HLA typing by next-generation sequencing - getting closer to reality.

Next generation sequencing (NGS) denotes novel sequencing technologies that enable the generation of a large number of clonal sequences in a single sequencing run. NGS was initially introduced for whole genome sequencing and for quantitation of viral variants or genetic mutations in tumor tissues; more recently, the potential for high resolution HLA typing and high throughput analyses has been explored. It became clear that the complexity of the HLA system implicates new challenges, especially for bioinformatics. From an economical point of view, NGS is becoming increasingly attractive for HLA typing laboratories currently relying on Sanger based sequencing. Realizing the full potential of NGS will require the development of specifically adapted typing strategies and software algorithms. In the present review, three laboratories that were among the first to perform HLA-typing using different NGS platforms, the Roche 454, the Illumina Miseq and the Ion Torrent system, respectively, give an overview of these applications and point out advantages and limitations.

A therapeutic option in nutcracker syndrome and ovarian vein insufficiency.

OBJECTIVES: The nutcracker syndrome (NS) may lead to insufficient perirenal collaterals as well as incompetence of the left ovarian vein with consecutive ovarian vein insufficiency. METHODS: A female patient with NS and severe genital varicosis was treated with dilation of the renal vein and coiling of a left perirenal collateral vein feeding an insufficient left ovarian vein (LOV) with pelvic vein varicosity. RESULTS: In re-evaluation 18 month later with left renal vein (LRV) and LOV phlebography, a widely patent LRV was found. The embolized LRV to LOV collateral was occluded. However, left hypogastric phlebography showed incompetent branches of the left hypogastric vein feeding the genital varicose veins. These were successfully embolized with coils and the genital varicosity decreased on follow-up. CONCLUSIONS: In our patient a combined therapeutic approach with balloon dilation of the NS and embolization of the genital varicose veins by left hypogastric vein coil was performed.

[Quality control and quality of life after uterine fibroid embolization: long-term results]. / Erfolgskontrolle und Lebensqualitat nach Myomembolisation: Langzeitergebnisse.

This study was performed in order to evaluate the changes in uterine fibroid symptoms and their impact on the quality of life after uterine fibroid embolization (UFE). The patients source of information about this novel treatment and their reasons for choosing UFE were also studied. Health-related quality of life and the status of uterine fibroid symptoms were assessed in 44 patients before and after treatment using a validated questionnaire. After 33.5 months on average, a significant change in symptoms of -60.4% and a change in health-related quality of life of +74.39% were reported. Over 50% of patients had heard about UFE for the first time through the media, and 62.9% of patients had opted for this form of treatment because it enabled them to keep their uterus; 91.5% of patients would recommend it. UFE is a novel, effective and minimally invasive alternative to more invasive, open or laparascopic treatment procedures in cases of uterine fibroid symptoms.

Magnetic resonance imaging of anterior cruciate ligament tears: evaluation of standard orthogonal and tailored paracoronal images.

PURPOSE: To evaluate the three standard orthogonal imaging planes and a paracoronal imaging plane for anterior cruciate ligament (ACL) tears. MATERIAL AND METHODS: Ninety patients (91 knees; 29 F and 61 M) aged between 15 and 84 years (mean 36.9 +/- 16.4 years) underwent magnetic resonance imaging (MRI) of the knee prior to arthroscopy. At surgery, 32 knees had an intact ACL, 4 a partial tear, and 55 a complete ACL tear. In all patients, axial, sagittal, coronal, and paracoronal T2-weighted turbo-SE images were acquired. The ACL was classified as intact, partially, or completely torn. Partial and complete tears were combined for statistical evaluation. RESULTS: Partial ACL tears (four cases) were not correctly diagnosed at MRI except in one knee by one observer on coronal images. Sensitivity in detecting ACL tears was 95%/63% (reader1/reader2) in the axial, 93%/95% in the sagittal, 93%/86% in the coronal, and 100%/93% in the paracoronal plane. Specificity was 75%/81% in the axial, 72%/81% in the sagittal, 78%/94% in the coronal, and 78%/88% in the paracoronal plane. CONCLUSION: ACL tears can be diagnosed accurately with each of the standard orthogonal planes. Based on reader confidence and interobserver agreement paracoronal images may be useful in equivocal cases.

Non-invasive distension of the small bowel for magnetic-resonance imaging.

