Endoscopic vacuum therapy significantly improves clinical outcomes of anastomotic leakages after 2-stage, 3-stage, and transhiatal esophagectomies.

BACKGROUND: Anastomotic leakages after esophagectomies continue to constitute significant morbidity and mortality. Intrathoracic anastomoses pose a high risk for mediastinitis, sepsis, and death, if a leak is not addressed timely and appropriately. However, there are no standardized treatment recommendations or algorithms as for how to treat these leakages. METHODS: The study included all patients at the University Hospital Regensburg, who developed an anastomotic leakage after esophagectomy with gastric pull-up reconstruction from 2007 to 2022. Patients receiving conventional treatment options for an anastomotic leakage (stents, drainage tubes, clips, etc.) were compared to patients receiving endoscopic vacuum-assisted closure (eVAC) therapy as their mainstay of treatment. Treatment failure was defined as cervical esophagostomy formation or death. RESULTS: In total, 37 patients developed an anastomotic leakage after esophagectomy with a gastric pull-up reconstruction. Twenty patients were included into the non-eVAC cohort, whereas 17 patients were treated with eVAC. Treatment failure was observed in 50% of patients (n = 10) in the non-eVAC cohort and in 6% of patients (n = 1) in the eVAC cohort (p < 0.05). The 90-day mortality in the non-eVAC cohort was 15% (n = 3) compared to 6% (n = 1) in the eVAC cohort. Cervical esophagostomy formation was required in 40% of cases (n = 8) in the non-eVAC cohort, whereas no patient in the eVAC cohort underwent cervical esophagostomy formation. CONCLUSION: eVAC therapy for leaking esophagogastric anastomoses appears to be superior to other treatment strategies as it significantly reduces morbidity and mortality. Therefore, we suggest eVAC as an essential component in the treatment algorithm for anastomotic leakages following esophagectomies, especially in patients with intrathoracic anastomoses.

Characterization and application of nonlinear plastic materials for post-CPA pulse compression.

We demonstrate the three-fold post-chirped-pulse-amplification (post-CPA) pulse compression of a high peak power laser pulse using allyl diglycol carbonate (CR39), which was selected as the optimal material for near-field self-phase modulation out of a set of various nonlinear plastic materials, each characterized with respect to its nonlinear refractive index and optical transmission. The investigated materials could be applied for further pulse compression at high peak powers, as well as for gain narrowing compensation within millijoule-class amplifiers. The post-CPA pulse compression technique was tested directly after the first CPA stage within the POLARIS laser system, with the compact setup containing a single 1 mm thick plastic sample and a chirped mirror pair, which enabled a substantial shortening of the compressed pulse duration and, hence, a significant increase in the laser peak power without any additional modifications to the existing CPA chain.

Efficient Laser-Driven Proton Acceleration from a Cryogenic Solid Hydrogen Target.

We report on the successful implementation and characterization of a cryogenic solid hydrogen target in experiments on high-power laser-driven proton acceleration. When irradiating a solid hydrogen filament of 10 µm diameter with 10-Terawatt laser pulses of 2.5 J energy, protons with kinetic energies in excess of 20 MeV exhibiting non-thermal features in their spectrum were observed. The protons were emitted into a large solid angle reaching a total conversion efficiency of several percent. Two-dimensional particle-in-cell simulations confirm our results indicating that the spectral modulations are caused by collisionless shocks launched from the surface of the the high-density filament into a low-density corona surrounding the target. The use of solid hydrogen targets may significantly improve the prospects of laser-accelerated proton pulses for future applications.

Preservation of the superior rectal artery: influence of surgical technique on anastomotic healing and postoperative morbidity in laparoscopic sigmoidectomy for diverticular disease.

