Randomized clinical trial of the effect of a fibrin sealant patch on pancreatic fistula formation after pancreatoduodenectomy.

BACKGROUND: The potential for a fibrin sealant patch to reduce the risk of postoperative pancreatic fistula (POPF) remains uncertain. The aim of this study was to evaluate whether a fibrin sealant patch is able to reduce POPF in patients undergoing pancreatoduodenectomy with pancreatojejunostomy. METHODS: In this multicentre trial, patients undergoing pancreatoduodenectomy were randomized to receive either a fibrin patch (patch group) or no patch (control group), and stratified by gland texture, pancreatic duct size and neoadjuvant treatment. The primary endpoint was POPF. Secondary endpoints included complications, drain-related factors and duration of hospital stay. Risk factors for POPF were identified by logistic regression analysis. RESULTS: A total of 142 patients were enrolled. Forty-five of 71 patients (63 per cent) in the patch group and 40 of 71 (56 per cent) in the control group developed biochemical leakage or POPF (P = 0·392). Fistulas were classified as grade B or C in 16 (23 per cent) and ten (14 per cent) patients respectively (P = 0·277). There were no differences in postoperative complications (54 patients in patch group and 50 in control group; P = 0·839), drain amylase concentration (P = 0·494), time until drain removal (mean(s.d.) 11·6(1·0) versus 13·3(1·3) days; P = 0·613), fistula closure (17·6(2·2) versus 16·5(2·1) days; P = 0·740) and duration of hospital stay (22·1(2·2) versus 18·2(0·9) days; P = 0·810) between the two groups. Multivariable logistic regression analysis confirmed that obesity (odds ratio (OR) 5·28, 95 per cent c.i. 1·20 to 23·18; P = 0·027), soft gland texture (OR 9·86, 3·41 to 28·54; P < 0·001) and a small duct (OR 5·50, 1·84 to 16·44; P = 0·002) were significant risk factors for POPF. A patch did not reduce the incidence of POPF in patients at higher risk. CONCLUSION: The use of a fibrin sealant patch did not reduce the occurrence of POPF and complications after pancreatoduodenectomy with pancreatojejunostomy. Registration number: 2013-000639-29 (EudraCT register).

Incisional hernia rate after open abdomen treatment with negative pressure and delayed primary fascia closure.

PURPOSE: Various techniques for delayed primary fascia closure have been published in patients treated with open abdomen (OA) and application of negative pressure, but to date, no data are available on incisional hernia (IH) rate. The aim of this retrospective analysis was to investigate the long-term outcome of this patient population with special interest in IH development. METHODS: Two hundred and nine consecutive patients, 90(43 %) female, were treated at our institution for various abdominal emergencies involving OA from June 2006 to June 2011. Mean age was 63(16-92) years. The indication was abdominal sepsis in 155(74 %) patients, ischemia in 24(12 %) and other reasons in 30(14 %). Hospital mortality was 21 %(n = 44); and planned ventral hernia was 7 %(n = 15); and mortality until follow-up was 16 %(n = 25), and 9 %(n = 13) patients were lost to follow-up, leaving 112 patients for evaluation of IH development. RESULTS: The rate of IH for patients with OA and delayed primary fascia closure was overall 35 % at a median (range) follow-up time of 26(12-81) months. Mean time for development of a ventral hernia was 11 months; 21(57 %) patients underwent surgery for symptomatic hernia (2 emergency operations for incarceration). Kaplan-Meier estimate for 5 years gave a 66 % IH rate. BMI, small bowel as source of infection and rapid adsorbable interrupted suture were identified risk factors. CONCLUSION: The rate of IH after open abdomen treatment with delayed primary fascia closure is high with a running suture with slow absorbable suture material showing the best results.

TROP2 expression as prognostic marker for gastric carcinoma.

