Embolization in an adrenocortical carcinoma as palliative therapy

Background: With an annual incidence of 0.2% of new cases per 100,000 inhabitants, adrenocortical carcinoma is rare. In advanced tumor only palliative treatment modalities are practicable. Because of scarcity of the tumor, standard treatment has not been defined. The decision on therapy frequently depends on the individual situation. Tumor embolization and chemotherapy are amongst the possible options. Patient and Methods: We report on a case of a 32-year-old female patient with a large-volume hormonally active adrenocortical carcinoma and hematogenous liver metastases. This carcinoma was confirmed histologically by means of liver biopsy. Owing to the large tumor extent and metastatic spreading and also in view of the poor general condition of the patient, curative surgical therapy was not possible. For this reason, a local approach was chosen primarily with transarterial tumor embolization at the capillary level. Systemic chemotherapy was given afterwards. Results: Improvement of the patient's general condition, especially the pronounced pain symptoms, could be achieved for a short time by the embolization: both, the patient's clinical condition and the laboratory test parameters improved. However, a rapid tumor progression occured under chemotherapy, which was started after embolization. Conclusion: In advanced adrenocortical carcinoma, tumor embolization can lead to a stabilization of the disease and improvement of the symptoms as appraised by palliative criteria in some patients

Light respiratory processes and gross photosynthesis in two scleractinian corals

© 2014 Schrameyer et al. The light dependency of respiratory activity of two scleractinian corals was examined using O2 microsensors and CO2 exchange measurements. Light respiration increased strongly but asymptotically with elevated irradiance in both species. Light respiration in Pocillopora damicornis was higher than in Pavona decussata under low irradiance, indicating species-specific differences in light-dependent metabolic processes. Overall, the coral P. decussata exhibited higher CO2 uptake rates than P. damicornis over the experimental irradiance range. P. decussata also harboured twice as many algal symbionts and higher total protein biomass compared to P. damicornis, possibly resulting in self-shading of the symbionts and/or changes in host tissue specific light distribution. Differences in light respiration and CO2 availability could be due to host-specific characteristics that modulate the symbiont microenvironment, its photosynthesis, and hence the overall performance of the coral holobiont

Different carbon isotope fractionation patterns during the development of phototrophic freshwater and marine biofilms

Natural phototrophic biofilms are influenced by a broad array of abiotic and biotic factors and vary over temporal and spatial scales. Different developmental stages can be distinguished and growth rates will vary due to the thickening of the biofilm, which is expected to lead to a limitation of light or mass transport. This study shows that variation in CO<sub>2(aq)</sub> availability leads to a fractionation shift and thereby affects δ<sup>13</sup>C signatures during biofilm development. For phototrophic freshwater biofilms it was found that the δ<sup>13</sup>C value became less negative with the thickening of the biofilm, while the opposite trend was found in marine biofilms. Modeling and pH profiling indicated that the trend in the freshwater system was caused by an increase in CO<sub>2(aq)</sub> limitation resulting in an increase of HCO<sub>3</sub><sup>−</sup> as C-source. The opposite trend in the marine system could be explained by a higher heterotrophic biomass and activity causing a higher carbon recycling and thereby lower δ<sup>13</sup>C values. We conclude that δ<sup>13</sup>C was more related to the net areal photosynthesis rate and carbon recycling, rather than to the growth rate of the biofilms

Deficiency in IκBα in the intestinal epithelium leads to spontaneous inflammation and mediates apoptosis in the gut

The IκB-Kinase (IKK)-NF-κB signalling pathway plays a multifaceted role in inflammatory bowel disease (IBD): on the one hand, it protects from apoptosis; on the other, it activates transcription of numerous inflammatory cytokines and chemokines. Although several murine models of IBD rely on disruption of IKK-NF-κB signalling, these involve either knockouts of a single family-member of NF-κB, or of upstream kinases that are known to have additional, NF-κB-independent, functions. This has made the distinct contribution of NF-κB to homeostasis in intestinal epithelium cells difficult to assess. To examine the role of constitutive NF-κB activation in intestinal epithelial cells, we generated a mouse model with a tissue-specific knockout of the direct inhibitor of NF-κB, Nfkbia/IκBα. We demonstrate that constitutive activation of NF-κB in intestinal epithelial cells induces several hallmarks of IBD including increased apoptosis, mucosal inflammation in both the small intestine and the colon, crypt hyperplasia, and depletion of Paneth cells, concomitant with aberrant Wnt signalling. To determine which NF-κB-driven phenotypes are cell-intrinsic, and which are extrinsic and thus require the immune compartment, we established a long-term organoid culture. Constitutive NF-κB promoted stem-cell proliferation, mis-localisation of Paneth cells, and sensitisation of intestinal epithelial cells to apoptosis in a cell-intrinsic manner. Increased number of stem cells was accompanied by a net increase in Wnt activity in organoids. Because aberrant Wnt signalling is associated with increased risk of cancer in IBD patients and because NFKBIA has recently emerged as a risk locus for IBD, our findings have critical implications for the clinic. In a context of constitutive NF-κB, our findings imply that general anti-inflammatory or immunosuppressive therapies should be supplemented with direct targeting of NF-κB within the epithelial compartment in order to attenuate apoptosis, inflammation, and hyperproliferation

Long-term outcomes of allogeneic haematopoietic stem cell transplantation for adult cerebral X-linked adrenoleukodystrophy

The adult cerebral inflammatory form of X-linked adrenoleukodystrophy is a rapidly progressive neurodegenerative disease, as devastating as childhood cerebral adrenoleukodystrophy. Allogeneic haematopoietic stem cell transplantation has been demonstrated to provide long-term neurological benefits for boys with the childhood cerebral form, but results in adults are sparse and inconclusive. We analysed data from 14 adult males with adult cerebral adrenoleukodystrophy treated with allogeneic haematopoietic stem cell transplantation on a compassionate basis in four European centres. All presented with cerebral demyelinating lesions and gadolinium enhancement. Median age at diagnosis of adult cerebral adrenoleukodystrophy was 33 years (range 21–48 years). In addition to cerebral inflammation, five patients had established severe motor disability from adrenomyeloneuropathy affecting only the spinal cord and peripheral nerves (Expanded Disability Status Scale score ≥ 6). Eight patients survived (estimated survival 57 ± 13%) with a median follow-up of 65 months (minimum 38 months). Death was directly transplant-/infection-related (n = 3), due to primary disease progression in advanced adult cerebral adrenoleukodystrophy (n = 1), or secondary disease progression (n = 2) after transient multi-organ failure or non-engraftment. Specific complications during stem cell transplantation included deterioration of motor and bladder functions (n = 12) as well as behavioural changes (n = 8). Arrest of progressive cerebral demyelination and prevention of severe loss of neurocognition was achieved in all eight survivors, but deterioration of motor function occurred in the majority (n = 5). Limited motor dysfunction (Expanded Disability Status Scale score < 6) prior to transplantation was associated with significantly improved survival [78 ± 14% (n = 9) versus 20 ± 18%(n = 5); P < 0.05] and maintenance of ambulation (Expanded Disability Status Scale score < 7) post-transplant (78% versus 0%; P = 0.021). In contrast, bilateral involvement of the internal capsule on brain MRI was associated with poorer survival [20 ± 18% (n = 5) versus 78 ± 14% (n = 9); P < 0.05]. This study is the first to support the feasibility, complications and potential long-term neurological benefit of allogeneic haematopoietic stem cell transplantation in adult cerebral adrenoleukodystrophy. Further studies are warranted to attempt to improve outcomes through patient selection and optimization of transplantation protocols