PURPOSE: To evaluate the impact of superior rectal artery (SRA) sparing technique on anastomotic leakage in laparoscopic sigmoidectomy for diverticular disease. MATERIAL AND METHODS: A retrospective multicenter analysis of all patients undergoing laparoscopic sigmoid resection for diverticular disease between 2002 and 2015 was conducted. Data were recorded in three hospitals: University Hospital Regensburg, Marienhospital Gelsenkirchen, and Städtisches Klinikum München Bogenhausen. The SRA was resected between 2002 and 2005. Since 2005, the artery was preserved in most cases. RESULTS: Two hundred sixty-seven patients were included. One hundred sixty patients presented with complicated diverticulitis (60%). The SRA was resected in 102 patients (group 1) and preserved in 157 patients (group 2, no data in eight cases). Anastomotic leakage occurred in 7% of patients in group 1 and 1.9% of patients in group 2 (p = 0.053). Duration of surgery was significantly shorter (157 vs. 183 min, p < 0.001) in group 2 patients. Length of hospital stay was without significant difference (group 1 8.2 days; group 2 8.3 days; p = 0.83). The conversion rate was higher in group 2 patients; however, the difference was not statistically significant (9 vs. 3%, p = 0.07). There was no significant difference between both groups regarding intraoperative complications and overall complication rate. The length of the resected specimen (19 vs. 21 cm, p = 0.001) was significantly shorter in group 2 patients. CONCLUSION: Preservation of the SRA seems to be associated with favorable outcome in patients undergoing laparoscopic sigmoid resection for diverticular disease.

Analysis of arterial dynamic micro-vascularization with contrast-enhanced ultrasound (CEUS) in thyroid lesions using external perfusion software: First results.

AIM: To determine different perfusion characteristics of histo-pathologically proven adenomas and carcinomas of the thyroid gland with CEUS and perfusion software. MATERIAL AND METHODS: Retrospective perfusion analysis of 25 patients with carcinomas and 41 cases of adenomas of the thyroid gland (30 males, 36 females; aged 18 - 85 years, mean 56 years). All cases were histologically analyzed. Perfusion analysis was independently performed using external perfusion software (VueBox®). TTP, mTT, Peak and Rise time were calculated. RESULTS: Lesions' sizes ranged from 0.2 to 10.2 cm in carcinomas (mean 2.18 cm), and from 0.6 to 5.0 cm in adenomas (mean 2.25 cm). In 20 out of 25 carcinomas that were evaluated with CEUS, a complete wash-out in the late venous phase was found. Adenomas showed wash-out at the border.Perfusion analysis in VueBox® revealed some parameters which tend to show differences between adenomas and carcinomas, however did not reach the level of significance.Median Peak in carcinomas was highest at the margins (2945 rU), and lowest in the surroundings (1110 rU). Mean Transit Time (mTT) values showed no differences between center, margin and surrounding.In adenomas healthy tissue showed higher mTT values compared to the center (24.6 vs. 20.7 sec). Median Peak was highest in the surrounding tissue and lowest in the margins (1999 vs. 1129 rU). No statistical differences could be found in the comparisons. CONCLUSION: CEUS with perfusion analysis offers new possibilities for the dynamic evaluation of micro-vascularization in thyroid adenomas and carcinomas. Using VueBox® the perfusion analysis of the arterial phase provides new parameters that help determine a lesion's malignancy or benignity. However a final assessment regarding malignancy and benignity of thyroid lesions using only CEUS and perfusion analysis of the arterial phase is not yet possible.

Intrasurgical dignity assessment of hepatic tumors using semi-quantitative strain elastography and contrast-enhanced ultrasound for optimisation of liver tumor surgery.

