Claudia Seifarth

RORγt+ Innate Lymphoid Cells Acquire a Proinflammatory Program upon Engagement of the Activating Receptor NKp44

RORγt⁺ innate lymphoid cells (ILCs) are crucial players of innate immune responses and represent a major source of interleukin-22 (IL-22), which has an important role in mucosal homeostasis. The signals required by RORγt⁺ ILCs to express IL-22 and other cytokines have been elucidated only partially. Here we showed that RORγt⁺ ILCs can directly sense the environment by the engagement of the activating receptor NKp44. NKp44 triggering in RORγt⁺ ILCs selectively activated a coordinated proinflammatory program, including tumor necrosis factor (TNF), whereas cytokine stimulation preferentially induced IL-22 expression. However, combined engagement of NKp44 and cytokine receptors resulted in a strong synergistic effect. These data support the concept that NKp44⁺ RORγt⁺ ILCs can be activated without cytokines and are able to switch between IL-22 or TNF production, depending on the triggering stimulus.

Determination of the temperature-dependent electric conductivity of liver tissue ex vivo and in vivo: Importance for therapy planning for the radiofrequency ablation of liver tumours

Introduction: Knowledge about the changes in the electric conductivity during the coagulation process of radiofrequency ablation of the liver is a prerequisite for the predictability of produceable thermonecrosis in the liver. Materials and methods: Continuous measurements of the electric conductivity σ in ex vivo porcine liver (n = 25) were done during the coagulation and cooling process at the temperature range of the radiofrequency ablation at a frequency of 470 kHz relevant for the radiofrequency ablation. Measurements of the electric conductivity were performed in both perfused porcine liver (n = 3) and a human surgical specimen from a colorectal liver metastasis. Results: At a body temperature of 37°C, conductance σ was 0.41 siemens per metre (0.32 S/m; 0.52 S/m). Conductance σ increased continuously and uniformly at a temperature of 77°C. Maximum conductance σ with 0.79 S/m (0.7 S/m; 0.87 S/m) was reached at 80°C. A continuous reduction of conductance was observed during the cooling phase. At 37°C, the specific conductance σ in the healthy perfused porcine liver was 0.52 S/m, 0.55 S/m and 0.57 S/m (mean 0.55 S/m). The electric conductivity of the human colorectal liver metastasis was clearly higher. Conclusion: Changes in the specific conductivity during the coagulation and the cooling phase play an important role for the produceable size of a coagulation necrosis and necessitates an adaptation of the therapy parameters during radiofrequency ablation.

Therapy of complicated Crohn's disease during pregnancy--an interdisciplinary challenge.

BackgroundSevere courses of Crohn’s disease (CD) during pregnancy are rare. However, if occurring, the risk of miscarriage and low birth weight is increased. At present, only limited data is available on the treatment of CD during pregnancy. In particular, there are no standard guidelines for surgical therapy. Nevertheless, surgery is often unavoidable if complications during the course of the disease arise.PurposeThis study provides a critical overview of conventional and interventional treatment options for CD complications during pregnancy and analyses the surgical experience gained thus far. For illustrative purposes, clinical cases of three young women with a severe clinical course during pregnancy are presented.MethodsAfter treatment-refractory for conservative and interventional measures, surgery remained as the only treatment option. In all cases, a split stoma was created after resection to avoid anastomotic leaks that would endanger the lives of mother and child. The postoperative course of all three patients was uneventful, and pregnancy remained intact until delivery. No further CD specific medication was required before birth.ConclusionsThe management of CD patients during pregnancy requires close interdisciplinary co-operation between gastroenterologists, obstetricians, anaesthetists and visceral surgeons. For the protection of mother and child treatment should thus be delivered in a specialised centre. This article demonstrates the advantages of surgical therapy by focusing on alleviating CD complaints and preventing postoperative complications.

[Proctocolectomy in ulcerative colitis : is a multistep procedure in cases of immunosuppression advisable?].

