Prosthetic supply of facial defects: long-term experience and retrospective analysis on 99 patients.

INTRODUCTION: Defects in the head region may be caused by tumour treatments, injuries, as well as congenital malformations. The restoration of these defects that can be performed through reconstructive plastic surgery and/or prosthetic surgery occupies a high priority in the physical and psychological rehabilitation of the patient. The present study reports on long-term experience in supply of facial prosthesis. MATERIALS AND METHODS: The medical records of 99 patients, who had been supplied with custom-made facial prostheses between 2001 and 2011, were evaluated retrospectively. RESULTS: There were 59 male (60%) and 40 (40%) female patients. The reason for prosthetic supplement was a tumour disease in 50 patients, congenital malformation in 39 patients, and trauma in 10 patients. Fifty-three patients were treated with ear prosthesis, twenty-seven patients were treated with eye prosthesis, and nineteen patients with nasal prosthesis. 82.8% of prosthetic supplies were designed as magnetic support prostheses. The most common complication was skin redness around the implants. 10% of patients suffered the loss of the osseointegrated implants. CONCLUSION: The osseointegrated titanium implants with magnet support provide a reliable attachment for prosthesis and constitute a promising alternative to surgical reconstruction of complex facial defects.

Epithetic nasal reconstruction for nasal carcinoma: retrospective analysis on 22 patients.

Advanced nasal cancers usually demand partial or total rhinectomy followed by radiotherapy. Reconstruction of the resulting defects can be achieved by means of reconstructive plastic surgery and/or epithetic surgery. The data of 22 patients who had been treated after nasal ablation by means of custom-made silicone nasal epithesis fixed by bone-anchored magnets between 2003 and 2014 were evaluated retrospectively. There were 15 male (68.2 %) and 7 (31.8 %) female patients. The most common etiology that led to epithetic rehabilitation was a squamous cell carcinoma in 16 patients. An operative revision was necessary in two patients due to screw loss. Twenty patients were still alive with no evidence of disease after minimum follow-up of 2 years (90.9 %). Epithetic rehabilitation after nasal ablation to treat nasal malignancies is an interesting alternative to plastic and reconstructive surgery. Bone-anchored fixation using magnets can achieve a stable epithetic fixation after nasal ablation necessitating, in numerous cases, additional adjuvant therapy like radiation.

GPR84 and TREM-1 Signaling Contribute to the Pathogenesis of Reflux Esophagitis.

Gastro-esophageal reflux disease (GERD) is one of the most common disorders in gastroenterology. Patients present with or without increased acid exposure indicating a nonuniform etiology. Thus, the common treatment with proton pump inhibitors (PPIs) fails to control symptoms in up to 40% of patients. To further elucidate the pathophysiology of the condition and explore new treatment targets, transcriptomics, proteomics and histological methods were applied to a surgically induced subchronic reflux esophagitis model in Wistar rats after treatment with either omeprazole (PPI) or STW5, a herbal preparation shown to ameliorate esophagitis without affecting refluxate pH. The normal human esophageal squamous cell line HET-1A and human endoscopic biopsies were used to confirm our findings to the G-protein-coupled receptor (GPR) 84 in human tissue. Both treatments reduced reflux-induced macroscopic and microscopic lesions of the esophagi as well as known proinflammatory cytokines. Proteomic and transcriptomic analyses identified CINC1-3, MIP-1/3α, MIG, RANTES and interleukin (IL)-1ß as prominent mediators in GERD. Most regulated cyto-/chemokines are linked to the TREM-1 signaling pathway. The fatty acid receptor GPR84 was upregulated in esophagitis but significantly decreased in treated groups, a finding supported by Western blot and immunohistochemistry in both rat tissue and HET-1A cells. GPR84 was also found to be significantly upregulated in patients with grade B reflux esophagitis. The expression of GPR84 in esophageal tissue and its potential involvement in GERD are reported for the first time. IL-8 (CINC1-3) and the TREM-1 signaling pathway are proposed, besides GPR84, to play an important role in the pathogenesis of GERD.org.

Novel modification of voice prosthesis.

