Tyrphostin AG 126 inhibits development of postoperative ileus induced by surgical manipulation of murine colon.
(1/151)
Manipulation of the bowel during abdominal surgery leads to a period of ileus, which is most severely manifested after procedures that directly involve the colon. Ileus is associated with the increased expression of proinflammatory cytokines and chemokines, a leukocytic infiltration into the muscularis, and the release of mediators from resident and infiltrating leukocytes that directly inhibit intestinal smooth muscle contractility. Phosphorylation of tyrosine residues on regulatory proteins by protein tyrosine kinases (PTKs) occurs at multiple steps in the signaling cascades that regulate the expression of proinflammatory genes. The purpose of this study was to determine whether inhibition of PTK activity will attenuate the inflammatory response associated with colonic ileus and lead to improved function. Using a rodent model of colonic postoperative ileus, we demonstrate that a single bolus injection of the PTK inhibitor tyrphostin AG 126 (15 mg/kg sc) before surgery significantly attenuates the surgically induced impairment of colonic contractility both in vivo and in vitro. Improvement in function was associated with a reduction in magnitude of inflammatory cell infiltrate and with a decrease in transcription of genes encoding proinflammatory mediators IL-1beta and monocyte chemoattractant protein (MCP)-1, inducible nitric oxide synthase, and cyclooxygenase-2. Furthermore, tyrphostin AG 126 pretreatment significantly inhibited activation of multifactorial transcription factor NF-kappaB, which could form the basis for reduction in proinflammatory mediator expression. These data demonstrate for the first time that inhibition of PTK activity may represent a novel approach for management of ileus in the clinical setting. (+info)
Bouveret's syndrome complicated by a distal gallstone ileus.
(2/151)
AIM: Gastric outlet obstruction caused by duodenal impaction of a large gallstone migrated through a cholecystoduodenal fistula has been referred as Bouveret's syndrome. Endoscopic lithotomy is the first-step treatment, however, surgery is indicated in case of failure or complication during this procedure. METHODS: We report herein an 84-year-old woman presenting with features of gastric outlet obstruction due to impacted gallstone. She underwent an endoscopic retrieval which was unsuccessful and was further complicated by distal gallstone ileus. Physical examination was irrelevant. RESULTS: Endoscopy revealed multiple erosions around the cardia, a large stone in the second part of the duodenum causing complete obstruction, and wide ulceration in the duodenal wall where the stone was impacted. Several attempts of endoscopic extraction by using foreign body forceps failed and surgical intervention was mandatory. Preoperative ultrasound evidenced pneumobilia whilst computerized tomography showed a large stone, 5 cm x 4 cm x 3 cm, logging at the proximal jejunum and another one, 2.5 cm x 2 cm x 2 cm, in the duodenal bulb causing a closed-loop syndrome. She underwent laparotomy and the jejunal stone was removed by enterotomy. Another stone reported as located in the duodenum preoperatively was found to be present in the gallbladder by intraoperative ultrasound. Therefore, cholecystoduodenal fistula was broken down, the stone was retrieved and cholecystectomy with duodenal repair was carried out. She was discharged after an uneventful postoperative course. CONCLUSION: As the simplest and the least morbid procedure, endoscopic stone retrieval should be attempted in the treatment of patients with Bouveret's syndrome. When it fails, surgical lithotomy consisting of simple enterotomy may solve the problem. Although cholecystectomy and cholecystoduodenal fistula breakdown is unnecessary in every case, conditions may urge the surgeon to perform such operations even though they carry high morbidity and mortality. (+info)
Induced nitric oxide promotes intestinal inflammation following hemorrhagic shock.
