscopy (n = 113; 15 vs. 40 percent; P = 0.0001). By 40 months, adenomas were detected in more than 40 percent of patients in both groups. The risk after a normal interim colonoscopy was not affected by time interval or number or size of polyps. Adenomas found subsequent to a normal interim colonoscopy were dispersed throughout the colon in 28 patients and isolated to the rectosigmoid in 6 patients. CONCLUSIONS: In patients with a history of adenomas, a normal follow-up colonoscopy is associated with a statistically but not clinically significant reduction in the risk of subsequent colonic neoplasms. These patients require follow-up surveillance colonoscopy at a four-year to five-year interval.

The natural history of isolated rectosigmoid adenomatous polyps: is flexible sigmoidoscopy a safe alternative for surveillance?

PURPOSE: Colonoscopic surveillance is recommended for patients with adenomatous polyps. Significant cost savings would result from identification of subgroups of patients in whom less costly surveillance would suffice. This study was performed to determine the natural history of patients undergoing removal of isolated rectosigmoid adenomas and to establish whether flexible sigmoidoscopy might be adequate for follow-up. METHODS: A retrospective review of a database of 7,677 colonoscopies, from 1990 to 1996, identified patients who had a minimal follow-up of two years after removal of adenomatous polyps isolated to the rectosigmoid. Polyps detected on surveillance colonoscopy were categorized as distal (< or =60 cm from anal verge), proximal (>60 cm from anal verge), and diffuse (proximal plus distal). The risk of polyp formation was determined by actuarial analysis using the Kaplan-Meier method. RESULTS: Sixty-two patients undergoing surveillance for adenomas met inclusion criteria. At the index colonoscopy, 124 isolated rectosigmoid polyps were identified. The median polyp size was 1 cm and median frequency was one polyp. The median follow-up time for the entire cohort (N = 62) was 53 months. At follow-up surveillance colonoscopy, 105 additional adenomas were discovered and removed in 40 patients. No malignant polyps were detected. The pattern of polyps detected were proximal (n = 19), rectosigmoid (n = 16), and diffuse (n = 5). CONCLUSIONS: The majority (65 percent) of patients with isolated rectosigmoid polyps have additional polyps on long-term surveillance, and 60 percent of patients will have these polyps located proximal to the reach of a sigmoidoscope. Therefore, flexible sigmoidoscopy is not a safe alternative for surveillance of patients with isolated rectosigmoid polyps.

Effect of previous surgery on abdominal opening time.

PURPOSE: The purpose of this study was to document prospectively the time required to gain access to the abdomen to perform a planned procedure in patients with and without previous surgery. METHODS: Patients were obtained from the consecutive cases of 11 surgeons at three colorectal surgery centers. Opening time (skin incision to retractor placement) was measured and recorded in the operating room by the circulating nurse or by an independent researcher. Demographic data including the number and type of previous operations and the presence and severity of adhesions were recorded by the staff surgeon. A comparison of opening times between patients with and without previous abdominal operations was conducted. RESULTS: One hundred ninety-eight patients had abdominal operations. Fifty-five percent had previous abdominal procedures. Patients with prior surgery required a mean of 21 minutes to open their abdomens, whereas patients without prior surgery required a mean of 6 minutes (P < 0.01). The median times were 17 and 6 minutes, respectively. Eighty-three percent of patients with prior surgery had adhesions, whereas only 7 percent of patients had adhesions on their initial operation. Patients with prior surgery also had higher grade adhesions (P < 0.001). Irrespective of previous surgery, comparing patients with adhesions with those without, patients with adhesions required a mean of 22 minutes to open, whereas the lack of adhesions resulted in a mean opening time of 6 minutes. CONCLUSIONS: Previous surgery and the presence of adhesions add significant time to opening the abdomen.

Discontinuous appendiceal involvement in ulcerative colitis: pathology and clinical correlation.