OBJECTIVE: To evaluate the efficacy of strain elastography (SE) using semi-quantitative measurement methods compared to constrast enhanced ultrasound during liver tumor surgery (Io-CEUS) for dignity assessment of focal liver lesions(FLL). MATERIAL AND METHODS: Prospective data acquisition and retrospective analysis of US data of 100 patients (116 lesions) who underwent liver tumor surgery between 10/2010 and 03/2016. Retrospective reading of SE color patterns was performed establishing groups depending on dominant color (>50% blue = stiff, inhomogenous, >50% yellow/red/green = soft tissue). Semi-quantitative analysis was performed by Q-analysis based on a scale from 0 (soft) to 6 (stiff). 2 ROIs were placed centrally, 5 ROIs in the lesion's surrounding tissue. Io-CEUS was performed by bolus injection of 5-10 ml sulphurhexaflourid microbubbles evaluating wash-in- and -out- kinetics in arterial, portal venous and late phase. Histopathology after surgical resection served as goldstandard. RESULTS: 100 patients (m: 65, f: 35, mean age 60.5 years) with 116 liver lesions were included. Lesion's size ranged from 0.5 to 8.4 cm (mean 2.42 cm SD±1.44 cm). Postoperative histology showed 105 malignant and 11 benign lesions. Semi-quantitative analysis showed central indurations of >2.5 in 76/105 cases suggesting malignancy. 7 benign lesions displayed no central indurations correctly characterized benign by SE. ROC-analysis and Youden index showed a sensitivity of 72.4% and specificity of 63.6% assuming a cut-off of 2.5. Io-CEUS correctly characterized 103/105 as malignant. Sensitivity was 98%, specificity 72.7%. CONCLUSION: Strain elastography is a valuable tool for non-invasive characterization of FLLs. Semi-quantitative intratumoral stiffness values of >2.5 suggested malignancy. However, sensitivity of Io-CEUS in detecting malignant lesions was higher compared to SE. In conclusion SE should be considered for routine use during intraoperative US in addition to Io-CEUS for optimization of curative liver surgery.

Preoperative differentiation of thyroid adenomas and thyroid carcinomas using high resolution contrast-enhanced ultrasound (CEUS).

BACKGROUND: To evaluate the impact of high-resolution contrast-enhanced ultrasound (CEUS) in combination with Color Coded and Power Doppler Sonography (CCDS/PD) in the preoperative differentiation of thyroid adenomas and thyroid carcinomas. METHODS: A total of 101 patients (55 female, median age 54 years) underwent surgery for thyroid adenoma and thyroid carcinoma. CCDS/PD and CEUS were performed in all patients by an experienced examiner using a multifrequency linear transducer (6-9 or 6-15 MHz) and were digitally stored. Reading of the ultrasound images was performed by two experienced radiologists in consensus. A histopathological evaluation was obtained as standard of reference in all patients. RESULTS: Altogether, 75 thyroid adenomas and 26 thyroid carcinomas were detected. Mean diameter of thyroid adenomas and thyroid carcinomas was 27 mm and 32 mm, respectively. The differences in microcirculation of thyroid adenomas and thyroid carcinomas were statistically highly significant (p <  0.01). Representative features for thyroid adenomas were either no wash-out or wash-out with persisting edge in late phase, for thyroid carcinomas a complete wash-out in late phase. Thus, a calculation of sensitivity, specificity, positive and negative predictive value of 81% , 92% , 97% and 63%, respectively, for the differentiation of benignity and malignancy was possible. CONCLUSIONS: Dynamic evaluation of microcirculation using CEUS and CCDS/PD enables a more reliable preoperative discrimination between thyroid adenomas and thyroid carcinomas.

Full characterization of the amplified spontaneous emission from a diode-pumped high-power laser system.

We present the first complete temporal and spatial characterization of the amplified spontaneous emission (ASE) of laser radiation generated by a diode-pumped high-power laser system. The ASE of the different amplifiers was measured independently from the main pulse and was characterized within a time window of -10ms ≤ t ≤ 10ms and an accuracy of up to 15fs around the main pulse. Furthermore, the focusability and the energy of the ASE from each amplifier was measured after recompression. Using our analysis method, the laser components, which need to be optimized for a further improvement of the laser contrast, can be identified. This will be essential for laser-matter interaction experiments requiring a minimized ASE intensity or fluence.

A rule-based expert system for chemical prioritization using effects-based chemical categories.

