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A wide spectrum of immunological functions has been attributed to Interleukin 9 (IL-9), including effects on the survival and proliferation of immune and parenchymal cells. In recent years, emerging evidence suggests that IL-9 expression can promote tissue repair in inflammatory conditions. However, data about the involvement of IL-9 in kidney tissue protection is very limited. Here, we investigated the role of IL-9 in Adriamycin-induced nephropathy (AN), a mouse model for proteinuric chronic kidney disease. Compared to wild type mice, IL-9 knockout (Il9−/−) mice with AN displayed accelerated development of proteinuria, aggravated glomerulosclerosis and deterioration of kidney function. At an early stage of disease, the Il9−/− mice already displayed a higher extent of glomerular podocyte injury and loss of podocyte number compared to wild type mice. In the kidney, T cells and innate lymphoid cells produced IL-9. However, selective deficiency of IL-9 in the innate immune system in Il9−/−Rag2−/− mice that lack T and B cells did not alter the outcome of AN, indicating that IL-9 derived from the adaptive immune system was the major driver of tissue protection in this model. Mechanistically, we could show that podocytes expressed the IL-9 receptor in vivo and that IL-9 signaling protects podocytes from Adriamycin-induced apoptosis in vitro. Finally, in vivo treatment with IL-9 effectively protected wild type mice from glomerulosclerosis and kidney failure in the AN model. The detection of increased serum IL-9 levels in patients with primary focal and segmental glomerulosclerosis further suggests that IL-9 production is induced by glomerular injury in humans. Thus, IL-9 confers protection against experimental glomerulosclerosis, identifying the IL-9 pathway as a potential therapeutic target in proteinuric chronic kidney disease.

Cancers 14(5), 1261 (2022). doi:10.3390/cancers14051261, Published by MDPI, Basel

What are the origins of direct democracy in Switzerland? How does the Swiss judiciary function? What are the principles of Swiss civil, contract and administrative law? What is the role of public service broadcasting in the political decision-making process? What are the leading cases in tax law? What forms of euthanasia are legal in Switzerland? In this introduction 19 legal scholars of the University of Zurich Law Faculty try to answer these questions and give the reader an overview of Swiss public, private, and criminal law. As the first comprehensive introduction to Swiss law in English, it is addressed to both lawyers from abroad and incoming students to the University of Zurich.

OBJECTIVES: Leukoencephalopathy (LEP, i.e. white matter T2-/FLAIR-hyperintensities on MRI) and impaired neuropsychological outcome are side effects of multimodal therapy of medulloblastoma. We identified risk factors for LEP and correlated LEP with neurocognitive functioning. PATIENTS AND METHODS: Severity of LEP either at the end of therapy (n=118), two years (n=126), or five years after surgery (n=139) was evaluated according to an adapted Fazekas classification for 162 survivors of medulloblastoma (median age: 7.4 years [range:0.67-19.8 years]). Severity of LEP two or five years after surgery was correlated with treatment and neurocognitive functioning ≥ five years after diagnosis using univariate analyses and multivariate generalized mixed linear models. RESULTS: Two and five years after surgery, incidences of mild/moderate/severe LEP were 21.4%/17.5%/9.5%, and 24.5%/23.7%/8.6%, respectively. Data on severity of LEP both at the end of therapy and five years after surgery was available for 103 patients: LEP grades increased for 1/2 degrees in 18/4 patients and decreased in 13/1 patients, respectively. Both treatment approaches - HIT-SKK chemotherapy including intraventricular methotrexate (SKK) and craniospinal irradiation (CSI) - were associated with increased severity of LEP (CSI+SKK > SKK only > CSI only; p30Gy, severe LEP, but not SKK including intraventricular MTX, correlated with impaired neurocognitive functioning. CONCLUSION: After therapy strong changes in LEP rarely occurred. Severe LEP was associated both with the combination of SKK and CSI, and impaired neurocognitive functioning. Further research will be needed to weigh potential benefits of SKK including intraventricular methotrexate with CSI against its neurotoxicity.