Magnetic resonance enteroclysis is a promising technique that allows assessment of the small bowel but needs invasive nasoduodenal intubation. We propose a non-invasive distension method for magnetic-resonance imaging (MRI) in which ispaghula, dissolved in an aqueous solution with meglumine gadoterate taken orally over 4 h forms a viscous hydrogel within the intestinal lumen. MRI results from ten volunteers showed good luminal distension, constant signal homogeneity, optimum demarcation of the bowel content from surrounding tissues, and a low rate of artefacts. Our method permits non-invasive high quality MRI of the small bowel.

Neanderthal cranial ontogeny and its implications for late hominid diversity.

Homo neanderthalensis has a unique combination of craniofacial features that are distinct from fossil and extant 'anatomically modern' Homo sapiens (modern humans). Morphological evidence, direct isotopic dates and fossil mitochondrial DNA from three Neanderthals indicate that the Neanderthals were a separate evolutionary lineage for at least 500,000 yr. However, it is unknown when and how Neanderthal craniofacial autapomorphies (unique, derived characters) emerged during ontogeny. Here we use computerized fossil reconstruction and geometric morphometrics to show that characteristic differences in cranial and mandibular shape between Neanderthals and modern humans arose very early during development, possibly prenatally, and were maintained throughout postnatal ontogeny. Postnatal differences in cranial ontogeny between the two taxa are characterized primarily by heterochronic modifications of a common spatial pattern of development. Evidence for early ontogenetic divergence together with evolutionary stasis of taxon-specific patterns of ontogeny is consistent with separation of Neanderthals and modern humans at the species level.

Diagnosis of symptomatic intestinal metastases using transabdominal sonography and sonographically guided puncture.

OBJECTIVE. We studied the sonographic findings of symptomatic intestinal metastases and the use and safety of subsequent sonographically guided 22-gauge fine-needle aspiration or 18-gauge core biopsy. CONCLUSION. Symptomatic intestinal metastases can be diagnosed by transabdominal sonography. Extensive hypoechoic segmental bowel wall thickening with loss of stratification and intussusception can be observed. Sonographically guided fine-needle aspiration or 18-gauge core biopsy performed at the end of the examination allows definite diagnosis and is a safe procedure.

Gastrointestinal stenting.

Acute obstructions of the gastric outlet, the duodenum, or the large bowel require rapid treatment to relieve symptoms of retention or ileus. Large-caliber stents of 16 to 22 mm offer a new non-surgical alternative for treating these patients with minimal risks and high success rates. For gastroduodenal outlet obstructions palliated by self-expanded metal stents, clinical success rates are in the range of 80-100 %. Preoperative treatment of colorectal obstructions successfully relieves acute symptoms of ileus in 87-100 % allowing primary anastomosis and thereby reducing the costs caused by multiple operations and the need of intensive care by approximately 25 %. It is the purpose of this review to familiarize the reader with the indications, possibilities, and limits of intestinal stenting.

Embolization of the vasa recta in acute lower gastrointestinal hemorrhage: A report of five cases.

PURPOSE: To present our preliminary experience in embolization of the vasa recta in acute gastrointestinal hemorrhage. METHODS: In four of five patients with acute gastrointestinal hemorrhage superselective embolization of the vasa recta was performed. In one patient in whom superselective catheterization of the bleeding vas rectum was technically impossible, the origin of this vessel was embolized at the level of the terminal arcade. The following embolization materials were used: microcoils and polyvinyl alcohol particles (355-500 microm), n = 2; microcoils only, n = 2; Gelfoam particles, n = 1. RESULTS: Bleeding was found in two patients in the small bowel (jejunum and ileum) and in three patients in the colon. Immediate hemostasis was achieved in all patients. No signs of ischemia or infarction were observed after intervention. CONCLUSIONS: Superselective embolization of the vasa recta proved efficient and safe in our small patient group. Advantages of this technique are reduction of the embolized area to a minimum and direct control of hemostasis.

New evidence from Le Moustier 1: computer-assisted reconstruction and morphometry of the skull.

