Alpha-defensin as a diagnostic tool in revision total knee arthroplasties with unexpected positive intraoperative cultures and unexpected culture negative intraoperative cultures.

PURPOSE: Unexpected-positive-intraoperative-cultures (UPIC) are common in presumed aseptic revision-total-knee-arthroplasties (rTKA). However, the clinical significance is not entirely clear. In contrast, in some presumably septic rTKA, identification of an underlying pathogen was not possible, so-called unexpected-negative-intraoperative-cultures (UNIC). The purpose of this study was to evaluate the potential use of synovial alpha-defensin (AD) levels in these patients. METHODS: Synovial AD levels from 143 rTKAs were evaluated retrospectively from our prospectively maintained institutional periprostetic joint infection (PJI) biobank and database. The 2018-International Consensus Meeting (ICM) criteria was used to define the study groups. Samples from UPICs with a minimum of one positive intraoperative culture (ICM 2- ≥ 6) (n = 20) and UNIC's (ICM ≥ 6) (n = 14) were compared to 34 septic culture-positive samples (ICM ≥ 6) and 75 aseptic culture-negative (ICM 0-1). Moreover, AD-lateral-flow-assay (ADLF) and an enzyme-linked-immunosorbent-assay (ELISA) in detecting the presence of AD in native and centrifuged synovial fluid specimens was performed. Concentration of AD determined by ELISA and ADLF methods, as well as microbiological, and histopathological results, serum and synovial parameters along with demographic factors were analysed. RESULTS: AD was positive in 31/34 (91.2%) samples from the septic culture-positive group and in 14/14 (100%) samples in the UNIC group. All UPIC samples showed a negative AD result. Positive AD samples were highly associated with culture positive and histopathological results (p < 0.001). No high-virulent microorganisms (0/20) were present in the UPIC group, compared to infected-group (19/34; 55.9%). High virulent microorganisms showed a positive AD result in 89.5% (17/19) of the cases. Methicillin resistant Staphylococcus epidermis (MRSE) infections had significantly higher AD levels than with methicillin susceptible S. epidermdis (MSSE) (p = 0.003). ELISA and ADLF tests were positive with centrifuged (8/8) and native (8/8) synovial fluid. CONCLUSION: AD showed a solid diagnostic performance in infected and non-infected revisions, and it provided an additional value in the diagnosis of UPIC and UNIC associated to rTKAs. Pathogen virulence as well as antibiotic resistance pattern may have an effect on AD levels. Centrifugation of synovial fluid had no influence on ADLF results.

It is not NOD2 - genetic and clinical risk factors for postoperative complications following ileocolic resection in Crohn's disease.

PURPOSE: To evaluate the role of the nucleotide oligomerization domain 2 (NOD2) mutation status and other risk factors for the incidence of postoperative complications after ileocolic resection for Crohn's disease (CD). METHODS: Data of 138 patients consecutively undergoing ileocolic resection for CD at a tertiary academic referral center were retrospectively analyzed including single nucleotide polymorphism (SNP) data of the NOD2 gene. Uni- and multivariate regression analysis was performed to identify factors associated with increased risk of severe postoperative complications. RESULTS: From 114 patients (83%), the NOD2 mutation status was available. Of these, 60 (53%) had a NOD2 wildtype, whereas eleven (10%) were homozygous for the high risk p.Leu1007fsX1008 (rs2066847) variant. Major postoperative complications occurred in 28 patients (20%). Twenty-seven of these (96%) were intraabdominal septic complications such as anastomotic leakage or abscess. Male gender (P = 0.029; OR 3.052, the duration of CD (time [months] from initial diagnosis of CD to surgery; P = 0.001; OR 1.009), previous abdominal surgery for CD (P = 0.017; OR 3.49), and the presence of enteric fistulas (P = 0.023; OR 3.21) were identified as independent risk factors for major postoperative complications. Homozygosity for the NOD2 high-risk variant p.Leu1007fsX1008 did not show increased postoperative morbidity in the short and long-term outcome. CONCLUSIONS: We could detect independent risk factors for major postoperative complications after ileocolic resection for Crohn's disease. However, patients with the high-risk variant p.Leu1007fsX1008 of the NOD2 gene did not show increased postoperative morbidity.

Time-Dependent Alterations of Gut Wall Integrity in Small Bowel Obstruction in Mice.

