Abstract Purpose: We demonstrate the multislice computed tomography (MSCT) findings of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA)-proven hilar and mediastinal lymph node enlargement with signs of anthracosis. Materials and Methods: 53 enlarged lymph nodes in 39 patients (28 male, 11 female) with EBUS-TBNA-confirmed anthracosis were analyzed retrospectively. Results: The mean short axis diameter of the enlarged lymph nodes with signs of anthracosis was 13.7 mm. Lymph nodes most often showed an oval shape (84 %) and were well defined in 66 % of cases. Lymph node confluence was observed in 32 % of cases. Calcifications were documented in 24.5 % of cases. Contrast enhancement and fatty involution were seen seldom (3.8 %). Lymph node necrosis was not seen. Conclusion: Lymph node anthracosis may be found most often in enlarged, well defined lymph nodes with an oval shape, frequently associated with confluence and calcifications. Citation Format: • Kirchner J, Mueller P, Broll M et al. Chest CT Findings in EBUS-TBNA-Proven Anthracosis in Enlarged Mediastinal Lymph Nodes. Fortschr Röntgenstr 2014; 186: 1122 – 1126

Nonerosive reflux disease (NERD) is commonly diagnosed in patients with symptoms of reflux. The aim of the present study was to determine whether high-definition endoscopy (HD) plus equipped with the iScan function or chromoendoscopy with Lugol's solution might permit the differentiation of NERD patients from those without reflux symptoms, proven by targeted biopsies of endoscopic lesions. A total of 100 patients without regular intake of proton pump inhibitors and with a normal conventional upper endoscopy were prospectively divided into NERD patients and controls. A second upper endoscopy was performed using HD+ with additional iScan function and then Lugol's solution was applied. Biopsy specimens were taken from the gastroesophageal junction in all patients. A total of 65 patients with reflux symptoms and 27 controls were included. HD(+) endoscopy with iScan revealed subtle mucosal breaks in 52 patients; the subsequent biopsies confirmed esophagitis in all cases. After Lugol's solution, 58 patients showed mucosal breaks. Sensitivity for the iScan procedure was 82.5%, whereas that for Lugol's solution was 92.06%. Excellent positive predictive values of 100% and 98.3%, respectively, were noted. The present study suggests that the majority of patients with NERD and typical symptoms of reflux disease can be identified by iScan or Lugol's chromoendoscopy as minimal erosive reflux disease (ERD) patients.

OBJECTIVES:Adjunctive techniques like DNA image cytometry (DNA-ICM) have been attributed to enhance the diagnostic performance of oral brush biopsies. The aim of the study was an evaluation of brush biopsies, analysed according to morphological criteria and by DNA-ICM vs. histological findings in a blinded prospective trial. MATERIALS AND METHODS:Eighty eight brush biopsies of 70 patients were sampled. Only clinical suspicious but not evident malignant oral lesions were included. Clinical diagnosis was leukoplakia (n = 36), lichen planus (n = 18), verruciform erythroplakia (n = 12), erythroleukoplakia (n = 9), erosion (n = 7) and induration (n = 6). Evaluation was conducted via histology, cytology and DNA-ICM. RESULTS:Histological diagnosis revealed eight cases of squamous intraepithelial dysplasia (SIN 1 n = 6, SIN 2 n = 2), four cases of carcinoma-in situ and 25 cases of oral T1-cancer. Remaining cases were leukoplakia (n = 28), lichen planus (n = 15) and local inflammation (n = 8). Brush biopsy detected malignant lesions including SIN>1 with a sensitivity of 55% and a specificity of 100%. DNA-ICM had a sensitivity of 70% and a specificity of 100%. The combination of both methods showed a sensitivity of 76% and a specificity of 100%. The predominant reason for false negative results were sampling errors with insufficient cells (86% in brush biopsy and 100% in DNA-ICM). CONCLUSION:DNA-ICM has the potential to substantially improve the sensitivity of a pure morphological interpretation of oral brush biopsies. Method inherent sampling errors may be accountable for a lower sensitivity compared to conventional histological diagnosis. Therefore, DNA-ICM should not be used to rule out malignancy, when lesions are already clinically suspicious for oral cancer.