Purpose Intracranial germ cell tumors (iGCT) comprise germinoma and non-germinoma. Their diagnosis predominantly relies on biopsy as only one-fifth of patients present with elevated biomarkers (AFP/ß-HCG) in serum or cerebrospinal fluid (CSF). MicroRNAs (miR/miRNA) have emerged as non-invasive biomarkers in extracranial GCT and may potentially facilitate non-invasive diagnosis in iGCT. Methods We analyzed eight miRNAs in serum and CSF from the miR-371~373- and miR-302/367-clusters and four miRNAs differentially expressed in iGCT tissue (miR-142-5p/miR-146a-5p/miR-335-5p/miR-654-3p) from eight iGCT patients (age 10–33 years) and 12 control subjects by pre-amplified RT-qPCR. MiR-30b-5p (serum) and miR-204-5p (CSF) acted as reference genes. ΔCt-values were expressed as $$2^{{ - \Delta \Delta C_{{\text{t}}} }}$$ 2 - Δ Δ C t after standardization against controls. Results Between iGCT and control patients’ serum ΔCt-values of miR-371a-3p (p = 0.0159), miR-372-3p (p= 0.0095, miR-367 (p = 0.0190), miR-302a (p = 0.0381) and miR-302d-3p (p = 0.0159) differed significantly. Discriminatory pattern in CSF was similar to serum as miR-371a (p = 0.0286), miR-372-3p (p = 0.0028), miR-367-3p (p = 0.0167) and miR-302d-3p (p = 0.0061) distinguished between patients and controls. Abundant $$2^{{ - \Delta \Delta C_{{\text{t}}} }}$$ 2 - Δ Δ C t levels of each of these miRNAs were found across all serum and CSF samples including biomarker-negative patients. Conclusion With the largest data set so far, we underline the suitability of miR-371a, miR-372, miR-367 and miR-302d in serum and CSF for diagnosis of iGCT, particularly in biomarker-negative germinoma. Diagnosis of iGCT by miRNA analysis is a feasible and valid approach, particularly as serum can be readily obtained by a less invasive procedure. MiRNA analysis may discriminate iGCT from other tumors with similar radiological findings and may allow to monitor response to therapy as well as early relapse during follow-up.

Pathologic conditions in the cornea, such as transplant rejection or trauma, can lead to corneal neovascularization, creating a high-risk environment that may compromise subsequent transplantation. This study aimed to evaluate the impact of different types of corneal injury on hemangiogenesis (HA), lymphangiogenesis (LA) and immune cell pattern in the cornea.We used five different corneal injury models, namely, incision injury, alkali burn, suture placement, and low-risk keratoplasty, as well as high-risk keratoplasty and naïve corneas as control. One week after incision and 2 weeks after all other different injuries, corneal HA and LA were quantified by morphometric analysis. In addition, immune cell patterns of the whole cornea and the recipient rim were analyzed by immunohistochemistry. Immune cells in the draining lymph nodes (dLNs) were quantified by flow cytometry.Different types of corneal injury caused significantly different HA and LA responses (both P0.0001). The infiltration of corneal macrophages, dendritic cells, neutrophils, major histocompatibility complex (MHC) II+ cells, CD4+ T cells, and CD8+ T cells varied significantly in different high-risk settings (all P0.0001). Both the expression of MHC II on macrophages (P = 0.0005) and the frequency of MHC II+ dendritic cells (P = 0.0014) in the draining lymph nodes were significantly different across the various high-risk scenarios.Murine high-risk settings caused by different underlying pathologies vary significantly in their (lymph)angiogenic and inflammatory cell patterns. Therefore, anti(lymph)angiogenic or immunomodulatory strategies to prevent and/or treat immune responses after subsequent corneal transplantation may need to be customized according to their immune-vascular "signatures."

In recent years, the cytokine interleukin (IL)-22 attracted considerable attention due to its important immunoregulatory function in barrier tissues, such as the gut, lung, and skin. Although a regenerative role of IL-22 in renal tubular damage has been demonstrated, the role of IL-22 in the immunopathogenesis of glomerular injury is still unknown. Here, we demonstrate that the IL-22 receptor is expressed in the glomerular compartment of the kidney and that IL-22 expression increases in the renal cortex after induction of glomerular injury in a mouse model for crescentic glomerulonephritis (cGN, nephrotoxic nephritis). We identified γδ T cells and TH17 cells as major sources for IL-22 in the nephritic kidney. However, neither genetic or antibody-mediated deletion of IL-22 nor genetic deficiency in its endogenous inhibitor IL-22Rα2 (IL-22 binding protein) resulted in substantial phenotypic differences in mice with cGN with respect to crescent formation, tubulointerstitial damage, and kidney function impairment. Similarly, we did not observe significant differences between wild-type or IL-22-deficient mice in a mouse model of secondary focal and segmental glomerulosclerosis (adriamycin-induced nephropathy). As shown previously, we detected concomitant upregulation of IL-17A and IFN-γ production by T cells during the course of cGN, providing alternative cytokine pathways that mediate glomerular injury in this model. In conclusion, we show here that endogenous IL-22 expression is redundant in different forms of glomerular injury, indicating that the IL-22-directed therapies that are being tested in various human diseases might not affect the kidney in patients with glomerular disease.