BACKGROUND: Small bowel obstruction (SBO) is one of the most common disorders in surgical emergency departments. Without resolution of the obstructed bowel segments, patients may develop multiorgan failure. The aim of this study was to investigate whether morphological damage of the intestinal wall during SBO may lead to molecular translocation and how this may impair intestinal motility. METHODS: C57Bl6 mice were laparotomized, and the small intestine was ligated 5 cm oral to the coecum for SBO. Controls received minilaparotomy only. Animals were sacrificed 3 h, 9 h, and 24 h after SBO. Morphological changes were evaluated on hematoxylin and eosin histology by a standardized score. Intestinal motility was determined by recording intraluminal pressure of the small intestine in vitro. Permeability was measured by fluorospectroscopy and ELISA of blood samples after oral gavage with fluorescein isothiocyanate (FITC)-dextrane and horse radish peroxidase. Data are mean ± SD. RESULTS: Three hours after SBO, FITC-dextrane uptake was increased to 187.6 ± 15.2 ng/mL compared to controls (P = 0.011). At 9 h, uptake of horse radish peroxidase (23.0 ± 8.6 ng/mL, 9.0 ± 6.3 ng/mL, P = 0.039) and FITC-dextrane (86.8 ± 17.8 ng/mL, 62.0 ± 1.6 ng/mL, P = 0.029) was higher compared to controls. Motility was increased to 162.2 ± 20.2 area under the curve (AUC) compared to 121.3 ± 20.3 AUC in controls, P = 0.009 and an increased histology score was observed at 9 h (3.2 ± 1.8 versus 0.6 ± 0.7, P = 0.003). Twenty-four hours after SBO, histology score was 3.8 ± 1.7, which was higher than 0.9 ± 0.7 in controls (P = 0.001). Intestinal motility was decreased 24 h after SBO compared to sham controls (146.0 ± 21.4 AUC versus 198.9 ± 21.2 AUC, P = 0.003). CONCLUSIONS: SBO entails a time dependent epithelial damage to the mucosa. In parallel, molecular changes in the gut mucosal barrier occur as early as 3 h after the onset of SBO with a subsequent increase in permeability. Initial intestinal hypermotility is followed by a decrease in motility.

Dual-energy CT and ceramic or titanium prostheses material reduce CT artifacts and provide superior image quality of total knee arthroplasty.

PURPOSE: To evaluate the influence of different scan parameters for single-energy CT and dual-energy CT, as well as the impact of different material used in a TKA prosthesis on image quality and the extent of metal artifacts. METHODS: Eight pairs of TKA prostheses from different vendors were examined in a phantom set-up. Each pair consisted of a conventional CoCr prosthesis and the corresponding anti-allergic prosthesis (full titanium, ceramic, or ceramic-coated) from the same vendor. Nine different (seven dual-energy CT and two single-energy CT) scan protocols with different characteristics were used to determine the most suitable CT protocol for TKA imaging. Quantitative image analysis included assessment of blooming artifacts (metal implants appear thicker on CT than they are, given as virtual growth in mm in this paper) and streak artifacts (thick dark lines around metal). Qualitative image analysis was used to investigate the bone-prosthesis interface. RESULTS: The full titanium prosthesis and full ceramic knee showed significantly fewer blooming artifacts compared to the standard CoCr prosthesis (mean virtual growth 0.6-2.2 mm compared to 2.9-4.6 mm, p < 0.001). Dual-energy CT protocols showed less blooming (range 3.3-3.8 mm) compared to single-energy protocols (4.6-5.5 mm). The full titanium and full ceramic prostheses showed significantly fewer streak artifacts (mean standard deviation 77-86 Hounsfield unit (HU)) compared to the standard CoCr prosthesis (277-334 HU, p < 0.001). All dual-energy CT protocols had fewer metal streak artifacts (215-296 HU compared to single-energy CT protocols (392-497 HU)). Full titanium and ceramic prostheses were ranked superior with regard to the image quality at the bone/prosthesis interface compared to a standard CoCr prosthesis, and all dual-energy CT protocols were ranked better than single-energy protocols. CONCLUSIONS: Dual-energy CT and ceramic or titanium prostheses reduce CT artifacts and provide superior image quality of total knee arthroplasty at the bone/prosthesis interface. These findings support the use of dual-energy CT as a solid imaging base for clinical decision-making and the use of full-titanium or ceramic prostheses to allow for better CT visualization of the bone-prosthesis interface.

Long-term Quality of Life of Patients With Permanent End Ileostomy: Results of a Nationwide Cross-Sectional Survey.

