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Mechanical small bowel obstruction (SBO) is a frequent indication for hospital admission. It is associated with significant morbidity and mortality and financial burden. The most common cause of SBO in medically underserved countries is hernia, but up to 70% of cases in the United States are due to adhesions.1 All patients who have had an operation in which the peritoneal cavity has been entered have a subsequent lifetime risk of obstruction secondary to adhesions. In an autopsy study of 752 cadavers, adhesions were found in 67% of those who had undergone a previous operation but in only 28% of cadavers with no previous operation.2 In a prospective analysis of 210 patients undergoing a laparotomy who had previously had one or more abdominal operations, 93% of patients had adhesions, compared with 10% of 115 patients who had asymptomatic adhesions at first-time laparotomy.3 The management of patients with acute SBO remains controversial. There are no uniform strategies regarding indications for or timing of operation. The decision to operate is at the discretion of the individual surgeon, but not based on high-quality evidence. Some surgeons support immediate operative management in almost all cases.4–7 However, studies on the natural history of adhesive obstructions have shown that more than 50% resolve with a conservative, nonoperative approach.8,9 Other surgeons use an initial nonoperative trial period of bowel decompression in stable patients without suspicion of bowel strangulation.10–14 As a result, the operative rates for SBO have been shown to vary widely, from 27% to 66%.15,16 The morbidity and mortality associated with operative management of SBO are recognized, but the responsible presurgical and intraoperative risk factors have not been identified. The Department of Veterans Affairs (VA) National Surgical Quality Improvement Program (NSQIP) was designed to overcome some of the limitations of retrospective analyses by prospectively gathering reliable, valid data about putative patient risk factors and outcomes of surgery in the VA healthcare system. These data are then used to construct mathematical models that report comparative risk-adjusted surgical morbidity and mortality rates. The initial National Veterans Affairs Surgical Risk Study that was conducted from October 1, 1991, through December 31, 1993, included 44 Veterans Affairs Medical Centers (VAMCs). The program was expanded on January 1, 1994, and now prospectively gathers data on surgical procedures performed at 123 VAMCs. There are more than 1 million entries to date. Each of these cases was selected according to defined criteria, assessed for 68 presurgical and 12 intraoperative variables judged likely to be predictors of complications and death, and monitored after surgery for 30-day mortality and for 21 specific and well-defined adverse outcomes. The reproducibility and accuracy of data collection have been demonstrated elsewhere.17–19 These data permit the construction of risk-prediction models using well-accepted statistical techniques.20 The present study uses these techniques to assess risk factors for morbidity and mortality following surgical treatment of SBO.

Background. Group II phospholipase A 2 (PLA 2 ) enzymes, the rate controlling enzymes in arachidonic acid metabolism, have been well characterized and subdivided into secretory 14-kDa PLA 2 (sPLA 2 ) and cytoplasmic 85-kDa PLA 2 (cPLA 2 ). Previous research has demonstrated increased PLA 2 in colorectal tumors. The present study was performed to determine the effect of specific PLA2 inhibitors on the proliferation and induction of apoptosis of intestinal epithelial cells. Methods. A continuously proliferating rat small intestinal cell line (IEC-18) and a mouse colon cancer cell line (WB-2054-M 4 ) were utilized for these experiments. The cells were placed in microwells with serum-free or serum-supplemented media. The effects of serum on proliferation were then evaluated in the presence of the cPLA 2 inhibitor, methylarachidonyl fluorophosphate (MAFP), or the sPLA 2 inhibitor p -bromophenacyl bromide (BPB). The sPLA 2 and cPLA 2 protein was estimated by Western blotting. Proliferation of intestinal cells was quantitated by incorporation of [ 3 H]thymidine into DNA and PLA 2 activity was evaluated by quantitating arachidonic acid formation and prostaglandin E 2 production. Results. Western blotting of IEC-18 and WB-2054 cell protein demonstrated sPLA 2 and cPLA 2 enzyme in cells incubated in media containing 10% serum. Spontaneous DNA synthesis was present in both cell lines and serum consistently increased proliferation. In IEC-18 cells [ 3 H]thymidine incorporation stimulated by serum was inhibited by MAFP and BPB, while in the malignant cell line, proliferation was inhibited only by BPB. BPB, but not MAFP, produced a dose-dependent increase in apoptotic ratios in both cell lines. Arachidonic acid and PGE 2 formation, stimulated by serum, was inhibited by MAFP and BPB. Conclusions. A differential effect on intestinal cell mitogenesis was seen with different PLA 2 inhibitors. The sPLA 2 inhibitor, but not the cPLA 2 inhibitor, significantly inhibited [ 3 H]thymidine incorporation in the malignant cell line. This occurred with an induction of apoptosis. sPLA 2 inhibitors may be specific inhibitors of growth of malignant cells. The inhibition of arachidonic acid and PGE 2 production did not correlate with the inhibition of proliferation, suggesting that the two processes may be unrelated.