Purpose In patients with bladder exstrophy-epispadias-complex (BEEC) or in selected patients with bladder loss for other reasons, ureterosigmoidostomy (USIG) & rectosigmoid pouch (Mainz Pouch (MZP) II) has been used at our institution. This diversion carries a lifelong risk for secondary malignancies. Therefore annual colonoscopy is recommended. Identification of potentially malignant structures can be challenging, and biopsies are taken in doubt, with the risk of injuring the ureterocolic implantation site. Using confocal laser endomicroscopy (CLE) and chromoendoscopy, the uretero-intestinal anastomosis is better visualized compared to conventional colonoscopy, and target biopsies could be taken to exclude malignancy. In this study we analyzed the feasibility and accuracy using the new technique in these patients for the first time. Material and Methods Over the last 3 years endomicroscopy and chromoendoscopy was used in patients with USIG or MZP II for surveillance colonoscopy. A high resolution coloscop (Hi-Line, Pentax, Japan) was used to identify ureteral orifices or other lesions. Chromoendoscopy using 0.1% Methylene blue spray was used to recognize macroscopically abnormal mucosal areas. The CLE allows a high magnification (1000x) and in-vivo imaging of deeper parts of the mucosal layer - up to 250μm. Results Endomicroscopy was performed in 68 patients (BEEC n=48, traumatic incontinence/tumor n=20). A total of 156 lesions with average size of 0.9 cm were identified by chromoendoscopy and CLE, verified by histology (9 Adenoma, 25 inflammatory changes, 122 hyperplasia). Prediction accuracy with chromoendoscopy was 94%, and with CLE 98%. Conclusions The newly developed high-resolution chromoendoscopy and endomicroscopy was used for the first time for surveillance sigmoidoscopy in patients with USIG or MZPII. Chromoendoscopy allows targeting biopsies; CLE has the advantage of accurate prediction concerning the malignant potential of the lesion. Allowing a unique visualisation at detailed cellular architecture, unnecessary biopsies can be avoided, reducing the risk of injuries of the ureteral implantation site.

Background: Sunitinib monotherapy in pretreated patients with advanced gastric cancer (AGC) was investigated. Preplanned analyses of tumour biomarkers on treatment outcome were performed.Patients and methods: Patients received sunitinib 50 mg/day for 4 weeks with 2 weeks rest until disease progression or unacceptable toxicity. The primary end-point was objective response rate (ORR). Secondary end-points included progression-free survival (PFS), overall survival (OS) and safety.Results: Fifty-two patients were enrolled and treated (safety population, SP). In the intention to treat population (n = 51); the ORR was 3.9%, median PFS was 1.28 months 195% CI, 1.18-1.90], median OS was 5.81 months [95% CI, 3.48-12.32], the estimated one-year survival rate was 23.7% [95%CI: 12.8-36.5]. In subgroup analyses, tumour VEGF-C expression compared with no expression was associated with significantly shorter median PFS (1.23 versus 2.86 months, logrank p = 0.0119) but there was no difference in tumour control rate (p = 0.142). In the SP, serious adverse events occurred in 26 patients, leading to 13 deaths, all sunitinib unrelated. Thirty-eight patients died from progressive disease, nine died <60 days after treatment start.Conclusion: Sunitinib monotherapy was associated with limited tumour response and good/moderate tolerability in this setting. (C) 2011 Elsevier Ltd. All rights reserved.