Continuous mucosal involvement from the rectum proximally is one of the hallmarks of ulcerative colitis. However, recent pathologic series report appendiceal ulcerative colitis in the presence of a histologically normal cecum, representing a "skip" lesion. The clinical significance of this finding has not been established. Eighty patients, 54 males and 26 females, average age 37.9 years (range 14 to 82 years) who underwent proctocolectomy for ulcerative colitis from January 1990 to September 1995 were examined to determine the rate of discontinuous appendiceal involvement. Excluded were 12 patients with prior appendectomy and 11 with fibrotic obliteration of the appendiceal lumen. Of the remaining 57 patients, seven (12.3%) had clear appendiceal involvement in the presence of a histologically normal cecum. These seven patients clinically were indistinguishable from the 50 patients without skip involvement of the appendix in terms of age at surgery, pretreatment medications, type of surgery, interval from diagnosis to definitive procedure, complications, functional results, and clinical course. Discontinuous appendiceal involvement was found in 12.3% of patients undergoing proctocolectomy for ulcerative colitis, and clinically these patients behave as those without this feature.

Incidence of small-bowel obstruction and adhesiolysis after open colorectal and general surgery.

PURPOSE: The study contained herein was undertaken to establish the incidence of small-bowel obstruction, adhesiolysis for obstruction, and additional abdominal surgery after open colorectal and general surgery. METHODS: A retrospective cohort study was performed using patient-specific Health Care Financing Administration data to evaluate a random 5 percent sample of all Medicare patients who underwent surgery in 1993. Of these, 18,912 patients had an index abdominal procedure. Two-year follow-up data documented outcomes of hospitalizations with obstruction, adhesiolysis for obstruction, and/or additional open colorectal or general surgery. RESULTS: Within two years of incision, excision, and anastomosis of intestine (International Classification of Dis eases (ICD)-9 code 45), 14.3 percent of patients had obstructions, 2.6 percent required adhesiolysis for obstructions, and 12.9 percent underwent additional open colorectal or general surgery. After other operations of intestine (ICD code 46), 17 percent of patients had obstructions, 3.1 percent required adhesiolysis for obstructions, and 20.2 percent underwent additional open colorectal or general surgery. After operations of rectum, rectosigmoid, and perirectal tissue (ICD code 48), 15.3 percent of patients had obstructions, 5.1 percent required adhesiolysis for obstructions, and 16.4 percent underwent additional open colorectal or general surgery. After other operations on the abdominal region (ICD code 54), 12.4 percent of patients had obstructions, 2.3 percent required adhesiolysis for obstructions, and 8.8 percent underwent additional open colorectal or general surgery. CONCLUSIONS: In this retrospective study of Medicare patients, we learned that bowel obstruction, adhesiolysis for obstructions, and additional abdominal surgery occurred more often after abdominal surgery than was previously published.

Quantitation of dolastatin-10 using HPLC/electrospray ionization mass spectrometry: application in a phase I clinical trial.

A highly sensitive and specific assay for the quantitation of the anticancer agent dolastatin-10 (DOL-10) in human plasma is described. The method was based on the use of electrospray ionization-high-performance liquid chromatography/mass spectrometry (ESP-LC/MS). The analytical procedure involved extraction of plasma samples containing DOL-10 and the internal standard (DOL-15) with n-butyl chloride, which was then evaporated under nitrogen. The residue was dissolved in 50 microl mobile phase and 10 microl was subjected to ESP-LC/MS analysis using a C18 microbore column. A linear gradient using water/acetonitrile was used to keep the retention times of the analytes of interest under 5 min. The method exhibited a linear range from 0.005 to 50 ng/ml with a lower limit of quantitation (LLQ) at 0.005 ng/ml. Absolute recoveries of extracted samples in the 85-90% range were obtained. The method's accuracy (< or =5% relative error) and precision (< or =10% CV) were well within industry standards. The analytical procedure was applied to extract DOL-10 metabolites from samples obtained following incubation of the drug with an activated S9 rat liver preparation. Two metabolic products were detected and were tentatively identified as a N-demethyl-DOL-10 and hydroxy-DOL-10. Structural assignments were made based on the fragmentation patterns obtained using the electrospray source to produce collision-induced dissociation (CID). The method was also applied to the measurement of DOL-10 in the plasma of patients treated with this drug. Preliminary investigation of the pharmacokinetics suggested that drug distribution and elimination may be best described by a three-compartment model with t1/2alpha = 0.087 h, t1/2beta = 0.69 h and t1/2gamma = 8.0 h. Plasma clearance was 3.7 l/h per m2.

Long-term survival after treatment of malignant colonic polyps.