Patients with spinal cord injury (SCI) typically have difficulty with constipation. Some undergo surgery for bowel management. We predicted that SCI patients would have higher mortality and/or morbidity rates following such surgery than neurally intact patients receiving the same procedures. We sought to evaluate this using a large population-based data set.Patients receiving care at Department of Veterans Affairs Medical Centers (DVAMCs) with computer codes for SCI and constipation who later underwent colectomy, colostomy, or ileostomy during fiscal years 1993-2002 were identified. Charts were requested from the VAMCs where the surgery had been performed and a retrospective chart review of these charts was done. We collected data on patient demographics, six specific pre-operative co-morbidities, surgical complications, and post-operative mortality. Comparisons were made to current literature evaluating a population receiving total abdominal colectomy and ileorectal anastomosis for constipation but not selected for SCI.Of 299 patients identified by computer search, 43 (14%) had codes for SCI and 10 of 43 (24%) met our inclusion criteria. All were symptomatic and had received appropriate medical management. Co-morbid conditions were present in 9 of 10 patients (90%). There were no deaths within 30 days. The complication rate was zero. The mean post-operative length of stay was 17 days.Patients with SCI comprise about 14% of the population who receive surgery for severe constipation in the Department of Veterans Affairs system. The mortality and morbidity rates in these patients are similar to those reported in other constipated patients who have surgery for intractable constipation. Our data suggest that stoma formation ± bowel resection in patients with SCI is a safe and effective treatment for chronic constipation.

Introduction Limited published information is available concerning the clinical course of spinal cord injured (SCI) patients who later develop rectal cancer and undergo proctectomy. We hypothesized that such patients would have poorer outcomes than comparable neurally-intact patients. Methods We conducted a retrospective study of all SCI veterans receiving care at all Department of Veterans Affairs (DVA) Medical Centers who subsequently underwent proctectomy for rectal cancer during fiscal years 1993–2002. Only patients with SCI due to trauma who met American Spinal Injury Association type A criteria (complete cord injury) were analyzed. The search strategy utilized DVA datasets plus data extracted from medical records. Results There were 33,758 patients with ICD-9-CM diagnosis codes for SCI and 5246 patients with ICD-9-CM procedure codes for proctectomy due to rectal cancer; 72 patients were in both datasets. We received records for 72 patients and excluded 67 after chart review. Incorrect coding (44) and incomplete spinal cord lesions (9) were the most common exclusion criteria. Five patients were considered evaluable. The mean age at diagnosis was 65 (range 49–80). All five had symptomatic cancers and two (40%) had major comorbidities at admission. Postoperative complications occurred in four (80%). The winsorized mean length of stay was 28 days. Conclusions The complication rate and length of stay for SCI patients undergoing proctectomy for rectal cancer were higher than those reported for otherwise comparable neurally-intact patients. SCI should be considered a risk factor for adverse outcomes in operations for rectal cancer as in other major surgery.