Introduction: Colonoscopy is the accepted gold standard for the detection of colorectal cancer. The aim of the current study was to prospectively compare high definition plus (HD+) colonoscopy with i-Scan functionality (electronic staining) vs. standard video colonoscopy. The primary end-point was the detection of patients having colon cancer or at least one adenoma.Methods: A total of 220 patients due to undergo screening colonoscopy, postpolypectomy surveillance or with a positive occult blood test were randomized in a 1 : 1 ratio to undergo HD+ colonoscopy in conjunction with i-Scan surface enhancement (90i series, Pentax, Tokyo, Japan) or standard video colonoscopy (EC-3870FZK, Pentax). Detected colorectal lesions were judged according to type, location, and size. Lesions were characterized in the HD+ group by using further i-Scan functionality (p-and v-modes) to analyze pattern and vessel architecture. Histology was predicted and biopsies or resections were performed on all identified lesions.Results: HD+ colonoscopy with i-Scan functionality detected significantly more patients with colorectal neoplasia (38 %) compared with standard resolution endoscopy (13 %) (200 patients finally analyzed; 100 per arm). Significantly more neoplastic (adenomatous and cancerous) lesions and more flat adenomas could be detected using high definition endoscopy with surface enhancement. Final histology could be predicted with high accuracy (98.6%) within the HD+ group.Conclusions: HD+ colonoscopy with i-Scan is superior to standard video colonoscopy in detecting patients with colorectal neoplasia based on this prospective, randomized, controlled trial.

OBJECTIVE The aim of this study was to evaluate osseointegration of one-piece zirconia vs. titanium implants depending on their insertion depth by histomorphometry. MATERIAL AND METHODS Four one-piece implants of identical geometry were inserted on each side of six mongrel dogs: (1) an uncoated zirconia implant, (2) a zirconia implant coated with a calcium-liberating titanium oxide coating, (3) a titanium implant and (4) an experimental implant made of a synthetic material (polyetheretherketone). In a split-mouth manner they were inserted in submerged and non-submerged gingival healing modes. After 4 months, dissected blocks were stained with toluidine blue in order to histologically assess the bone-to-implant contact (BIC) rates and the bone levels (BL) of the implants. RESULTS All 48 implants were osseointegrated clinically and histologically. Histomorphometrically, BL in the crestal implant part did not differ significantly with regard to material type or healing modality. The submerged coated zirconia implants tended to offer the most stable crestal BL. The histometric results reflected the different healing modes by establishing different BL. The median BIC of the apical implant part of the zirconia and titanium group amounted to 59.2% for uncoated zirconia, 58.3% for coated zirconia, 26.8% for the synthetic material and 41.2% for titanium implants. CONCLUSIONS Within the limits of this animal study, it is concluded that zirconia implants are capable of establishing close BIC rates similar to what is known from the osseointegration behaviour of titanium implants with the same surface modification and roughness.

Background The EPKi system (Pentax, Japan) enables resolution above HDTV. Aim of the study was to test the efficacy of HD+ alone and with the new post-processing digital filter i-Scan or chromoendoscopy (Methylene blue 0.1%) in screening for colorectal cancer. We focused on lesions less than 5 mm as a surrogate marker for the optical possibilities of the EPKi system. Methods The last 30 cm of the colon in a screening population were inspected with HD+ alone, in combination with i-Scan (2:1 randomisation) and subsequently with chromoendoscopy. All lesions were characterized and targeted biopsies were performed. Results i-Scan augmented in 69 patients the identification of lesions from 176 to 335 (p < 0.001) and chromoendoscopy to 646 (p < 0.001). The additional lesions were mainly flat (type IIb, 74%), which were only recognized using i-Scan or chromoendoscopy. The amount of neoplasias was not significantly different (HD+: 5, i-Scan: 11, Chromoendoscopy: 11), but all could correctly be predicted using i-Scan or chromoendoscopy. Conclusions HD+ colonoscopy with and without i-Scan unmask a plethora of small lesions but chromoendoscopy can even advance the number. However, i-Scan was able to predict neoplasia as precisely as chromoendoscopy and might shortly replace chromoendoscopy as a more time efficient tool.

