Recurrent non-melanoma skin cancer: remission of field cancerization after conversion from calcineurin inhibitor- to proliferation signal inhibitor-based immunosuppression in a cardiac transplant recipient

Non-melanoma skin cancers (NMSCs) are the most common malignancies after solid organ transplantation. Their incidence increases with time after transplantation. Calcineurin-inhibitors (CNIs) and azathioprine are known as skin neoplasia-initiating and -enhancing immunosuppressants. In contrast, increasing clinical experience suggests a relevant antiproliferative effect of mammalian target of rapamycin inhibitors, also named proliferation signal inhibitors (PSIs). We report the case of a cardiac allograft recipient with an impressive and consolidated reduction of recurrent NMSC, observed after conversion from CNI-therapy to a PSI-based protocol.

Low-profile titanium mesh in the use of orbital reconstruction: A pilot study

The purpose of this study was to share our clinical experience in the use and accuracy of a newly designed, low-profile titanium mesh (Modus OPS 1.5; Medartis, Basel, Switzerland) for primary internal orbital reconstruction.

[Anaesthesia and breast-feeding: should breast-feeding be discouraged?]

Until a few years ago an interruption of breast-feeding for 12 or even 24 hours was recommended for breast-feeding mothers after anaesthesia, this is no longer valid. If it is the mother's wish, if she is sufficiently awake and physically able, there is no reason not to start breast-feeding a mature and healthy baby immediately after recovery from a general or regional anaesthesia. Even breast-feeding after a Caesarean delivery with administration of the common anaesthetics in the usual (single) doses is no longer considered to be a problem since the amount of the substance taken up from colostrum is vanishingly small in comparison to the amount that is transferred by transplacental routes. Neither the pharmacological properties of the drugs used in association with anaesthesia nor clinical experience justify an interruption of breast-feeding.

GLP-2 receptors in human disease: high expression in gastrointestinal stromal tumors and Crohn's disease

Peptide hormones of the glucagon-like peptide (GLP) family play an increasing clinical role, as reported for GLP-1 in diabetes therapy and insulinoma diagnostics. GLP-2, despite its known trophic and anti-inflammatory intestinal actions translated into preliminary clinical studies using the GLP-2 analogue teduglutide for treatment of short bowel syndrome and Crohn's disease, remains poorly characterized in terms of expression of its receptor in tissues of interest. Therefore, the GLP-2 receptor expression was assessed in 237 tumor and 148 non-neoplastic tissue samples with in vitro receptor autoradiography. A GLP-2 receptor expression was present in 68% of gastrointestinal stromal tumors (GIST). Furthermore, GLP-2 receptors were identified in the intestinal myenteric plexus, with significant up-regulation in active Crohn's disease. The GLP-2 receptors in GIST may be used for clinical applications like in vivo targeting with radiolabelled GLP-2 analogues for imaging and therapy. Moreover, the over-expressed GLP-2 receptor in the myenteric plexus may represent the morphological correlate of the clinical target of teduglutide in Crohn's disease.

Fertility preservation methods in young women with systemic lupus erythematosus prior to cytotoxic therapy: experiences from the FertiPROTEKT network

Despite new treatment options, some patients with systemic lupus erythematosus (SLE) need to be treated with the cytotoxic agent cyclophosphamide (CYC). Unlike malignant disease, there are no recommendations for ovarian protection in SLE. The clinical experience of the FertiPROTEKT network as well as recommendations after literature review will be presented in this paper.

The Validation of a New Visual Anaemia Evaluation Tool HemoHue HH1 in Patients with End-Stage Renal Disease

In chronic haemodialysis patients, anaemia is a frequent finding associated with high therapeutic costs and further expenses resulting from serial laboratory measurements. HemoHue HH1, HemoHue Ltd, is a novel tool consisting of a visual scale for the noninvasive assessment of anaemia by matching the coloration of the conjunctiva with a calibrated hue scale. The aim of the study was to investigate the usefulness of HemoHue in estimating individual haemoglobin concentrations and binary treatment outcomes in haemodialysis patients. A prospective blinded study with 80 hemodialysis patients comparing the visual haemoglobin assessment with the standard laboratory measurement was performed. Each patient's haemoglobin concentration was estimated by seven different medical and nonmedical observers with variable degrees of clinical experience on two different occasions. The estimated population mean was close to the measured one (11.06 ± 1.67 versus 11.32 ± 1.23 g/dL, P < 0.0005). A learning effect could be detected. Relative errors in individual estimates reached, however, up to 50%. Insufficient performance in predicting binary outcomes (ROC AUC: 0.72 to 0.78) and poor interrater reliability (Kappa < 0.6) further characterised this method.