The follow-up of patients with rectal cancer after potentially curative resection has significant financial and clinical implications for patients and society. The ideal regimen for monitoring patients is unknown. We evaluated the self-reported practice patterns of a large, diverse group of experts. There is little information available describing the actual practice of clinicians who perform potentially curative surgery on rectal cancer patients and follow them after recovery. The 1795 members of the American Society of Colon and Rectal Surgeons were asked, via a detailed questionnaire, how often they request 14 discrete follow-up modalities in their patients treated for cure with TNM stage I, II, or III rectal cancer over the first five post-treatment years. 566/1782 (32%) responded and 347 of the respondents (61%) provided evaluable data. Members of the American Society of Colon and Rectal Surgeons typically follow their own patients postoperatively rather than sending them back to their referral source. Office visit and serum CEA level are the most frequently requested items for each of the first five postoperative years. Endoscopy and imaging tests are also used regularly. Considerable variation exists among these highly experienced, highly credentialed experts. The surveillance strategies reported here rely most heavily on relatively simple and inexpensive tests. Endoscopy is employed frequently; imaging tests are employed less often. The observed variation in the intensity of postoperative monitoring is of concern.

Purpose : Surgery remains the primary treatment of colorectal cancer. Data are lacking to delineate the optimal surveillance strategy following resection. A large-scale multi-center European study is underway to address this issue (Gruppo Italiano di Lavoro per la Diagnosi Anticipata—GILDA). Methods : Following primary surgery with curative intent, stratification, and randomization at GILDA headquarters, colon cancer patients are then assigned to a more intensive or less intensive surveillance regimen. Rectal cancer patients undergoing curative resection are similarly randomized, with their follow-up regimens placing more emphasis on detection of local recurrence. Target recruitment for the study will be 1500 patients to achieve a statistical power of 80% (assuming an alpha of 0.05 and a hazard-rate reduction of >24%). Results : Since the trial opened in 1998, 985 patients have been randomized from 41 centers as of February 2004. There were 496 patients randomized to the less intensive regimens, and 489 randomized to the more intensive regimens. The mean duration of follow-up is 14 months. 75 relapses (15%) and 32 deaths (7%) had been observed in the two more intensive follow-up arms, while 64 relapses (13%) and 24 deaths (5%) had been observed in the two less intensive arms as of February 2004. Conclusions : This trial should provide the first evidence based on an adequately powered randomized trial to determine the optimal follow-up strategy for colorectal cancer patients. This trial is open to US centers, and recruitment continues.

The purpose of this study was to define risk factors that predict 30-day morbidity and mortality after gastrectomy for cancer in Veterans Affairs (VA) Medical Centers.The VA National Surgical Quality Improvement Program prospectively collected data on 708 patients undergoing gastrectomy for cancer in 123 participating VA medical centers from 1991 to 1998. Independent variables included 68 preoperative patient characteristics and 12 intraoperative variables; the dependent variables were 21 defined adverse outcomes and death. Predictive models for 30-day morbidity and mortality were constructed by using stepwise logistic regression analysis.The 30-day morbidity rate was 33.3% (236 of 708). The overall 30-day mortality rate was 7.6% (54 of 708). Significant positive predictors of morbidity (P.05) included current pneumonia, American Society of Anesthesiologists class IV (threat to life), partially dependent functional status, dyspnea on minimal exertion, preoperative transfusion, extended operative time, and increasing age. Significant positive predictors of mortality (P.05) included do not resuscitate status, prior stroke, intraoperative transfusion, preoperative weight loss, preoperative transfusion, and elevated preoperative alkaline phosphatase level.Risk factors predicting morbidity and mortality rates at VA hospitals after gastrectomy for gastric cancer are reported by using a prospectively collected, multi-institutional database. Assigning relative weights to factors associated with adverse outcomes may help improve patient care.

