Fibrosis is the production of excessive amounts of connective tissue, i.e., scar formation, in the course of reactive and reparative processes. Fibrosis develops as a consequence of various underlying diseases and presents a major diagnostically and therapeutically unsolved problem. In this review, we postulate that fibrosis is always a sequela of inflammatory processes and that the many different causes of fibrosis all channel into the same final stereotypical pathways. During the inflammatory phase, both innate and adaptive immune mechanisms are operative. This concept is exemplified by fibrotic diseases that develop as a consequence of tissue damage, primary inflammatory diseases, fibrotic alterations induced by foreign body implants, "spontaneous" fibrosis, and tumor-associated fibrotic changes.

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Indeterminate cell histiocytosis is a rare disorder, in which the predominant cells have the characteristics of both Langerhans cells and macrophages. We, in this study, describe 18 patients and compare them with those previously published. Most patients were adults with either solitary or multiple red-brown papules or nodules. While most lesions were confined to the skin, both conjunctival and bony involvement was seen. Histologically, the lesions showed patterns resembling those described for xanthogranulomas, with predominantly oncocytic (nine patients), spindled (five patients), scalloped (two patients) or vacuolated (two patients) macrophages. The accompanying infiltrate was mainly lymphocytic, although eosinophils and occasionally plasma cells were seen. All lesions were positive for macrophage markers, such as KP1 (CD68) and Ki-M1p, as well as for S-100 protein and showed variable reactivity for CD1a. No Birbeck granules were seen ultrastructurally in one patient. Some patients shared features with sinus histiocytosis with massive lymphadenopathy. It is unclear whether this disorder is a separate entity or represents various macrophage disorders identified at various time points in the inflammatory response. Ratzinger G, Burgdorf WHC, Metze D, Zelger BG, Zelger B. Indeterminate cell histiocytosis: fact or fiction? A clinicopathological series of 18 patients.

Breath analysis for the purpose of non-invasive diagnosis of lung cancer has yielded numerous candidate compounds with still questionable clinical relevance. To arrive at suitable volatile organic compounds our approach combined the analysis of different sources: isolated tumor samples compared to healthy lung tissues, and exhaled breath from lung cancer patients and healthy controls. Candidate compounds were further compared to substances previously identified in the comparison of transformed and normal lung epithelial cell lines. For human studies, a breath sampling device was developed enabling automated and CO2-controlled collection of the end-tidal air. All samples were first preconcentrated on multibed sorption tubes and analyzed with gas chromatography mass spectrometry (GC-MS). Significantly (p < 0.05) higher concentrations in all three types of cancer samples studied were observed for ethanol and n-octane. Additional metabolites (inter alia 2-methylpentane, n-hexane) significantly released by lung cancer cells were observed at higher levels in cancer lung tissues and breath samples (compared to respective healthy controls) with statistical significance (p < 0.05) only in breath samples. The results obtained confirmed the cancer-related origin of volatile metabolites, e.g. ethanol and octane that were both detected at significantly (p < 0.05) elevated concentrations in all three kinds of cancer samples studied. This work is an important step towards identification of volatile breath markers of lung cancer through the demonstration of cancer-related origin of certain volatile metabolites.

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Coordinated filling and drainage of the anorectal vascular plexus is regulated by intrinsic vascular sphincter mechanisms. Both morphological and functional failure of this vascular system may contribute to the development of hemorrhoidal disease.

Echinococcosis, also known as hydatid disease, is an infection of larval stage animal tapeworm, Echinococcus. The larvae reside in the liver and lungs, producing multiloculated fluid-filled cysts. Imaging findings of Echinococcosis caused by E. granulosus are single, unilocular cyst or multiseptated cysts, showing "wheel-like", "rosette-like" or "honeycomb-like" appearances. There may be "snow-flakes" sign, reflecting free floating protoscoleces (hydatid-sand) within the cyst cavity. Degenerating cysts show wavy or serpentine bands or floating membranes representing detached or ruptured membranes. Degenerated cysts show heterogeneous, solid-looking pseudotumor that may show "ball of wool sign". Dead cysts show calcified cyst wall. Echinococcosis caused by E. multilocularis produces multilocular alveolar cysts with exogeneous proliferation, progressively invading the liver parenchyma and other tissues of the body. Imaging findings are ill-defined infiltrating lesions of the liver parenchyma, consisting of multiple small clustered cystic and solid components. On sonography, lesions are heterogeneous with indistinct margins, showing "hailstorm appearance" or "vesicular or alveolar appearance". CT and MR imaging displays multiple, irregular, ill-defined lesions. Multiple small round cysts with solid components are frequent. Large lesions show "geographical map" appearance. Calcifications are very frequent, appearing as peripheral calcification or punctuate scattered calcific foci. Invasion into the bile ducts, portal vein or hepatic vein may occur. Direct spread of infected tissue may result in cysts in the peritoneal cavity, kidneys, adrenal gland or bones.

Skin rejection remains a major hurdle in reconstructive transplantation. We investigated molecular markers of skin rejection with particular attention to lymphocyte trafficking. Skin biopsies (n = 174) from five human hand transplant recipients were analyzed for rejection, characteristics of the infiltrate and lymphocytic adhesion markers. The cellular infiltrate predominantly comprised CD3+ T cells. CD68, Foxp3 and indoleamine 2, 3-dioxygenase expression and the CD4/CD8 increased with severity of rejection. Lymphocyte adhesion markers were upregulated upon rejection, intercellular adhesion molecule-1 and E-selectin correlated best with severity of rejection. Guided by the findings, a specific E-and P-selectin inhibitor was investigated for its effect on skin rejection in a rat hind limb allotransplant model. While efomycine M (weekly s.c. injection into the graft) alone had no effect, long-term allograft survival was achieved when combined with antithymocyte globulin and tacrolimus (control group without efomycine M rejected at postoperative day [POD] 61 ± 1). Upregulation of lymphocyte trafficking markers correlates with severity of skin rejection and time after transplantation in human hand transplantation. Blocking E-and P-selectin in the skin holds potential to significantly prolong limb allograft survival.