In this study, we present a new computerized reconstruction of the Le Moustier 1 Neanderthal skull and discuss its significance for Neanderthal growth and variability. Because of the precarious state of preservation of the original material, we applied entirely noninvasive methods of fossil reconstruction and morphometry, using a combination of computed tomography, computer graphics, and stereolithography. After electronic restoration, the isolated original pieces were recomposed on the computer screen using external and internal anatomical clues to position the bone fragments and mirror images to complete missing parts. The inferred effects of general compressive deformation that occurred during fossilization were corrected by virtual decompression of the skull. The resulting new reconstruction of the Le Moustier 1 skull shows morphologic features close to the typical Neanderthal adult state. Residual asymmetry of skeletal parts can be traced to in vivo skeletal modification: the left mandibular joint shows signs of a healed condylar fracture, and the anatomy of the occipital region suggests mild plagiocephaly. Using micro-CT analysis, the left incus could be recovered from the matrix filling of the middle ear cavity. Its morphometric dimensions are similar to those of the La Ferrassie III incus. The morphometric characteristics of the inner ear deviate substantially from the condition reported as typical for Neanderthals and fall within the range of modern human variability.

The value of stereolithographic models for preoperative diagnosis of craniofacial deformities and planning of surgical corrections.

The purpose of this study was to assess the importance of stereolithographic models (SLMs) for preoperative diagnosis and planning in craniofacial surgery and to examine whether these models offer valuable additional information as compared to normal CT scans and 3D CT images. Craniofacial SLMs of 20 patients with craniomaxillofacial pathology were made. A helical volume CT scan of the anatomic area involved delivered the necessary data for their construction. These were built with an SLA 250 stereolithography apparatus (3D-Systems, Valencia, CA, USA), steered by FORM-IT/DCS software (University of Zurich, Switzerland). The stereolithography models were classified according to pathology, type of surgery and their relevance for surgical planning. Though not objectively measurable, it was beyond doubt that relevant additional information for the surgeon was obtained in cases of hypertelorism, severe asymmetries of the neuro- and viscerocranium, complex cranial synostoses and large skull defects. The value of these models as realistic "duplicates" of complex or rare dysmorphic craniofacial pathology for the purpose of creating a didactic collection should also be emphasized. The models proved to be less useful in cases of consolidated fractures of the periorbital and naso-ethmoidal complex, except where there was major dislocation.

Superselective coil embolization in acute gastrointestinal hemorrhage: personal experience in 10 patients and review of the literature.

PURPOSE: To evaluate the safety and efficiency of microcoil embolization in upper and lower gastrointestinal hemorrhage. PATIENTS AND METHODS: Superselective microcoil embolization was performed in 10 patients (upper gastrointestinal bleeding, n = 3; lower gastrointestinal bleeding, n = 7) who had acute gastrointestinal hemorrhage. Embolization was performed as peripherally as possible with use of coaxial catheter systems. Embolization materials included microcoils (2-4 mm) alone (n = 5), microcoils and polyvinyl alcohol particles (355-500 microm) (n = 4), and microcoils and gelatin sponge particles (n = 1). RESULTS: Immediate hemostasis was achieved in eight patients. In two patients with dual blood supply of the bleeding site, significant reduction of hemorrhage resulted. In these two patients, it was technically impossible to place the coaxial catheter distally enough to allow safe embolization of both feeding vessels. No clinical signs of ischemia or infarction were observed after intervention. CONCLUSION: Microcoil embolization is a safe and efficient procedure for controlling acute lower gastrointestinal bleeding if performed in a superselective catheter position. In upper gastrointestinal bleeding, microcoil embolization is an established treatment and can be performed more proximally.

[Preoperative diagnosis of complex craniofacial syndromes]. / Präoperative Diagnostik komplexer kraniofazialer Syndrome.

The aim of this study was to evaluate stereolithography as a tool in craniofacial surgery. The indications were classified according to the usefulness of stereolithography for different craniofacial pathologies. Stereolithography models of 21 patients were built; in three cases two models were made. The age of the 7 male and 14 female patients was 17 years on average (range: 15 months-44 years). First a helical volume CT scan of the anatomical region was performed. After transformation of the data set, the models were built by an SLA 250 stereolithography apparatus (3D-Systems, Valencia, Calif., USA), steered by FORM-IT/DCS-Software (University of Zurich, Switzerland). The stereolithography models were constructed by superposition of epoxy resin slices of 0.05 mm thickness, which were polymerized by a helium-cadmium laser. These models were classified according to the indication for stereolithography, the operation performed, the relevance for surgical planning and the usefulness for the fabrication of implants and protheses. In craniofacial syndromes, severe asymmetries of the viscerocranium, large skull defects and before surgical correction of hypertelorism these models provided important additional information for the surgeon. Before complex interventions in these fields the construction of a stereolithography model should be considered. In multiple fractures consolidated in dislocation, the models proved to be less useful.