BACKGROUND: In gastric cancer the recurrence rate is unacceptably high, even after R0 resection and (neo)adjuvant chemotherapy. Therefore, there is an urgent need for identification of predictive and/or prognostic biomarkers to select high-risk patients who might benefit from additional therapies. Expression of TROP2 has been shown to be associated with tumour aggressiveness and poor prognosis in patients with various epithelial cancers. AIMS: To investigate TROP2 expression in gastric cancer and its correlation with clinicopathological features and disease outcome. METHODS: Expression of TROP2 was investigated by immunohistochemistry of tumour specimens from 104 patients who underwent resection for gastric cancer. Parameters found to be of prognostic significance in univariate analysis were verified in a multivariate Cox regression model. RESULTS: TROP2 was found to be overexpressed in 58 (56%) tumour samples. Significantly higher expression of TROP2 could be detected in intestinal-type carcinomas (p = 0.03). In intestinal-type gastric cancer, TROP2 overexpression was significantly correlated with shorter disease-free survival (DFS) (p = 0.03). Among the total group, TROP2 overexpression was predictive for poor disease-free (p<0.01) and overall (p = 0.03) survival in lymph node positive patients. Multivariate Cox regression analysis revealed TROP2 overexpression to be an independent prognostic marker for poor DFS in the subgroup of patients with intestinal-type gastric cancer irrespective of lymph node involvement. CONCLUSION: Results show that TROP2 is an independent prognostic marker for disease recurrence in intestinal type gastric cancer. Due to its wide distribution TROP2 may become an attractive therapeutic target in a subgroup of patients with gastric cancer.

Ventral hernia repair in bariatric surgery.

BACKGROUND: Obesity is an important risk factor for perioperative complications including the development of ventral hernias. METHODS: This retrospective study comprises patients who underwent abdominal hernia repair simultaneously with or following implantation of a Swedish Adjustable Gastric Band(R) (SAGB). RESULTS: 9 out of 415 patients (2.2%) who received a SAGB between January 1996 and June 2001 underwent ventral hernia repair. In 6 patients, hernias preexisted from previous abdominal surgery at the time of the bariatric procedure, and another 3 hernias occurred at the median and left upper abdominal trocar position following SAGB placement. Median BMI at time of SAGB implantation was 44 (range 35-52), and at time of hernia repair was 36 (range 25-46). 2 hernias were repaired during SAGB placement, 3 during redo surgery, and 2 during abdominoplasty. In 2 patients, significant weight loss with loss of soft tissue support of the hernia sac led to recurrent episodes of small bowel obstruction necessitating emergency repair. Repair included direct defect closure in 7 patients and sublay polypropylene net implantation in 2 patients. Recoveries have been uneventful without wound infections or recurrence in all patients after a median follow-up of 34 months (range 13-69). CONCLUSION: In morbidly obese patients, the optimal management and timing of incisional hernia repair should weigh the risk of recurrence and perioperative complications against the risk of hernia-associated complications.

Colonoscopically placed hemoclips as treatment for massive appendiceal stump bleeding.

Massive bleeding from an appendiceal stump is a rare but occasionally seen severe complication. The bleeding may drain into the abdominal cavity, the retroperitoneum, or the digestive tract. Gastrointestinal hemorrhage may occur early or even years after appendectomy. The typical management includes ligation of the bleeding vessel or cecal resection done by either emergency laparotomy or laparoscopy. An alternative treatment option would be an angiographic embolization of the bleeding vessel. We report on a 33-year-old woman with severe lower gastrointestinal hemorrhage 1 day after an apparently uncomplicated appendectomy for acute phlegmonous appendicitis with ligation and invagination of the appendiceal stump. Hemoglobin level dropped to 6.3 g/dl and made blood transfusion necessary. The cause of bleeding was a small intramural branch of the appendiceal artery at the appendiceal stump, which was diagnosed by emergency colonoscopy. The hemorrhage could be controlled endoscopically by placing hemoclips on the distinct vessel in combination with a biological tissue adhesive. The patient recovered thereafter without further intervention. Endoscopic clipping for the treatment of appendiceal stump bleeding is a novel, effective, and safe procedure. Thereby, conventional emergency laparotomy or laparoscopy or angiographic embolization can be avoided.

Effect of mometasone furoate on early and late phase inflammation in patients with seasonal allergic rhinitis.