(3/151)
In hemorrhagic shock (HS), increased cytokine production contributes to tissue inflammation and injury through the recruitment of neutrophils [polymorphonuclear cells (PMN)]. HS stimulates the early expression of inducible nitric oxide synthase (iNOS) that modulates proinflammatory activation after hemorrhage. Experiments were performed to determine the contribution of iNOS to gut inflammation and dysmotility after HS. Rats subjected to HS (mean arterial pressure 40 mmHg for 2.5 h followed by resuscitation and death at 4 h) demonstrated histological signs of mucosal injury, impairment of intestinal smooth muscle contractility, extravasation of PMN, and increased gut mRNA levels of ICAM-1, IL-6, and granulocyte colony-stimulating factor (G-CSF). In addition, DNA binding activity of NF-kappaB and Stat3, an IL-6 signaling intermediate, was significantly increased. In shocked rats treated with the selective iNOS inhibitor l-N(6)-(1-iminoethyl)lysine at the time of resuscitation, histological signs of intestinal injury and PMN infiltration were reduced and muscle contractility was almost completely restored. Selective iNOS inhibition in shocked animals reduced the binding activity of NF-kappaB and Stat3 and reduced mRNA levels of ICAM-1, IL-6, and G-CSF. The results of studies using iNOS knockout mice subjected to HS were similar. We propose that early upregulation of iNOS contributes to the inflammatory response in the gut wall and participates in the activation of signaling cascades and cytokine expression that regulate intestinal injury, PMN recruitment, and impaired gut motility. (+info)
A comparison of two surgical strategies for the emergency treatment of gallstone ileus.
(4/151)
INTRODUCTION: Debate currently exists regarding the appropriate surgical strategy for emergency treatment of gallstone ileus. This relates to the need for definitive biliary tract surgery after relief of mechanical obstruction. Our study reviews treatment by enterolithotomy alone and enterolithotomy combined with definitive biliary tract surgery and fistula closure to determine if there is advantage of one treatment option over the other. METHODS: The clinical, operative and follow-up data on 19 consecutive patients treated by emergency surgery for gallstone ileus from January 1992 to December 2000 was retrospectively reviewed. RESULTS: There were 15 women and four men, with a mean age of 74.6 (range 62-91) years. Pre-operative diagnosis was made in only nine of 19 patients. Enterolithotomy alone (E group) was performed in seven patients and enterolithotomy with cholecystectomy and fistula closure (E+C group) in 12 patients. In the E group, more patients had significant co-morbidity as identified by poorer American Society of Anesthesiologists (ASA) status, poorer pre-operative status (shock at presentation) than in the E+C group. Operative time was significantly shorter in the E group. However, there were no significant differences in morbidity, and both groups had zero mortality. CONCLUSION: Both procedures can be carried out safely and with zero mortality. Relief of obstruction remains the mainstay of treatment. The better surgical option in our series is enterolithotomy alone. It is safe in both low and high-risk patients, and requires a shorter operating time as it is technically less demanding. In the longer term, the remnant fistula also does not appear to lead to further complications. (+info)
A prospective randomized study of laparoscopy and minilaparotomy in the management of benign adnexal masses.
(5/151)
BACKGROUND: Recent prospective and randomized studies have demonstrated that laparoscopy is better than laparotomy in the treatment of benign adnexal masses. The aim of this study is to analyse the perioperative outcomes of laparoscopy and minilaparotomy in these patients, in a prospective and randomized manner. METHODS: Between January 2003 and August 2003, 100 consecutive women with a diagnosis of presumed benign adnexal mass and requiring surgical treatment were randomly assigned to minilaparotomy and laparoscopy. Randomization was centralized and computer-based. RESULTS: All operative procedures were performed without conversion to laparotomy. In the group of patients submitted to minilaparotomy, a shorter operating time than patients submitted to operative laparoscopy (mean+/-SD: 71.9+/-31.8 versus 87.0+/-44.8 min; P<0.05) was found. On the other hand, there were significant differences in terms of postoperative ileus (1.1+/-0.4 days in laparoscopy and 1.4+/-0.6 in minilaparotomy P<0.023), without affecting the day of discharge. No intraoperative or early complications were registered in either group. CONCLUSIONS: Taking into account that laparoscopy has to be considered the first choice for benign adnexal surgery, our data suggest that minilaparotomy could offer the gynaecology surgeon a valid alternative in the minimally invasive surgery field, especially in specific settings. (+info)
Mechanisms of polymicrobial sepsis-induced ileus.