PURPOSE: This study was designed to evaluate the long-term outcome and survival of patients treated for malignant colonic polyps. METHODS: A retrospective review of 15,975 cases of colonoscopies with 8,685 endoscopic polypectomies performed between 1972 and 1990 was undertaken. In 65 patients, the polypectomy specimens contained invasive carcinoma. Six patients were excluded (follow-up, <6 months). Polyp data, operative findings, and follow-up on the remaining 59 patients were recorded. RESULTS: Malignant polyps were found in 35 males and 24 females who had an average age of 64 (range, 39-81) years. Follow-up ranged from 12 to 202 (mean, 90) months. Tumor differentiation was poor in one and well or moderately differentiated in 58 patients. Positive or indeterminate margins were found in 13 patients. Thirty-seven (63 percent) patients were managed with polypectomy and surveillance. Four of these (with rectal tumors) also had an additional local excision for questionable margins. One recurrence was noted in a patient who refused surgery, which was recommended because of indeterminate margins. Twenty-two patients (37 percent) underwent colectomy. Indications included Haggitt Level 3 or 4 invasion (19), inadequate margins (7), patient preference (1), and poor differentiation (1). Residual disease was found in colectomy specimens of three patients (14 percent). There were no cancer-related deaths in either treatment group. Life table analysis demonstrated a five-year survival of 82 percent for the colectomy group and 95 percent for the polypectomy group (P = 0.15). CONCLUSION: Treatment of patients with malignant polyps must be individualized based on evolving criteria. Patients in whom polypectomy margins are inadequate should undergo colectomy. With appropriate selection criteria, patients selected for colectomy had a five-year survival rate similar to the rate of those treated by polypectomy alone.

Treatment of colorectal and ileoanal anastomotic sinuses.

PURPOSE: This study is designed to describe a technique and report results for treating low anastomotic sinuses. METHODS: Restorative proctocolectomy and complicated low anterior resections were protected with diverting loop ileostomy. Contrast enemas identified anastomotic problems before ileostomy closure. Pouch-anal or colorectal anastomotic sinuses that failed to resolve with observation were treated before intestinal continuity was restored. With the patient receiving regional or general anesthesia, a rigid proctoscope or anoscope was used to identify the sinus opening. The common wall between the sinus and the bowel lumen was divided under direct vision with laparoscopic cautery scissors, and the sinus cavity was debrided with a suction cautery wand placed through the scope. RESULTS: Six patients with anastomotic sinuses have received outpatient treatment in the described manner during the past two years. Four patients had restorative proctocolectomies for ulcerative colitis, and two had low anastomosis for rectal cancer. Three patients presented with pelvic sepsis before the contrast study; the remainder were asymptomatic. Division of anastomotic sinus was performed one to eight months after diagnosis of the sinus. Following division, anastomotic cavities resolved in five patients by 1 month and in one patient by 12 months. In these six patients, there was one dilatable anastomotic stricture but no other anastomotic complications at follow-up 5 to 16 (mean, 9.2) months after sinus division. CONCLUSION: When used in conjunction with fecal diversion, sinus unroofing by division of the common wall between the sinus and bowel lumen treats low pelvic sinuses.

Outpatient bowel preparation for elective colon resection.

To determine the safety and cost-effectiveness of outpatient preoperative bowel preparation with polyethylene glycol-electrolyte lavage solution, we retrospectively analyzed 726 cases of colectomy done by colon and rectal surgeons between July 1987 and July 1991. Included were 319 patients who had elective segmental or total abdominal colectomy with primary anastomosis. Patients who required protective proximal stoma were excluded. Patients requiring emergency surgery, colostomy closure, and restorative proctocolectomy were excluded. Patients were separated into two groups equally matched by age, sex, procedure done, and comorbidity: 145 had bowel preparation as outpatients and 174 as inpatients. Both groups had similar numbers of days hospitalized, days receiving nothing by mouth, and days requiring nasogastric intubation or gastrostomy tube, as well as similar postoperative complications. There was one wound infection, one anastomotic leak, and one death in each group. Cost of outpatient preparation was approximately $40. Cost of inpatient preparation, including a semiprivate room, was approximately $400. Outpatient preparation with polyethylene glycol-electrolyte lavage solution and oral antibiotics before elective colon resection can be done with equivalent safety and at a substantial cost savings.