BACKGROUND: Patients with permanent end ileostomy are at high risk for detrimental stomal effects on their quality of life. However, little is known about the long-term quality of life of these patients. OBJECTIVE: The purpose of this study was to assess long-term quality of life in patients with permanent end ileostomy. DATA SOURCES: Registration at the German self-help organization ILCO was used for this study. STUDY SELECTION: Selection included a cross-sectional survey of 1434 patients with permanent end ileostomy. MAIN OUTCOME MEASURES: Quality of life was assessed using the Medical Outcomes Study Short Form 36, including physical and mental component summary scores, the Gastrointestinal Quality of Life Index, and the Cleveland Global Quality of Life Index. Multivariate risk factor analysis was performed. RESULTS: A total of 783 responders were included. Indications for ileostomy included ulcerative colitis (44%), Crohn's disease (38%), and colorectal cancer (7%). Adverse effects on daily life because of stoma were reported by 72% of participants. Quality of life was significantly impaired compared with the general population on all of the summary scores and several subscales (physical component summary: 44.6 ± 10.4 (mean ± SD) vs 50.2 ± 10.2, p < 0.001; mental component summary: 47.5 ± 10.7 vs 51.5 ± 10.2, p < 0.001; Gastrointestinal Quality of Life Index: 94.4 ± 16.4 vs 126.0, p < 0.001). Stoma care problems affecting quality of life were reported by 63% of respondents. These included parastomal hernia (p < 0.001), stenosis (p = 0.003), and prolapse (p = 0.008). Vitamin B12, iron, and zinc deficiencies were also associated with diminished quality of life; in particular, vitamin B12 deficiency was associated with reduced mental and emotional quality of life. LIMITATIONS: Not all patients undergoing ileostomy in Germany are registered at ILCO, and there were many nonresponders. In addition, the inherent limitations of cross-sectional studies should be considered, including the response-shift phenomenon. CONCLUSIONS: Quality of life was markedly impaired in patients with permanent end ileostomy as compared with the general population. The main reasons were stoma-associated morbidity and nutritional deficiency syndromes. These findings highlight the importance of prevention, screening, and adequate treatment.

Intraoperative Diagnosis of Periprosthetic Joint Infection Using a Novel Alpha-Defensin Lateral Flow Assay.

BACKGROUND: The present study investigates the novel Synovasure periprosthetic joint infection (PJI) lateral flow test device for detection of alpha-defensin and attempts to determine its diagnostic accuracy for the intraoperative diagnosis of PJI and compares it to frozen section. METHODS: Forty consecutive patients, who underwent revision surgery, between September 2014 and September 2015 were included. The patients underwent 29 revision total knee arthroplasties and 11 revision total hip arthroplasties. Twelve patients had a confirmed PJI based on Musculoskeletal Infection Society criteria, and 28 patients were considered aseptic. RESULTS: The overall accuracy to detect PJI using the lateral flow assay was 85% (95% CI 70%-93%). The device has a positive predictive value of 80% (95% CI 44%-96%) and a negative predictive value of 87% (95% CI 68%-96%) and showed a sensitivity of 67% (95% CI 35%-89%) and specificity of 93% (95% CI 75%-99%). Frozen section had a lower sensitivity (58% [95% CI 29%-84%]) but a higher specificity (96% [95% CI 80%-100%]). Receiver operator curve analysis demonstrates an area under the curve of the Synovasure PJI Lateral Flow Test Kit and frozen section of 0.80 and 0.77, respectively. CONCLUSION: The present study suggests that the intraoperative lateral flow test is at least equivalent to intraoperative frozen section and is a useful tool to confirm the absence of PJI. Although the clinical results are promising, they are not as good as previous studies using alpha-defensin levels measured in a laboratory.

Impact of perioperative allogeneic red blood cell transfusion on recurrence and overall survival after resection of colorectal liver metastases.

BACKGROUND: Perioperative allogeneic red blood cell transfusion has been conclusively shown to be associated with adverse oncologic outcomes after resection of nonmetastatic colorectal adenocarcinoma. OBJECTIVE: The aim of the study was to identify risk factors for a perioperative transfusion and to assess the effects of transfusion on survival after curative-intended resection of hepatic metastases in patients featuring stage IV colorectal cancer. DESIGN: This was an observational study with a retrospective analysis of a prospective data collection. SETTING: The study was conducted at a tertiary care center. PATIENTS: A total of 292 patients undergoing curative-intended liver resection for colorectal liver metastases were included in the study. MAIN OUTCOME MEASURES: Univariate and multivariate analyses were performed identifying factors influencing transfusion, recurrence-free survival, and overall survival. RESULTS: A total of 106 patients (36%) received allogeneic red blood cells. Female sex (p = 0.00004), preoperative anemia (p = 0.001), major intraoperative blood loss (p < 0.00001), and major postoperative complications (p = 0.02) were independently associated with the necessity of transfusion. Median recurrence-free and overall survival were 58 months. Allogeneic red blood cell transfusion was significantly associated with reduced recurrence-free survival (32 vs 72 months; p = 0.008). It was reduced further by administration of >2 units (27 months; p = 0.02). Overall survival was not significantly influenced by transfusion (48 vs 63 months; p = 0.08). When multivariately adjusted for major intraoperative blood loss and factors univariately associated, namely comorbidities, tumor load, and positive resection margins, transfusion was an independent predictor for reduced recurrence-free survival (p = 0.03). LIMITATIONS: These include the retrospective and observational design, as well as the impossibility to prove causality of the association between transfusion and poor outcome. CONCLUSIONS: In patients undergoing liver resection for colorectal liver metastases, perioperative transfusion is independently associated with earlier disease recurrence. This emphasizes appropriate blood management measures, including the conservative correction of preoperative anemia, the use of low transfusion triggers, and the minimization of intraoperative blood loss.

