Platelet activating factor antagonism reduces the systemic inflammatory response in a murine model of acute pancreatitis.

BACKGROUND: The platelet activating factor (PAF) antagonist, Lexipafant, has been used in experimental models and clinical trials to treat severe acute pancreatitis (AP). The purpose of this study was to determine whether Lexipafant reduces the local and systemic components of AP in a murine model of mild, edematous AP. MATERIALS AND METHODS: Forty-eight female Swiss-Webster mice were divided into four groups. Group 1 received 50 microl of saline ip every hour for 6 h (sham). Group 2 received saline treatment, plus Lexipafant (25 mg/kg dose ip, every 3 h starting 1 h after the first saline injection) (sham/Lex). Group 3 received cerulein (50 microg/kg dose ip, every hour for 6 h) (AP). Group 4 received AP, plus therapeutic treatment with Lexipafant (AP/Lex). Animals were sacrificed 3 h after the last injection. Serum cytokine levels were determined by ELISA. Standard assays were performed for serum amylase activity and lung myeloperoxidase activity (MPO). Histology was scored by two blinded investigators. RESULTS: Serum cytokines (TNFalpha, IL-1beta), lung MPO, and serum amylase activity were reduced by PAF antagonism. Histology showed a trend toward improvement with Lexipafant, but did not reach statistical significance. CONCLUSION: The PAF antagonism reduces the severity of systemic inflammation when given after the induction of mild AP in mice. These results suggest that Lexipafant may be useful in the treatment of mild pancreatitis after its clinical onset.

Ileocecectomy is definitive treatment for advanced appendicitis.

Although appendectomy is the most commonly performed emergency operation septic complications of appendectomy remain a major source of morbidity. Historically, advanced appendicitis has been treated by appendectomy with cecostomy and/or drainage tubes. Our objective was to evaluate the use of ileocecal resection for the immediate treatment of advanced appendicitis. We examined the cases of all patients undergoing ileocecal resection for appendicitis from August 1989 through April 2000. There were 92 patients (60 male and 32 female) with a median age of 34 (range 6-71). Abdominal pain was present in 98 per cent of patients with duration of 5.1+/-0.6 days. Right lower quadrant tenderness was present in 91 per cent with accompanying right lower quadrant mass in 30 per cent. Temperature on admission was 38.0+/-0.1 degrees C with a white blood cell count of 15,300+/-500. Preoperative radiological studies included abdominal X-rays (33), contrast enemas (two), CT scans (41), and abdominal ultrasound (17); these studies yielded a correct preoperative diagnosis in 89 per cent. Previous appendectomy had been performed in six patients with failed percutaneous drainage of intra-abdominal abscesses in five. There were 94 cecal resections performed in 92 patients. The extent of surgical resection varied between patients and ranged from partial cecectomy (34) to ileocecectomy (55) to ileocecectomy with diverting ileostomy (five). Intra-abdominal abscesses were present at operation in 46 cases (50%), and drains were placed in 38 (41%). Skin incisions were packed open in most cases (65); there was skin closure in 27. There was no mortality encountered in this period. There were 25 complications in 23 patients (25%). Complications included postoperative abscess (10; 11%), wound infection (10; 11%), partial small bowel obstruction (two) and pulmonary embolus (one). Reoperation was required in seven patients and CT-guided percutaneous drainage in five patients. Anastomic leaks occurred in two cases of partial cecectomy and required conversion to ileocecectomy. Mean hospital stay was 10.5+/-1.0 days with adjusted hospital costs of $31,689+/-3018. We conclude that definitive treatment of advanced appendicitis can be performed by resection of the involved areas of the ileocecum. This can be accomplished with a primary anastomosis obviating the need for ileostomy and secondary operation. This aggressive surgical approach may reduce infectious complications and reduce hospital costs.

Surgical diverticulitis: treatment options.

Acute diverticulitis requiring surgical intervention has conventionally been treated by resection with colostomy or delayed resection with primary anastomosis at a second admission. Our objective was to determine the outcome for treatment of diverticulitis with resection and primary anastomosis during the same hospitalization. We conducted a retrospective review of patients (n = 74) undergoing surgery for diverticulitis. Groups included: 1) resection with primary anastomosis (n = 33), 2) resection with colostomy followed by a takedown colostomy (n = 32), and 3) delayed resection with primary anastomosis at a second admission (n = 9). Despite local perforation primary anastomosis was often performed unless patients were clinically unstable or had fecal contamination. The operation was urgent in five (15%) patients in Group 1 as compared with 26 patients (88%) in Group 2. Serious intra-abdominal complications occurred in two patients (6%) in Group 1 as compared with nine patients (28%) in Group 2 and one patient (11%) in Group 3. Postoperative abscesses occurred in two patients in Group 1, five patients in Group 2, and one patient in Group 3. We have shown that resection with primary anastomosis for acute diverticulitis--even in selected patients requiring urgent operation--can be safely performed during the same hospital admission with a low complication rate.

