Position statement by the Pelvic Floor Society on behalf of the Association of Coloproctology of Great Britain and Ireland on the use of mesh in ventral mesh rectopexy.

The following position statement forms part of a response to the current concerns regarding use of mesh to perform rectal prolapse surgery. It highlights the actions being pursued by the Pelvic Floor Society (TPFS) regarding clinical governance in relation to ventral mesh rectopexy (VMR). The following are summary recommendations. Available evidence suggests that mesh morbidity for VMR is far lower than that seen in transvaginal procedures (the main subject of current concern) and lower than that observed following other abdomino-pelvic procedures for urogenital prolapse, e.g. laparoscopic sacrocolpopexy. VMR should be performed by adequately trained surgeons who work within a multidisciplinary team (MDT) framework. Within this, it is mandatory to discuss all patients considered for surgery at an MDT meeting. Clinical outcomes of surgery and any complications resulting from surgery should be recorded in the TPFS-hosted national database (registry) available for this purpose; in addition, all patients should be considered for entry into ongoing and planned UK/European randomized studies where this is feasible. A move towards accreditation of UK units performing VMR will improve performance and outcomes in the long term. An enhanced programme of training including staged porcine, cadaveric and preceptorship sessions will ensure the competence of surgeons undertaking VMR. Enhanced consent forms and patient information booklets are being developed, and these will help both surgeons and patients. There is weak observational evidence that technical aspects of the procedure can be optimized to reduce morbidity rates. Suture material choice may contribute towards morbidity. The available evidence is insufficient to support the use of one mesh over another (biologic vs synthetic); however, the use of polyester mesh is associated with increased morbidity.

Short- and long-term clinical and patient-reported outcomes following laparoscopic ventral mesh rectopexy using biological mesh for pelvic organ prolapse: a prospective cohort study of 224 consecutive patients.

AIM: Laparoscopic ventral mesh rectopexy (LVMR) is potentially a safe and effective operation to correct pelvic organ prolapse and to treat obstructive defaecation and solitary rectal ulcer syndrome. This study aimed to evaluate, in a prospective, consecutive cohort of patients, the long-term clinical outcomes following LVMR, patient-reported functional and quality of life outcomes, and urinary and sexual dysfunction. METHOD: Data on 224 patients who underwent LVMR with Permacol™ biological mesh were collected prospectively from May 2008 to October 2016. Outcome measures were complications, recurrence, mortality, patient satisfaction, patient-reported functional and quality of life outcomes, and urinary and sexual dysfunction. Scores were compared using the two-tailed Wilcoxon signed rank test. P < 0.05 was considered statistically significant. RESULTS: There was no mortalities associated with LVMR in this series; complications occurred in 10.7% of patients (4.9% early, 5.8% late). Mesh-related morbidity was 0.45% and vaginal suture-related morbidity was 1.33%. Recurrence occurred in 25 patients (11.4%), 5% at 12 months, 10.7% at 5 years. Significant improvement in patient-reported functional outcomes were seen (P < 0.001) for both constipation and faecal incontinence symptoms. Furthermore, significant improvement in quality of life outcomes for patients with constipation, faecal incontinence and prolapse persisted through follow-up (P < 0.001). Patient satisfaction was positive for > 90% of patients during follow-up. Symptoms of stress urinary incontinence, urge incontinence and dyspareunia improved significantly postoperatively (P < 0.001). CONCLUSION: LVMR using Permacol is associated with low morbidity and mortality, recurrence and, additionally, significantly improved constipation, faecal incontinence and prolapse functional and quality of life outcomes, with associated improvement in urogynaecological symptoms.

Surgery for constipation: systematic review and practice recommendations: Graded practice and future research recommendations.

AIM: This manuscript forms the final of seven that address the surgical management of chronic constipation (CC) in adults. The content coalesces results from the five systematic reviews that precede it and of the European Consensus process to derive graded practice recommendations (GPR). METHODS: Summary of review data, development of GPR and future research recommendations as outlined in detail in the 'introduction and methods' paper. RESULTS: The overall quality of data in the five reviews was poor with 113/156(72.4%) of included studies providing only level IV evidence and only four included level I RCTs. Coalescence of data from the five procedural classes revealed that few firm conclusions could be drawn regarding procedural choice or patient selection: no single procedure dominated in addressing dynamic structural abnormalities of the anorectum and pelvic floor with each having similar overall efficacy. Of one hundred 'prototype' GPRs developed by the clinical guideline group, 85/100 were deemed 'appropriate' based on the independent scoring of a panel of 18 European experts and use of RAND-UCLA consensus methodology. The remaining 15 were all deemed uncertain. Future research recommendations included some potential RCTs but also a strong emphasis on delivery of large multinational high-quality prospective cohort studies. CONCLUSION: While the evidence base for surgery in CC is poor, the widespread European consensus for GPRs is encouraging. Professional bodies have the opportunity to build on this work by supporting the efforts of their membership to help convert the documented recommendations into clinical guidelines.