Although it is well established that microbial infections predispose to autoimmune diseases, the underlying mechanisms remain poorly understood. After infection, tissue-resident memory T (TRM) cells persist in peripheral organs and provide immune protection against reinfection. However, whether TRM cells participate in responses unrelated to the primary infection, such as autoimmune inflammation, is unknown. By using high-dimensional single-cell analysis, we identified CD4+ TRM cells with a TH17 signature (termed TRM17 cells) in kidneys of patients with ANCA-associated glomerulonephritis. Experimental models demonstrated that renal TRM17 cells were induced by pathogens infecting the kidney, such as Staphylococcus aureus, Candida albicans, and uropathogenic Escherichia coli, and persisted after the clearance of infections. Upon induction of experimental glomerulonephritis, these kidney TRM17 cells rapidly responded to local proinflammatory cytokines by producing IL-17A and thereby exacerbate renal pathology. Thus, our data show that pathogen-induced TRM17 cells have a previously unrecognized function in aggravating autoimmune disease.

Objective Evaluate the impact of endoscopic partial inferior turbinectomy (EPIT) associated with primary rhinoseptoplasty on quality-of-life outcomes (QOL), complications, and surgical duration. Study design Randomized clinical trial. Methods Individuals with nasal obstruction aged ≥ 16 years who were candidates for functional and aesthetics primary rhinoseptoplasty were evaluated from March 2014 through May 2015. Eligible participants were randomly allocated to rhinoseptoplasty with or without EPIT (excision of one-third of the inferior turbinates). Results Fifty patients were studied. Most were Caucasian and had moderate/severe allergic rhinitis symptoms. Mean age was 36 ( ± 14.5) years. Rhinoseptoplasty was associated with improvement in all QOL scores irrespective of turbinate intervention (P 0.05). There were no differences between the groups regarding presence of the complications. Surgical duration was higher in the EPIT group (212 minutes ± 7.8 vs. 159.1 ± 5.6; P ? 0.001). Conclusions Turbinate reduction through EPIT during primary rhinoseptoplasty did not improve short-term general and specific QOL outcomes. The use of EPIT increases surgical time considerably without improving QOL scores. There was no difference in postoperative incidence of complications, suggesting that EPIT is a safe technique. Level of evidence 1b. Laryngoscope, 128:57-63, 2018.

Innate lymphoid cells (ILCs) have an important role in the immune system's response to different forms of infectious and noninfectious pathologies. In particular, IL-5- and IL-13-producing type 2 ILCs (ILC2s) have been implicated in repair mechanisms that restore tissue integrity after injury. However, the presence of renal ILCs in humans has not been reported. In this study, we show that ILC populations are present in the healthy human kidney. A detailed characterization of kidney-residing ILC populations revealed that IL-33 receptor-positive ILC2s are a major ILC subtype in the kidney of humans and mice. Short-term IL-33 treatment in mice led to sustained expansion of IL-33 receptor-positive kidney ILC2s and ameliorated adriamycin-induced glomerulosclerosis. Furthermore, the expansion of ILC2s modulated the inflammatory response in the diseased kidney in favor of an anti-inflammatory milieu with a reduction of pathogenic myeloid cell infiltration and a marked accumulation of eosinophils that was required for tissue protection. In summary, kidney-residing ILC2s can be effectively expanded in the mouse kidney by IL-33 treatment and are central regulators of renal repair mechanisms. The presence of ILC2s in the human kidney tissue identifies these cells as attractive therapeutic targets for CKD in humans.

Although it is well established that microbial infections predispose to autoimmune diseases, the underlying mechanisms remain poorly understood. After infection, tissue-resident memory T (T

Since their identification as a separate family of leukocytes, Innate lymphoid cells (ILCs) have been shown to play crucial roles in immune-mediated diseases and repair mechanisms that restore tissue integrity after injury. ILCs mainly populate non-lymphoid tissues where they form intricate circuits with parenchymal cells to regulate tissue immunity and organ homeostasis. However, the specific phenotype and function of ILC populations that reside in specific anatomical locations, such as the kidney, still remains poorly understood. In this review, we discuss tissue-specific properties of kidney-residing ILCs and summarize recent advances in the understanding of ILC biology in kidney diseases that might pave the way for development of novel treatment strategies in humans.

With extensive use of systemic treatment, the issue of cardiac mortality after breast cancer radiation (RT) is still important. The aim of our analysis was to clarify whether the dose to one surrogate parameter (e. g., mean heart dose, as used in most studies) reflects the dose to the other cardiovascular structures especially the left anterior descending artery depending on breathing-adapted RT. A total of 130 patients who underwent adjuvant RT (50.4 Gy plus boost 9–16 Gy) were evaluated. In all, 71 patients were treated with free-breathing and 59 patients using respiratory monitoring (gated RT). Dosimetric associations were calculated. The mean dose to the heart (Dmean heart) was reduced from 2.7 (0.8–5.2) Gy to 2.4 (1.1–4.6) Gy, the Dmean LAD (left anterior descending artery) decreased from 11.1 (1.3–28.6) Gy to 9.3 (2.2–19.9) Gy with gated RT (p = 0.04). A significant relationship was shown for Dmean heart–Dmean LAD, V25heart–Dmean LAD and Dmax heart–Dmax LAD for gated patients only (p < 0.01). For every 1 Gy increase in Dmean heart, mean LAD doses rose by 3.6 Gy, without gating V25 ≤5 % did not assure a benefit and resulted in Dmean LAD between 1.3 and 28.6 Gy. A significant reduction and association of heart and coronary artery (LAD) doses using inspiratory gating was shown. However, in free-breathing plans commonly measured dose constraints do not allow precise estimation of the dose to the coronary arteries.