The undesired dilatation of the tracheooesophageal shunt after surgical implantation of voice prosthesis is a typical complication of this procedure. Temporary removal of the prosthesis and reinsertion after a short period of time is a first-line therapeutical option aiming shrinkage of the shunt. Failure of this measure generally is an indication of revision surgery. We present first experiences treating leakage problems with novel modified voice prosthesis without surgical intervention in specified cases. 11 patients (1 female, 10 male) aging between 51 and 71 years were presented with shunt leakage between 11/2008 and 11/2012 in the ENT-Department of the University Hospital of Homburg/Saar after a custom built voice prosthesis had been used initially successfully. A "Provox 2"(®) voice prosthesis was modified with two discs made of silicone each on the tracheal and oesophageal side and additionally reinforcing the diameter of the prosthesis by a silicone tube. The modified prosthesis was inserted in a retrograde way under general anesthesia, analogical to the approach used with the "Provox 1"(®)-prosthesis. The period of observation ranged between 12 and 48 months. As a measure of control swallowing of methylene blue was used. In all cases leakage suspended. Durability of the modified prosthesis ranged between 2 and 6 months. Neither the patients' complained about, nor did the physicians notice subjectively an impairment of the voice quality. Modifications of "Provox 2"(®)-prosthesis should be regarded in individual cases and constitute a reasonable alternative to revision surgery. A surgical approach is more intricate and costly, more taxing for the patient and susceptible to failure. We regard the necessity of general anesthesia for the insertion of the modified prosthesis as a disadvantage.

Customized individual applicators for endocavitary brachytherapy in patients with cancers of the nasal cavity, sinonasal region and nasopharynx.

Brachytherapy has become an established therapeutic regimen for primary, persistent, recurrent and metastatic tumour disease in the head and neck region. This study presents the authors' preliminary experience with intracavitary brachytherapy by means of an individual silicone applicator in the treatment of patients with nasal, sinonasal, orbital and nasopharyngeal cancer. Between January 2001 and January 2013, twenty patients with cancer of the nasal cavity, the paranasal sinuses and nasopharynx underwent surgery and intracavitary brachytherapy with the aid of an individually manufactured silicone applicator in the Department of Otolaryngology, Head and Neck Surgery and in the Department of Radiotherapy and Radiooncology at the Saarland University Medical Center of Homburg, Germany. The tumour was localized in the nasal cavity/paranasal sinuses (15) affecting the orbit twice and the nasopharynx (5). There were 14 patients with squamous cell carcinoma, 2 patients with mixed tumours and one patient with adenocarcinoma, adenoid cystic carcinoma, mucosal melanoma or plasmocytoma. The majority of the patients presented with advanced disease (T3 or T4 tumours). In 18/20 patients, brachytherapy was performed as a boost technique, in the remaining two solely because of a previous radiation series. All surgical interventions were performed endonasally. Three to six weeks after surgery, a cast of the nasal cavity was created under general anaesthesia. Subsequently, an individual brachytherapy silicon applicator with two to four plastic tubes was manufactured. The radiation therapy was applied using the Ir-192 high-dose-rate-afterloading method (total dose 10-20 Gy) in two to five sessions, additionally in 18/20 patients a percutaneous radiotherapy with a total dose of 30-60 Gy was applied. After a mean duration of follow-up of 2 years, 7/20 patients experienced a local progression, 5/19 a regional recurrence in the neck nodes and 4/19 distant metastases. The 2-year survival was 57.3 %. No serious complications were reported. The silicone applicator was well tolerated by all patients. Because of the complexity of the sinonasal anatomy with the finding of mainly advanced tumours, the presented individual silicone brachytherapy applicator has proven to be useful and meaningful for endocavitary brachytherapy of malignancies of the nasal cavities, paranasal sinuses and nasopharynx.

First experiences with an individual nasal olive in patients with hereditary haemorrhagic telangiectasia (HHT).