BACKGROUND The coloproctomucosectomy (CPM) is the procedure of the choice for the surgical treatment of ulcerative colitis (UC). In cases with pronounced immunosuppression (IS), a 3-step (3S) procedure [i.e., subtotal colectomy and ileal pouch-anal anastomosis (IPAA) and finally ileostomy reconstruction] is often selected. Fewer perioperative complications can be expected compared to the 2-step (2S) procedure; however, an additional in-hospital stay and surgical intervention are necessary. The aim of the present study was to compare both approaches using the clinical outcome of our patients undergoing IPAA to determine efficacy of these two concepts. PATIENTS AND METHODS From 1997-2010, a total of 225 patients were operated using a 2S or 3S IPAA procedure. Clinical outcomes were evaluated based on the number of surgical steps for the ileoanal pouch procedure and IPAA. The survey was performed within the scope of prospective study. RESULTS Of the 225 patients with CPM, 66 were excluded due to a diagnosis other than UC (familial adenomatous polyposis, indeterminate colitis, Crohns disease) and patients with permanent ILS procedures without the possibility or wish for an IPAA (n =  54). Included were 71 patients with 2S (w = 30, m = 41) and 34 patients with 3S procedures (w = 21, m = 13). Compared to the 2S procedure, the 3S procedure was shown to have shorter operation times (246 versus 296 min; p  = 0.05), shorter hospital stays (15.5 versus 24.6 days; p = 0.05), shorter intensive care unit stays (3.3 versus 7.2 days; p = 0.05), and fewer major complications (5.9 % versus 22.5 %; p = 0.035). Patients with 3S procedures had a higher BMI (26.2 versus 23.1 kg/m²; p = 0.05) and fewer required IS (10 % vs. 62 %; p < 0.05). CONCLUSION The decision for a 3S procedure in UC and pronounced IS is advisable and justified. Using a 3S procedure, immunosuppression and its influence on perioperative morbidity are thus reduced. The IPAA can be performed with shorter operation times, shorter hospital stays and fewer major complications.

Die Proktokolektomie bei Colitis ulcerosa

BACKGROUND The coloproctomucosectomy (CPM) is the procedure of the choice for the surgical treatment of ulcerative colitis (UC). In cases with pronounced immunosuppression (IS), a 3-step (3S) procedure [i.e., subtotal colectomy and ileal pouch-anal anastomosis (IPAA) and finally ileostomy reconstruction] is often selected. Fewer perioperative complications can be expected compared to the 2-step (2S) procedure; however, an additional in-hospital stay and surgical intervention are necessary. The aim of the present study was to compare both approaches using the clinical outcome of our patients undergoing IPAA to determine efficacy of these two concepts. PATIENTS AND METHODS From 1997-2010, a total of 225 patients were operated using a 2S or 3S IPAA procedure. Clinical outcomes were evaluated based on the number of surgical steps for the ileoanal pouch procedure and IPAA. The survey was performed within the scope of prospective study. RESULTS Of the 225 patients with CPM, 66 were excluded due to a diagnosis other than UC (familial adenomatous polyposis, indeterminate colitis, Crohns disease) and patients with permanent ILS procedures without the possibility or wish for an IPAA (n =  54). Included were 71 patients with 2S (w = 30, m = 41) and 34 patients with 3S procedures (w = 21, m = 13). Compared to the 2S procedure, the 3S procedure was shown to have shorter operation times (246 versus 296 min; p  = 0.05), shorter hospital stays (15.5 versus 24.6 days; p = 0.05), shorter intensive care unit stays (3.3 versus 7.2 days; p = 0.05), and fewer major complications (5.9 % versus 22.5 %; p = 0.035). Patients with 3S procedures had a higher BMI (26.2 versus 23.1 kg/m²; p = 0.05) and fewer required IS (10 % vs. 62 %; p < 0.05). CONCLUSION The decision for a 3S procedure in UC and pronounced IS is advisable and justified. Using a 3S procedure, immunosuppression and its influence on perioperative morbidity are thus reduced. The IPAA can be performed with shorter operation times, shorter hospital stays and fewer major complications.

Die Proktokolektomie bei Colitis ulcerosaProctocolectomy in ulcerative colitis

BACKGROUND The coloproctomucosectomy (CPM) is the procedure of the choice for the surgical treatment of ulcerative colitis (UC). In cases with pronounced immunosuppression (IS), a 3-step (3S) procedure [i.e., subtotal colectomy and ileal pouch-anal anastomosis (IPAA) and finally ileostomy reconstruction] is often selected. Fewer perioperative complications can be expected compared to the 2-step (2S) procedure; however, an additional in-hospital stay and surgical intervention are necessary. The aim of the present study was to compare both approaches using the clinical outcome of our patients undergoing IPAA to determine efficacy of these two concepts. PATIENTS AND METHODS From 1997-2010, a total of 225 patients were operated using a 2S or 3S IPAA procedure. Clinical outcomes were evaluated based on the number of surgical steps for the ileoanal pouch procedure and IPAA. The survey was performed within the scope of prospective study. RESULTS Of the 225 patients with CPM, 66 were excluded due to a diagnosis other than UC (familial adenomatous polyposis, indeterminate colitis, Crohns disease) and patients with permanent ILS procedures without the possibility or wish for an IPAA (n =  54). Included were 71 patients with 2S (w = 30, m = 41) and 34 patients with 3S procedures (w = 21, m = 13). Compared to the 2S procedure, the 3S procedure was shown to have shorter operation times (246 versus 296 min; p  = 0.05), shorter hospital stays (15.5 versus 24.6 days; p = 0.05), shorter intensive care unit stays (3.3 versus 7.2 days; p = 0.05), and fewer major complications (5.9 % versus 22.5 %; p = 0.035). Patients with 3S procedures had a higher BMI (26.2 versus 23.1 kg/m²; p = 0.05) and fewer required IS (10 % vs. 62 %; p < 0.05). CONCLUSION The decision for a 3S procedure in UC and pronounced IS is advisable and justified. Using a 3S procedure, immunosuppression and its influence on perioperative morbidity are thus reduced. The IPAA can be performed with shorter operation times, shorter hospital stays and fewer major complications.

