TGF-beta receptor 2 downregulation in tumour-associated stroma worsens prognosis and high-grade tumours show more tumour-associated macrophages and lower TGF-beta1 expression in colon carcinoma: a retrospective study

<p>Abstract</p> <p>Background</p> <p>Histological phenotype and clinical behaviour of malignant tumours are not only dependent on alterations in the epithelial cell compartment, but are affected by their interaction with inflammatory cells and tumour-associated stroma. Studies in animal models have shown influence of tumour-associated macrophages (TAM) on histological grade of differentiation in colon carcinoma. Disruption of transforming growth factor beta (TGF-beta) signalling in tumour cells is related to more aggressive clinical behaviour. Expression data of components of this pathway in tumour-associated stroma is limited.</p> <p>Methods</p> <p>Tissue micro arrays of 310 colon carcinomas from curatively resected patients in UICC stage II and III were established. In a first step we quantified amount of CD68 positive TAMs and expression of components of TGF-beta signalling (TGF-beta1, TGF-beta receptors type 1 and 2, Smad 3 and 4) in tumour and associated stroma. Further we analyzed correlation to histological and clinical parameters (histological grade of differentiation (low-grade (i.e. grade 1 and 2) vs. high-grade (i.e. grade 3 and 4)), lymph node metastasis, distant metastasis, 5 year cancer related survival) using Chi-square or Fisher's exact test, when appropriate, to compare frequencies, Kaplan-Meier method to calculate 5-year rates of distant metastases and cancer-related survival and log rank test to compare the rates of distant metastases and survival. To identify independent prognostic factors Cox regression analysis including lymph node status and grading was performed.</p> <p>Results</p> <p>High-grade tumours and those with lymph node metastases showed higher rates of TAMs and lower expression of TGF-beta1. Loss of nuclear Smad4 expression in tumor was associated with presence of lymph node metastasis, but no influence on prognosis could be demonstrated. Decrease of both TGF-beta receptors in tumour-associated stroma was associated with increased lymph node metastasis and shorter survival. Stromal TGF-beta receptor 2 expression was an independent prognostic factor for cancer related survival.</p> <p>Conclusion</p> <p>Histological phenotype and clinical behaviour of colon cancer is not only influenced by mutational incidents in tumour cells but also affected by interaction of tumour tissue with inflammatory cells like macrophages and associated stroma and TGF-beta signalling is one important part of this crosstalk. Further studies are needed to elucidate the exact mechanisms.</p

Lobectomy due to pulmonary vein occlusion after radiofrequency ablation for atrial fibrillation

Radiofrequency ablation is an effective treatment for atrial fibrillation. Pulmonary vein stenosis/occlusion is one of its rare complications. Herein, the case of a 50-year-old man with hemoptysis and migratory pulmonary infiltrations after transcatheter radiofrequency ablation for atrial fibrillation is presented. Initially, pneumonia, interstitial pulmonary disease, or lung cancer was suspected, but wedge resection revealed hemorrhagic infiltrations. Chest computed tomography pulmonary angiography detected no left superior pulmonary vein due to its total occlusion, and left upper lobectomy was performed. Post-ablation pulmonary vein occlusion must be strongly suspected in cases of migratory pulmonary infiltrations and/or hemoptysis. © The Korean Society for Thoracic and Cardiovascular Surgery. 2018

EFFECT OF FORCEPS SIZE AND MODE OF ORIENTATION ON ENDOSCOPIC SMALL-BOWEL BIOPSY EVALUATION

Endoscopy is increasingly being used to obtain duodenal biopsy specimens in suspected small intestinal malabsorption. We have prospectively evaluated the effect of standard and jumbo biopsy forceps, as well as the mode of orientation of the specimens (naked eye or stereomicroscopy), on duodenal biopsy weight, length, depth, and orientation in 18 consecutive patients. A pair of biopsy specimens was obtained from each patient by each type of forceps in random order. After they had been weighed, one biopsy specimen from each pair was oriented stereomicroscopically and all four were blindly evaluated by two pathologists. The biopsy specimens obtained with the jumbo forceps were significantly larger (15.9 +/- 6.9 mg, mean +/- SD) and longer (0.6 + 0.2 cm) than those obtained with the standard forceps (8.0 +/- 1.3 mg, 0.4 +/- 0.2 cm, respectively; p &lt; 0.001). Seventy-two percent of the jumbo biopsy specimens that were oriented with stereomicroscopy included a minimum of four villi in a row, as compared to 44% of the eye-oriented jumbo specimens and less than 39% of the standard specimens, irrespective of the mode of orientation (p = 0.02). These results indicate that the jumbo forceps is superior to the standard, because it produces a larger duodenal mucosal specimen, usually suitable for optimal histologic evaluation when oriented with stereomicroscopy

Potential role of apoptosis and apoptotic regulatory proteins in colorectal neoplasia: Correlations with clinico-pathological parameters and survival

An imbalance between apoptotic and proliferative processes is believed to underlie colorectal neoplasia. We evaluated the expression of bcl-2, p53, mdm2 proteins, and apoptosis in colorectal neoplasms, as well as their correlation with clinico-pathological parameters, using image analysis. Biopsies from 46 colorectal cancers, 121 adenomas, and 25 controls were studied using monoclonal antibodies against p53, bcl-2, mdm2 and the terminal deoxynucleotidyl- transferase-mediated dUTP nick end labeling (TUNEL) method for apoptosis. P53 and bcl2 protein expression was higher in adenomas ≥1 cm (P &lt; 0.03) and tubulovillous-villous adenomas (P &lt; 0.03), and correlated with dysplasia (P &lt; 0.03). In Cox regression analysis, Dukes&apos; stage was the most significant independent prognostic indicator of a worse survival (P &lt; 0.019), whereas when stage was eliminated, bcl-2 expression was also a powerful predictor for bad prognosis (P = 0.02). In conclusion, both bcl-2 and p53 immunohistochemical profiles may be useful adjuncts in detecting adenomas with a malignant potential, whereas bcl-2 could be used in combination with Dukes&apos; stage as a predictor of prognosis in colorectal cancer. © 2007 Springer Science+Business Media, LLC

Survivin Expression in Colorectal Carcinomas: Correlations with Clinicopathological Parameters and Survival

Background Survivin is a new member of the Inhibitor of apoptosis protein family that has a dual function as a mitotic regulator and apoptosis inhibitor. Survivin is prominently expressed in transformed cell lines and in many human cancers, including colorectal carcinoma. The aim of this study is to investigate the expression of survivin in colorectal carcinomas and its possible associations with clinicopathological parameters and patient survival. Materials and Methods Sections of formalin-fixed paraffin-embedded tissues from 77 colorectal carcinomas were immunohistochemistry stained for survivin. Results Survivin was mainly detected in the bottom of the glands of normal mucosa with mainly cytoplasmic localization. No survivin expression was found in infiltrating lymphocytes, fibroblasts, smooth muscle cells or neural tissue. Survivin staining was detected in 68/77 (88.3%) colorectal carcinomas. Survivin expression was found to be significantly associated with tumor differentiation (P = 0.02) but not with gender, age or Dukes stage. Survival did not differ according to survivin expression. Conclusion Survivin was found in the majority of colorectal carcinomas, suggesting that its expression is an early event in colorectal carcinogenesis. Its expression is statistically significantly associated with tumor differentiation but not with patient survival