H.W. Tilanus

Use of large-diameter metallic stents to seal traumatic nonmalignant perforations of the esophagus

BACKGROUND Surgery for traumatic, non-malignant perforation of the esophagus in patients presenting more than 24 hours after its occurrence carries a high morbidity and mortality. Covered metallic stents have been used to effectively seal perforations in individual patients with Boerhaaves syndrome. METHODS Eleven consecutive patients presented with esophageal perforation that was caused by Boerhaaves syndrome (n = 5), resection of an epiphrenic diverticulum (n = 2), rigid esophagoscopy (n = 2), extended gastric resection (n = 1), or pneumatic dilation for achalasia (n = 1). A large diameter Flamingo Wallstent (proximal/distal diameters, 30/20 mm) (7 patients) or a large diameter Ultraflex stent (proximal/distal diameters, 28/23 mm) (4 patients) was placed. Pleural cavities were drained with thoracostomy drains, and antibiotics were administered. RESULTS The median time from perforation to stent insertion was 60 hours (range, 24 hours to 28 days). The perforation was totally sealed in 10 of 11 patients. Two patients underwent esophageal resection because of incomplete sealing of the perforation or incomplete drainage of the pleural cavity and mediastinum. The other 9 patients recovered uneventfully and resumed a normal diet within 7 to 18 days. In 7 patients, the stents were retrieved endoscopically after a median of 7 weeks (range, 6 to 14 weeks), whereas two patients refused to have the stent retrieved (in one, the stent migrated into the stomach; the other patient died 6 months after stent placement from an unrelated cause). CONCLUSIONS Traumatic perforation of the esophagus can be treated successfully with large diameter metallic stents, together with adequate drainage of the thoracic cavity.

Persistent fatigue in liver transplant recipients: a two-year follow-up study.

van Ginneken BTJ, van den Berg‐Emons RJG, van der Windt A, Tilanus HW, Metselaar HJ, Stam HJ, Kazemier G. Persistent fatigue in liver transplant recipients: a two‐year follow‐up study.
Clin Transplant 2010: 24: E10–E16.

Effects of a rehabilitation programme on daily functioning, participation, health-related quality of life, anxiety and depression in liver transplant recipients

Purpose. Fatigue is a chronic problem in liver transplant recipients and may influence daily functioning and health-related quality of life (HRQoL). This study aimed to evaluate the effects of a fatigue-reducing physical rehabilitation programme on daily functioning, participation, HRQoL, anxiety and depression among liver transplant recipients. Method. Eighteen fatigued liver transplant recipients (mean age 51 years, 10 men/8 women) participated in a 12-week rehabilitation programme, which included supervised exercise training and daily physical activity counselling. We assessed pre- and post-programme health-related daily functioning, participation, HRQoL, anxiety and depression using questionnaires. Results. After the programme, patients showed improvements in daily functioning (23.6%, p = 0.007), the participation domain ‘autonomy outdoors’ (34.1%, p = 0.001), and the HRQoL domains ‘physical functioning’ (11.5%, p = 0.007) and ‘vitality’ (21.5%, p = 0.022). Anxiety and depression were unchanged post-programme. Conclusions. Rehabilitation using supervised exercise training and daily physical activity counselling can positively influence daily functioning, participation and HRQoL among fatigued liver transplant recipients.

Functional analysis of CD4+ CD25bright T cells in kidney transplant patients : improving suppression of donor-directed responses after transplantation

Abstract:  Background:  The role of CD4+ CD25bright regulatory T cells (Treg) in controlling alloreactivity is established, but little is known whether antigen‐specific Treg are induced in fully immunosuppressed kidney transplant patients.