Treatment of pelvic venous spur (May-Thurner syndrome) with self-expanding metallic endoprostheses.

PURPOSE: The application of self-expanding metallic endoprostheses (stents) to treat symptomatic pelvic venous spurs as an alternative to surgery. METHODS: Wallstents with a diameter from 14 to 16 mm and one Cragg stent were placed in the left common iliac vein of eight patients (seven women, one man; mean age 42 years) with a symptomatic pelvic venous spur (left deep venous thrombosis or post-thrombotic leg swelling). Four patients had surgical thrombectomy prior to stent placement. RESULTS: Technical success with immediate reduction of left leg circumference was achieved in all eight patients. A primary patency rate of 100% was observed during an average follow-up of 3 years (range 10-121 months). There were no procedural or stent-related complications. CONCLUSION: The percutaneous transfemoral placement of self-expanding metallic stents is an effective minimally invasive alternative to surgery in the treatment of symptomatic pelvic venous spur.

Treatment of malignant biliary obstruction with polyurethane-covered Wallstents.

OBJECTIVE: This study was undertaken to determine the safety, efficacy, and performance of polyurethane-covered Wallstents in the treatment of malignant biliary obstruction. SUBJECTS AND METHODS: This pilot study included 30 patients with malignant biliary obstruction. Palliative decompression of the obstructed bile duct was attempted with a polyurethane-covered Wallstent that is a prototype. Patients with hilar obstructions were excluded. All stents were inserted percutaneously. Kaplan-Meier analysis was used to determine stent patency. RESULTS: Effective biliary decompression was achieved in all patients initially. No acute stent-related complications occurred. The 30-day mortality rate was 20%. During follow-up, 11 stent occlusions occurred; therefore, the occlusion rate was 37%. The patency rates after 1, 3, 6, and 12 months were 96%, 69%, 47%, and 31%, respectively. Tumor growth through the stent covering that was proven both histologically and by biopsy observed in two patients, causing stent occlusion in one of them. Other reasons for stent occlusion were distal tumor ingrowth (n = 1) and biopsy-proven granulation tissue inside the stent (n = 2). Otherwise, the reasons for stent occlusion remained unclear. CONCLUSION: This prototype of a covered stent did not provide better results than did conventional uncovered stents in patients with malignant biliary obstruction. The covering did not effectively prevent tumor ingrowth in at least two patients. The stent also seems prone to premature occlusion.

Acute colonic obstruction: clinical aspects and cost-effectiveness of preoperative and palliative treatment with self-expanding metallic stents--a preliminary report.

PURPOSE: Evaluation of clinical aspects and cost-effectiveness of use of self-expanding metallic stents in the treatment of acute colonic obstruction as either a preoperative procedure or palliation. MATERIALS AND METHODS: Thirteen consecutive patients, aged 49-83 years (mean, 67 years), with clinical and radiologic signs of colonic obstruction were treated as a preoperative procedure in 10 patients and as a palliative treatment in three. A total of 16 self-expanding metallic stents (diameter, 16 mm; length fully expanded, 56 mm) were implanted with combined fluoroscopic and endoscopic guidance. The costs (hospitalization, intensive care unit, stent placement, and surgery) were compared with costs for 13 surgically treated patients at the same hospital. RESULTS: Stent placement was successful in 12 of the 13 patients; all recovered from mechanical obstruction, and single-stage surgery was possible in eight of nine patients treated preoperatively. One very narrow stenosis could not be passed. Dysfunction occurred in two long stenoses after 5 days with reocclusion 2 and 6 weeks, respectively, after stent placement. A cost reduction of 19.7% was observed as a result of shorter hospitalization and a lower complication rate. In patients with colon cancer in the preoperative treatment group, the cost reduction increased to 28.8%. CONCLUSION: Metallic stent placement in patients with acute colonic obstruction was a minimally invasive and cost-effective preoperative procedure that allowed single-stage surgery in most cases. Stent placement for palliation should be limited to patient with special indications.