Prospective evaluation of early versus delayed laparoscopic cholecystectomy for treatment of acute cholecystitis.

Although laparoscopic cholecystectomy (LC) is known to be safe in the treatment of acute cholecystitis (AC), the optimal timing of laparoscopic intervention remains controversial. The objective of this study is to prospectively compare the safety and cost effectiveness of early versus delayed LC in AC. Our study population consisted of 43 patients presenting with AC (localized tenderness, white blood cell count >10.0 or temperature >38.0 degrees C, and ultrasound confirmation) who were prospectively randomized to early versus delayed LC during their first admission. Exclusion criteria included a history of peptic ulcer disease or evidence of gallbladder perforation. All patients were treated with bowel rest and antibiotics (piperacillin 2 g intravenous piggyback every 6 hours). Early treatment patients underwent LC as soon as the operating schedule allowed. Delayed treatment patients received anti-inflammatory medication (indomethacin 50 mg per rectum every 12 hours) in addition to bowel rest and antibiotics and underwent operation after resolution of symptoms or within 5 days if symptoms failed to resolve. Early LC was performed in 21 patients, whereas 22 patients underwent delayed LC. There was no difference in age, temperature, or white blood cell count on admission between groups. Early LC slightly reduced operative time and conversion rate. There was no difference in complications. Estimated blood loss was significantly lower in those receiving early LC. There was also a significant reduction in total hospital stay and hospital charges with early LC. We conclude that delay in operation combined with anti-inflammatory medication showed no advantage with regard to operative time, conversion, or complication rate. Furthermore, early laparoscopic intervention significantly reduced operative blood loss, hospital days, and hospital charges.

Same admission colon resection with primary anastomosis for acute diverticulitis.

Current standard of care for complicated diverticulitis includes urgent resection with colostomy versus antibiotic treatment, followed by delayed resection with primary anastomosis at a second admission. In certain circumstances, it is possible to perform resection and anastomosis on the same admission for acute diverticulitis. A retrospective review was completed for patients undergoing surgery for diverticulitis from 1991 to 1998. Groups included: 1) sigmoid resection with primary anastomosis on same admission (n = 18); 2) resection with protective end colostomy (n = 16); and 3) in-patient antibiotic treatment alone, followed by a second admission for resection with primary anastomosis (n = 5). Four patients initially treated with antibiotics worsened symptomatically or developed radiographic evidence of perforation and required resection with colostomy. Five patients in Group 1 had abscesses or contained perforations based on radiographic studies. Findings on CT scans did not predict treatment. Group 1 patients had uneventful recoveries and few minor complications (wound infections and an incisional hernia). One anastomotic leak occurred in Group 2 after colostomy closure. Although there will continue to be a role for emergent operation for diverticulitis, same admission sigmoid resection with primary anastomosis after antibiotic treatment is safe, uses a shorter course of antibiotics, and has a low complication rate.

Surgical approach to cecal diverticulitis.

BACKGROUND: Cecal diverticulitis is a rare condition in the Western world, with a higher incidence in people of Asian descent. The treatment for cecal diverticulitis has ranged from expectant medical management, which is similar to uncomplicated left-sided diverticulitis, to right hemicolectomy. STUDY DESIGN: A retrospective chart review was conducted of the 49 patients treated for cecal diverticulitis at Olive View-UCLA Medical Center from 1976 to 1998. This was the largest-ever single-institution review of cecal diverticulitis reported in the mainland US. RESULTS: The clinical presentation was similar to that of acute appendicitis, with abdominal pain, low-grade fever, nausea/vomiting, abdominal tenderness, and leukocytosis. Operations performed included right hemicolectomy in 39 patients (80%), diverticulectomy in 7 patients (14%), and appendectomy with drainage of intraabdominal abscess in 3 patients (6%). Of the 7 patients who had diverticulectomy, 1 required right hemicolectomy at 6 months followup for continued symptoms. Of the three patients who underwent appendectomy with drainage, all required subsequent hemicolectomy for continued inflammation. Of the 39 patients who received immediate hemicolectomies, there were complications in 7 (18%), with no mortality. CONCLUSIONS: We endorse an aggressive operative approach to the management of cecal diverticulitis, with the resection of all clinically apparent disease at the time of the initial operation. In cases of a solitary diverticulum, we recommend the use of diverticulectomy when it is technically feasible. When confronted with multiple diverticuli and cecal phlegmon, or when neoplastic disease cannot be excluded, we advocate immediate right hemicolectomy. This procedure can be safely performed in the unprepared colon with few complications. Excisional treatment for cecal diverticulitis prevents the recurrence of symptoms, which may be more common in the Western population.

Diverting loop versus end ileostomy during ileoanal pullthrough procedure for ulcerative colitis.