Intravenous nitroglycerin does not preserve gastric microcirculation during gastric tube reconstruction: A randomized controlled trial

IntroductionComplications of oesophagectomy and gastric tube reconstruction include leakage and stenosis, which may be due to compromised microvascular blood flow (MBF) in gastric tissue. We recently demonstrated that decreased MBF could be improved perioperatively by topical administration of nitroglycerin. The aim of the present study was to investigate whether nitroglycerin, administered intravenously during gastric tube reconstruction, could preserve tissue blood flow and oxygenation in the gastric fundus, and reduce the incidence of postoperative leakage.MethodsIn this single-centre, prospective, double-blinded study, we randomized 32 patients scheduled for oesophagectomy into two groups. The intervention group received intravenous nitroglycerin during gastric tube reconstruction, and the control group received normal saline. Baseline values for MBF, microvascular haemoglobin oxygen saturation and microvascular haemoglobin concentration were determined at the gastric fundus before and after gastric tube construction and after pulling up the gastric tube to the neck.ResultsMBF and microvascular haemoglobin oxygen saturation decreased similarly in both groups during gastric tube reconstruction and were comparable. The oesophageal anastomosis was controlled by contrast radiography before discharge from the hospital; leakage was observed in two patients (13%) in the nitroglycerin group and five patients (31 %) in the control group (not significant).ConclusionUnder stable systemic haemodynamic conditions, continuous intravenous administration of nitroglycerin could not prevent deterioration in gastric microvascular perfusion and microvascular haemoglobin saturation during gastric tube reconstruction. (Trial registration number NCT 00335010.)

Two-Lung High-Frequency Jet Ventilation as an Alternative Ventilation Technique During Transthoracic Esophagectomy

OBJECTIVE The aim of this study was to evaluate two-lung high-frequency jet ventilation during esophagectomy and evaluate the influence of high-frequency jet ventilation on pulmonary complications as compared with one-lung ventilation. DESIGN A retrospective study. SETTINGS A single-center study in a university hospital. PARTICIPANTS The authors analyzed the data of patients who had undergone an elective esophagectomy by transthoracic esophagectomy between January 2000 and December 2006. INTERVENTION The patients had undergone a cervicothoracoabdominal subtotal esophagectomy via a right-sided thoracotomy. Patients with high-frequency jet ventilation were intubated with a single-lumen endotracheal tube, and an oxygen insufflation catheter was placed inside the endotracheal tube and connected to a high-frequency jet ventilator. MEASUREMENTS AND MAIN RESULTS Eighty-seven patients were enrolled, 30 with high-frequency jet ventilation and 57 with 1-lung ventilation. Both groups were adequately oxygenated, but patients in the one-lung ventilation group had a higher PaCO2 (42.75 +/- 7.5 mm Hg) compared with that for the high-frequency jet ventilation group (35.25 +/- 8.25 mm Hg) (p < 0.05). There were no differences in postoperative respiratory complications between the 2 groups. Mean blood loss was significantly lower for patients in the high-frequency jet ventilation group (1,243 +/- 787 mL). CONCLUSIONS High-frequency jet ventilation to 2 lungs, using a single-lumen tube, is a safe and adequate ventilation technique for use during esophagectomy. High-frequency jet ventilation had no influence on the incidence of postoperative pulmonary complications but reduced perioperative blood loss and led to a decreased need for fluid replacement.

Results of a Two-Center Study Comparing Hepatic Fibrosis Progression in HCV-positive Liver Transplant Patients Receiving Cyclosporine or Tacrolimus

A 2-center retrospective analysis was performed in 60 patients undergoing liver transplantation for hepatitis C virus (HCV)-related disease (cyclosporine in 20, tacrolimus in 40). Mean (±SEM) follow-up was 23.6 ± 22.5 and 22.3 ± 13.7 months in patients receiving cyclosporine or tacrolimus, respectively. Clinically indicated biopsies were performed in 15/20 cyclosporine patients (75%) and 22/40 tacrolimus patients (55%; P = .17). The Ishak fibrosis score was significantly lower in cyclosporine-treated patients versus tacrolimus-treated patients (mean 1.7 ± 0.4 vs 3.1 ± 0.4; P = .023), as was percentage of fibrosis grade Ishak ≥4 (7% vs 41%; P = .028). The mean time to moderate fibrosis (Ishak score ≥3) was 38.2 ± 15.1 months in cyclosporine patients (4/15) and 23.5 ± 12.6 months in tacrolimus patients (14/22); the difference was not statistically significant (P = .09). This retrospective study suggests that cyclosporine-based immunosuppression is associated with less severe hepatic fibrosis in HCV-positive liver transplant recipients compared with tacrolimus-based regimens, but a larger prospective comparative trial is necessary to confirm these findings.