Post-mortem tissue sampling using computed tomography guidance

PURPOSE: Currently, in forensic medicine cross-sectional imaging gains recognition and a wide use as a non-invasive examination approach. Today, computed tomography (CT) or magnetic resonance imaging that are available for patients are unable to provide tissue information on the cellular level in a non-invasive manner and also diatom detection, DNA, bacteriological, chemical toxicological and other specific tissue analyses are impossible using radiology. We hypothesised that post-mortem minimally invasive tissue sampling using needle biopsies under CT guidance might significantly enhance the potential of virtual autopsy. The purpose of this study was to test the use of a clinically approved biopsy needle for minimally invasive post-mortem sampling of tissue specimens under CT guidance. MATERIAL AND METHODS: ACN III biopsy core needles 14 gauge x 160 mm with automatic pistol device were used on three bodies dedicated to research from the local anatomical institute. Tissue probes from the brain, heart, lung, liver, spleen, kidney and muscle tissue were obtained under CT fluoroscopy. RESULTS: CT fluoroscopy enabled accurate placement of the needle within the organs and tissues. The needles allowed for sampling of tissue probes with a mean width of 1.7 mm (range 1.2-2 mm) and the maximal length of 20 mm at all locations. The obtained tissue specimens were of sufficient size and adequate quality for histological analysis. CONCLUSION: Our results indicate that, similar to the clinical experience but in many more organs, the tissue specimens obtained using the clinically approved biopsy needle are of a sufficient size and adequate quality for a histological examination. We suggest that post-mortem biopsy using the ACN III needle under CT guidance may become a reliable method for targeted sampling of tissue probes of the body.

Oral mucosal lesions diagnosed in a stomatology service. An examination of clinico-pathological findings from the year 2003

During 2003, a total of 258 new patients with oral soft tissue lesions were admitted at the Stomatology Service of the Department of Oral Surgery and Stomatology at the University of Berne. For the present study, 185 patients with clinically and histopathologically verified diagnoses were included. The following data was collected: prevalence of oral mucosal lesions, distribution of benign, precancerous and malign lesions in different age groups, and the concordance of the referral with the working diagnosis at the Stomatology Service. The most frequent pathological soft tissue findings were fibrous hyperplasias (n = 44) and oral lichen planus (n = 30). Precancerous lesions were present in 41 cases (30 patients with oral lichen planus, eleven oral leukoplakias), and ten patients had oral malignomas. Most lesions were found in patients between the age of 40 and 60 years. The referral diagnosis concurred in 36.6% (n = 67) of the cases with the definite diagnosis before initiation of treatment, the working diagnosis in 70% (n = 128) of the cases. Therefore, it can be concluded that a specialised Stomatology Service serves as a center of competence due to large numbers of patients/cases seen and treated, and the resulting high level of clinical experience of the staff. Moreover, it is important in the primary diagnosis of oral squamous cell carcinoma, in collaboration with the referring dentist in private practice.