A rule-based expert system (ES) was developed to predict chemical binding to the estrogen receptor (ER) patterned on the research approaches championed by Gilman Veith to whom this article and journal issue are dedicated. The ERES was built to be mechanistically transparent and meet the needs of a specific application, i.e. predict for all chemicals within two well-defined inventories (industrial chemicals used as pesticide inerts and antimicrobial pesticides). These chemicals all lack structural features associated with high affinity binders and thus any binding should be low affinity. Similar to the high-quality fathead minnow database upon which Veith QSARs were built, the ERES was derived from what has been termed gold standard data, systematically collected in assays optimized to detect even low affinity binding and maximizing confidence in the negatives determinations. The resultant logic-based decision tree ERES, determined to be a robust model, contains seven major nodes with multiple effects-based chemicals categories within each. Predicted results are presented in the context of empirical data within local chemical structural groups facilitating informed decision-making. Even using optimized detection assays, the ERES applied to two inventories of >600 chemicals resulted in only ~5% of the chemicals predicted to bind ER.

Effects-based chemical category approach for prioritization of low affinity estrogenic chemicals.

Regulatory agencies are charged with addressing the endocrine disrupting potential of large numbers of chemicals for which there is often little or no data on which to make decisions. Prioritizing the chemicals of greatest concern for further screening for potential hazard to humans and wildlife is an initial step in the process. This paper presents the collection of in vitro data using assays optimized to detect low affinity estrogen receptor (ER) binding chemicals and the use of that data to build effects-based chemical categories following QSAR approaches and principles pioneered by Gilman Veith and colleagues for application to environmental regulatory challenges. Effects-based chemical categories were built using these QSAR principles focused on the types of chemicals in the specific regulatory domain of concern, i.e. non-steroidal industrial chemicals, and based upon a mechanistic hypothesis of how these non-steroidal chemicals of seemingly dissimilar structure to 17ß-estradiol (E2) could interact with the ER via two distinct binding types. Chemicals were also tested to solubility thereby minimizing false negatives and providing confidence in determination of chemicals as inactive. The high-quality data collected in this manner were used to build an ER expert system for chemical prioritization described in a companion article in this journal.

PFO closure: rational, procedure and devices.

Patent foramen ovale (PFO) is a common anatomical variant occurring in 20-25% of the population. In most cases, a PFO remains asymptomatic. However it allows for any venous particle such as thrombus, air or vasoactive substances to bypass the lung and enter the arterial circulation. Accordingly, PFO's have been linked to cryptogenic stroke, migraine and decompression illness. While the number of device closures have been increasing the therapy remains controversial as ­ until recently ­ data supporting PFO closure came from non randomized studies only. In this review we will discuss the existing data on PFO closure including results of the three randomized controlled trials comparing device closure with medical therapy in patients with cryptogenic stroke. We will also focus on the implantation technique, the complications and the different devices that are used for this procedure.

Preoperative diagnosis of thyroid adenomas using high resolution contrast-enhanced ultrasound (CEUS).

To evaluate the impact of high-resolution contrast-enhanced ultrasound (CEUS), Color Coded and Power Doppler Sonography (CCDS/PD), in the preoperative recognition of thyroid adenomas. A total of 64 patients (36 female, median age 54 years) underwent surgery for thyroid adenoma. CEUS with linear multifrequency probes (6-9 or 6-15 MHz) and CCDS/PD was performed in all patients preoperatively by an experienced examiner and images were stored in PACS. Reading of the ultrasound images was performed in consensus by two experienced radiologists. Histopathology was achieved as standard of reference in all patients. Median diameter of the tumor lesions was 27 mm. 31 nodules were found on the left side. In B-Scan mode 13 (20%) adenomas showed complex cystic echo pattern and 44 (69%) had a complete and sharp hypoechoic edge. 43 (67%) thyroid adenomas had strong hypervascularization in CCDS/PD. In 61 (95%) adenomas early contrast enhancement was present in CEUS and 50 (78%) adenomas proved no wash-out or central wash-out with persisting edge enhancement. In 47 (73%) cases early contrast enhancement was combined with no washout or with central wash-out with persisting edge enhancement. 45 (70%) thyroid lesions had preoperatively been classified as benign lesions correctly. Dynamic evaluation of microcirculation by CEUS and CCDS/PD enables a more reliable preoperative characterization of thyroid adenomas.