Pregnancy often exacerbates constipation in young women with chronic constipation syndromes. The presence of the fetus presents a challenge in both the diagnosis and treatment of these syndromes. This study was conducted to report a rare case of idiopathic megarectum complicating a pregnancy. An aggressive polyethylene glycol (PEG) regimen allowed the patient to carry the child to term and to have a normal vaginal delivery. Successful proctocolectomy was performed with coloanal anastomosis 3 months postpartum. The patient has been free of constipation for 18 months without the need for cathartics or laxatives. All efforts to avoid operative intervention should be made in constipated patients during pregnancy. This principle holds true even in the setting of dilated large bowel. Idiopathic megarectum and the management of constipation in pregnancy are discussed.

Hypothesis Clostridium difficile toxins require interleukin 1 (IL-1) production or a functioning IL-1 receptor to elicit acute-phase protein production by murine hepatocytes. Design Experimental study. Setting Research laboratory at the DVA Medical Center, St Louis, Mo. Cells Studied Hepatocytes prepared from normal mice, from knockout mice deficient in IL-1 production due to loss of IL-1 converting enzyme, or from knockout mice deficient in the IL-1 p80 receptor. Interventions Cells were treated with lipopolysaccharide, a crude C difficile toxin extract, or purified C difficile toxins A or B for 24 hours in vitro, then radiolabeled with 35 S methionine. Newly synthesized acute-phase proteins were identified by electrophoresis and autoradiography. Main Outcome Measures Synthesis of a 23-kd acute-phase protein in response to the various stimuli. Results Lipopolysaccharide, C difficile culture extract, and purified toxins A and B stimulated the synthesis of the 23-kd acute-phase protein by hepatocytes from normal mice and by hepatocytes from knockout mice deficient in the IL-1 converting enzyme. However, hepatocytes from knockout mice deficient in the IL-1 p80 receptor failed to produce this acute-phase protein when treated with the C difficile toxins, although they responded fully to lipopolysaccharide. Conclusions Stimulation of acute-phase protein synthesis by C difficile toxins does not require IL-1 production, but does require a functioning IL-1 p80 receptor. This suggests that some of the actions of these toxins are mediated by this receptor.

PURPOSE: Sigmoid volvulus is the third leading cause of large-bowel obstruction. The optimal management strategy remains controversial. This study was undertaken to evaluate the care of patients with sigmoid volvulus recently treated at Department of Veterans Affairs hospitals. METHODS: All patients with the International Classification of Diseases, Ninth Revision, Clinical Modification, Third Edition code for colonic volvulus during the period 1991 to 1995 were identified in the computerized national Department of Veterans Affairs database. Data on patient demographics, clinical course, and outcomes were analyzed. RESULTS: Two hundred twenty-eight patients had volvulus of the sigmoid colon and sufficient clinical data for evaluation. The mean age was 70; all were males. Endoscopic decompression was attempted in 189 of 228 (83 percent) patients and was successful in 154 of 189 (81 percent). Management included celiotomy in 178 of 228 (78 percent) patients. There were no intraoperative deaths. Twenty-five of 178 (14 percent) patients died within 30 days of surgery. The mortality rate was 24 percent for emergency operations (19/79), and 6 percent for elective procedures (6/99). Mortality was correlated with emergent surgery (P

Eicosanoids are involved in gallbladder inflammation, epithelial water transport, and mucous secretion. Phospholipase Asubscript2 enzymes liberate arachidonic acid from membrane phospholipids for the synthesis of eicosanoids. The purpose of this study was to determine the effect of selective cytoplasmic and secretory phospholipase A2 inhibitors on basal and stimulated arachidonic acid and prostaglandin E2 release in gallbladder cells. Western immunoblotting was employed to evaluate both cytosolic and secretory phospholipase A2 enzymes in human gallbladder cells. Cells were incubated for 22 hours with (3)H-labeled arachidonic acid. Arachidonic acid and prostaglandin E2 release was then measured in the supernate after 2 hours of exposure to human interleukin-1beta, alone or after pretreatment for 1 hour with the inhibitors. Unstimulated gallbladder cells express both 85 kDa cytosolic and 14 kDa secretory phospholipase A2++. The 85 kDa phospholipase A2 was induced by interleukin-1beta, whereas there was no apparent change in secretory phospholipase A2 enzyme concentrations. Both the secretory phospholipase A2 inhibitor p-bromophenylacyl bromide and the cytosolic phospholipase A2 inhibitor arachidonyl trifluoromethyl ketone decreased basal and interleukin-1beta-stimulated arachidonic acid release. In contrast, only inhibition of cytosolic phospholipase A2 led to a decrease in interleukin-1beta-stimulated prostaglandin E2 release. Basal and interleukin-1beta-stimulated arachidonic acid release appears to be the result of the activity of both cytosolic and secretory phospholipase A2. Interleukin-1beta-stimulated prostaglandin E2 release appears to be dependent on the activity of cytosolic phospholipase A2.