BACKGROUND:In this study the potential of a new and entirely synthetic, nano-structured hydroxyapatite-based biomaterial for sinus floor augmentation is evaluated.METHODS:20 sinus floor elevations were carried out in a total of 20 patients. After a healing period of 6 months, in 10 cases cylinder-shaped bone biopsies were taken from the augmented maxillary region using trephine burs.RESULTS:The healing period progressed without any complications. General and specific histological analysis of the bone biopsies showed a high osteoclast activity at the margin of the biomaterial which was well integrated into the newly formed bone.CONCLUSION:This study demonstrates that new trabecular bone is formed after grafting with the nanocrystalline bone substitute after 6 months. Ongoing histomorphological studies are necessary to quantify the biomaterial-bone ratio and the exact amount of newly built bone in the augmented cavity after 6 months.

Einleitung: Die Vorsorgekoloskopie ist der Goldstandard in der Erkennung von (früh-) neoplastischen Adenomen. Ziel unserer prospektiven randomisierten Studie war der Vergleich zwischen der hochauflösenden Koloskopie mit i-scan Funktion (Pentax EPKi processor, Pentax Japan mit surface enhancement SE, vessel und pattern enhancement) im Vergleich zur Standardkoloskopie. Primärer Endpunkt: Patienten mit mind. einem neoplastischen Adenom (Fallzahlberechnung –86 Pts. pro Gruppe)

UV-exposures result in accumulation of genetic lesions that facilitate the development of skin cancer. Numerous pharmacologic agents are currently under development to both inhibit formation of DNA lesions and enhance repair. Drugs must be evaluated in vitro, currently performed in cell culture systems, before being tested on humans. Current systems do not account for the architecture and diverse cellularity of intact human skin.To establish a novel, functionally viable, and reproducible in vitro skin organ culture system for studying the effects of various pharmacologic agents on DNA repair.Human skin was obtained from neonatal foreskins. Intact skin punches derived from foreskins were cultured in vitro prior to exposure to UV-irradiation, and evaluated for DNA-damage using a DNA dot blot. Serial skin biopsies were obtained from patients with actinic keratoses treated with topical imiquimod. Expression of immune-stimulating and DNA repair genes was evaluated in ex vivo and in vitro samples.DNA dot blots revealed active repair of UV induced lesions in our in vitro skin organ culture. The photo-protective effect of sunscreen was detected, while imiquimod treatment did not enhance DNA repair in vitro. The DNA repair molecules XPA and XPF were up-regulated in the skin of imiquimod treated patients with actinic keratoses and imiquimod treated bone marrow-derived cell lines, but not keratinocytes.Our in vitro human skin organ culture model detected repair of UV-induced DNA lesions, and may be easily adapted to investigate various photo-protective drugs intended to prevent or treat skin cancer.

Einleitung: Der Einfluss des Apoptoseprozesses bezüglich Pathogenese und Prognose wurde für verschiedene Tumorentitäten beschrieben. Bcl-2 und Bcl-xL sind zentrale antiapoptotischen Proteine, pp32/PHAPI sensibilisiert für proapoptotische Stimuli. Für nicht-kleinzellige Lungenkarzinomen (NSCLC) existieren widersprüchliche Daten in Bezug auf die klinische Bedeutung dieser Apoptosefaktoren.

BACKGROUND:Recurrent cirrhosis (RC) due to pretransplant underlying disease leads to organ failure and subsequent death after orthotopic liver transplantation (OLT). RC occurs in up to 30% of patients with recurrent hepatitis C (HCV) within 5 years after OLT. We sought to identify early risk factors for rapid RC within the first year after OLT in HCV-positive patients.METHODS:Among 404 liver transplanted patients at the University of Mainz between 1998 and 2008, 90 were HCV-RNA positive. To identify predictive factors for rapid RC, we compared HCV-positive patients with advanced fibrosis stages within 1 year after OLT (n = 13) with these without RC at 5 years after OLT (n = 23).RESULTS:Overall, poorer patient survival was associated with advanced fibrosis scores in the 1-year protocol biopsy and nonresponse to interferon treatment before OLT. The strongest predictive factors for rapid RC were persistently high levels of alkaline phosphatase, bilirubin, viral load at 6 months after OLT, and multiple steroid pulse therapies. The CCR2-V64I polymorphism was not associated with rapid RC.CONCLUSION:We presented a group of patients with HCV-related rapid RC within the first year after OLT to identify predictive factors for rapid fibrosis progression.