Surgery for constipation: systematic review and clinical guidance: Paper 1: Introduction & Methods.

AIM: This manuscript provides the introduction and detailed methodology used in subsequent reviews to assess the outcomes of surgical interventions with the primary intent of treating chronic constipation in adults and to develop recommendations for practice. METHOD: PRISMA guidance was adhered to throughout. A literature search was performed in public databases between January 1960 and February 2016. Studies that fulfilled strictly-defined PICOS (patients, interventions, controls, outcome, and study design) criteria were included. The process involved two groups of participants: (i): 'a clinical guidance group' of 18 UK experts (including junior support) who performed the systematic reviews and produced summary evidence statements (SES) based strictly on data synthesis in each review. The same group then produced prototype graded practice recommendations (GPRs) based on coalescence of SES and expert opinion; (ii): a European Consensus group of 18 ESCP (European Society of Coloproctology) nominated experts from nine European countries evaluated the appropriateness of each prototype GPR based on published RAND/UCLA methodology. RESULTS: An overview of the search results is provided in this manuscript. A total of 156 studies from 307 full text articles (from 2551 initially screened records) were included, providing data on procedures characterized by: (i) colonic resection (n = 40); (ii) rectal suspension (n = 18); (iii) rectal wall excision (n = 44); (iv) rectovaginal septum reinforcement (n = 47); (v) sacral nerve stimulation (n = 7). The overall quality of evidence was poor with 113/156 (72.4%) studies providing only Oxford level IV evidence. The best evidence was extracted for rectal excisional procedures, where the majority of studies were Oxford level I or II. The five subsequent reviews provide a total of 99 SES (reflecting perioperative variables, efficacy, harms and prognostic variables) that contributed to 100 prototype GPRs covering patient selection, procedural considerations and patient counselling. The final manuscript details the 85/100 GPRs that were deemed appropriate by European Consensus (remaining 15 were all uncertain) and future research recommendations. CONCLUSION: This manuscript and the following 6 papers suggest that the evidence base for surgical management of chronic constipation is currently poor although some expert consensus exists on best practice. Further studies are required to inform future commissioning of treatments and of research funding.

Surgery for constipation: systematic review and practice recommendations: Results III: Rectal wall excisional procedures (Rectal Excision).

AIM: To assess the outcomes of rectal excisional procedures in adults with chronic constipation. METHOD: Standardised methods and reporting of benefits and harms were used for all CapaCiTY reviews that closely adhered to PRISMA 2016 guidance. Main conclusions were presented as summary evidence statements with a summative Oxford Centre for Evidence-Based Medicine (2009) level. RESULTS: Forty-seven studies were identified, providing data on outcomes in 8340 patients. Average length of procedures was 44 min and length of stay (LOS) was 3 days. There was inadequate evidence to determine variations in procedural duration or LOS by type of procedure. Overall morbidity rate was 16.9% (0-61%), with lower rates observed after Contour Transtar procedure (8.9%). No mortality was reported after any procedures in a total of 5896 patients. Although inconsistently reported, good or satisfactory outcome occurred in 73-80% of patients; a reduction of 53-91% in Longo scoring system for obstructive defecation syndrome (ODS) occurred in about 68-76% of patients. The most common long-term adverse outcome is faecal urgency, typically occurring in up to 10% of patients. Recurrent prolapse occurred in 4.3% of patients. Patients with at least 3 ODS symptoms together with a rectocoele with or without an intussusception, who have failed conservative management, may benefit from a rectal excisional procedure. CONCLUSION: Rectal excisional procedures are safe with little major morbidity. It is not possible to advise which excisional technique is superior from the point of view of efficacy, peri-operative variables, or harms. Future study is required.

The role of biologics in pelvic floor surgery.