Complications during carotid artery stenting.

Carotid stenting has become a commonly used procedure for the treatment of carotid artery stenosis. Though equipment and techniques have improved tremendously over the recent 3 decades, complications do occur. It is important for carotid operators to be familiar with potential complications and adverse events. In this article complications and adverse events of carotid stenting including those that are related to the vascular access site, vessel spasm, dissection, perforation, thrombotic occlusion and hemodynamic instability and arrhythmias are reviewed. In addition, management strategies are discussed.

Acute and long-term results of carotid stenting under proximal embolic protection using the Gore Flow Reversal System.

OBJECTIVE: This study evaluates short- and long-term results of CAS with the Gore Flow Reversal System (GFRS). BACKGROUND: Embolic protection devices are of fundamental importance in carotid artery stenting (CAS). Proximal protection has potential advantages compared with distal protection. Limited data are available regarding the safety of the proximal GFRS. METHODS: CAS was performed with the GFRS. Patients' neurological status was assessed during the intervention and at follow-up. Results of patients treated before 2006 were also compared to those of patients treated after 2006 because of changes in device design. RESULTS: CAS was performed in 86 patients with 87 stenoses (symptomatic in 37%). The procedure was technically successful in all cases. In 11 patients a transient periprocedural neurologic deficit occurred related to temporary cerebral flow compromise during balloon occlusion with complete resolution at completion of the procedure. The stroke/death rate at one month was 2.3% with a combined ipsilateral stroke and death rate at one year of 4.6%. There was no significant difference in event rates between the newer and older device version. Overall follow-up time was 484 ± 3.4 patient years with a range of 0 to 119 months. The average yearly ipsilateral stroke rate including the first 30 days was 0.96%. CONCLUSION: Our results demonstrate that CAS using the GFRS is safe whether the original or new device versions were used. The periprocedural stroke rate is at least as low as the stroke rate reported using distal protection. The long-term stroke rate after CAS is low.

All-reflective, highly accurate polarization rotator for high-power short-pulse laser systems.

We present the setup of a polarization rotating device and its adaption for high-power short-pulse laser systems. Compared to conventional halfwave plates, the all-reflective principle using three zero-phase shift mirrors provides a higher accuracy and a higher damage threshold. Since plan-parallel plates, e.g. these halfwave plates, generate postpulses, which could lead to the generation of prepulses during the subsequent laser chain, the presented device avoids parasitic pulses and is therefore the preferable alternative for high-contrast applications. Moreover the device is easily scalable for large beam diameters and its spectral reflectivity can be adjusted by an appropriate mirror coating to be well suited for ultra-short laser pulses.

Evaluation of the microvascularization of pathologic parathyroid glands in patients with primary hyperparathyroidism using conventional ultrasound and contrast-enhanced ultrasound.

PURPOSE: The objective was to characterize the microcirculation of parathyroid adenomas using contrast-enhanced ultrasound (CEUS) and to evaluate if it can be used for diagnosis and localization of pathologic glands. PATIENTS AND METHODS: Thirty patients with primary hyperparathyroidism scheduled for parathyroidectomy were enrolled. Preoperatively, all patients underwent B-Scan sonography, Colour coded Doppler Sonography (CCDS), Power Doppler (PD) and CEUS. The diagnostic confidence concerning B-Scan, CCDS, PD and CEUS was classified into six grades (0: no adenoma; 5: adenoma). RESULTS: Using CEUS, all adenomatous glands showed a typical dynamic microvascularization. B-Scan showed a mean grade of 2.18, CCDS 2.29, PD 2.33, CEUS 4.29 (6-9 MHz transducer) and 3.52 (6-15 MHz). The differences between CEUS and conventional sonography were all statistically significant (p < 0.05). CEUS noted a sensitivity of 98.4% and specificity of 98.4% for the detection of adenomatous glands. CONCLUSION: CEUS facilitates the detection and diagnosis of pathologic parathyroid glands due to their typical microvascularization.