Aim To determine the influence of IGRT in terms of toxicities compared to non-IGRT patients undergoing definitive RT. Background Image-guided radiotherapy (IGRT) enables immediate correction of target movement by online imaging. For prostate cancer patients undergoing radiation therapy (RT), a geographical miss of the prostate may result in increased dose–volume effects in the rectum and bladder. Methods A total of 198 prostate cancer patients treated between 2003 and 2013 were recruited randomly for this evaluation. The rates of genitourinary (GU) and gastrointestinal (GI) toxicity for 96 non-IGRT patients (total dose: 72/73.8 Gy) were compared to those for 102 IGRT patients (total dose: 77.4 Gy) according to the Common Toxicity Criteria Version 3.0 (CTCAEv3.0). Follow-up information included treatment-related symptoms and PSA relapse. Results After a median follow-up of 55.4 months, a statistically significant difference was noted for acute GI toxicities ≥1 in favour of IGRT. Significantly more patients treated by IGRT were free of acute GI symptoms (43% vs. 19%, p = 0.0012). In the non-IGRT group, more patients experienced acute GU side effects (89% vs. 80%, p = 0.07). Late toxicity scores were comparable for both cohorts. Conclusions Based on the data, we demonstrated that despite dose escalation, IGRT enabled us to reduce the GI side effects of radiation. IGRT can therefore be considered to be the standard of care for dose-escalated RT of localized prostate cancer.

Tumors of the central nervous system represent the largest group of solid tumors found in pediatric patients. Pilocytic astrocytoma is the most common pediatric glioma, mostly located in the posterior fossa. The majority of brainstem tumors, however, are classified as highly aggressive diffuse intrinsic pontine gliomas (DIPGs) and their prognosis is dismal.The authors report on the case of a neonate in whom MRI and neuropathological assessment were used to diagnose DIPG. Before initiation of the planned chemotherapy, the tumor regressed spontaneously, and the newborn exhibited a normal neurological development. Meanwhile, Illumina Human Methylation450 BeadChip analysis reclassified the tumor as pilocytic astrocytoma of the posterior fossa.In conclusion, the authors advocate not initiating immediate intensive therapy in newborns with brain tumors, even with classical appearance of a DIPG; rather, they would like to encourage a biopsy to define the best individual therapeutic approach and avoid ineffective chemotherapy.

Background: The evaluation of collagen in the abdominal wall has been increasingly studied because of the relevance on collagen in the healing process after laparotomy. Aim: To evaluate the amount of collagen in the linea alba of patients undergoing laparotomic bariatric surgery and comparing with non-obese cadavers. Methods: Were evaluated 88 samples of aponeurosis from abdominal linea alba of 44 obese patients (obesity group) and 44 non-obese cadavers (control group). The samples were collected in 2013 and 2104, and were sorted according to age (18-30, 31-45 and 46-60), gender, BMI, waist and cervical circumference, and subcutaneous tissue thickness. Material for biopsy was collected from the supraumbilical region of the linea alba for immunohistochemical analysis differentiating collagen type 1 and type 3 and the 1/3 ratio. Image-Pro Plus pixel counting software was used to measure the amount of collagen. Results: The obesity group evidenced mean age 44.11±9.90 years; 18-30 age group had three (6.8%) obese individuals; 31-45 had 22 (50%) and 46-60 had 19 (43.1%). Females were present in 81.8% (n=36); BMI (kg/m²) was 48.81±6.5; waist circumference (cm) was 136.761±13.55; subcutaneous tissue thickness (cm) 4.873±0.916. Considering age groups, gender and BMI, there were statistical differences in all tests when compared with the cadavers. Conclusion: The amount of collagen in the linea alba above the umbilical region in the morbidly obese patients was smaller than in the non-obese cadavers in the same age group. RESUMO Racional: A avaliação do colágeno na parede abdominal é cada vez mais estudada, em virtude da relevância dele no processo cicatricial após laparotomia. Objetivo: Avaliar a quantidade de colágeno na linha alba de pacientes submetidos à cirurgia bariátrica e compará-la com a de cadáveres não-obesos. Método: Foram avaliados dois grupos com total de 88 amostras da aponeurose da linha alba abdominal, divididas em 44 de pacientes obesos (grupo obesidade) com indicação de cirurgia bariátrica e 44 de cadáveres não-obesos (grupo controle). As amostras foram retiradas da linha alba abdominal no período de 2013 a 2014 e inicialmente foram separadas conforme faixas etárias (18-30, 31-45 e 46-60), gênero, medidas de IMC, circunferência abdominal e cervical e espessura do subcutâneo do indivíduo. Foi coletado material para biópsia da linha alba supraumbilical para análise imunoistoquímica, diferenciando o colágeno tipo I e III e sua relação de tipo I/III. Utilizou-se o programa de contagem de pixels Image-Pro Plus(r), que mensurou a quantidade do colágeno. Resultados: O grupo obesidade teve idade 44,11±9,90 anos, Na faixa etária de 18-30 anos foram incluídos três (6,8%) obesos; na de 31-45 anos 22 (50%) e na de 46-60 anos 19 (43,1%). O gênero feminino apresentou predomínio, com 36 (81,8%) pacientes. O IMC (kg/m²) foi de 48,81±6,5; a circunferência abdominal (cm) foi de 136,761±13,55; a espessura do subcutâneo (cm) foi de 4,873±0,916. A quantidade de colágeno tipo I foi de 134.683,3±206.657,4; a de colágeno tipo III foi de 413.137,2±283.656,1; a razão do colágeno tipo I/III foi 0,419±0,636. Considerando-se faixas de idade, gênero e IMC, foram constatadas diferenças estatísticas em todas as análises quando comparadas com às dos cadáveres. Conclusão: Os obesos mórbidos apresentaram quantidade de colágeno na linha alba supraumbilical menor que a do grupo controle de cadáveres não-obesos na mesma faixa etária.