Quality of life after proctocolectomy and ileal pouch-anal anastomosis in patients with ulcerative colitis.

PURPOSE: While ileal pouch-anal anastomosis is performed in many patients with ulcerative colitis, conflicting data exist about its effects on quality of life. We aimed to determine quality of life and to identify risk factors for impaired quality of life in these patients. METHODS: Forty-eight of 82 patients (59%; median follow-up 57 months [range 21-93 months]) after ileal pouch-anal anastomosis for ulcerative colitis were compared to 48 matched healthy controls. Generic, health-, and disease-related, as well as symptom-specific quality of life was analyzed using five well-established quality of life instruments. RESULTS: Although generic quality of life was comparable between groups, health-related quality of life was impaired after ileal pouch-anal anastomosis. While high stool frequency was associated with impaired health-related and disease-specific quality of life, fecal incontinence and history of pouchitis also caused a deterioration of generic and symptom-related quality of life. Seventy-seven percent of patients reported their quality of life to be better compared to the situation before surgery and 88% would undergo ileal pouch-anal anastomosis again. CONCLUSIONS: Overall quality of life after ileal pouch-anal anastomosis is good. However, high stool frequency, fecal incontinence, and pouchitis are associated with impaired quality of life and should be prevented or treated to the best possible extent.

Long-term quality of life and sexual and urinary function after abdominoperineal resection for distal rectal cancer.

BACKGROUND: Permanent colostomy, pelvic dissection, and radiotherapy after abdominoperineal resection can put quality of life and sexual and urinary function at risk; however, there are limited data using validated instruments on patients undergoing abdominoperineal resection regarding these outcome measures. OBJECTIVE: We evaluated the quality of life and the sexual and urinary function of patients undergoing abdominoperineal resection for rectal cancer and compared the outcomes of patients who received and did not receive pre- or postoperative pelvic radiotherapy. METHODS: European Organization for Research and Treatment of Cancer Quality of Life Questionnaires C30 and CR38, International Consultation on Incontinence Questionnaire, American Urological Association Symptom Index, Brief Sexual Function Inventory for men, and sexual function module of the Cancer Rehabilitation Evaluation System for women were mailed to 219 patients who underwent abdominoperineal resection between 1994 and 2004. RESULTS: One-hundred forty-three patients responded (response rate, 65%), of whom 55 (38%) were treated with surgery alone and 88 (62%) received pelvic radiotherapy. Generic and disease-specific quality of life and sexual and urinary function were similar between patients not receiving and receiving pelvic radiotherapy. However, a proportion of patients experienced adverse quality of life after surgery, and this was associated with a younger age, male sex, and sexual inactivity. In sexually active men, sexual function after abdominoperineal resection was diminished compared with population-based controls. LIMITATIONS: This study was limited by the lack of baseline data and cross-sectional nature of survey. CONCLUSIONS: Quality of life and sexual function can be impaired after abdominoperineal resection, although the impact of pelvic radiotherapy appears to be limited. Indication and timing of radiotherapy should be based on oncological indications, but quality of life and functional outcomes should be considered when counseling patients.

Hydrogen sulfide modulates contractile function in rat jejunum.

BACKGROUND: Effects of hydrogen sulfide (H(2)S), a third gasotransmitter of the gut, are not well understood. The aim of this study was to determine effects/mechanisms of H(2)S action on contractile function in rat jejunal muscle. METHODS: Transmural strips of longitudinal muscle were evaluated. Response to sodium hydrosulfide (NaHS, H(2)S donor; 10(-5)-10(-3)M) was studied on spontaneous contractile activity and after precontraction (bethanechol, 3 × 10(-6)M). Atropine, propranolol, phentolamine, tetrodotoxin, capsaicin, L-N(G)-nitro arginine (L-NNA), and glibenclamide were used to determine mechanisms. L-cysteine (10(-4)-10(-2)M; substrate for H(2)S production) and aminooxyacetic acid and DL-propargylglycine (inhibitors of enzymes generating H(2)S endogenously) were used to study endogenous production. Aminooxyacetic acid, DL-propargylglycine, L-NNA, and vasoactive intestinal polypeptide (VIP) antagonist [D-p-Cl-Phe(6),Leu(17)]-VIP were used to study H(2)S release during electrical field stimulation (EFS) and interaction with VIP and nitric oxide. Immunohistofluorescence of jejunal whole mounts was performed for endogenous H(2)S-producing enzymes. RESULTS: Cystathionine-ß-synthase and cystathionine-γ-lyase were expressed only in myenteric plexus. NaHS suppressed spontaneous and stimulated contractile activity (P < 0.01). Glibenclamide prevented some suppression by NaHS (P = 0.01) of stimulated contractile activity but did not prevent suppression of spontaneous contractile activity. Other drugs had no effect on spontaneous contractile activity but increased inhibitory effects of NaHS on spontaneous and stimulated contractile activity (P < 0.05). L-cysteine had no effects on contractile activity. Inhibitors altered basal and stimulated activity suggesting endogenous release of H(2)S. CONCLUSIONS: H(2)S presumably suppresses contractile activity in jejunum by direct effects on smooth muscle. Mechanism(s) of inhibition remains unclear, because blocking known neurotransmitters enhanced H(2)S-induced suppression, while blocking adenosine triphosphate (ATP)-sensitive K(+)-channels did not block H(2)S-induced inhibition.