Noninvasive functional liver blood flow measurement: comparison between bolus dose and steady-state clearance of sorbitol in a small-rodent model

Plasma clearance of D-sorbitol, a nontoxic polyol, occurs predominantly in the liver and has been used to measure functional liver blood flow after bolus and steady- state intravenous administration. However, it is not known which of these two administration methods is superior. Therefore, plasma D-sorbitol clearance was studied in an animal model both after a bolus dose and under steady-state (SS) conditions and compared directly with liver blood flow, under normal conditions, and after the induction of endotoxin (LPS) sepsis. Adult male Wistar rats (526 +/- 38 g body wt; n = 27) were anesthetized and mechanically ventilated. Hemodynamics, hepatic arterial flow, and portal venous flow were measured. Two groups were studied, namely healthy animals that served as controls and a sepsis group that received 5 mg/kg LPS intravenously (Escherichia coli O127:B8). Each animal received either a SS infusion (0.1 mg/100 g body wt per min) or a bolus (3 mg/100 g body wt) of a 5% D-sorbitol solution intravenously in a randomized order. After the initial measurements and a 60-min pause time in between (T(1/2,sorbitol) = 9 min), a crossover was done. The hepatic clearance of D-sorbitol in the control group showed a good correlation between bolus and SS (Spearmans r = 0.7681, P = 0.0004), and both techniques correlated well with total liver blood flow (TLBF) (r = 0.7239, P = 0.0023 and r = 0.7226, P = 0.0023, respectively). Also in the sepsis group there was a good correlation between bolus and SS sorbitol clearance (r = 0.6655, P = 0.0182). In the sepsis group, only the SS clearance correlated with TLBF (r = 0.6434, P = 0.024). In conclusion, in normal and under septic conditions, hepatic clearance of D-sorbitol either by bolus or a SS infusion is comparable. In healthy animals, this also correlated well with TLBF but not in septic conditions. However, this is expected because of the changes in the liver microcirculation, shunting, and decreased hepatocyte function in sepsis.

341 CORTICOSTEROIDS AFFECT HEPATITIS C INFECTION BY MODULATING PLASMACYTOID DENDRITIC CELL FUNCTION

340 T CELLS REDIRECTED BY A CHIMERIC ANTIGEN RECEPTOR RECOGNIZING HBsAg EFFICIENTLY CONTROL HBV IN VIVO IN TRANSGENIC MICE K. Krebs, N. Bottinger, L.-R. Huang, M. Chmielewski, S. Arzberger, G. Gasteiger, E. Schmitt, F. Bohne, M. Aichler, W. Uckert, H. Abken, M. Heikenwalder, P. Knolle, U. Protzer. Institute of Virology, Technische Universitat Munchen, Helmholtz Zentrum Munchen, Munich, Institute of Molecular Medicine, University of Bonn, Bonn, Department of Internal Medicine I, University Hospital Cologne, Cologne, Institute of Immunology, University of Mainz, Mainz, Institute of Pathology, Helmholtz Zentrum Munchen, Munich, Max Delbruck Center for Molecular Medicine, Berlin, Germany E-mail: krebs@virologie.med.tum.de