Hereditary haemorrhagic teleangiectasia (HHT) is most notably characterized by vulnerable vascular formations of the nasal superficial mucosa. Epistaxis is one of the most common symptoms of the afflicted patients, with an incidence of more than 90 %. A variable series of treatments have been described, ranging from nasal ointments to the complete surgical occlusion of the nose. The objective of this pilot study is the presentation of first experiences in treating patients suffering from HHT and chronically recurrent epistaxis with an individual nasal olive made from silicone. Eleven patients (six men, five women) aging from 44 to 80 years with known HHT were treated at the ENT department of Homburg/Saar between October 2008 and July 2012 because of nasal bleeding by Nd:YAG laser or argon plasma coagulation. After the surgical treatment, an imprint of the nasal aditus was taken to manufacture an individual custom-made silicone nasal olive. Patients were wearing the nasal olive for 3-8 h a day. Check-ups were made every 6 months. Epistaxis severity score (ESS) was used pre- and post-nasal olive application. The observation period was 12-48 months. The utilization of the silicone nasal olive led to a distinct reduction of epistaxis events. Apart from the nasal olive, our patients needed no further treatment of the nose during the observation period except for a nasal ointment. Insertion and removal of the nasal olive were handled by the patients themselves. The local manipulation in handling the nasal olive caused no epistaxis itself. A significant improvement of the ESS and satisfaction was reported in all patients. Use of an individually manufactured silicone nasal olive is a promising extension to the established treatments of epistaxis in HHT patients. Tolerance towards this treatment by the patients was high due to the low personal burden and encumbrance. The extended use of the presented method in HHT patients may be beneficial. However, a more prolonged observation period is necessary in the future to judge the long-term efficiency of individual nasal olives.

Genetic drift and host-adaptive features likely underlie cladogenesis of insect-associated Lachnospiraceae.

Phylogenetic and functional group analysis of the genomes of anaerobic bacteria isolated from Periplaneta americana digestive tracts suggest that they represent novel Lachnospiraceae genera. PAL113 and PAL227 isolate genomes encoded short-chain fatty acid biosynthetic pathways and plant fiber and chitin catabolism and other carbohydrate utilization genes common in related Lachnospiraceae species, yet the presence of operons containing flagellar assembly pathways were among several distinguishing features. In general, PAL113 and PAL227 isolates encode an array of gene products that would enable them to thrive in the insect gut environment and potentially play a role in host diet processing. We hypothesize that cladogenesis of these isolates could be due to their oxygen sensitivity, reliance upon the host for dispersal and genetic drift and not necessarily as a result of an ongoing mutualism.

Auricular reconstruction with polyethylene implants or silicone prosthesis: A single institution experience.

Auricular reconstruction is usually necessary in patients with congenital malformations, after traumatic ear amputations or in cases of neoplastic ear disease. Thirty-nine patients who underwent an auricular reconstruction with either silicon prosthesis (21 patients) or porous polyethylene (18 patients) between 2002 and 2013 were retrospectively analyzed at a tertiary academic institution. A total of 25 male und 14 female patients were included in the study. In all, 43 implants were installed in 39 patients. An implant failure was not observed in any of the examined groups. An operative revision was necessary in 5 patients in the silicon prosthesis group (N = 21) and in 4 patients in the porous polyethylene group (N = 18). The most common side effect in the porous polyethylene group was the formation of retroauricular adhesions in 11.1 % by postoperative scaring, while in the silicone prosthesis group 71.4 % of the patients presented with skin reactions around the titanium implants. Our study shows that both techniques are valuable and should be offered to patients in cases of auricular reconstruction due to the low rate of severe complications and the good functional results of both techniques.

Genetic Mouse Models with Intestinal-Specific Tight Junction Deletion Resemble an Ulcerative Colitis Phenotype.

