[Injury patterns in interstitial lung diseases]. / Schädigungsmuster interstitieller Lungenerkrankungen.

Interstitial lung diseases (ILD) consist of a complex group of hundreds of non-neoplastic pulmonary diseases with divergent clinical presentation, morphology and progression tendency. This great number of clinical entities contrasts with a limited number of injury patterns. By definition, an adequate classification requires a synopsis of the clinical, radiological and morphological findings. The ATS/ERS (American Thoracic Society/ European Respiratory Society) guidelines recommend an open lung biopsy if high-resolution computed tomography does not provide conclusive results. Due to the focal nature and overlapping features of injury patterns, microscopic categorization is not always possible. In order to broaden the diagnostic criteria by using molecular patterns the Lung Research Working Group of the Institute of Pathology of Hannover Medical School, Europe's leading transplant center, is working up fresh explanted human lungs in a standardized manner. These fresh specimens are used for translational research by means of functional, morphological and molecular techniques in order to identify disease-specific regulatory processes and to make them usable diagnostically and therapeutically.

Evaluation of the Effectiveness of Peritoneal Adhesion Prevention Devices in a Rat Model.

BACKGROUND: Abdominal operations are followed by adhesions, a prevalent cause of abdominal pain, and the most frequent cause for bowel obstruction and secondary female infertility. This rat study addresses adhesion prevention capability of Adept(®), Interceed(®), Seprafilm(®), and a novel device, 4DryField(®) PH which is provided as powder and generates its effect as gel. METHODS: Sixty-eight male Lewis rats had cecal abrasion and creation of an equally sized abdominal wall defect, and were grouped randomly: A control group without treatment (n=10); two groups treated with 4DryField(®) PH using premixed gel (n=15) or in-situ gel technique (n=16); one group each was treated with Seprafilm(®) (n=8), Interceed(®) (n=9), or Adept(®) (n=10). Sacrifice was on day 7 to evaluate incidence, quality, and quantity of adhesions, as expressed via adhesion reduction rate (AR). Histologic specimens were evaluated. Statistical analyses used ANOVA and unpaired t-tests. RESULTS: 4DryField(®) PH significantly reduced incidence and severity of adhesions both as premixed gel (AR: 85.2%) and as in-situ made gel (AR: 100%), a comparison between these two application techniques showed no differences in efficacy. Seprafilm(®) did not reduce incidence but severity of adhesions significantly (AR: 53.5%). With Interceed(®) (AR: 3.7%) and Adept(®) (AR: 16.1%) no significant adhesion-reduction was achieved. Except for inflammatory response with Interceed(®), histopathology showed good tissue compatibility of all other devices. CONCLUSION: 4DryField(®) PH and Seprafilm(®) showed significant adhesion prevention capabilities. 4DryField(®) PH achieved the highest adhesion prevention effectiveness without restrictions concerning mode of application and compatibility and, thus, is a promising strategy to prevent abdominal adhesions.

Impairment of the Peritoneal Surface as a Decisive Factor for Intestinal Adhesions in Intraperitoneal Onlay Mesh Surgery - Introducing a New Rat Model.

BACKGROUND: Meshes implanted intraperitoneally are known to cause adhesions potentially resulting in complications such as chronic pain, enterocutaneous fistula, or mesh infection. This study introduces a model for investigation of intestine-to-mesh adhesions and evaluates as to whether missing of visceral peritoneum is causative. METHODS: In 18 rats, rectangular 1.5 x 2 cm patches of an uncoated polypropylene mesh (Ultrapro(®)) were sewn to the inner abdominal wall next to the cecum. Additionally, a meso-suture ensured contact between cecum and mesh. Rats were assigned to 2 groups: in 8 rats the peritoneum was left intact, in 10 the cecum was depleted from peritoneum with abrasion. Sacrifice was on day 7. Macroscopic evaluation used two adhesion scores. Specimens were evaluated microscopically, statistical analyses employed student's t-test. RESULTS: On day 7, rats with mesh implantation combined with locally de-peritonealization by cecal abrasion mostly showed severe cecum-to-mesh agglutination (mean Lauder score 92%, mean total Hoffmann score 90%), whereas meshes of most animals without cecal abrasion only had some coverage with intraabdominal fat (33%, 24%; p = 0.0002). Histological work-up showed adequate wall ingrowth of mesh in all rats. In animals with cecal abrasion, meshes were mostly adhesive with cecal wall. However, when the peritoneum of cecum was unimpaired, abdominal wall above the mesh as well as cecum usually revealed sub-peritoneal tissue and a mono-layer cell coverage as seen in normal peritoneum. CONCLUSION: This study introduces a model mimicking a clinical situation of e.g. hernia repair by intraperitoneally implanted meshes when mesh has contact with normal and with de-peritonealized intestine. The model might be useful for testing mesh types and coatings as well as other devices for their efficacy in adhesion prevention. The high adhesion scores of rats with local de-peritonealization compared with the low scores of animals with intact peritoneum indicate that the integrity of intestinal peritoneum is a decisive factor for adhesion formation.