Background. We have found that Clostridium difficile toxins can evoke hepatocyte acute-phase protein synthesis, and that this effect is dependent on a functioning interleukin-1 (IL-1) receptor. The present study was undertaken to determine if C. difficile toxicity, as determined by actin rearrangement and lactate dehydrogenase (LDH) release, also requires a functioning IL-1 receptor. Methods. Primary hepatocyte cultures were prepared from normal mice, knockout mice deficient in the IL-1-converting enzyme (ICE), and knockout mice deficient in the IL-1 p80 receptor. Hepatocytes were treated for 24 h with C. difficile culture extract, purified C. difficile toxin A, or purified C. difficile toxin B. The actin cytoskeleton was examined using confocal microscopy, and LDH release was measured by spectrophotometric analysis. Results. C. difficile culture extract, toxin A, and toxin B induced collapse of the actin cytoskeleton in hepatocytes from normal mice. Hepatocytes from both the ICE-deficient mice and the IL-1 p80 receptor-deficient mice demonstrated similar responses to both toxins. These toxins also induced significant LDH release in a concentration-dependent fashion in the normal hepatocytes and the ICE-deficient hepatocytes. However, no significant increase in LDH release was observed in hepatocytes from IL-1 p80 receptor-deficient mice. Conclusions. C. difficile toxins induce actin cytoskeletal collapse independent of IL-1 or the IL-1 receptor. In contrast, toxin-stimulated LDH release was dependent on the presence of the IL-1 receptor. Thus, separate pathways appear to mediate toxic effects as manifested by actin rearrangement and LDH release.

3713 Background: In wealthy societies, most patients with rectal cancer treated with curative intent enter some type of follow-up regimen. A recent survey of the members of the American Society of ...

3695 Background: In wealthy societies, most patients with colorectal cancer are treated with curative intent and enter some type of follow-up regimen but the optimum surveillance strategy has not been defined. There are no active adequately-powered trials dealing with this topic originating in North America, as far as we are aware, but one is open in Europe (Gruppo Italiano di Lavoro per la Diagnosi Anticipata - GILDA). Methods: After primary curative-intent treatment, stratification, and randomization at GILDA headquarters, colon cancer patients are followed according to a more intensive or less intensive surveillance regimen. Rectal cancer patients are also followed according to a more intensive or less intensive regimen; these arms are similar to the arms for colon cancer patients but focus more on local-regional recurrence. To ensure adequate statistical power, the target number of patients is 1,500. Health-related quality of life and cost-effectiveness measures are incorporated in the trial. Results:...

3645 Background: Surgery is the mainstay of treatment for colorectal cancer. In western industrial societies most patients are treated with curative intent and enter some type of follow-up regimen. Surgeons often follow their own patients after colorectal cancer surgery but the optimum surveillance strategy has not been defined. There are no active adequately powered trials dealing with this topic originating in North America, as far as we are aware, but one based in Milan, Italy, is open (Gruppo Italiano di Lavoro per la Diagnosi Anticipata - GILDA). Methods: After primary curative-intent treatment, stratification, and randomization at GILDA headquarters, colon cancer patients are followed according to a more intensive or less intensive surveillance regimen. Rectal cancer patients are also followed according to a more intensive or less intensive regimen; these arms are similar to the arms for colon cancer patients but focus more on local-regional recurrence. To ensure adequate statistical power, the targ...