BACKGROUND: Mometasone furoate is a potent glucocorticoid that can markedly inhibit proinflammatory Th2 cytokines in vitro. An aqueous nasal spray formulation has been shown to be clinically active in reducing the symptoms of perennial and seasonal allergic rhinitis. OBJECTIVE: To determine whether pretreatment with mometasone furoate 200 microg once daily decreases specific indices of early and late phase nasal inflammation compared with placebo. METHODS: A randomized, double-blind, placebo-controlled crossover study was conducted using nasal provocation with ragweed antigen in 21 patients with ragweed-induced allergic rhinitis out of the ragweed season; the treatment period was 2 weeks. Symptom scores, rhinoprobe cytology, and nasal lavage fluid were collected during early and late phase periods for nasal cytokines (interleukin, 1, 4, 5, 6, and 8) and leukotriene B4 determinations using ELISA and RIA. RESULTS: Mean nasal symptom scores and sneezing frequency were consistently lower with mometasone furoate compared with placebo. Treatment was associated with a statistically significant early phase (30-minute time point) reduction in nasal lavage histamine levels compared with placebo (14.3 versus 20.2 ng/mL, P = .02). Within-treatment comparisons suggested that mometasone furoate reduced the antigen-induced late-phase response for IL-6, IL-8, and eosinophils compared with pretreatment. There were similar, but smaller, changes seen in the placebo group for these measurements. There were no statistically significant changes following antigen challenge in IL-1, IL-4, IL-5, LTB4, or in other nasal cytology parameters. CONCLUSION: These results suggest that the clinical activity of mometasone furoate nasal spray in seasonal allergic rhinitis is likely due, in part, to a reduction in the levels of histamine in nasal secretions related to the early phase response, and reductions in IL-6, IL-8, and eosinophils during the late phase response.

Allergen-stimulated leukotriene B4 and interleukin-8 levels in patients with asthma and allergic rhinitis-modulation by a lipid pathway inhibitor.

BACKGROUND: Leukotriene B4 (LTB4), a potent chemokinetic mediator for neutrophils, is enhanced by interleukin-8 (IL-8) and may play a key role in the inflammatory response of asthma. OBJECTIVE: The aim of the present study was to investigate whether zileuton, a 5-lipoxygenase antagonist known to inhibit LTB4 production and recruitment of eosinophils/neutrophils in bronchoalveolar fluid, could affect the production of LTB4 and IL-8 by allergen-stimulated peripheral blood mononuclear cells in vitro from patients with asthma and/or allergic rhinitis. METHODS: Peripheral blood mononuclear cells were isolated using Ficoll-Hypaque density gradient from 14 subjects (2 with asthma, 11 with asthma and allergic rhinitis, and 1 with allergic rhinitis) and were stimulated by selected allergens (grass, tree, mite, and mold) in the absence or presence of 1 and 10 microM of zileuton. Supernatants were collected and assayed for LTB4 and IL-8 levels using RIA and ELISA, respectively. RESULTS: Levels of LTB4 were significantly elevated in peripheral blood mononuclear cells stimulated with mold, grass, and tree compared with the unstimulated control group (P<.05). Levels of IL-8 were significantly elevated in all allergen-stimulated peripheral blood mononuclear cells, except mold, compared with the unstimulated control group (P<.05). Zileuton significantly reduced production of LTB4 by mold and tree-stimulated peripheral blood mononuclear cells. By contrast, no effect of zileuton on IL-8 production was observed in allergen-stimulated peripheral blood mononuclear cells. CONCLUSIONS: The zileuton-induced attenuation of LTB4 production by allergen-stimulated peripheral blood mononuclear cells from patients with asthma and/or allergic rhinitis occurs independently from the allergen-stimulated IL-8 production.

Nedocromil in the outpatient management of asthma.

OBJECTIVE: To more closely approximate the use of a nonsteroidal inhaled anti-inflammatory medication for asthma, nedocromil sodium, under actual ambulatory practice conditions. DESIGN: Large, open-label trial. PATIENTS: One thousand two hundred one patients from 286 primary care and specialty centers. INTERVENTION: Four weeks of treatment with nedocromil sodium (4 mg delivered from the valve and 3.5 mg delivered from the mouthpiece of a metered inhalor [2 puffs, four times daily]). MAIN OUTCOME MEASURES: Asthma symptom scores, peak expiratory flow rate, a lifestyle assessment measures questionnaire, and mean number of days missed per month from work or school. RESULTS: Statistically significant improvements were seen after 1 and 4 weeks of treatment for cough, daytime and nighttime asthma, morning tightness, peak expiratory flow rate, and all four measured lifestyle assessment factors (P < .001). An additional clinically relevant outcome measure, mean number of days missed per month from work or school, was reduced by 75% (P < .001). No serious adverse reactions were reported. CONCLUSION: This study reproduces the high level of efficacy and safety of nedocromil that was previously reported in placebo-controlled clinical studies.