Einleitung: Komplikationen der Gallengänge betreffen ca. 10–15% der Patienten nach orthotoper Lebertransplantations (OLT). Diffuse Gallengangprozesse, auch „Ischemic type biliary lesions“ (ITBL) genannt, sind hierbei mit einer schlechten Prognose assoziiert. Ziel der vorgestellten Untersuchung war die Charakterisierung der histologischen Lebeveränderungen in Gegenwart der ITBL im Vergleich zu einem Kontrollkollektiv nach OLT ohne Gallengangskomplikationen. Methode: Von 1996 bis 2006 erfolgte die Analyse der Leberbiopsien von OLT-Patienten. Leberfibrose (F0–4) und Entzündungsaktivität (A0–4) wurden nach Desmet quantifiziert. Zudem wurde einer Cholestase und einer Cholangitis nachgegangen. Die Nachbeobachtung betrug 2 Jahren nach OLT. Ergebnisse: Ausgewertet wurden 43 ITBL-Patienten und eine gleichgroße Kontrollgruppe. Die Gruppen zeigten ein medianes Alter von 53 Jahren und das gleiche Geschlechterverhältnis (m/w: 28/17). Die OLT erfolgte in beiden Gruppen in 86% aufgrund eines chronischen Leberversagens. In der ITBL-Gruppe entwickelten 46,5% der Patienten (20/43) innerhalb von 2 Jahren eine Leberfibrose (≥F2). Die Kontrollgruppe zeigte eine Fibroserate (≥F2) von 16,2% (7/43). Eine komplette Zirrhose (F4) wurde in 7% (3/43) der ITBL-Gruppe und in 2,3% (1/43) der Kontrolle beobachtet. Entzündliche Aktivität (≥A2) fand sich in 27,9% (12/43) der ITBL-Gruppe und in 20,9% (9/43) der Kontrolle. Die Cholangitis- und Cholestase- Raten verhielten sich in der ITBL-Gruppe gegenüber der Kontroll- Gruppe mit 58% zu 23% bzw. mit 50% zu 22%. Diskussion: Die Ergebnisse dieser Analyse zeigen, dass die ITBL mit einer vermehrten Fibroseprogression einhergeht. Die Tatsache, dass vor allem Cholestase und Cholangitis, regelmäßig in Zusammenhang mit der ITBL beobachtet werden, verweisen auf deren Rolle bei der Leberschädigung während einer ITBL. Durch die Fortsetzung dieser retrospektiven Analyse erhoffen wir uns eine präzisere Risikoeinschätzung für die ITBL treffen zu können.