Role of human papillomaviruses in persistent and glucocorticoid-resistant juvenile phimosis.

BACKGROUND: In adults, human papillomaviruses (HPV), lichen sclerosus et atrophicus (LSA) and phimosis are considered to be major risk factors for penile cancer. In boys, a possible association between phimosis, LSA and HPV has been suggested. OBJECTIVE: To investigate the role of HPV in the persistence of phimosis in children. PATIENTS AND METHODS: Out of a cohort of 420 boys presenting with foreskin problems, we prospectively sampled the preputial tissue of 82 patients during circumcision: 46 with steroid-naïve and 36 with steroid-resistant phimosis. All foreskins were assessed clinically and histopathologically with regard to appearance, inflammation, oedema, epithelial degeneration and fibrosis. The viral status of the foreskins was determined by immunohistochemistry and highly sensitive PCR, with subsequent subtyping by DNA hybridization (HPV types 6, 11, 16, 18, 31, 33, 35, 39, 42, 44, 45, 51-54, 56, 58, 59, 61, 62, 66-68, 70, 72, 73, 81-84, 90, 91). RESULTS: The foreskins appeared normal in 62 boys and suggestive of LSA in one single case. Small cracks or white scars were present in seven steroid-naïve and 12 steroid-resistant foreskins. LSA was diagnosed microscopically in two of the steroid-naïve and six of the steroid-pretreated group. No evidence of HPV was found in any of the juvenile foreskins. CONCLUSIONS: Our prospective study has provided evidence that HPV is not usually present in the foreskin of boys with persistent phimosis after their first year of life and that topical glucocorticoid treatment failure is not associated with HPV or any specific histopathological changes.

Molecular and clinicopathological analysis of Epstein-Barr virus-associated posttransplant smooth muscle tumors.

Epstein-Barr virus (EBV)-associated posttransplant smooth muscle tumors (PTSMT) are very rare complications. We aimed to provide a clinicopathological characterization which is based on our own case series (n = 5) as well as previously reported PTSMT cases (n = 63). Meta-analysis of PTSMT and molecular analysis of tumor cells from our cohort was performed. Most PTSMT developed in kidney-transplanted patients (n = 41/68, 60%). Liver/transplant liver was the main site of manifestation (n = 38/68, 56%). Tumors occurred after a median interval of 48 months (range 5-348) and developed earlier in children than in adults. Most tumors showed no marked cellular atypia, low mitosis rate and no tumor necrosis. Gene expression analysis of 20 EBV-related genes, including two microRNAs, revealed overexpression of MYC (p = 0.0357). Therapy was mainly based on surgical resection or reduced immunosuppression but no significant differences in overall survival were evident. Lower overall survival was associated with multiorgan involvement (n = 33/68, 48.5%) and particularly with intracranial PTSMT manifestation (n = 7/68, 10%; p < 0.02), but not transplant involvement (n = 11/68, 16%). In summary, PTSMT differ from conventional leiomyosarcomas by their lack of marked atypia, unusual sites of involvement and defining EBV association. Surgery and reduced immunosuppression show comparable clinical results and prognosis is associated with intracranial manifestation.