The advent of laparoscopic surgery and with it Laparoscopic Ventral Mesh Rectopexy (LVMR) has revolutionised the management of internal/external rectal and vaginal vault prolapse. These procedures have traditionally been performed with synthetic meshes. Biologics have gained a prominent role over the last decade in LVMR as well as perineal procedures for rectocoele and cystocoele repair. We examine the existing literature on the use of biologics in pelvic floor surgery comparing this with literature on synthetic mesh for the key outcomes of infection rates, bowel/sexual function and recurrence.

Short-term results for laparoscopic ventral rectopexy using biological mesh for pelvic organ prolapse.

AIM: There is growing evidence that laparoscopic ventral rectopexy (LVR) is an effective treatment for pelvic organ prolapse and obstructive defaecation caused by rectocele. LVR is usually performed using synthetic mesh despite concerns about mesh erosion. We present our experience of using a porcine dermal collagen mesh (Permacol™) for LVR, which is the largest such case series to date. METHOD: Data on 65 patients were collected prospectively from May 2008 to October 2010. Outcome measures were complications, recurrence, length of hospital stay, patient satisfaction, Wexner constipation score and Wexner incontinence score. Preoperative and postoperative scores were compared using the two-tailed Wilcoxon signed rank test. P<0.05 was considered statistically significant. RESULTS: There were statistically significant improvements in the Wexner constipation scores at 6 months and 1 year (both P<0.0001) and in faecal incontinence scores at 6 months (P<0.0001) and 1year (P=0.0002). There were no cases of mesh erosion or mesh-related infection in our series. Recurrence of symptoms occurred in two patients (3.1%). Symptoms were rated as much better or better by 93% of patients at 6months and this was sustained at 1year (96%). CONCLUSION: In the short term, LVR using biological mesh is safe and as effective as synthetic mesh, with high patient satisfaction. Constipation and faecal incontinence scores were both improved.

Surgical training in gastrointestinal procedures within a UK gynaecological oncology subspecialty programme.

OBJECTIVE: An analysis of surgical experience in gastrointestinal procedures within a UK-based gynaecological oncology centre to which subspecialty fellows within the subject are exposed. DESIGN: Retrospective study. SETTING: Northern Gynaecological Oncology Centre, Gateshead, UK. POPULATION: All women undergoing bowel surgery over a six-year period, 1 January 2000 to 31 December 2005. METHODS: Cases were analysed by specialty and grade of surgeon performing the procedure. MAIN OUTCOME MEASURE: Proportion of cases to which subspecialty fellows were exposed. RESULTS: Two hundred and sixty-two women (11.5%) underwent bowel surgery out of 2280 women undergoing major surgery for gynaecological cancer. This included ovarian/primary peritoneal cancer in 186 women (71%). Of these 262 cases, 238 operations (91%) were performed by a gynaecological oncologist, 20 (7.5%) were performed jointly with the gastrointestinal surgeons and four (1.5%) were performed solely by the gastrointestinal surgeons. A gynaecological oncology subspecialty fellow performed 21 (8%) and assisted in an additional 204 operations (78%). Perioperative morbidity and mortality statistics in addition to overall survival outcomes were comparable to the published literature. CONCLUSIONS: A significant proportion of major surgical operations performed within a gynaecological oncology centre require gastrointestinal procedures. The majority of these procedures can be performed by gynaecological oncologists with an acceptable perioperative morbidity and mortality rate. Subspecialty training has the potential to allow trainees significant exposure to these procedures. An accredited post-Fellowship Training Programme can provide the opportunity for hands-on experience to allow gynaecological oncologists the confidence and credibility to perform these procedures independently.

Laparoscopic repair of a Littre's hernia with porcine dermal collagen implant (Permacol).

BACKGROUND: Littre's hernia was originally defined as "the presence of a Meckel's diverticulum in any hernia sac" by Rieke in 1841. It is a rare finding at any age, and its true incidence is unknown. The conventional treatment for Littre's hernia is wedge resection of the diverticulum and repair of the hernia from within the sac. However, the advent of laparoscopic surgery has altered the management of all abdominal hernias, including Littre's hernia. CASE REPORT: We present a case of a 55-year-old woman who presented as an emergency with right iliac fossa pain and tenderness. A CT scan demonstrated a 46 x 25 x 25 mm lesion related to the distal ileum extending towards the inguinal canal. At laparoscopy she was found to have a Meckel's diverticulum herniating through the deep inguinal ring into the right inguinal canal. We report the laparoscopic excision of the Meckel's diverticulum using an endoscopic stapling device and repair of this hernia with Permacol, an acellular porcine collagen mesh. The patient made a quick recovery and was discharged 5 days post-operatively. A complication of an umbilical port site infection was treated 2 weeks post-operatively with oral antibiotics. To date there has been no recurrence of the hernia and no right inguinal pain. Laparoscopic repair of Littre's hernia using Permacol has not been reported previously. CONCLUSIONS: Laparoscopy is a safe, inexpensive and efficient method for the diagnosis and treatment of Littre's hernia. Permacol is a strong yet supple material for hernia repair.