Treatment with (90)Y- and (177)Lu-DOTATOC in patients with metastatic neuroendocrine tumors

BACKGROUND: Treatment with (90)Y- or (177)Lu-DOTATOC has recently been introduced in the palliative treatment of somatostatin receptor-expressing neuroendocrine tumors (NETs). The aim of the study was to present clinical experience with (90)Y- and (177)Lu-DOTATOC therapy in the management of NET. METHODS: To prove suitability for treatment each patient underwent scanning with (111)In-DTPAOC or (68)Ga-DOTATOC positron emission tomography/computed tomography. All patients received [(90)Y-DOTATOC] as initial treatment. In case of disease relapse the treatment was repeated. To avoid side effects of repeated [(90)Y] applications, a switch to [(177)Lu-DOTATOC] was carried out. Clinical, biochemical, and radioimaging responses were documented. RESULTS: Twenty patients with metastatic nonresectable NETs (15 pancreas NETs, 2 midgut NETs, 1 gastrinoma, 1 paraganglioma, 1 NET of unknown primary origin) were included. In 8 patients the treatment was repeated more than once (mean, 3 times; range, 2-5 times). After [(90)Y] treatment moderate toxicity was observed in 8 patients. No serious adverse events were documentable. After restaging, a partial remission was found in 5 patients, stable disease in 11 patients, and tumor progression in 4 patients. CONCLUSIONS: Peptide receptor-targeted radionuclide therapy is a promising, safe, and feasible approach in the palliative therapy of patients with NET.

Cerebral correlates of muscle tone fluctuations in restless legs syndrome: A pilot study with combined functional magnetic resonance imaging and anterior tibial muscle electromyography

BACKGROUND: The pathology of restless legs syndrome (RLS) is still not understood. To investigate the pathomechanism of the disorder further we recorded a surface electromyogram (EMG) of the anterior tibial muscle during functional magnetic resonance imaging (fMRI) in patients with idiopathic RLS. METHODS: Seven subjects with moderate to severe RLS were investigated in the present pilot study. Patients were lying supine in the scanner for over 50min and were instructed not to move voluntarily. Sensory leg discomfort (SLD) was evaluated on a 10-point Likert scale. For brain image analysis, an algorithm for the calculation of tonic EMG values was developed. RESULTS: We found a negative correlation of tonic EMG and SLD (p <0.01). This finding provides evidence for the clinical experience that RLS-related subjective leg discomfort increases during muscle relaxation at rest. In the fMRI analysis, the tonic EMG was associated with activation in motor and somatosensory pathways and also in some regions that are not primarily related to motor or somatosensory functions. CONCLUSIONS: By using a newly developed algorithm for the investigation of muscle tone-related changes in cerebral activity, we identified structures that are potentially involved in RLS pathology. Our method, with some modification, may also be suitable for the investigation of phasic muscle activity that occurs during periodic leg movements.

Potential of chemically modified hydrophilic surface characteristics to support tissue integration of titanium dental implants

In the past, several modifications of specific surface properties such as topography, structure, chemistry, surface charge, and wettability have been investigated to predictably improve the osseointegration of titanium implants. The aim of the present review was to evaluate, based on the currently available evidence, the impact of hydrophilic surface modifications of titanium for dental implants. A surface treatment was performed to produce hydroxylated/hydrated titanium surfaces with identical microstructure to either acid-etched, or sand-blasted, large grit and acid-etched substrates, but with hydrophilic character. Preliminary in vitro studies have indicated that the specific properties noted for hydrophilic titanium surfaces have a significant influence on cell differentiation and growth factor production. Animal experiments have pointed out that hydrophilic surfaces improve early stages of soft tissue and hard tissue integration of either nonsubmerged or submerged titanium implants. This data was also corroborated by the results from preliminary clinical studies. In conclusion, the present review has pointed to a potential of hydrophilic surface modifications to support tissue integration of titanium dental implants.

Aurora kinases as anticancer drug targets

The human aurora family of serine-threonine kinases comprises three members, which act in concert with many other proteins to control chromosome assembly and segregation during mitosis. Aurora dysfunction can cause aneuploidy, mitotic arrest, and cell death. Aurora kinases are strongly expressed in a broad range of cancer types. Aurora A expression in tumors is often associated with gene amplification, genetic instability, poor histologic differentiation, and poor prognosis. Aurora B is frequently expressed at high levels in a variety of tumors, often coincidently with aurora A, and expression level has also been associated with increased genetic instability and clinical outcome. Further, aurora kinase gene polymorphisms are associated with increased risk or early onset of cancer. The expression of aurora C in cancer is less well studied. In recent years, several small-molecule aurora kinase inhibitors have been developed that exhibit preclinical activity against a wide range of solid tumors. Preliminary clinical data from phase I trials have largely been consistent with cytostatic effects, with disease stabilization as the best response achieved in solid tumors. Objective responses have been noted in leukemia patients, although this might conceivably be due to inhibition of the Abl kinase. Current challenges include the optimization of drug administration, the identification of potential biomarkers of tumor sensitivity, and combination studies with cytotoxic drugs. Here, we summarize the most recent preclinical and clinical data and discuss new directions in the development of aurora kinase inhibitors as antineoplastic agents.

