Prognostic relevance of tumour-associated macrophages and von Willebrand factor-positive microvessels in colorectal cancer

Tumour-associated macrophages (TAM) are involved in tumour angiogenesis and anti-tumour immune response. In colorectal cancer (CRC), an association of high microvascular density (MVD) and unfavourable prognosis has been reported by some investigators. However, heterogeneous patient groups were studied. We, therefore, analysed the correlation between TAM and MVD and the prognostic relevance of MVD, TAM and T lymphocyte infiltration for long-term survival in a homogeneous group of 70 patients with moderately differentiated cancers of the International Union Against Cancer (UICC) stages II and III, who did not receive chemotherapy. MVD was evaluated using immunohistochemistry with antibodies against CD34 and von Willebrand factor (vWF). TAM and T lymphocytes were visualised with antibodies against CD68 and CD3, respectively. Statistical analysis did not reveal a significant correlation between TAM and T lymphocyte numbers and MVD. Multivariate analysis of immunohistochemical data from all CRC patients and the subgroup of patients with UICC stage-II CRC identified TAM- and vWF-positive microvessel numbers as prognostically relevant markers. Low numbers of TAM- and high numbers of vWF-positive microvessels were associated with an unfavourable prognosis. In conclusion, TAM- and vWF-positive microvessel numbers may serve as independent prognostic markers for patients with UICC stage-II and -III CRC and may help to identify patients with an unfavourable prognosis.     

Hyperphosphatemia and cardiovascular risk in patients on dialysis

Cardiovascular diseases are the leading causes of mortality among patients with end-stage renal disease (ESRD), with arterial disease and left ventricular hypertrophy being the two principal factors of the high mortality rate in this population. In addition to traditional risk factors (age, gender, diabetes, hypertension, lifestyle, hyperlipidemia, smoking, hyperhomocystinemia), inflammation, oxidative stress and disorders of mineral metabolism may contribute to cardiovascular risk in patients with uremic syndrome. High serum phosphate may influence vascular calcifications directly and indirectly, by worsening secondary hyperparathyroidism. Several treatment options are available for the treatment of hyperphosphatemia and secondary hyperparathyroidism in patients with ESRD. The treatment approach includes a diet low in phosphorus, with less than 1 g/kg/day of protein. Vitamin D supplementation is an important part of treatment. Phosphate binding agents are in most of the patients necessary in addition to diet. Aluminum hydroxide has been widely used for many years. It is very potent, but also very toxic, with severe encephalopathy as the most dangerous side effect. Calcium salts are less potent, and were considered safe for use in patients on dialysis. However, improvement in the understanding of vascular calcifications has demonstrated that calcium overload significantly contributes to widespread atherosclerosis in patients with ESRD. Sevelamer-hydrochloride is a novel non-aluminum, non-calcium containing phosphate binder, which is capable of reducing the levels of phosphorus as well as of low-density lipoprotein cholesterol, and increasing high-density lipoprotein cholesterol.     

A 71-year-old man with spindle-cell neoplasm of unknown origin: a difficult-to-diagnose clear-cell sarcoma

A patient initially presented in 1988 with a solitary axillary mass, diagnosed as a high-grade neuroendocrine spindle-cell neoplasm; there was no history of a primary cutaneous malignancy. After subsequent development of a pulmonary nodule in 2001 (14-years post initial diagnosis), the case was reviewed and the possibility of metastatic melanoma was raised. The histopathologic and immunohistochemical profile of this melanocytic neoplasm was diagnostic of clear cell sarcoma (CCS) of tendons and aponeuroses, although the differential diagnosis included malignant melanoma, follicular dendritic and interdigitating cell tumors, malignant peripheral nerve sheath tumor, and a category of so-called PEComas. It is the role of pathologists, particularly dermatopathologists, to distinguish CCS from malignant melanoma, and to alert the clinician, because proper diagnosis ultimately influences treatment. We discuss the immunophenotype, differential diagnosis, and molecular signatures of these neoplasms, and review the pertinent literature on these entities.     

Endonasal endoscopic dacryocystorhinostomy in a four-month-old infant

The authors present a case of endonasal endoscopic dacryocystorhinostomy in a 4-month-old girl suffering from remarkable epiphora, persistent bulging and recurrent abscesses in the medial canthal region of the left eye. All conservative therapeutic attempts failed. Several external incisions were performed in order to solve the acute phases of the inflamed lacrimal sac. The procedure was performed by means of otologic microsurgical instruments under endoscopic control. No silicone stent was used. Ten months after surgery, the girl is doing very well.     

Hereditary basaloid follicular hamartoma syndrome

Basaloid follicular hamartoma syndrome (BFHS) is a rare adnexal tumor genodermatosis. We present a case of hereditary BFHS and review the literature concerning the clinical and histologic features of this entity.     

Insulin‐like growth factor binding protein 5 induces skin fibrosis: A novel murine model for dermal fibrosis

Objective

To determine the role of insulin‐like growth factor binding protein 5 (IGFBP‐5) in the development of skin fibrosis in vivo, by examining the effect of overexpression of IGFBP‐5 in mouse skin.

Methods

Wild‐type C57BL/6J mice were injected subcutaneously with replication‐deficient serotype 5 adenovirus expressing human IGFBP‐3 (Ad3), IGFBP‐5 (Ad5), or no complementary DNA (cAd). Mice were killed 3, 8, or 22 days postinjection. The dermal thickness and dermal collagen bundle thickness in skin sections were measured. The deposition of collagen in the extracellular matrix (ECM) was quantified using the Sircol assay. Expression of proliferating cell nuclear antigen (PCNA) and fibronectin, as determined by immunohistochemical analysis, was used to evaluate fibroblast activation, and vimentin and α‐smooth muscle actin (α‐SMA) were used to evaluate the fibroblast phenotype.

Results

Adenovirally expressed IGFBP was detected in dermal fibroblasts, endothelial cells, epithelial cells, and muscle bundles in Ad3‐ and Ad5‐injected mice. Increased collagen deposition, denser dermal connective tissue, and increased collagen bundle thickness were observed in IGFBP‐5–overexpressing mice. Dermal thickness and collagen bundle thickness were significantly increased in Ad5‐injected mice compared with cAd‐ and Ad3‐injected mice. Treatment with Ad5 resulted in a dose‐dependent increase in dermal and collagen bundle thickness. Increased deposition of collagen and fibronectin, increased numbers of PCNA‐positive fibroblasts, as well as increased numbers of vimentin– and α‐SMA–double‐positive fibroblasts were detected in the dermis of IGFBP‐5–overexpressing mouse skin.

Conclusion

IGFBP‐5 is a key mediator of fibrosis. IGFBP‐5 mediates its profibrotic effects through fibroblast activation, increased ECM deposition, and myofibroblastic transformation of dermal fibroblasts. Overexpression of IGFBP‐5 provides a novel model for studying the pathogenesis of skin fibrosis in systemic sclerosis.

     

Influence of nano and bulk copper on agile frog development

Ecotoxicology - Nanotechnology, as one of the fastest-growing industries, offers many benefits in various fields. However, properties that contribute to its positive effects, in other context, can...