Outcome after transperineal mesh repair of rectocele: a case series.

PURPOSE: This study was designed to establish the safety and efficacy of transperineal mesh repair in patients with obstructed defecation caused by rectocele. METHODS: Between 1998 and 2002, 24 consecutive females with symptomatic rectocele were retrospectively reviewed after mesh repair of rectocele. Two patients had inadvertent rectal perforation during operation and had no mesh implantation. Of the remaining 22 patients, 14 had a prolene mesh implanted, and 8 had a Vipro II mesh implanted. Median age at the time of presentation was 55 (range, 28-66) years. Patients were selected for operation based on clinical and evacuation proctogram findings. All patients complained of incomplete rectal evacuation, and the majority complained of excessive straining, constipation, and the need for vaginal/perineal digital pressure to aid defecation. Patients were followed up in clinic at six weeks, and a telephone questionnaire was performed at a median time of 12.5 (range, 3-47) months. Functional/objective outcomes were assessed for the following five symptoms preoperatively and postoperatively: excessive straining, incomplete evacuation, perineal/vaginal digital pressure, vaginal bulging, and constipation (always, usually, occasionally, never). Subjective outcomes were assessed as excellent, good, moderate, or poor. In addition, patients were asked about preexisting and postoperative dyspareunia. RESULTS: Objective outcomes based on symptoms showed an improvement in two or more symptoms in 20 patients (91 percent). For all symptoms, there was a significant reduction in mean values after repair. Subjective outcomes showed that 17 patients (77 percent) had a moderate/good/excellent result. Patients with abnormal preoperative colonic transit marker studies did as well as those who had no transit studies performed or those who had normal studies. Patients who did not vaginally digitate did as well as those who did not digitate. Only one patient complained of new onset dyspareunia. Two patients with sphincter defects on endoanal ultrasound had a sphincteroplasty performed (1 prerectocele repair and 1 at the same time). There were two superficial wound infections and one deep infection. All infections responded to antibiotic therapy. No mesh has been removed. Semiabsorbable mesh repair was superior to nonabsorbable mesh repair. CONCLUSIONS: Transperineal mesh repair of symptomatic rectocele is a safe technique that avoids the anal dilation and sphincter injury associated with endorectal repair. Objective and subjective results are good in the majority of patients, although a longer follow-up is required to confirm no deterioration.

Heparin binding protein increases survival in murine fecal peritonitis.

OBJECTIVE: To test the effectiveness of recombinant heparin-binding protein (HBP), a neutrophil-derived multifunctional protein with monocytic-specific properties, in fecal peritonitis and polymicrobial sepsis. DESIGN: Prospective, controlled animal trial. SETTING: Animal research laboratory. SUBJECTS: Swiss Webster mice challenged with cecal ligation and puncture (CLP) and treated with recombinant HBP and 60 mg/kg cefoxitin twice a day. INTERVENTIONS: HBP was administered to mice at different concentrations and different intervals before and after CLP. Rat albumin (1%) was administered to control animals. MEASUREMENTS AND MAIN RESULTS: MORTALITY RATE: Survival was increased in mice pretreated intraperitoneally 24 hrs before CLP with 10 microg or 100 microg of HBP without cefoxitin (p = .01, Cox-Mantel log-rank test). Compared with control animals, survival was increased significantly (from 5% to 47%, p = .014) in mice that received cefoxitin and 50 microg ip HBP immediately after CLP, followed by continuous administration of HBP (12 microg/24 hrs). Intravenous administration of HBP (0.1, 1, and 10 microg) at the time of CLP showed an opposite dose effect; low doses (0.1 microg) prolonged early survival, whereas high dose (10 microg) shortened survival (p = .036). Compared with control animals, overall survival was not different. CHEMOTAXIS: Cytospin preparations from peritoneal exudate cells (PECs) 48 hrs after administration of 10 microg and 100 microg ip HBP demonstrated a 1.7-fold increase in the total number of macrophages compared with carrier control (p < .05). PHAGOCYTOSIS: A flow cytometric in vitro assay demonstrated that administration of 10 microg ip HBP alone did not enhance phagocytosis of fluorescent Escherichia coli in PECs. However, 24-hr pretreatment with 10 microg of HBP followed by CLP increased phagocytosis in PECs 1.8-fold compared with the control CLP group (p = .04). RECEPTOR EXPRESSION: CD16/CD32w expression in PECs did not change after HBP or CLP. CD11b and CD18 expression in PECs was increased significantly after CLP compared with PECs from non-CLP-challenged animals (p < .05). Pretreatment with 10 microg of HBP did not further enhance CD11b/CD18 expression in PECs. CONCLUSIONS: Recombinant HBP increases survival in murine fecal peritonitis. The mechanisms by which HBP reduces septic death are not fully understood, but they include monocyte chemotaxis and increased phagocytosis of E. coli by PECs. Our data suggest that the inflammatory response induced by CLP is important for the effect of HBP to enhance phagocytosis.