Current subunit vaccines are incapable of inducing Ag-specific CD8+ T cell cytotoxicity needed for the defense of certain infections and for therapy of neoplastic diseases. In experimental vaccines, cytotoxic responses can be elicited by targeting of Ag into cross-presenting dendritic cells (DC), but almost all available systems use target molecules also expressed on other cells and thus lack the desired specificity. In the present work, we induced CD8+ T cell cytotoxicity by targeting of Ag to XCR1, a chemokine receptor exclusively expressed on murine and human cross-presenting DC. Targeting of Ag with a mAb or the chemokine ligand XCL1 was highly specific, as determined with XCR1-deficient mice. When applied together with an adjuvant, both vector systems induced a potent cytotoxic response preventing the outgrowth of an inoculated aggressive tumor. By generating a transgenic mouse only expressing the human XCR1 on its cross-presenting DC, we could demonstrate that targeting of Ag using human XCL1 as vector is fully effective in vivo. The specificity and efficiency of XCR1-mediated Ag targeting to cross-presenting DC, combined with its lack of adverse effects, make this system a prime candidate for the development of therapeutic cytotoxic vaccines in humans.

It has become evident that nonlymphoid tissues are populated by distinct subsets of innate and adaptive lymphocytes that are characterized by minimal exchange with recirculating counterparts. Especially at barrier sites, such as the skin, gut, and lung, these tissue-resident lymphocyte populations are ideally positioned to quickly respond to pathogens and other environmental stimuli. The kidney harbors several classes of innate and innate-like lymphocytes that have been described to contribute to this tissue-resident population in other organs, including innate lymphoid cells, natural killer cells, natural killer T cells, mucosal-associated invariant T cells, and γδ T cells. Additionally, a substantial proportion of the adaptive lymphocytes that are found in the kidney displays a surface phenotype suggestive of tissue residency, such as CD69+CD4+ T cells. In this review, we summarize recent advances in the understanding of tissue-resident lymphocyte populations, review the available evidence for the existence of these populations in the kidney, and discuss the potential physiologic and pathophysiologic roles thereof in kidney.

Innate lymphoid cells (ILCs) are important regulators of the immune response and play a crucial role in the restoration of tissue homeostasis after injury. GATA-3+ IL-13- and IL-5-producing group 2 innate lymphoid cells (ILC2s) have been shown to promote tissue repair in barrier organs, but despite extensive research on ILCs in the recent years, their potential role in autoimmune diseases is still incompletely understood. In the present study, we investigate the role of ILC2s in the MRL/MpJ-Faslpr (MRL-lpr) mouse model for severe organ manifestation of systemic lupus erythematosus (SLE). We show that in these MRL-lpr mice, progression of lupus nephritis is accompanied with a reduction of ILC2 abundance in the inflamed renal tissue. Proliferation/survival and cytokine production of kidney-residing ILC2s was suppressed by IFN-γ and, to a lesser extent, by IL-27 which were produced by activated T cells and myeloid cells in the nephritic kidney, respectively. Most importantly, restoration of ILC2 numbers by IL-33-mediated expansion ameliorated lupus nephritis and prevented mortality in MRL-lpr mice. In summary, we show here that development of SLE-like kidney inflammation leads to a downregulation of the renal ILC2 response and identify an ILC2-expanding therapy as a promising treatment approach for autoimmune diseases.