The role of vagal innervation on the early development of postoperative ileus in mice.

BACKGROUND: Postoperative ileus (POI) involves an intestinal inflammatory response that is modulated by afferent and efferent vagal activation. We aimed to identify the potential influence of the vagus nerve on POI by tracking central vagal activation and its role for peripheral inflammatory changes during the early hours after surgery. METHODS: C57BL6 mice were vagotomized (V) 3-4 days prior to experiments, while control animals received sham vagotomy (SV). Subgroups underwent either laparotomy (sham operation; S-POI) or laparotomy followed by standardized small bowel manipulation to induce postoperative ileus (POI). Three hours and 9 h later, respectively, a jejunal segment was harvested and infiltration of inflammatory cells in intestinal muscularis was evaluated by fluorescein isothiocyanate (FITC) avidin and myeloperoxidase (MPO) staining. Moreover, the brain stem was harvested, and central nervous activation was investigated by Fos immunochemistry in both the nucleus of the solitary tract (NTS) and the area postrema (AP). Data are presented as mean ± SEM, and a p < 0.05 was considered statistically significant. KEY RESULTS: Three hour experiments revealed no significant differences between all experimental groups, except MPO staining: 3 h after abdominal surgery, there were significantly more MPO-positive cells in vagotomized S-POI animals compared to sham-vagotomized S-POI animals (26.7 ± 7.1 vs. 5.1 ± 2.4, p < 0.01). Nine hour postoperatively intramuscular mast cells (IMMC) were significantly decreased in the intestinal muscularis of V/POI animals compared to SV/POI animals (1.5 ± 0.3 vs. 5.9 ± 0.2, p < 0.05), while MPO-positive cells were increased in V/POI animals compared to SV/POI animals (713.2 ± 99.4 vs. 46.9 ± 5.8, p < 0.05). There were less Fos-positive cells in the NTS of V/POI animals compared to SV/POI animals (64.7 ± 7.8 vs. 132.8 ± 23.9, p < 0.05) and more Fos-positive cells in the AP of V/POI animals compared to SV/POI animals 9 h postoperatively (38.0 ± 2.0 vs. 13.7 ± 0.9, p < 0.001). CONCLUSIONS AND INTERFERENCES: Afferent nerve signaling to the central nervous system during the development of early POI seems to be mediated mainly via the vagus nerve and to a lesser degree via systemic circulation. During the early hours of POI, the intestinal immune response may be attenuated by vagal modulation, suggesting interactions between the central nervous system and the intestine.

Co-morbidity and postsurgical outcome in patients with perforated sigmoid diverticulitis.

INTRODUCTION: It was previously reported that in patients with acute perforated diverticulitis with Hinchey categories I to III sigmoidectomy with primary anastomosis (PA) is superior to Hartmann's procedure (HP) as later closure of colostomy involves substantial morbidity. We evaluated our experience with PA for patients with perforated diverticulitis over a 10-year period and aimed to investigate whether Hinchey category or co-morbidity are more relevant for postoperative outcome. METHODS: Records of all patients treated at our institution for sigmoid diverticulitis between 1996 and 2006 were retrieved from an in-hospital database (N = 787, median age 66 years, range 30 to 94, female:male ratio 1.3:1); 73 patients who underwent immediate emergency surgery for perforated diverticulitis were included in this study. American Society of Anesthesiology (ASA) classification to gauge co-morbidity and Hinchey category for intraoperative extent of inflammation were evaluated as regards their relevance for postoperative mortality and major complications. RESULTS: 47 patients (64%) underwent sigmoid colectomy and PA, which was combined with loop ileostomy in 11 patients (15%). Sigmoid colectomy and HP was performed in 26 patients (36%). Major postoperative complications occurred in 26 patients (36%). In the PA group, 10 of 47 patients (21%) had anastomotic leakage. Three leakages occurred despite a loop ileostomy. Anastomotic leakage was independent of Hinchey category (Hinchey I: three patients, Hinchey II: four patients, Hinchey III: three patients, n.s.), but associated with co-morbidity (one patient ASA II, six patients ASA III, three patients ASA IV, P < 0.05). Total mortality was 12%. Seven patients died after HP and two patients after PA. No mortality was observed in PA patients with loop ileostomy. CONCLUSIONS: Emergency surgery for perforated sigmoid diverticulitis is associated with high morbidity and mortality rates. Anastomotic leakage was associated with patient co-morbidity rather than with intraoperative Hinchey category, suggesting that the decision to perform PA should better be based on patient's general condition rather than on intraoperative extent of inflammation.