The pulmonary artery catheter: in medio virtus

OBJECTIVE: To clarify the role of the pulmonary artery catheter in the intensive care unit. DATA SOURCES: Recent and relevant literature from MEDLINE and authors' personal databases. STUDY SELECTION: Studies on pulmonary artery catheter use and use of other monitoring devices in critically ill patients. DATA EXTRACTION: Based largely on clinical experience and assessment of the relevant published literature and in response to recent articles attacking the pulmonary artery catheter, we propose that the pulmonary artery catheter is still a valuable tool for the hemodynamic monitoring of patients with complex disease processes in whom the information obtained from the pulmonary artery catheter may influence management. We suggest that there is a need to revisit the basics of hemodynamic management and reassess the way in which the pulmonary artery catheter is used, applying three key principles: correct measurement, correct data interpretation, and correct application. CONCLUSION: The pulmonary artery catheter is still a valuable tool for hemodynamic monitoring when used in selected patients and by physicians adequately trained to correctly interpret and apply the data provided.

Policy of routine titanium miniplate removal after maxillofacial trauma

PURPOSE: The literature shows that hardware removal rates after the fixation of maxillofacial fractures with miniplates are not insignificant. The aim of the present survey was to clarify the policies of Finnish oral and maxillofacial consultants for the removal of titanium miniplates after the treatment of facial fractures in adults. Additional aims were to clarify the factors influencing plate removal policy in general, and the reasons for routine plate removal in particular. MATERIALS AND METHODS: Twenty-six consultant oral and maxillofacial surgeons responded to a questionnaire about miniplate removal policy after treating 5 types of simple, noncomminuted fractures. RESULTS: Overall, routine plate removal was uncommon. However, 12 consultants (46.2%) routinely removed the plate after treating mandibular angle fractures, and simultaneously extracted the third molar because of an increased risk of infection. Most respondents (88.5%) stated that clinical experience guided their plate-removal policy. A policy of routine plate removal was most infrequent among the consultants who had the most experience. CONCLUSIONS: The literature provides no definitive answer to the question of whether routine removal of miniplates could or should be indicated, and in what situations. Considering the fairly significant frequency of plate-related complications in general and infection-related complications in particular, long-term follow-up after treatment is indicated.

Photodynamic therapy for cholangiocarcinoma: overview and new developments

PURPOSE OF REVIEW: Photodynamic therapy (PDT) with hematoporphyrins has emerged as promising treatment for nonresectable cholangiocarcinoma in several prospective observational studies and two randomized studies. This review describes the mechanism of action of PDT, gives an overview of clinical experience in cholangiocarcinoma and summarizes the results published in 2007 and 2008. RECENT FINDINGS: The mechanism of action of PDT has been further elucidated. PDT induces an apoptotic, antiangiogenic as well as an immunomodulatory response. Interleukin-6, a bile duct epithelium growth factor correlating with tumor burden, decreases after PDT. The efficacy of PDT was confirmed in a comparative study in the United States. Patients with no visible mass on imaging studies, high serum albumin levels and treatment immediately after diagnosis seem to benefit most from PDT. Although it is recommended to perform PDT in bile ducts without stents in place, illumination through metal stents is possible if the light dose is adjusted. Meso-tetrahydroxyphenyl chlorine is a new potent photosensitizer for PDT of cholangiocarcinoma. SUMMARY: In advanced nonresectable cholangiocarcinoma, PDT is the only evidence-based treatment that improves survival when compared with stenting. Therefore, PDT should be offered to those who are unsuitable for surgery.