Inflammatory myofibroblastic tumor (IMT) and its subtype epithelioid inflammatory myofibroblastic sarcoma (EIMS) are rare soft-tissue tumors. As about 50% of IMT and 100% of EIMS contain activating rearrangements of the anaplastic lymphoma kinase (ALK) gene, targeted kinase inhibition of ALK by compounds such as crizotinib is a potential treatment option. We performed a literature review and analyzed a total of 30 patients with IMT/EIMS treated with crizotinib. A total of 12 patients achieved complete or partial remission. As preliminary data are promising, a prospective study evaluating crizotinib treatment in patients with unresectable/multifocal ALK

Management of anal cancer shifted from radical surgical procedures to sphincter-preserving approaches by combined radio-chemotherapy (RCT). Several randomized trials investigated the most appropriate chemotherapy schedule, radiation doses, and treatment techniques. RCT employing 5-fluorouracil (5-FU)/mitomycin C (MMC) remains the standard treatment. Cisplatin was proposed as an alternative drug but failed to improve outcome when given instead of MMC or during maintenance chemotherapy. Currently, studies are ongoing that investigate staging procedures like PET-CT and diagnostic workup processes in treatment follow-up.

Hintergrund: Die Behandlung der Peritonealkarzinose ist eine interdisziplinäre medizinische Herausforderung. Betreffend der medikamentösen Therapie fehlt bislang eine Standardisierung. Methode: Relevante Artikel zum Thema Peritonealkarzinose aus den Datenbanken der U.S. National Library of Medicine (PubMed) sowie der Kongressregister der American Society of Clinical Oncology und der European Society of Medical Oncology wurden durchsucht. Die Bedeutung der Berichte für die klinische Praxis wurde zwischen den Autoren diskutiert und interdisziplinär abgestimmt. Es wurden praxisnahe Folgerungen und Empfehlungen abgeleitet. Ergebnisse: PubMed weist eine ansteigende Zahl an Publikationen zum Thema Peritonealkarzinose auf. In 2012 wurden 563 Arbeiten unter dem Stichwort abgelegt. Die medikamentöse Therapie der Peritonealkarzinose ist ein Teil der multimodalen Behandlung, zu der die lokalen chirurgischen und physikalischen Therapiemaßnahmen zählen. Die Auswahl der Chemotherapeutika richtet sich nach der entsprechenden malignen Grunderkrankung. Aktuelle zielgerichtete Ansätze wie die anti-angiogene Therapie und die gegen das epitheliale Zelladhäsionsmolekül (EpCAM) gerichtete Immuntherapie ergänzen neuerdings das Behandlungsspektrum bei Peritonealkarzinose und malignem Aszites. Schlussfolgerungen: Die medikamentöse Behandlung der Peritonealkarzinose bleibt eine medizinische Herausforderung. Die zunehmende Zahl an Publikationen und Studien auf dem Gebiet lässt aber mittlerweile mehr evidenzbasierte Entscheidungen zu. Die interdisziplinäre Abstimmung eines individuellen Behandlungskonzepts bleibt bis auf Weiteres der Goldstandard auch für die medikamentöse Therapie der Peritonealkarzinose.

Bronchus-associated Lymphoid Tissue (BALT) lymphoma is a rare type of extranodal marginal zone lymphoma. It is defined as subgroup of B-cell non-Hodgkin’s lymphoma typically with an indolent clinical course. Often the clinical symptoms of pulmonary mucosa-associated lymphoid tissue (MALT) lymphomas are highly heterogeneous with more than half of the patients initially suffering from multiple manifestations. Due to the rarity of this tumour and lack of randomized data, the optimal therapeutical pathway remains controversial. We report a case of this rare tumour with characteristic histological features. The patient complained about severe hemoptysis caused by an isolated tracheobronchial manifestation. According to treatment recommendations of extranodal MALT lymphomas, curative radiotherapy was administered, resulting in a complete and sustaining tumour remission and relief of symptoms.