Quantification of phagocytosis in human neutrophils by flow cytometry.

Phagocytosis represents a central element of the host response to microbial invasion. We describe a flow cytometric method for measuring the kinetics of phagocytosis of two bacteria by human polymorphonuclear leukocytes (PMNs). Over a 60-min period, isolated human PMNs were exposed to Staphylococcus aureus (rapidly phagocytosed) and Klebsiella pneumoniae (slowly phagocytosed). This method distinguished adherent from ingested bacteria by quenching fluorescein isothiocyanate-labeled extracellular bacteria with ethidium bromide. This further allowed the exclusion of dead, highly permeable, and subsequently bright-red fluorescent PMNs. Our experiments with two different bacteria, various PMN-to-bacteria ratios (1:1, 1:10, 1:100), and different individuals proved that 1) flow cytometric analysis is accurate and useful for characterizing phagocytosis, 2) adherent bacteria can be distinguished from ingested bacteria after quenching with ethidium bromide, and that 3) phagocytosis kinetics of two bacteria with different onsets of phagocytosis can be determined by flow cytometry and the assessment of a score that quantifies phagocytosis.

Neutrophil sequestration in liver and lung is differentially regulated by C-X-C chemokines during experimental peritonitis.

C-X-C chemokines play an important role in the migration and activation of neutrophils (PMNs) during an inflammatory event. We measured mRNA and protein expression of the murine C-X-C chemokines macrophage inflammatory protein-2 (MIP-2) and KC in the lungs, liver, blood, and peritoneal cavity of Swiss Webster mice after cecal ligation and puncture (CLP). Neutralizing antibodies to MIP-2 and KC were also used to determine the biological effects of these chemokines on neutrophil sequestration and organ injury in the CLP model. The data showed that early after CLP, MIP-2 mRNA and protein were expressed predominantly by the lung, whereas KC mRNA and protein were expressed by the liver. Inhibition of MIP-2 reduced both lung neutrophil sequestration and peritoneal neutrophil migration. Inhibition of KC had no effect on overall neutrophil sequestration in liver but reduced injury as measured by serum transaminases. An early survival benefit was found with anti-KC treatment, although overall survival was not different. Our study showed a differential expression by organs of C-X-C chemokines during sepsis and suggested that such chemokine effects are tissue-specific.

Neutrophils and renal failure.

In many diseases and acute inflammatory disorders, important components of pathological processes are linked to the neutrophils' ability to release a complex assortment of agents that can destroy normal cells and dissolve connective tissue. This review summarizes the mechanisms of tissue destruction by neutrophils and the role of kidney-specific factors that promote this effect. Nicotinamide adenine dinucleotide phosphate H (NADPH) oxidase is a membrane-associated enzyme that generates a family of reactive oxygen intermediates (ROI). There is increasing evidence that ROIs are implicated in glomerular pathophysiology: ROIs contribute to the development of proteinuria, alter glomerular filtration rate, and induce morphological changes in glomerular cells. Specific neutrophil granules contain microbicidal peptides, proteins, and proteolytic enzymes, which mediate the dissolution of extracellular matrix, harm cell structures or cell function, and induce acute and potentially irreparable damage. Although both ROI and neutrophil-derived proteases alone have the potential for tissue destruction, it is their synergism that circumvents the intrinsic barriers designed to protect the host. Even small amounts of ROI can generate hypochlorus acid (HOCl) in the presence of neutrophil-derived myeloperoxidase (MPO) and initiate the deactivation of antiproteases and activation of latent proteases, which lead to tissue damage if not properly controlled. In addition, neutrophil-derived phospholipase products such as leukotrienes and platelet-activating factor contribute to vascular changes in acute inflammation and amplify tissue damage. Increasing evidence suggests that mesangial cells and neutrophils release chemotactic substances (eg, interleukin 8), which further promote neutrophil migration to the kidney, activate neutrophils, and increase glomerular injury. Also, the expression of adhesion molecules (eg, intercellular adhesion molecule 1 on kidney-specific cells and beta-2-integrins on leukocytes) has been correlated with the degree of injury in various forms of glomerulonephritis or after ischemia and reperfusion. Together, these results suggest that neutrophils and adhesion molecules play an important role in mediating tissue injury with subsequent renal failure. Conversely, chronic renal failure reduces neutrophil function and thereby can increase susceptibility to infection and sepsis.

