The role of arachidonic acid regulatory enzymes in colorectal disease.

PURPOSE: Nonsteroidal anti-inflammatory drugs have a wide ranging effect on diseases of the colon and rectum. Interestingly, nonsteroidal anti-inflammatory drugs seem to play a beneficial role in colorectal cancer chemoprevention and adenoma regression, but may have a deleterious effect in inflammatory bowel disease. Prostaglandin inhibition is central to both the beneficial and toxic effects of this class of drugs. Arachidonic acid metabolism is essential to prostaglandin synthesis. METHODS: A Medline search using "nonsteroidal anti-inflammatory drugs," "colon cancer," "inflammatory bowel disease," "colitis," "COX inhibitors," "arachidonic acid," and "chemoprevention" as key words was performed for English-language articles. Further references were obtained through cross-referencing the bibliography cited in each work. RESULTS: Based on numerous studies, nonsteroidal anti-inflammatory drugs have a beneficial role in colon cancer and colonic adenomas. However, they have been reported to have a deleterious effect on the colon in inflammatory bowel disease and have been shown to cause colitis. Nonsteroidal anti-inflammatory drugs work via multiple pathways, some well defined, and others unknown. CONCLUSIONS: In the new millennium, nonsteroidal anti-inflammatory drugs may be used for chemoprevention of colorectal and other cancers. In addition, they may be used in combination with surgery and chemotherapy to primarily treat colorectal carcinoma. Undoubtedly, the use of novel cyclooxygenase inhibitors with less of a toxicity profile will allow more widespread use of nonsteroidal anti-inflammatory drugs for a variety of diseases. The future of this class of drugs is promising.

Spectrum of disease and outcome of complicated diverticular disease.

BACKGROUND: Diverticular disease is a common entity. The presentation, investigations performed, and management are variable. Our objectives were to assess the presentation, extent of disease, and treatment of a cohort of patients with colonic diverticulitis. METHODS: All patients with a diagnosis of diverticulitis over a 9-year period were reviewed. Patients were assessed as to age, sex, presenting symptoms, diagnostic studies, extent of disease, treatment, and outcome. RESULTS: Over a 9-year period (1992 to 2001), 192 patients were admitted with a diagnosis of colonic diverticulitis. The mean age was 61 years (range 28 to 90); 113 of 192 (59%) were female. The mean duration of symptoms prior to presentation was 14 days (range 1 to 270 days). One hundred eighteen of 192 (61%) had a previous documented attack of diverticulitis. Of the investigations performed 128 of 192 (66.7%) had a computed tomography (CT) scan of the abdomen and pelvis, 37 of 192 (20%) underwent a contrast enema, 61 of 192 (32%) underwent colonoscopy and 2 of 192 (1%) underwent a small bowel series. The abnormal findings on the CT scan were as follows: diverticular abscess (16%), diverticulitis (37%), diverticulosis without inflammation (15%), free air (10%) and fistula (1%). The locations of the diverticular abscesses were: pelvic (36%), pericolic sigmoid (36%), and "other," which included interloop (28%). Preoperative abscess drainage occurred in 10 of 192 (5%), which were either percutaneous, 6 of 192 (3%), or transrectal, 4 of 192 (2%). Nine of 192 (6%) presented with a fistula, colovesical fistulae (3%), colocutaneous (1%), enterocolic (1%), or colovaginal (1%). Overall, 73 of 192 (38%) underwent surgery. All patients undergoing surgery had a resection of their colon. The operative findings were localized abscess in 16 of 73 (22%), purulent/feculent peritonitis in 12 of 73 (17%), and phlegmon in 10 of 73 (14%). Sixty-seven of 73 (92%) had a primary resection with anastomosis; 38 of 67 (56%) had a protecting stoma. Five of 73 (7%) patients were found to have an unsuspected carcinoma. Overall, 29 of 192 (15%) developed a complication related to diverticulitis. Morbidity was 15.1%, of which 34% was infection related. Four of 192 patients (2%) died. CONCLUSIONS: In our experience, most patients presented with abdominal pain predominantly in the left lower quadrant. The symptoms were present on average of 14 days, most were female (59%), and most patients had a previous attack of diverticulitis. The commonest investigation performed was a CT scan (66.7%); however, other investigations were performed, for example, barium enemas. The practice of resection and primary anastomosis for acute diverticulitis has an acceptable morbidity and mortality. For high-risk anastomoses, a covering loop ileostomy and not a Hartmann's procedure is preferred. Surgery remains safe for the majority of patients and is associated with resolution of symptoms. We believe that because of the high number of patients in our series who had a previous attack of diverticulitis, therapy should be focused on preventing recurrent and virulent attacks by earlier operative intervention.

Ischemic colitis: spectrum of disease and outcome.

BACKGROUND: The aim of this study was to identify risk factors, clinical characteristics, and outcome of patients with colon ischemia. METHODS: A 10-year (1992-2002) retrospective study was undertaken. Patients were identified from computerized hospital discharge information. Patient variables were entered into a computerized database and analyzed. RESULTS: One hundred twenty-nine patients were identified. The mean age was 66 years (range, 29-98 years); 47% were male. Forty-three patients (33%) had chronic renal failure; 73 patients (57%) were receiving vasoactive drugs, and 72 patients (56%) had atherosclerosis. Fifty-four of 129 patients (42%) had ischemic colitis in-hospital. Fifty-six of 129 patients (43%) had melena; 49 of 56 patients (88%) survived. Forty-three of 129 patients (33%) had an acute abdomen; 22 of 43 patients (51%) died. Seventy of 129 patients (54%) were treated nonoperatively initially; the condition of 17 of 70 patients (24%) required surgery. Of 76 patients who were treated operatively, 31 patients (41%) died. Eleven patients at operation had ischemia without colon infarction or perforation; 5 of these patients (45%) died. The overall mortality rate was 29% (37/129 patients). CONCLUSION: Ischemic colitis is associated with chronic renal failure and atherosclerosis. Patients commonly have an acute abdomen. The absence of colonic infarction does not ensure a favorable outcome. Patients who are felt to be candidates for nonoperative therapy have significant mortality rates. Mortality rates remain high, despite treatment.