Endoscopic Ablation of Intraepithelial Neoplasia in Barrett's Patients

Endoscopic Ablation of Intraepithelial Neoplasia in Barrett’s Patients Jelle Haringsma, Ilona Kerkhof, Jan Werner-Poley, Peter Siersema, Huug Tilanus, Ernst Kuipers Background: There is no generally accepted strategy for patients with intraepithelial neoplasia (IEN) in Barrett’s esophagus (BE). Esophagectomy is considered standard therapy for advanced cancer, and in many centers also for IEN. Surgical resection, however, carries considerable mortality and morbidity. Endoscopic ablation is developed as a minimally invasive organ-preserving therapy for IEN. There are limited data on outcome of such a strategy. We therefore aimed to determine the results of endoscopic ablation in patients referred for superficial neoplasia in BE. Methods: Prospective cohort study of all subjects with IEN referred to our tertiary center. 35 patients underwent endoscopic Mucosal Resection (EMR) of suspected BE lesions with a capped technique. In patients with high-grade neoplasia (Vienna class 4) endoscopic ablation was subsequently completed with Photodynamic Therapy (PDT) using 5-aminolevulinic acid 40 mg/kg at 633 nm 100J/ cm. Endoscopic biopsies were taken at 6 weeks, 3 mo and subsequently every 6 mo after PDT. Results: 56 patients (mean age 66 yrs, range 42-85) referred for superficial neoplasia in BE were evaluated. 7 patients with only low-grade IEN were followed. Primary surgical resection was performed in 10 of 49 patients based on endoscopic criteria, histological differentiation, and patient’s preference. 39 patients (80%) consented and were considered suitable for endoscopic ablation. Due to submucosal infiltration, poor differentiation and angio-invasion in the EMR specimen at histology, 5 were treated surgically, 4 were followed and 4 were treated otherwise. Endoscopic ablation was completed in 26. Of the latter group 21 patients had a sustained remission of severe neoplasia, 3 were subsequently treated surgically, 2 were followed. After a mean follow-up of 22 months, a total of 18/56 patients (32%) were operated upon. In 3 patients who had undergone EMR, no invasive cancer was found in the resection specimen. Operative mortality was 1/18 (5,5%). Three other patients died post-surgically: 1 from tumor recurrence, 2 from unrelated causes. Of 26 patients treated endoscopically, remission was sustained in 21 patients (81%). No major complications occurred. Conclusions: Endoscopic ablation can replace primary surgery in well-selected patients with severe intraepithelial neoplasia. Endoscopic ablation using EMR and PDT is safe and effective. Selection and endoscopic treatment of neoplasia in Barrett’s should be performed in expert centers. 495 A Randomized, Prospective Trial of Electrosurgical Incision Followed by Rabeprazole Versus Bougie Dilation Followed by Rabeprazole of Symptomatic Esophageal (Schatzki’s) Rings Jason C. Wills, Kristen Hilden, James DiSario, John C. Fang Background: Lower esophageal (Schatzki’s) rings are a common cause of solid food dysphagia. Standard treatment involves passage of a single large bougie to disrupt the ring but symptoms recur in the majority of patients. Electrosurgical incision of the ring may provide a longer duration of symptom improvement as suggested in a retrospective trial. Acid suppression has been shown to decrease the recurrence rate of peptic strictures but there is no data on the treatment of Schatzki’s rings. Aim: To compare the efficacy of bougie dilation to electrosurgical incision of symptomatic Schatzki’s rings at one year follow up in the presence of rabeprazole treatment. Methods: Forty-nine consecutive patients referred for endoscopic evaluation of dysphagia were randomized prior to EGD to Bougie dilation using a 52-54 French Maloney dilator or electrosurgical incision using a standard needle knife papillotome with 3-4 longitudinal incisions placed radially around the Schatzki’s ring. All patients completed validated GERD and dysphagia questionnaires at 0, 1, 3, 6, 9, and 12 months. All patients were placed on rabeprazole (20 mg/day) for the duration of the study. Analysis was made using Wilcoxon rank-sum (Mann-Whitney U) non-parametric test for independent samples (dysphagia score) and independent samples t-test (GERD scores and pH results). Results: Twenty-five patients underwent bougie dilation and 24 underwent electrosurgical incision. All patients had been followed for at least six months and an interim analysis was performed. There was one episode of bleeding in the incision group controlled with epinephrine injection. Dysphagia scores at 12 months decreased significantly in the incision group (median 5 / 0) compared with bougie group (median 7 / 3) (p Z 0.269). Both groups had significant improvement in GERD scores at 9 and 12 (p! 0.05). There was no difference in GERD improvement between the two groups at 12 (p Z 0.927). Conclusion: Electrosurgical incision of lower esophageal (Schatzki’s) rings is safe and offers similar improvement in dysphagia scores. Electrosurgical incision may offer more definitive relief of dysphagia (5/0) than bougie dilation (7/3) and require less frequent future interventions. Further follow up is needed. The addition of rabeprazole offered significant improvement in GERD scores in both groups.