Mini-incision for strictly retroperitoneal nephrectomy in living kidney donation vs flank incision.

BACKGROUND: Mini-incision donor nephrectomies (MIDNs) were established during the last decade, as an alternative to traditional open donor nephrectomy (ODN) via flank incision. In this study, we investigated intra-operative and post-operative data on outcome following MIDN in comparison with ODN data. METHODS: Data of 70 living kidney donations, performed at the University of Regensburg Medical Center since 1996, were evaluated. Donor operation was performed as either strictly retroperitoneal MIDN (n = 34) or as traditional ODN (n = 36) via flank incision. Total operation time, warm ischaemia time (WIT), perioperative pain-medication usage and creatinine levels as well as length of hospital stay, return to complete enteral nutrition and regular digestion were evaluated retrospectively. RESULTS: Total operation times were similar in MIDN, n = 34 (132 +/- 26 min) and in ODN, n = 36 (140 +/- 37 min) (P = 0.424). WIT was also similar in both: MIDN (0.9 +/- 0.4 min) and ODN (0.9 +/- 0.4 min) (P = 0.568). The requirement for post-operative opioids in morphine equivalent doses was significantly lower in MIDN (8.4 +/- 16 mg) compared with ODN (44 +/- 57 mg) (P = 0.001). Additional application of non-opioids (metamizole) (MIDN: 4.8 +/- 6.3 g, ODN: 3.4 +/- 3.9 g) and non-steroidal antirheumatic (NSAR) (diclofenac) (MIDN: 322 +/- 361 mg, ODN: 247 +/- 474 mg) revealed no significant differences between the groups. The hospital stay was 4.9 +/- 1.4 days in MIDN which was significantly shorter than that in ODN (9.3 +/- 3.3 days) (P = 0.001). Patients achieved fully independent mobility earlier in MIDN than in ODN (P = 0.934). Start of enteral nutrition with fluids was significantly quicker in MIDN (1.9 +/- 7 h) compared with ODN (12 +/- 13 h) (P = 0.05). Full enteral nutrition was accomplished significantly earlier in MIDN (1.6 +/- 0.8 days) (P = 0.023). Return to normal digestion revealed no significant differences between groups. Serum creatinine levels of all kidney donors were in the normal range (66 +/- 18 micromol/l) one day before nephrectomy, increased on day 1 after surgery (119 micromol/l +/- 31 micromol/l) and were stable on day 3 (115 micromol/l +/- 30 micromol/l) without significant differences. CONCLUSION: Strictly, retroperitoneal MIDN in living kidney donation is a fast and safe method for the procurement of a living donor graft, giving the patient a significantly shorter period of recovery, and thus is an attractive and recommendable alternative to traditional ODN procedures.

[Pararectal mini-incision for strictly retroperitoneal nephrectomy in living kidney donation]. / Pararektale Miniinzision zur streng retroperitonealen Nephrektomie in der Lebendspende.

PURPOSE: In this study we present the technique of a strictly retroperitoneal donor nephrectomy via a pararectal mini-incision. MATERIAL AND METHODS: Data of 34 living kidney donations were analyzed. All donors underwent a pararectal mini-incision and strictly retroperitoneal nephrectomy (MIDN). RESULTS: Total operation time, perioperative use of pain medication, length of hospital stay after successful mobilization, and return to full enteral nutrition and regular digestion were evaluated retrospectively. Total operation time for MIDN was 132+/-26 min. The total average application was 22.2+/-19.4 mg of opioid in morphine equivalent dosage (MED), 7.7+/-6.1 g metamizol, and 512+/-325 mg NSAR during hospital stay, which was 4.9+/-1.4 days. Patients were mobilized primarily 2.9+/-8.0 h after surgery. Mobility was achieved 33.8+/-15.8 h after surgery. Enteral nutrition with fluids was started after 1.9+/-7.0 h, full enteral nutrition was accomplished after 37.4+/-19.0 h, and normal digestion returned 58.6+/-23.0 h after the procedure. CONCLUSIONS: The strictly retroperitoneal nephrectomy via a mini-incision is an elegant, minimally traumatic, safe, and quickly learnable method, resulting in short hospital stays, good cosmetic results, and a low grade of complications.