Predictive value of technetium Tc 99m-labeled red blood cell scintigraphy for positive angiogram in massive lower gastrointestinal hemorrhage.

PURPOSE: This study was performed to evaluate whether the time interval from injection of technetium Tc 99m (99mTc)-labeled red blood cells to the time of a radionuclide "blush" (positive scan) can be used to improve the efficacy in predicting a positive angiogram. METHOD: A retrospective review revealed 160 patients who received 99mTc-labeled red blood cell scintigraphy for evaluation of massive lower gastrointestinal hemorrhage between 1989 and 1994. Patients were included who demonstrated signs of shock on admission, had an initial decrease in hematocrit of > or = 6 percent, or required a minimum transfusion of two units of packed red blood cells. Scanning duration was 90 minutes, with imaging every 2 minutes. Time interval from injection to a positive scan was analyzed to determine predictability of a positive angiography. RESULTS: Of 160 patients, 86 demonstrated positive scans, of whom 47 underwent angiography. These 47 patients were divided into two groups according to scan results. Group 1 (n = 33) had immediate appearance of blush; Group 2 (n = 14) had blush after two minutes. In Group 1, 20 of 33 patients had a positive angiogram, yielding a positive predictive value of 60 percent (P = 0.033). Of the 14 patients with negative angiograms (13 from Group 1, and 1 with a negative scan), 6 had radiographic occlusion of the inferior mesenteric artery and 1 had spasm of the right colic artery, with scans that blushed in the respective distributions. Excluding these seven patients yielded a positive predictive value of 75 percent (P = 0.0072) for angiography. In patients with a delayed blush (Group 2), 13 of 14 had negative angiograms, yielding a negative predictive value of 93 percent (92 percent excluding those with nonvisualization of the inferior mesenteric artery). Twenty of 21 (95 percent) positive angiograms occurred in Group 1 patients. Of the 27 patients with negative angiograms, 13 were Group 2 patients. CONCLUSION: Patients with immediate blush on 99mTc-labeled red blood cell scintigraphy required urgent angiography. Patients with delayed blush have low angiographic yields. These data suggest that patients with delayed blush or negative scans may be observed and evaluated with colonoscopy.

Perineal repair of rectal prolapse.

Perineal approaches to the repair of rectal prolapse are frequently used in elderly or high-risk patients. These repairs have lower operative mortality and morbidity than intra-abdominal repairs but in general have higher recurrence rates. This study reviews our recent results with perineal prolapse repairs, briefly summarizes the literature, and discusses the available perineal operations. Eight patients (mean age 75 years) underwent surgical prolapse repair over an 18-month period. Treatment was by Altemeier's procedure (perineal rectosigmoidectomy) in 6 patients and Delorme's procedure in 2 patients. There were no operative mortalities, and an anastomotic dehiscence in 1 patient was managed nonoperatively. All patients with preoperative constipation improved and no patient reported worsening of continence. Surgical approaches from the perineum may be used in elderly and poor risk patients to treat rectal prolapse with low mortality and morbidity. These techniques have not adversely affected fecal continence and have improved symptoms of constipation with an acceptable rate of recurrence.

The role of Seprafilm bioresorbable membrane in adhesion prevention.