Effect of inhaled corticosteroid on bone density in asthmatic patients: a pilot study.

We investigated the effect of long-term inhaled (ICS) and oral corticosteroid (OCS) therapy on bone density by using single and dual photon absorptiometry. We studied a group of five asthmatic patients who inhaled an average of 326 micrograms/day of beclomethasone dipropionate equivalents for 50 months (range 36 to 62 months) and a control group of five asthmatic patients on OCS, who used 12.5 mg of prednisone equivalents daily for an average of 57 months (range 22 to 120 months). The ICS group's average bone densities relative to age and sex-matched controls were 99.7%, 99.2%, and 90.0% for the radius, spine, and hip, respectively. The OCS group's average bone densities relative to age-matched and sex-matched controls were 94.4%, 85.4%, and 84.5% for the identical sites. A dose-response relationship between the cumulative dose of ICS and the relative bone density was absent in the study group but demonstrable in the control group of asthmatics on long-term OCS therapy. These results suggest that ICS therapy, unlike OCS, may not induce bone loss at the doses used by our subjects. Further research is required to determine whether a single user of ICS with unusually low bone density measurements represents a biologic variant, or a subgroup of patients who are especially sensitive to the systemic effects of ICS.

Preliminary investigation on humoral and cellular immune responses to selected food proteins in patients with Crohn's disease.

Crohn's disease is a chronic inflammatory disorder for which an immunologic etiology has been proposed. Food hypersensitivity may contribute to part of the pathogenesis of this disorder. In preliminary studies, we evaluated 11 Crohn's patients by history, skin testing (ST), total and specific(s) IgE and sIgE/sIgG4 levels to five food proteins [egg (E), milk (M), wheat (W), soy (S), and corn (C)] using a sensitive enzyme monoclonal antibody assay. Skin testing was also performed using grass and mold allergens. Lymphocyte concanavalin (Con A) mitogenic and antigenic responses to food proteins were also determined by tritiated thymidine incorporation. Mean sIgG4 values for four food proteins are listed below: (Table: see text). No patient reacted with elevated sIgE or sIgG4 to corn. All patients had low to negative sIgE levels to all foods and only three had increased total IgE. Three of eight were history and ST positive to M, E, and W. Six of eight had at least one positive ST to M, E, W, and S. All patients had negative sIgG4 to tested inhalants and two had elevated sIgE to grass pollen. Although mean lymphocyte Con A mitogenesis was significantly decreased in eight patients compared with controls (P less than .05), an increased food stimulatory response to milk protein was observed (P less than .05). Perhaps, decreased sIgE and cell-mediated mitogenic responsiveness may lead to an enhanced humoral IgG response. The increased sIgG4 humoral response to egg protein and cellular sensitivity to milk protein may indicate mucosal antigenic stimulation or leakage in patients with Crohn's disease in spite of negative sIgE levels.

The immunogenicity of Hemophilus influenzae type B polysaccharide-Neisseria meningitidis group B outer membrane protein complex vaccine in infants and young children.

Hemophilus influenzae type b polysaccharide-Neisseria meningitidis group B outer membrane protein complex vaccine was administered in a single dose to 38 children ages 24-53 mo (group 1) and to 78 children ages 12-23 mo (group 2) and in two doses to 84 children ages 2-11 mo (group 3). The geometric mean concentration of the capsular antibody before and after the vaccine regimen, respectively, were 0.35 microgram/ml and 12.59 micrograms/ml in group 1, 0.18 microgram/ml and 4.79 microgram/ml in group 2, and 0.15 microgram/ml and 3.80 micrograms/ml in group 3. After completing the vaccine regimen, concentrations of capsular antibody were greater than or equal to 0.15 microgram/ml in 199 (99.5%) of the 200 children and greater than or equal to 1.0 microgram/ml in 168 (84%) of the children. There were no serious and few minor adverse reactions to the vaccine. This vaccine is immunogenic in infants and young children.