During radiotherapy 80% to 90% of all patients will develop some degree of inflammation symptoms, such as erythema, dry or wet desquamation, skin folds, or mucositis depending on radiation-and patient-related factors and the extent of irradiated skin or mucosal areas. Up to now radiation induced local reactions represent still an important toxicity factor. Cutaneous and mucosal side effects may reduce the patient's compliance and can be limiting factors to follow radiotherapy protocols. Therefore, there is a high need for effective prophylactic and therapeutic treatments. Basically, guidelines recommend the avoidance of mechanical, chemical and thermal irritants, especially the exposure to high temperatures. To delay onset of radiodermatitis various preventive topicals may be applied like aqueous cream formula with or without antioxidative agents. In general, the treatment of radiodermatitis primarily should maintain moisture and skin permeability and consists of hydrophilic creams, antioxidative and anti-inflammatory topicals. Hydrocolloid dressings may reduce and improve wound healing in grade 2 and 3 reactions. Supportive therapy of radiation-induced mucositis includes the maintenance of oral care protocols and adequate nutrition during the course of treatment. A sufficient oral health status is one of the most important factors for prevention of severe oral complications. The MASCC guidelines recommend furthermore the use of non-medicated rinses with saline or sodium bicarbonate 4 to 6 times daily. Further approaches suggest the use of local anaesthetics and systemic analgesics for severe mucositis. Besides local preventive agents and supportive care protocols, modern radiation treatment techniques remain the most promising intervention in reducing the degree of skin reactions.

Purpose Currently, a routine bone marrow biopsy (BMB) is performed to detect bone marrow (BM) involvement in pediatric Hodgkin's lymphoma (HL) stage greater than IIA. [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) is increasingly used for the initial staging of HL. The value of using FDG-PET to detect BM involvement has not been sufficiently defined. We compared the results of BMBs and FDG-PET for the diagnosis of BM involvement in a large pediatric group with HL. Patients and Methods The initial staging of 175 pediatric patients with newly diagnosed classical HL stage greater than IIA was determined by using BMB, FDG-PET, chest computed tomography (CT), and magnetic resonance imaging (MRI) or CT of the neck, abdomen, and pelvis. Staging images were prospectively evaluated by a central review board. Skeletal regions that were suggestive of BM involvement by either method were re-evaluated by using different imaging modalities. In suspicious cases, bone scintigraphy was performed. If follow-up FDG-PET scans were available, the remission of skeletal lesions during treatment was evaluated. Results BMB results were positive in seven of 175 patients and were identified by FDG-PET. FDG-PET scans showed BM involvement in 45 patients. In addition, the lesions of 32 of these 45 patients had a typical multifocal pattern. In 38 of 39 follow-up positron emission tomography scans, most of the skeletal lesions disappeared after chemotherapy. There was no patient with skeletal findings suggestive of BM involvement by MRI or CT with a negative FDG-PET. Conclusion FDG-PET is a sensitive and specific method for the detection of BM involvement in pediatric HL. The sensitivity of a BMB appears compromised by the focal pattern of BM involvement. Thus, FDG-PET may safely be substituted for a BMB in routine staging procedures.

To the Editor,Muir Torre syndrome (MTS) represents a rare genodermatosis characterized by cutaneous sebaceous tumors and/or keratoakanthomas preceding or existing coincidently with one or more visc...

Even in the era of improved surgical resection techniques adjuvant or neoadjuvant radio/-chemotherapy contributes to a better local control. Short-course preoperative radiotherapy or long-term preoperative radiochemotherapy are two different options with proven efficacy. The first approach may be reasonable for patients in whom a complete surgical removal is possible upfront. Preoperative combined radiochemotherapy is certainly more appropriate for patients who need significant downsizing of the tumour to achieve a resection with clear surgical margins. Acute toxicity is more pronounced during combined preoperative treatment, but long-term side-effects may be more prevalent when using short-course radiation. So far the increase in local control following neoadjuvant treatment could not be translated in a substantial survival benefit. Improvements in surgical and radiation techniques as well as a more effective systemic treatment may offer further advantages. However the results of ongoing trials employing newer cytotoxic agents together with neoadjuvant radiation have to be awaited before their use can be advocated routinely. RC is a malignant disease that warrants close multidisciplinary cooperation and each discipline should treat the patients with the highest standard of quality to achieve optimal results.

Gastric cancer is the fourth most common malignant tumour and the second-most common cause of cancer-related death worldwide. Multidisciplinary care and stage-specific treatment lead to improvements of this very aggressive disease. Accurate staging should include high-resolution computed tomography. Localised disease should also be staged with endoscopic ultrasound. In mucosal gastric cancer, endoscopic resection can replace surgical resection if specific criteria are present. In cancer infiltrating the submucosal layer or beyond, surgical resection including resection of the D2 lymph nodes is regarded as standard of care. In the stages II and III, perioperative chemotherapy has been studied with positive results. In the metastatic setting, treatment goals are palliative. Chemotherapy can prolong survival, improve symptoms and can maintain a better quality of life. Combination chemotherapy including a platinum compound and a fluoropyrimidine is the current standard. 22% of gastric cancers exhibit overexpression of the growth factor receptor Her2. Trastuzumab is a monoclonal antibody directed against Her2 and has shown to prolong survival when combined with cisplatin and fluoropyrimidines in the treatment of Her2-positive gastric cancer. The current role of other biologically targeted therapies like anti-EGFR directed treatment still needs to be established.