Role of the vagus nerve on the development of postoperative ileus.

INTRODUCTION: Postoperative ileus involves reflex inhibition of intestinal motility within hours after surgery and a subsequent intestinal inflammatory response that is characterized by efferent vagal modulation via acetylcholine receptors on intestinal macrophages. We aimed to characterize the role of vagal modulation of intestinal motility during the early hours after surgery. METHODS: C57BL6 mice underwent laparotomy and standardized small bowel manipulation to induce postoperative ileus. Subgroups were vagotomized 3-4 days prior to experiments or received pharmacological inhibition of the acetylcholine alpha7 subunit with the inhibitor alpha-bungarotoxin, while control animals were sham operated and remained otherwise untreated. Three hours later, a 2-cm jejunal segment was harvested with the mesentery attached. Mesenteric afferent nerve recordings were established in an organ bath generating a multiunit signal with subsequent computerized analysis. Intraluminal pressure was continuously recorded to assess intestinal motility. Afferent nerve responses were quantified at baseline and to chemical stimulation with bradykinin (0.5 microM) or serotonin (5-HT; 500 microM) and following mechanical stimulation by continuous ramp distension to 60 mmHg. RESULTS: Peak amplitudes of intestinal motility and afferent nerve discharge at baseline were not different following chronic vagotomy, alpha-bungarotoxin or sham operation. Maximum afferent discharge to 5-HT following alpha-bungarotoxin was comparable to sham controls, while the response was reduced in chronically vagotomized animals (p < 0.05). Maximum afferent nerve discharge to bradykinin and peak firing during maximum distension at 60 mmHg was similar in the different subgroups. At luminal distension from 10 to 30 mmHg, afferent discharge was lower in vagotomized animals compared to sham controls (p < 0.05) but unchanged after alpha-bungarotoxin. CONCLUSIONS: Sensitivity to low-threshold distension and 5-HT is mediated via vagal afferents during postoperative ileus, while sensitivity to high-threshold distension and bradykinin is independent of vagal afferent innervation. Early inhibition of intestinal motility at 3 h after onset of postoperative ileus does not appear to depend on vagal innervation.

Differential sensitization of afferent neuronal pathways during postoperative ileus in the mouse jejunum.

BACKGROUND: Postoperative ileus induces reflex inhibition of gastrointestinal motility and an intestinal inflammatory response. We aimed to determine whether afferent sensitivity is increased during postoperative ileus and whether alterations are cyclooxygenase-2 (COX-2)-dependent. METHODS: C57BL/6 mice underwent laparotomy followed by standardized small bowel manipulation to induce ileus or sham treatment. After 24 hours, extracellular multiunit mesenteric afferent nerve discharge was recorded in vitro from 2-cm segments of jejunum. Fos immunoreactivity was determined for neuronal activation in the vagal nucleus of the solitary tract (nTS) of the brain stem and leukocyte infiltration in the intestinal muscularis by myeloperoxidase stains. RESULTS: Serosal bradykinin (1 microM) was followed by an increase in afferent discharge to 65 +/- 5 imp x s(-1) in ileus segments compared with 37 +/- 6 imp x s(-1) in sham controls (P < 0.05). The response was attenuated to 31 +/- 7 imp x s(-1) after the selective COX-2 inhibitor 5,5-dimethyl-3-(flurorophenyl)-4-(4-methylsulfonyl) phenyl-2(5H)-furanone (DFU) in ileus segments. Afferent firing during ileus was augmented at luminal distension at 20 mm Hg but not at pressures up to 60 mm Hg. The number of Fos-positive neurons in the nTS was 110 +/- 45 during ileus compared with 7 +/- 4 in sham controls (-7.32 mm from bregma, P < 0.05) and did not differ after DFU. The intestinal muscularis contained more leukocytes during ileus compared with ileus segments after DFU and controls (both P < 0.05). CONCLUSION: This study provides direct evidence from afferent nerve recordings that sensitivity to bradykinin, which stimulates predominantly spinal afferents, is augmented during postoperative ileus involving a COX-2 pathway. Vagal afferents were also sensitized because low-threshold mechanosensitivity and neuronal activation in the nTS were increased.