Colon and rectal cancer in the elderly. High incidence of asymptomatic disease, less surgical emergencies, and a favorable short-term outcome.

BACKGROUND: This is a retrospective study aimed to report short-term outcome among patients age > or =70 years surgically treated for colorectal cancer. METHODS: All patients with the discharge diagnosis of colon and rectal cancer at St. Louis University Hospital from 1992 to 2002 were reviewed. Patients were assessed as to demographics, presenting symptoms, therapy, surgical morbidity and mortality. RESULTS: One hundred eighty-one patients age > or =70 years with colorectal cancer were identified. The mean age was 78 years; 107/181 (59%) were females. Rectal bleeding and change in bowel habits were the most common presenting symptoms. Fifty-four out of 181 (30%) were asymptomatic at diagnosis. The diagnosis was made by colonoscopy in 75% of the patients. One hundred forty-three out of 181 (79%) had colon cancer; 38/181 (21%) had rectal cancer. Fourteen out of 181 (8%) did not undergo surgery. Twenty-two out of 181 (12%) were operated on as a surgical emergency. ASA classification was I-II in 52%, III in 34%, and IV-V in 14%. Nineteen out of 38 (50%) with rectal cancer underwent a sphincter-preserving procedure. Overall, there was a 29% major morbidity from surgery. Thirty-day mortality was 11% (21 deaths). Only the development of a postoperative complication predicted mortality. CONCLUSIONS: Elderly patients tolerate surgery well for colon and rectal cancer in the short-term. Many patients are asymptomatic at diagnosis. Surgical emergencies are few and patients have a favorable stage of disease. This data supports aggressive detection of colorectal cancer in asymptomatic elderly patients who may harbor occult colorectal cancer.

Human intestinal epithelial and smooth muscle cells are potent producers of IL-6.

BACKGROUND: Interleukin-6 (IL-6), a pluripotent cytokine, has traditionally been considered the product of proinflammatory cells. However, many other cell types have been shown to produce IL-6. Since intestinal inflammation is commonly associated with a vigorous systemic inflammatory response, we hypothesized that intestinal epithelial and smooth muscle cells might contribute to that response by producing IL-6. We therefore studied the capacity of differentiated human intestinal epithelial and smooth muscle cell lines to produce IL-6 in response to various proinflammatory stimuli. MATERIALS AND METHODS: CCL-241, a human intestinal epithelial cell line, and HISM, a human intestinal muscle cell line, were grown to confluency and then treated for 24 h with various concentrations of lipopolysaccharide, Clostridium difficile culture extract containing both toxin A and toxin B, recombinant human tumor necrosis factor-alpha (TNF-alpha), or recombinant human interleukin-1 beta (IL-1beta). Supernatants were then collected for IL-6 determination using an enzyme-linked immunosorbent assay. Cell numbers were determined using a Coulter counter. For comparison, parallel studies were performed using phorbol ester-primed U-937 and THP-1 human macrophage cell lines. RESULTS: Both human intestinal epithelial and smooth muscle cells produced IL-6 under basal conditions. In HISM cells, but not in CCL-241 cells, IL-6 release was increased slightly by treatment with C. difficile culture extract containing both toxin A and toxin B and with lipopolysaccharide. In both cell lines, IL-6 production was profoundly stimulated by treatment with IL-1beta and less so with TNF-alpha. Combinations of high-dose TNF-alpha and IL-1beta may have a slightly additive, but not synergistic, effect on IL-6 release. The amount of IL-6 produced by IL-1-stimulated intestinal cell lines was 70-fold higher than that produced by stimulated macrophage cell lines. CONCLUSIONS; Both intestinal epithelial and smooth muscle cells demonstrate the ability to release significant amounts of IL-6. The profound response to IL-1beta and TNF-alpha stimulation by both cell lines suggests that human intestinal parenchymal cells, influenced by paracrine mediators liberated from proinflammatory cells, might significantly contribute to the overall systemic inflammatory response by producing IL-6.

Acute surgical emergencies in inflammatory bowel disease.

BACKGROUND: Acute surgical emergencies in patients with inflammatory bowel disease may carry a substantial morbidity, but fortunately today, a low mortality. The aim of this review is to delineate the treatment of acute surgical emergencies that occur in patients with ulcerative colitis and Crohn's disease. METHODS: Suitable English language reports were identified using PubMed search. RESULTS: Inflammatory bowel disease can present in numerous ways as an acute surgical emergency. These include toxic colitis, hemorrhage, perforation, intra-abdominal masses or abscesses with sepsis, and intestinal obstruction. Toxic colitis and perforation are best managed with intestinal resection and fecal diversion. Hemorrhage in ulcerative colitis initially requires colectomy with rectal preservation and ileostomy. In Crohn's disease hemorrhage is often focal and localization and segmental resection are performed. Intra-abdominal abscesses should initially be attempted by computed tomography-guided percutaneous drainage followed subsequently by definitive resection. Perianal disease requires abscess drainage with minimal tissue trauma. Intestinal obstruction should be initially managed nonoperatively, with surgery reserved for complete obstruction or intractability. CONCLUSIONS: Acute surgical emergencies in patients with inflammatory bowel disease are rare and can have a high morbidity. With a multidisciplinary approach, morbidity can be reduced and patients can have a rapid return and improved quality of life.