BACKGROUND AND AIMS: A key pathogenetic feature of ulcerative colitis [UC] is an intrinsic low mucus phosphatidylcholine[PC] content. Recently, a paracellular transport for PC across tight junctions[TJs] was described, suggesting TJ disturbance as a cause of diminished luminal PC transport. Therefore, we aimed to generate mutant mice with TJ deletion to evaluate whether a UC phenotype developed. METHODS: CL57BL/6 control wild-type mice were compared to mutant mice with tamoxifen-induced villin-Cre-dependent intestinal deletion of kindlin 1 and 2. RESULTS: Electron microscopy of mucosal biopsies obtained from both mutants before overt inflammation following only 2 days of tamoxifen exposure revealed a defective TJ morphology with extended paracellular space and, by light microscopy, expanded mucosal crypt lumina. PC secretion into mucus was reduced by >65% and the mucus PC content dropped by >50%, causing a >50 % decrease of mucus hydrophobicity in both mutants. Consequently, the microbiota was able to penetrate the submucosa. After 3 days of tamoxifen exposure, intestinal inflammation was present in both mutants, with loose bloody stools as well as macroscopic and histological features of colitis. Oral PC supplementation was able to suppress inflammation. By analogy, colonic biopsies obtained from patients with UC in remission also showed a defective epithelium with widened intercellular clefts, and enlarged crypt luminal diameters with functionally impaired luminal PC secretion. CONCLUSIONS: Genetic mouse models with intestinal deletion of kindlin 1 and 2 resulted in TJ deletion and revealed pathophysiological features of impaired PC secretion to the mucus leading to mucosal inflammation compatible with human UC.

Anti-inflammatory Effects of Herbal Preparations STW5 and STW5-II in Cytokine-Challenged Normal Human Colon Cells.

Inflammatory bowel diseases (IBD) are chronic relapsing intestinal disorders characterized by up-regulation of pro-inflammatory cytokines followed by invasion of immune cells to the intestinal lamina propria. Standard therapies consist of anti-inflammatory or immunosuppressive drugs. Since clinical efficiency is not satisfactory and the established drugs have massive side effects, new strategies to treat IBD are required. Herein, we investigate the protective effect of the fixed combination herbal preparations STW5 and STW5-II and the contribution of the corresponding single components in an in vitro inflammation model. The normal human colon epithelial cell line, NCM460, was treated with STW5, STW5-II or their single components for 4 h followed by experimental conditions comparable to induction of colitis. A pro-inflammatory cytokine cocktail consisting of TNF-α, IL-ß, and IFN-γ was used to simulate inflammatory stimuli normally caused by immune cells. The effects on NCM460 cells were investigated by enzyme-linked immunoassay and Proteome Profiler®. Levels of IP-10, MCP-1, I-TAC, Groα, and IL-8 were elevated in chemokine-treated cells compared to untreated cells, but significantly reduced upon pretreatment with STW5 or STW5-II. However, the single compounds revealed only little effects on protein expression. Furthermore, we investigated the effect of both combination preparations on pro-inflammatory transcription factors of the STAT family using Western blot. In addition, we tested the effects on upstream MAPK p38. Both, STW5 and STW5-II did not show any effect on MAPK p38, but were effective in reducing phosphorylated levels of STAT1. In conclusion, both combination preparations act in an anti-inflammatory manner by influencing cytokine secretion via reduced activity of the JAK/STAT1 pathway. Relevant differences between STW5 and STW5-II were not found indicating similar efficacies.

Biopiracy of natural products and good bioprospecting practice.

BACKGROUND: Biopiracy mainly focuses on the use of biological resources and/or knowledge of indigenous tribes or communities without allowing them to share the revenues generated out of economic exploitation or other non-monetary incentives associated with the resource/knowledge. METHODS: Based on collaborations of scientists from five continents, we have created a communication platform to discuss not only scientific topics, but also more general issues with social relevance. This platform was termed 'PhytCancer -Phytotherapy to Fight Cancer' (www.phyt-cancer.uni-mainz.de). As a starting point, we have chosen the topic "biopiracy", since we feel this is of pragmatic significance for scientists working with medicinal plants. RESULTS: It was argued that the patenting of herbs or natural products by pharmaceutical corporations disregarded the ownership of the knowledge possessed by the indigenous communities on how these substances worked. Despite numerous court decisions in U.S.A. and Europe, several international treaties, (e.g. from United Nations, World Health Organization, World Trade Organization, the African Unity and others), sharing of a rational set of benefits amongst producers (mainly pharmaceutical companies) and indigenous communities is yet a distant reality. In this paper, we present an overview of the legal frameworks, discuss some exemplary cases of biopiracy and bioprospecting as excellent forms of utilization of natural resources. CONCLUSIONS: We suggest certain perspectives, by which we as scientists, may contribute towards prevention of biopiracy and also to foster the fair utilization of natural resources. We discuss ways, in which the interests of indigenous people especially from developing countries can be secured.