Short-term treatment with anti-CD44v7 antibody, but not CD44v4, restores the gut mucosa in established chronic dextran sulphate sodium (DSS)-induced colitis in mice.

Increased expression of CD44 variant isoforms have been shown on the inflammatory infiltrates in human and mouse colitis and blockade or deletion of CD44 isoforms inhibit experimental colitis. The objective of this study was to find out if short-term treatment of CD44 antibodies specific to CD44v7, but not to other variant isoforms, suppresses leucocyte-endothelial interaction in chronic dextran sodium sulphate (DSS)-induced colitis in mice. Chronic colitis was induced by oral administration of four cycles of 5% DSS in BALB/c mice. Expression of CD44 was investigated on isolated mononuclear cells of the gut immune system. In established colitis, mice were treated with antibodies against CD44v7 or CD44v4 three times in 7 days. Intravital microscopy was used to study leucocyte-endothelial interactions and leucocyte extravasation. As a marker of inflammatory infiltrates myeloperoxidase was quantified in gut tissue. CD44-induced apoptosis was determined by fluorescence staining of hypodiploidic cell nuclei. In chronic DSS-induced colitis both CD44 variant isoforms, v4 and v7 were significantly up-regulated on mononuclear cells. However, whereas anti-CD44v7 antibody treatment induced a marked restoration of the gut mucosa and significantly reduced endothelial sticking and extravasation of circulating leucocyte in vivo (P < 0.01), application of anti-CD44v4 or an isotype control antibody had no anti-inflammatory effect. A significant reduction of myeloperoxidase activity was detected after blockade of CD44v7, but not v4. Short-term treatment with anti-CD44v7 antibody blocks T cell extravasation and recruitment to the intestinal mucosa and cures established experimental colitis.

Preferential migration of CD62L cells into the appendix in mice with experimental chronic colitis.

BACKGROUND: Clinical and experimental studies suggest that appendectomy can protect against development of ulcerative colitis and Crohn's disease. However, how T cells in the appendix affect the development of colitis has not been clarified. AIM: To investigate the in vivo migration and activation of colitis-inducing CD62L+ cells during development of chronic colitis. METHODS: CD62L+CD4+ cells were fluorescently labeled and transferred to severe combined immunodeficient (SCID) mice to induce colitis. In vivo migration of T cells into the mucosa of the appendix and colon was quantified by in vivo microscopy after 7 weeks. In a second experiment, unlabeled CD62L+CD4+ cells were transferred, reisolated after 7 weeks, and adhesion molecule (integrin alpha4beta7) and costimulatory molecule (CD154) expression was analyzed. RESULTS: Six to eight weeks after CD62L+CD4+ cell transfer, SCID mice developed chronic colitis. In vivo microscopic analysis demonstrated a preferential migration of fluorescence-labeled CD62L+CD4+ cells into the mucosa of the appendix versus the colon. Re-isolation of lamina propria cells from mice with colitis confirmed that CD62L+CD4+ cell migration was significantly enhanced in the appendix, compared to the colon (3.5-fold). Furthermore, a higher proportion of CD62L+CD4+ cells re-isolated from the appendix expressed integrin alpha4beta7 and CD154 than from the colon. CONCLUSION: This study demonstrates the preferential migration of CD62L+CD4+ cells into the appendix as compared to the colon. This migration pattern correlated with upregulation of integrin alpha4beta7 and CD154 (CD40 ligand) on T cells. Our results suggest an important role of the appendix in the pathogenesis of colitis.