Postoperative complications have little influence on long-term quality of life in Crohn's patients.

PURPOSE: The purpose of the study was to determine the influence of postoperative complications on long-term quality of life in patients after abdominal operations for Crohn's disease. MATERIALS AND METHODS: From 1996 to 2002, 305 Crohn's patients underwent abdominal surgery, and 66 patients developed postoperative complications. Quality of life was studied using a standardized questionnaire and four quality of life instruments. Sixty-six Crohn's patients with uneventful postoperative course matched for age, and follow-up time served as controls. RESULTS: Forty-eight patients (81%) in the complication group (32 major and 16 minor) and 43 patients (75%) in the control group answered the questionnaire. Postoperative follow-up time was 42 (10-94) and 41 months (13-94; median (range)). Quality of life was comparable between groups, except on the subscale "physical functioning" of the Short-form 36 on which patients with minor and major complications showed impaired quality of life compared to controls (67+/-6, 69+/-4, and 84+/-2%; mean+/-standard error of the mean; both p<0.05 vs controls). The incidence of Crohn's disease-related symptoms at follow-up was unaffected by complications (minor 63%, major 56% vs controls 70%; both not significant). CONCLUSION: Postoperative complications after abdominal operations for Crohn's disease do not impair long-term quality of life in general but may affect specific dimensions of quality of life like patients' physical function.

Long-term quality-of-life after open and laparoscopic sigmoid colectomy.

PURPOSE: Laparoscopic sigmoid colectomy (LSC) is frequently performed for sigmoid diseases with excellent prognosis. We aimed to determine the long-term quality-of-life after open sigmoid colectomy (OSC) compared with LSC. METHODS: Thirty-nine patients were investigated 40.5+/-2.8 months (mean+/-SEM) after LSC. Each LSC patient was matched to a patient after OSC. Patients were interviewed by telephone and the Eypasch quality-of-life questionnaire was answered by mail. RESULTS: LSC entailed fewer minor complications (P=0.0003) and 97% of the patients were satisfied with the cosmetic result, which was more compared with 63% after OSC (P=0.001). Patients suffering from recurrent diverticulitis had a similar quality-of-life index after LSC and OSC (P=0.945). A minor trend was observed in patients with early-staged colorectal neoplasia in favor of LSC (113.6+/-3.3 vs. 106.0+/-4.2; P=0.21, mean+/-SEM). CONCLUSIONS: LSC is superior concerning minor complications and cosmesis, whereas quality-of-life is similar in the long term.

Long-term effects of extrinsic denervation on VIP and substance P innervation in circular muscle of rat jejunum.

Intestinal denervation contributes to enteric motor dysfunction after small bowel transplantation (SBT). Our aim was to determine long-term effects of extrinsic denervation on function of nonadrenergic, noncholinergic innervation with substance P and vasoactive intestinal polypeptide (VIP). Contractile activity of jejunal circular muscle strips from six age-matched, naive control rats (NC) and eight rats 1 year after syngeneic SBT was studied in tissue chambers. Spontaneous contractile activity did not differ between groups. Exogenous VIP inhibited contractile activity dose-dependently to a comparable degree in both groups. The VIP antagonist ([D-p-Cl-Phe(6),Leu(17)]-VIP) and the nitric oxide synthase inhibitor L-NG-nitro-arginine did not affect VIP-induced inhibition but increased contractile activity during electrical field stimulation (EFS) in both groups. Exogenous substance P increased contractile activity dose-dependently, greater in NC than SBT. The substance P antagonist ([D-Pro(2),D-Trp(7,9)]-substance P) inhibited effects of exogenous substance P and decreased the excitatory EFS response. Immunohistofluorescence showed tyrosine hydroxylase staining after SBT indicating sympathetic reinnervation. In jejunal circular muscle after chronic denervation, response to exogenous substance P, but not VIP, is decreased, whereas endogenous release of both neurotransmitters is preserved. Alterations in balance of excitatory and inhibitory pathways occur despite extrinsic reinnervation and might contribute to enteric motor dysfunction after SBT.

Enteral immunonutrition during sepsis prevents pulmonary dysfunction in a rat model.