OBJECTIVE: To evaluate, the safety and efficacy of Seprafilm, a novel bioresorbable membrane of chemically modified hyaluronic acid and carboxymethylcellulose, in preventing and reducing postoperative adhesion formation. DESIGN: Randomized, controlled, blinded, prospective multicenter study. SETTING: Major academic surgical centers. SUBJECTS: 183 (treatment, n = 91; control, n = 92) patients with ulcerative colitis or familial polyposis. INTERVENTIONS: Restorative proctocolectomy and ileal J-pouch anastomosis with diverting ileostomy followed by second-stage laparoscopy for ileostomy closure and direct visual assessment of the peritoneal cavity. Before abdominal closure in treated patients, Seprafilm, averaging 406.9 cm2 per patient, was applied without suturing between the midline incision and underlying tissues and organs. MAIN OUTCOME MEASURES: Determination of the incidence, extent (mean percentage of midline incision associated with adhesions), severity (grade 1, least severe; grade 2, moderately severe; grade 3, very severe), and distribution of adhesions. RESULTS: In 175 (treatment, n = 90) evaluable patients, Seprafilm significantly reduced the incidence (49% and 94%, respectively, p < 0.0001), extent (23% and 63%, respectively, p < 0.0001), and severity (15% versus 58% grade 3 severity, respectively, p < 0.0001) of postoperative adhesions. Seprafilm decreased the rate of adhesion formation by nearly 50%. More than half (51%) of Seprafilm recipients were adhesion-free, versus only 6% of untreated patients. Thus treated patients were eight times more likely to be free of adhesions than untreated controls. The incidence of incisional adhesions associated with the omentum, small bowel, left sidewall, bladder, ileostomy, and stomach was significantly reduced in the Seprafilm patients. Effects on vital signs and laboratory parameters were comparable in the two groups and were attributable to the operative procedure, concomitant therapy, or comorbid disease. All reported adverse events were associated with the surgical procedure and/or comorbid disease and did not differ significantly between the two groups (p > 0.05). CONCLUSION: Seprafilm is safe and significantly reduces the incidence, extent, and severity of postoperative adhesions to the midline incision compared with no treatment, the current standard of surgical care.

Adhesions: pathogenesis and prevention-panel discussion and summary.

This article summarizes the discussions of the faculty and chairpersons on four major topics on postsurgical adhesions examined at the symposium, "Adhesions: Pathogenesis and Prevention". These topics are: 1) clinical significance; 2) pathogenesis; 3) research status and directions; and 4) recommendations for reduction or prevention. Abdominal postsurgical adhesions develop following trauma to the mesothelium, which is damaged often by surgical handling and instrument contact, foreign materials such as sutures and glove dusting powder, desiccation, and overheating. Postoperative adhesions occur after most surgical procedures and can result in serious complications, including intestinal obstruction, infertility, and pain. A long-term and unpredictable problem, postoperative adhesions impact the surgical workload and hospital resources, resulting in considerable health care expenditures. Although understanding of the pathogenesis of adhesions has improved recently, the molecular mechanisms involved continue to be delineated. Adhesions result from the normal peritoneal wound healing response and develop in the first five to seven days after injury. Adhesion formation and adhesion-free re-epithelialization are alternative pathways, both of which begin with coagulation which initiates a cascade of events resulting in the buildup of fibrin gel matrix. If not removed, the fibrin gel matrix serves as the progenitor to adhesions by forming a band or bridge when two peritoneal surfaces coated with it are apposed. The band or bridge becomes the basis for the organization of an adhesion. Protective fibrinolytic enzyme systems of the peritoneum, such as the plasmin system, can remove the fibrin gel matrix. However, surgery dramatically diminishes fibrinolytic activity. The pivotal events determining whether the pathway taken is adhesion formation or re-epithelialization are therefore the apposition of two damaged surfaces and the extent of fibrinolysis. Research in postsurgical adhesion formation and prevention abounds in a variety of avenues of investigation, including: 1) identification on a molecular level of the components involved in adhesiogenesis and their interactions; 2) clarification of the role of fibrin and fibrinolysis in adhesion formation; 3) standardization of design in preclinical and clinical studies of adhesion formation and prevention; 4) delineation of the relationship between adhesion formation and adhesive complications; and 5) elucidation of efficient, site-specific methods of prophylactic drug delivery. Currently, it seems logical to focus preventive research on development of barriers, fibrinolytic drugs, and selected agents such as phospholipids. The major strategies for adhesion prevention or reduction are adjusting surgical practice and applying adjuvants. Surgeons should adjust their major practices by: 1) becoming aware of the potential adhesive complications of a procedure; 2) minimizing the invasiveness of surgery; and 3) minimizing surgical trauma, ischemia, exposure to intestinal contents, introduction of foreign material into the body, and the use of talc- or starch-containing gloves. Available adjuvants include a newly developed by hyaluronic acid-phosphate-buffered saline solution applied intraoperatively to protect peritoneal surfaces from indirect surgical trauma and three mechanical barriers. One of these, a bioresorbable membrane consisting of hyaluronic acid and carboxymethylcellulose, has demonstrated efficacy and safety in both general and gynecological surgery. The other two barriers, one made of expanded polytetrafluoroethylene and one developed from oxidized regenerated cellulose, are indicated only for use in gynecological surgery.