Regulation of early peritoneal neutrophil migration by macrophage inflammatory protein-2 and mast cells in experimental peritonitis.

Neutrophil (PMN) migration into the peritoneal cavity in response to fecal peritonitis is an important mechanism of host defense against bacterial invasion. We show that the murine C-X-C (PMN-specific) chemokine, macrophage inflammatory protein-2 (MIP-2), on intraperitoneal injection in mice, causes PMN migration into the peritoneum. MIP-2 mRNA and protein were expressed by peritoneal leukocytes after cecal ligation and puncture (CLP) in mice and neutralization of MIP-2 reduced peritoneal PMN migration. A prerequisite for neutrophil-endothelial adhesion and subsequent migration from the circulation is selectin-mediated rolling. Pretreatment of mice with an anti-P-selectin antibody before intraperitoneal injection of MIP-2 significantly reduced peritoneal PMN migration. However, there are no reports that a C-X-C chemokine can up-regulate endothelial selectins. We postulated that MIP-2, when injected intraperitoneally, interacts with a cell that is known to release factors that up-regulate endothelial selectins. A likely candidate is the mast cell, which contains histamine and tumor necrosis factor alpha (TNF-alpha), and both of these factors induce selectins. Intraperitoneally injected MIP-2 caused an early significant increase in peritoneal TNF-alpha, whereas histamine levels were unaffected. In a subsequent experiment, mast cell-deficient mice and their normal controls were then injected intraperitoneally with MIP-2 or underwent CLP. Significantly fewer PMNs migrated into the peritoneal cavity in the mast cell-deficient mice after MIP-2 injection or CLP. Thus, our findings indicate that mast cells and MIP-2 are necessary for PMN migration into the peritoneum in response to intra-abdominal infection, and that MIP-2 appears to facilitate this through an increase in TNF-alpha release.

Neutrophil migration into the peritoneum is P-selectin dependent, but sequestration in lungs is selectin independent during peritonitis.

Neutrophil (PMN) influx into the peritoneal cavity in response to bacterial peritonitis is an indispensable aspect of host defense. PMNs also are responsible for the remote organ injury observed after major abdominal infection. The aim of this study was to examine the effect of selectin blockade on PMN migration into the peritoneum and on PMN sequestration in the lungs, early in the course of peritonitis. Cecal ligation and puncture (CLP) was performed on P-selectin-deficient (P-def) mice and their genetic controls (C57). Both groups were treated with anti-E-selectin antibody, anti-L-selectin, or isotypic control immunoglobulin G at the time of CLP. 6 h after CLP, mice were sacrificed. Peritoneal PMN migration decreased in P-def mice compared with C57 controls after CLP. Blockade of E- or L-selectin alone in controls did not alter peritoneal PMN influx or circulating PMNs after CLP. In the P-def mice, treatment with anti-E-antibody or anti-L-antibody nearly eliminated PMN influx into the peritoneum. In contrast, circulating PMNs markedly increased after CLP in P-def mice when compared with baseline values. Lung myeloperoxidase increased in all groups of mice following CLP. Blockade of P-selectin with anti-P-selectin antibody elicited a response similar to that observed in the P-def mice. In conclusion, P-selectin mediates PMN influx into the peritoneal cavity, while E- and L-selectins do not appear to play any significant role in the 6 h time period following CLP. Lung PMN sequestration, after CLP, occurred independent of P-, E-, or L-selectin expression. Blockade of P-selectin during peritonitis appears to be potentially deleterious by preventing early PMN influx into the compartment containing the septic focus.