Après injection intra-veineuse de fluoroscéine (10 %), l’endomicroscopie confocal (EMC) permet l’étude in vivo de la muqueuse intestinale de 0 à 250 μm au cours d’une endoscopie standard. La fluoroscéine, diffusant des vaisseaux jusqu’à la lumière intestinale, est absorbée par les bactéries localisées dans l’épithélium et dans la lamina propria. De nombreux travaux ont mis en évidence l’implication des bactéries intestinales dans la pathogénie des maladies inflammatoires chroniques de l’intestin (maladie de Crohn (MC), rectocolite hémorragique (RCH)). Le but de notre étude était d’identifier par EMC les bactéries au sein de la muqueuse intestinale in vivo et de les quantifier dans les différents segments coliques. Il s’agit d’une étude rétrospective réalisée chez des patients atteints de RCH, MC, colites infectieuses (CI) et des patients contrôles (PC). Dans tous les cas, l’EMC, Pentax EC3870K (Pentax, Tokyo ; Japon) était utilisé. La présence ou l’absence de bactéries était confirmée par la technique fluorescente d’hybridation in situ à partir de biopsies coliques dont les images étaient comparées à celles obtenues par EMC. Les bactéries ont ainsi pu être analysées (taille, forme, localisation au sein de la muqueuse colique) et dénombrées sur les différents segments coliques. Cent soixante-quinze patients (102 hommes, 73 femmes) ont été inclus (RCH : 84 ; MC : 29 ; CI : 12 ; PC : 50). Le nombre moyen d’images par patients (moy ± DS) analysées était de 162 ± 94, 160 ± 68, 131 ± 54 et 143 ± 78 pour la RCH, MC, CI et PC respectivement. Le nombre moyen d’images par segment était de 66 ± 52, 85 ± 60, 64 ± 43 et 87 ± 58 pour la RCH, MC, CI et PC respectivement (p > 0,05). Les bactéries étaient observées chez 60 % (50/84), 65 % (19/29) et 58 % (7/12) des patients porteurs de RCH, MC et CI respectivement comparativement à 14 % (7/50) des PC (p < 0,001). Leur localisation principale était le rectum, le côlon transverse et droit pour la RCH et MC, la distribution était homogène pour les CI avec une absence totale de bactéries au niveau de l’iléon. La présence des bactéries n’était pas corrélée au degré d’inflammation endoscopique et endomicroscopique. Chez les patients porteurs de colites (maladies inflammatoires et infectieuses), l’EMC montre la présence plus importante de bactéries dans la muqueuse colique ce qui pourrait aider à la compréhension du rôle pathogène des bactéries dans ces pathologies. L’absence de bactérie dans l’iléon pourrait permettre de distinguer les colites inflammatoires des colites infectieuses. Ce travail a été réalisé au cours d’une année post-doctorale financée par une bourse d’étude de l’Association Française Aupetit (AFA) que nous remercions chaleureusement.

Einleitung: Die nicht erosive Refluxerkrankung (NERD) ist eine häufige Diagnose bei symptomatischen Refluxpatienten. Kleinste Läsionen wurden bisher bei NERD Patienten in der Standardvideoendoskopie nur unzureichend erfasst. Ziel der aktuellen Studie war die Erfassung auch kleinster Läsionen mittels High Definition plus (HD+) Endoskopie mit i-Scan Funktion (Pentax EPKi processor, Pentax Japan mit surface enhancement SE, vessel und pattern enhancement), nachfolgender Chromoendoskopie mit Lugol'scher Lösung und nachfolgend histologischer Kontrolle.

Einleitung: Patienten mit Refluxbeschwerden weisen entweder typische Refluxläsionen (GERD) oder eine endoskopsich negative Refluxerkrankung (NERD) auf. Das neue EPKi System (I-Scan HD+, Pentax Japan) ermöglicht neben einer höheren Auflösung als der High Definition (HD) Standard den Einsatz von speziellen Digitalfiltern zur Oberflächenakzentuierung (p Mode) und besseren Gefäßdarstellung (v Mode). Ziel der Studie war der Nachweis von Läsionen im Ösophagus unter HD Endoskopie, den zusätzlichen Einsatz von Digitalfiltern und Chromoendoskopie (Lugol). Lugol besitz die Eigenschaft neben dysplastischen Arealen auch kleine entzündliche Läsionen zu demaskieren.

Einleitung: Die Koloskopie ist der Goldstandard in der Vorsorge des kolorektalen Karzinoms. Gerade endoskopisch schwer zu detektierbare kleine flache und eingesunkene Adenome zeigen eine erhöhte Entartungsfrequenz. Das EPKi System (I-Scan HD+, Pentax Japan) ermöglicht neben einer höheren Auflösung als der High Definition (HD) Standard den Einsatz von speziellen Digitalfiltern zur Oberflächenakzentuierung (p Mode) und besseren Gefäßdarstellung (v Mode). Ziel der aktuellen Studie war ein Vergleich zwischen reiner HD Koloskopie, den Einsatz von Digitalfiltern und Chromoendoskopie (Methylenblau). Primärern Endpunkt stellte die Anzahl an gefundenen Läsionen dar.