(6/151)
Sepsis frequently occurs after hemorrhage, trauma, burn, or abdominal surgery and is a leading cause of morbidity and mortality in severely ill patients. We performed experiments to delineate intestinal molecular and functional motility consequences of polymicrobial sepsis in the clinically relevant cecal ligation and puncture (CLP) sepsis model. CLP was performed on male Sprague-Dawley rats. Gastrointestinal transit, colonic in vivo pressure recordings, and in vitro muscle contractions were recorded. Histochemistry was performed for macrophages, monocytes, and neutrophils. Inflammatory gene expressions were quantified by real-time RT-PCR. CLP delayed gastrointestinal transit, decreased colonic pressures, and suppressed in vivo circular muscle contractility of the jejunum and colon over a 4-day period. A leukocytic infiltrate of monocytes and neutrophils developed over 24 h. Real-time RT-PCR demonstrated a significant temporal elevation in IL-6, IL-1beta, monocyte chemoattractant protein-1, and inducible nitric oxide synthase, with higher expression levels of IL-6 and inducible nitric oxide synthase in colonic extracts compared with small intestine. Polymicrobial CLP sepsis induces a complex inflammatory response within the intestinal muscularis with the recruitment of leukocytes and elaboration of mediators that inhibit intestinal muscle function. Differences were elucidated between endotoxin and CLP models of sepsis, as well as a heterogeneous regional response of the gastrointestinal tract to CLP. Thus the intestine is not only a source of bacteremia but also an important target of bacterial products with major functional consequences to intestinal motility and the generation of cytokines, which participate in the development of multiple organ failure. (+info)
Churg-Strauss syndrome (allergic granulomatous angiitis) associated with T lymphoblastic lymphoma.
(7/151)
We report a rare case of Churg-Strauss syndrome in a 37-year-old man, presented as ileus intestinal and associated with Tlymphoblastic lymphoma, that was located in the retroperitoneal space and infiltrated the suprarenal gland. The T lymphoblasts, with the immunohistochemical method, disclosed positivity for CD3 and CD8, while they were negative for Pan B and CD20. (+info)
Alvimopan, a novel, peripherally acting mu opioid antagonist: results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial of major abdominal surgery and postoperative ileus.
(8/151)
OBJECTIVE: To demonstrate that alvimopan (6 or 12 mg) accelerates recovery of gastrointestinal (GI) function in patients undergoing laparotomy for bowel resection or radical hysterectomy. SUMMARY BACKGROUND DATA: Postoperative ileus (POI) following laparotomy may increase morbidity and extend hospitalization. Opioids can contribute to the duration of POI. Alvimopan is a novel opioid receptor antagonist in development for the management of POI. METHODS: A total of 510 patients scheduled for bowel resection or radical hysterectomy were randomized (1:1:1) to receive alvimopan 6 mg, alvimopan 12 mg, or placebo orally > or =2 hours before surgery, then twice a day (b.i.d.) until hospital discharge or for up to 7 days. The primary efficacy end point was a composite of time to recovery of upper and lower GI function. An associated secondary end point was time to hospital discharge order written. RESULTS: The modified intent-to-treat population included 469 patients (451 bowel resection and 18 radical hysterectomy patients). Time to recovery of GI function was accelerated for the alvimopan 6 mg (hazard ratio [HR] = 1.28; P < 0.05) and 12 mg (HR = 1.54; P < 0.001) groups with a mean difference of 15 and 22 hours, respectively, compared with placebo. The time to hospital discharge order written was also accelerated in the alvimopan 12 mg group (HR = 1.42; P = 0.003) with a mean difference of 20 hours compared with placebo. The incidence of adverse events was similar among treatment groups. CONCLUSIONS: Alvimopan accelerated GI recovery and time to hospital discharge order written compared with placebo in patients undergoing laparotomy and was well tolerated. (+info)