BACKGROUND: Sepsis often results in severe pulmonary dysfunction. Via the thoracic duct, the lung is the first organ exposed to gut-derived inflammatory mediators released into mesenteric lymph during sepsis. AIM: To investigate whether an enteral immunonutrition during sepsis improves pulmonary function. METHODS: Mesenteric lymph was obtained from lymph fistula donor rats after intra peritoneal (i.p.) saline (control lymph) or lipopolysaccharide (sepsis lymph) injection. Sepsis lymph was also collected during enteral immunonutrition with omega-3 enriched, long-chain fatty acids (SMOF lipid). Control, sepsis, or sepsis-SMOF lymph was reinfused into the jugular vein of separate recipient rats. The lungs were then harvested, stained with hematoxylin-eosin, and analyzed for: (1) perpendicular parenchyma thickness of the alveolar wall; (2) myeloperoxidase-positive cells; and (3) terminal deoxynucleotidyl transferase Biotin-dUTP nick end labeling (TUNEL)-positive cells. RESULTS: Enteral immunonutrition during sepsis reduced the release of TNFalpha into mesenteric lymph by about 4.5-fold within the first 2 h. Infusion of sepsis lymph into recipient rats induced thickening of alveolar walls, inflammatory reaction, and apoptosis. Infusion of sepsis lymph obtained during enteral immunonutrition did not cause anatomical changes, induced only a mild inflammatory reaction, and prevented apoptosis in the lungs of recipient rats. CONCLUSIONS: Mediators in sepsis lymph induce pulmonary dysfunction such as an increased distance for oxygen transport, inflammatory reaction, and apoptosis. The lung may be protected by an enteral immunonutrition containing long-chain fatty acids.

Extrinsic intestinal denervation modulates tumor development in the small intestine of Apc(Min/+) mice.

BACKGROUND: Innervation interacts with enteric immune responses. Chronic intestinal inflammation is associated with increased risk of colorectal cancer. We aimed to study potential extrinsic neuronal modulation of intestinal tumor development in a mouse model. METHODS: Experiments were performed with male Apc(Min/+) or wild type mice (4 weeks old, body weight approximately 20 g). Subgroups with subdiaphragmatic vagotomy (apcV/wtV), sympathetic denervation of the small intestine (apcS/wtS) or sham operated controls (apcC/wtC) were investigated (n = 6-14 per group). Three months after surgical manipulation, 10 cm of terminal ileum were excised, fixed for 48 h in 4% paraformaldehyde and all tumors were counted and their area determined in mm(2) (mean ± standard error of the mean (SEM)). Whole mounts of the muscularis of terminal ileum and duodenum (internal positive control) were also stained for tyrosine hydroxylase to confirm successful sympathetic denervation. RESULTS: Tumor count in Apc(Min/+) mice was 62 ± 8 (apcC), 46 ± 11 (apcV) and 54 ± 8 (apcS) which was increased compared to wildtype controls with 4 ± 0.5 (wtC), 5 ± 0.5 (wtV) and 5 ± 0.6 (wtS; all p < 0.05). For Apc(Min/+) groups, vagotomized animals showed a trend towards decreased tumor counts compared to sham operated Apc(Min/+) controls while sympathetic denervation was similar to sham Apc(Min/+). Area covered by tumors in Apc(Min/+) mice was 55 ± 10 (apcC), 31 ± 8 (apcV) and 42 ± 8 (apcS) mm(2), which was generally increased compared to wildtype controls with 7 ± 0.6 (wtC), 7 ± 0.4 (wtV) and 7 ± 0.6 (wtS) mm(2) (all p < 0.05). In Apc(Min/+) groups, tumor area was decreased in vagotomized animals compared to sham operated controls (p < 0.05) while sympathetically denervated mice showed a minor trend to decreased tumor area compared to controls. CONCLUSIONS: Extrinsic innervation of the small bowel is likely to modulate tumor development in Apc(Min/+) mice. Interrupted vagal innervation, but not sympathetic denervation, seems to inhibit tumor growth.

Postoperative colonic motility increases after early food intake in patients undergoing colorectal surgery.

BACKGROUND: Stimulation of colonic motility by the gastrocolonic response may help to reduce inhibition of gastrointestinal motility after colorectal surgery. We aimed to investigate whether postoperative colonic motility is increased after early food intake. METHODS: Nineteen patients undergoing colorectal surgery and 7 healthy volunteers were investigated. Colonic motility was recorded with a combined manometry/barostat system, and the effect of a standard 500-kcal meal was evaluated once in healthy volunteers and in 15 patients on the first and second postoperative day. Four patients remained unfed, serving as controls. RESULTS: In patients, the colonic motility index increased from 12 +/- 5 at baseline to 65 +/- 24 mm Hg after the meal on postoperative day 1 (mean +/- SEM; P < .01), while barostat bag volumes decreased, indicating a rise in colonic tone. On day 2, the motility index was 62 +/- 17 mm Hg at baseline and did not change after the meal. In unfed controls, no change was observed during colonic motility recordings on both postoperative days. In healthy volunteers, the colonic motility index increased from 98 +/- 52 at baseline to 151 +/- 58 mm Hg postprandially (P < .05). CONCLUSIONS: As in healthy volunteers, there is a potential to stimulate colonic motility by early food intake in postoperative patients. This may help to improve prolonged colonic motility disorders after colorectal surgery.