A multidisciplinary approach integrating surgery, radiotherapy and systemic treatment has gained importance in the treatment of gastrointestinal (GI) cancer. Significant progress in curing localized cancer and prolonging lives in metastatic cancer has been reached. However, side effects, predominantly GI toxicity, are frequent and often dose-limiting. Patients encounter mucosal injuries resulting in oesophagitis, gastritis, nausea and vomiting, colitis causing diarrhoea or constipation. In rarer cases drugs cause hepatotoxicity or pancreatitis. Nausea, vomiting and diarrhoea are the main digestive toxicities in GI cancer patient undergoing chemo- and/or-radiotherapy. Quick relief from these side effects is important to improve the quality of life and also to prevent hospitalization. Professional prophylactic and on demand care to prevent or treat these toxicities are warranted. Supportive care should be tailored to the individual patient and to the underlying pathophysiology. This review focuses on the acute side effects in gastrointestinal cancer treatment and emphasizes therapeutic approaches which could ameliorate severity and incidence of toxicities.

Objective According to a widespread opinion the vast majority of infant febrile seizures (IFS) are harmless. However, IFS are often associated with hippocampal sclerosis, which should lead to deficient episodic memory with spared context-free semantic memories. Although IFS represent the most common convulsive disorder in children, these consequences are rarely examined. Methods We measured the hippocampal volume of 17 IFS children (7–9 years old) and an age-matched control group on the basis of MR images. Furthermore, we examined episodic and semantic memory performance with standardized neuropsychological tests. Two processes underlying recognition memory, namely familiarity and recollection, were assessed by means of event-related potentials (ERP). Results The IFS children did not show a decreased hippocampus volume. Intelligence, working memory, semantic and episodic memory were intact. However, ERP indices of recognition memory subprocesses revealed deficits in recollection-based remembering that presumably relies on the integrity of the hippocampus, whereas familiarity-based remembering seemed to be intact. Conclusions Although hippocampus volume remains unaffected, IFS seems to induce functional changes in the MTL memory network, characterized by a compensation of recollection by familiarity-based remembering. Significance This study significantly adds to the debate on the consequences of IFS by differentiating the impact on memory processing.

The serodiagnostics of extracellular domain (ECD) HER-2/neu has turned into an evidenced-based tumour marker for HER-2/neu-positive breast cancer patients. This study investigated the clinical relevance of immunohistochemical and serum HER-2/neu in 44 patients with advanced ovarian cancer. The Hercept-Test® from DAKO Diagnostics was used to analyse immunohistochemical HER-2/neu expression. The HER-2/neu ECD in serum was determined quantitatively by Bayer Immuno 1™ Immunoanalyser. The HER-2/neu serum values were correlated to the clinical course of disease and to established prognostic factors, i.e. progression-free and overall survival. Some 23% of patients (n = 11) expressed HER-2/neu serum levels higher than 15 ng/mL, whereas only 7.7% (n = 2) of the patients examined by immunohistochemistry showed a HER-2/neu overexpression of the tissue. None of them revealed an overexpression of HER-2/neu ECD by serodiagnostics. HER-2/neu overexpression did not correlate significantly to any of the analysed prognostic factors. According to progression-free and overall survival, there was no significant difference between serologically HER-2/neu-positive or negative patients. For ovarian cancer patients, neither high HER-2/neu serum levels, nor immunohistochemically determined HER-2/neu positivity, appear to predict the course of disease. This study shows a lack of association between the immunohistochemical HER-2/neu status and the serum level of solute extracelluar HER-2/neu domain.

This article investigates the incoherence of art practices in the early Turkish Republic using the example of the variations present in Malik Aksel’s (1901–1987) work. The article starts from three conventional angles and then branches out along Aksel’s specific trajectories. It inquires into his relationship to a) the modernization processes in Ankara, b) the Art-Craft Department, the state institution at which he had been employed as an art teacher, and c) Europe, where he studied for four years in preparation for his position at the Art-Craft Department. The inquiry relies only on tangible traces of these relationships. In doing so, it recovers fragments of the complex actuality of creative practices, and identifies layers of what specifically the abstract notions of modernization, the institution and the state, as well as Westernization, actually covered in the case of this artist. These fragments also steer the investigation towards facets of Aksel’s work that the established notions do not encompass. With this approach this article seeks to supplement the prevailing reception-oriented studies on art in the early Turkish Republic and to contribute to the critical discussion of the methodological implications of art-historical research that expands the traditional disciplinary confines. The aim is to open avenues to recognize and account for art practices, or facets of them, that do not relate to the preserved, processed, and easily accessible art histories, thus aiming for an extended, more inclusive art historiography.