A two-stage ileoanal pullthrough procedure (IAPP) is often used for patients with ulcerative colitis (UC) requiring proctocolectomy. We analyzed the recent University of California at Los Angeles experience with diverting end and loop ileostomies in patients undergoing a two-stage IAPP. A retrospective analysis of 21 patients with UC undergoing loop ileostomy between March 1992 and March 1995 was performed. Comparison was made with 21 age- and gender-matched patients undergoing end ileostomy between January 1991 and December 1995. There was no mortality or major septic complications. A second laparotomy was required in all patients with end ileostomies, whereas loop ileostomies were closed without abdominal exploration. During ileostomy closure, operative time and mean hospital stay were significantly reduced with the use of loop ileostomy. The time to oral feeding was not significantly different between end and loop ileostomy groups after ileostomy closure. The complication rate after IAPP was similar between groups. However, after ileostomy closure, the complication rate was significantly reduced with the use of loop ileostomy. We conclude that loop ileostomy is a desirable option for UC patients undergoing intestinal diversion during IAPP. Loop ileostomies can be created easily and without an increase in operative time. Subsequent ileostomy closure can be performed as a local procedure, which may shorten operative time and length of hospital stay.

Seatbelt sign following blunt trauma is associated with increased incidence of abdominal injury.

The use of seatbelts has reduced the overall mortality associated with motor vehicle accidents. The use of lap belts has, however, been associated with a constellation of abdominal injuries, which has been termed "the seatbelt syndrome." Previous studies have shown no increase in overall rates of abdominal injury but an increase in intestinal injury with the use of lap belts. Retrospective reviews suggest that the presence of a "seatbelt sign" may further increase the risk of intestinal injury. The purpose of this study is to prospectively evaluate the incidence of abdominal and intestinal injuries in patients with a "seatbelt sign." A consecutive sample of 117 adult motor vehicle accident victims were studied between July 1993 and January 1994. The use of seatbelts and the presence or absence of a seatbelt sign were determined on admission. Patients were evaluated with computed tomography scan of the abdomen, diagnostic peritoneal lavage, serial abdominal examinations, and operative findings. On arrival, 14 of 117 (12%) had an abdominal seatbelt sign. Of these 14, 9 (64%) had abdominal injury, 5 (36%) required operative intervention, and 3 (21%) had small bowel perforation. In contrast, the 103 patients without a seatbelt sign had significantly fewer abdominal injuries (9; 8.7%), laparotomies (4; 3.8%), and small intestine perforations (2; 103; 1.9%). We conclude that the presence of a seatbelt sign is associated with an increased likelihood of abdominal and intestinal injuries and mandates a heightened index of suspicion.

Interleukin-10 reduces the systemic inflammatory response in a murine model of intestinal ischemia/reperfusion.

BACKGROUND: Intestinal ischemia/reperfusion (I/R) is known to increase systemic cytokine levels, as well as to activate neutrophils in distant organs. This study was designed to investigate the effect of interleukin-10 (IL-10) on cytokine release, pulmonary neutrophil accumulation, and histologic changes in a murine model of I/R. METHODS: Forty female Swiss-Webster mice were divided into four groups. Group 1 underwent 45 minutes of superior mesenteric artery occlusion followed by 3-hour reperfusion (I/R). Group 2 underwent laparotomy alone (Sham). Group 3 underwent I/R, but was treated with IL-10, 10,000 units IP every 2 hours, starting 1 hour before reperfusion (Pretreatment). Group 4 was treated with an equal dose of IL-10, starting 1 hour after reperfusion (Posttreatment). All animals were killed at 3 hours, standard assays were performed for serum cytokine levels, and lung myeloperoxidase activity and intestinal histology were scored. RESULTS: Serum cytokines (TNF-alpha and IL-6), lung myeloperoxidase levels, and histologic score were significantly reduced when IL-10 was administered either before or after reperfusion. CONCLUSIONS: IL-10 reduced the severity of local and systemic inflammation in a murine model of intestinal I/R when given before or after reperfusion injury. These observations suggest that IL-10 may exert its effect by blocking cytokine production and distant organ neutrophil accumulation.

Interleukin-6 production by human melanoma cell lines.

We examined the expression of interleukin-6 (IL-6) by 12 established human melanoma cell lines. Two constitutively produced low levels of IL-6 protein, as measured by enzyme-linked immunosorbent assay. Cells from these two lines, as well as those from two non-IL-6-producing cell lines, contained IL-6-specific mRNA as demonstrated by Northern hybridization. Treatment of the two IL-6-producing melanoma cell lines with interleukin-1 beta, tumor necrosis factor-alpha, or phorbol myristate acetate caused a marked increase in IL-6 production. These induction signals failed to stimulate IL-6 production in the nonproducing cells, even those that expressed IL-6 mRNA. IL-6 did not appear to act as an autocrine growth factor since the addition of exogenous human recombinant IL-6 or polyclonal anti-IL-6 antibody did not alter cellular proliferation. The production of this multifunctional cytokine by tumors may play a role in tumor-host interactions and this should be recognized in the design of biologic therapy trials.