Die Proktokolektomie bei Colitis ulcerosa@@@Proctocolectomy in ulcerative colitis: Ist ein mehrzeitiges Vorgehen bei Immunsuppression sinnvoll?@@@Is a multistep procedure in cases of immunosuppression advisable?

BACKGROUND The coloproctomucosectomy (CPM) is the procedure of the choice for the surgical treatment of ulcerative colitis (UC). In cases with pronounced immunosuppression (IS), a 3-step (3S) procedure [i.e., subtotal colectomy and ileal pouch-anal anastomosis (IPAA) and finally ileostomy reconstruction] is often selected. Fewer perioperative complications can be expected compared to the 2-step (2S) procedure; however, an additional in-hospital stay and surgical intervention are necessary. The aim of the present study was to compare both approaches using the clinical outcome of our patients undergoing IPAA to determine efficacy of these two concepts. PATIENTS AND METHODS From 1997-2010, a total of 225 patients were operated using a 2S or 3S IPAA procedure. Clinical outcomes were evaluated based on the number of surgical steps for the ileoanal pouch procedure and IPAA. The survey was performed within the scope of prospective study. RESULTS Of the 225 patients with CPM, 66 were excluded due to a diagnosis other than UC (familial adenomatous polyposis, indeterminate colitis, Crohns disease) and patients with permanent ILS procedures without the possibility or wish for an IPAA (n =  54). Included were 71 patients with 2S (w = 30, m = 41) and 34 patients with 3S procedures (w = 21, m = 13). Compared to the 2S procedure, the 3S procedure was shown to have shorter operation times (246 versus 296 min; p  = 0.05), shorter hospital stays (15.5 versus 24.6 days; p = 0.05), shorter intensive care unit stays (3.3 versus 7.2 days; p = 0.05), and fewer major complications (5.9 % versus 22.5 %; p = 0.035). Patients with 3S procedures had a higher BMI (26.2 versus 23.1 kg/m²; p = 0.05) and fewer required IS (10 % vs. 62 %; p < 0.05). CONCLUSION The decision for a 3S procedure in UC and pronounced IS is advisable and justified. Using a 3S procedure, immunosuppression and its influence on perioperative morbidity are thus reduced. The IPAA can be performed with shorter operation times, shorter hospital stays and fewer major complications.

Die bipolare Radiofrequenzablation für noduläre Schilddrüsenerkrankungen – Ex vivo und in vivo Evaluierung einer Dosis-Wirkungs-Beziehung

Radiofrequency ablation (RFA) is an established procedure for therapy of tumors of parenchymatous organs like the liver. RFA could also be suitable for the minimally invasive therapy of singular thyroid nodules. The aim of this study was to establish a dose-response relationship for RFA of thyroid nodules. Thermal lesions were induced in healthy porcine thyroid glands ex vivo (n = 110) and in vivo (n = 10) using a bipolar radiofrequency system. RF was applied in a power range of 10–20 watts. During the ablation, continuous temperature measurement at a distance of 5 and 10 mm from the applicator was performed. The transversal and axial lesion diameters were measured, and the volume was calculated. Furthermore, enzyme histochemical analysis of the thyroid tissue was performed. The inducible lesion volumes were between 2.43 ± 0.68 cm3 at 10 W and 0.91 ± 0.21 cm3 at 20 W. The maximum temperatures after RF ablation were between 30.0 ± 8.6 °C and 53.5 ± 8.6 °C at a distance of 5 mm and between 44.0 ± 9.7 °C and 61.6 ± 13.9 °C at a distance of 10 mm from the applicator. The histochemical analysis demonstrates a complete loss of NADPH dehydrogenase activity in thermal lesions as a sign of irreversible cell damage. RFA induces reproducible clinically relevant lesions with irreversible cell damage and seems to be suitable for therapy of singular thyroid nodules.