RKIP expression in primary CRCs correlates with overall and disease-free survival, and can be useful for identifying early-stage CRC patients at risk of relapse.

Colorectal cancer (CRC) is a major cause of mortality and morbidity worldwide. Inflammatory activity within the stroma of invasive colorectal tumours is known to be a key predictor of disease activity with type, density and location of immune cells impacting on patient prognosis. To date, there has been no report of inflammatory phenotype within pre-malignant human colonic adenomas. Assessing the stromal microenvironment and particularly, inflammatory activity within colorectal neoplastic lesions is central to understanding early colorectal carcinogenesis. Inflammatory cell infiltrate was assessed by immunohistochemistry in paired colonic adenoma and adjacent normal colonic mucosa samples, and adenomas exhibiting increasing degrees of epithelial cell dysplasia. Macrophage phenotype was assessed using double stain immunohistochemistry incorporating expression of an intracellular enzyme of function. A targeted array of inflammatory cytokine and receptor genes, validated by RT-PCR, was used to assess inflammatory gene expression. Inflammatory cell infiltrates are a key feature of sporadic adenomatous colonic polyps with increased macrophage, neutrophil and T cell (specifically helper and activated subsets) infiltration in adenomatous colonic polyps, that increases in association with characteristics of high malignant potential, namely, increasing degree of cell dysplasia and adenoma size. Macrophages within adenomas express iNOS, suggestive of a pro-inflammatory phenotype. Several inflammatory cytokine genes (CXCL1, CXCL2, CXCL3, CCL20, IL8, CCL23, CCL19, CCL21, CCL5) are dysregulated in adenomas. This study has provided evidence of increased inflammation within pre-malignant colonic adenomas. This may allow potential mechanistic pathways in the initiation and promotion of early colorectal carcinogenesis to be identified.

Aims: To discover whether variations in thyroid transcription factor 1 (TTF-1) staining in different subtypes and patterns of pulmonary adenocarcinoma are related to the putative origin of the tumour. In addition, to confirm the specificity of TTF-1 for pulmonary (as opposed to other sites) adenocarcinoma, to examine the possible prognostic relevance of TTF-1 positivity in lung cancer, and to review this laboratory's experience of TTF-1 in diagnostic practice. Materials/Methods: In total, 128 primary lung adenocarcinomas, 106 primary non-pulmonary adenocarcinomas, and 37 pulmonary non-adenocarcinoma tumours were studied. In addition, 100 cases where TTF-1 was used in routine surgical pathology practice were investigated. Immunoperoxidase staining was performed on formalin fixed, paraffin wax embedded sections using anti-TTF-1 antibody. Staining was evaluated semiquantitatively using the frequency and intensity of nuclear positivity. Results: None of the 106 non-pulmonary adenocarcinomas expressed TTF-1 and only three of the 37 nonadenocarcinoma lung cancers, all neuroendocrine carcinomas, were positive. Of the pulmonary adenocarcinomas, 75% were strongly positive for TTF-1. Mucinous (two of six) and poorly differentiated adenocarcinomas (four of 10) were less likely to stain. Of the peripheral adenocarcinomas, 33 of 37 were positive, whereas only seven of 14 of those of bronchial origin stained strongly. Atypical adenomatous hyperplasia strongly expressed TTF-1. No ''false positives'' were encountered in the 100 routine diagnostic cases. Conclusion: Positive TTF-1 staining is useful in the differential diagnosis of pulmonary adenocarcinomas. TTF-1 may be a lineage marker for tumours arising from the peripheral airway or alveolar epithelium and has no prognostic relevance.

Bile peritonitis can occur when a T-tube is electively removed from the common bile duct, but this is regarded as a rare complication. Plastic T-tubes are known to increase the risk and should not be used. Latex rubber T-tubes are preferred but the complication can still occur. We present three patients with this complication despite the use of a latex T-tube. A questionnaire was sent to 107 surgeons in the South East Thames Region. The replies showed that the complication is far more common than generally realized. Based on these replies the risk of bile peritonitis each time a latex T-tube is electively removed from the common bile duct is calculated to be 0.84 per cent or 1 in every 119 explorations.

This study associates COX-2 epithelial expression with a number of adenoma characteristics that convey an increased risk of malignant transformation. This is in keeping with a positive role for COX-2 in early colorectal carcinogenesis.

cm posterior mediastinal mas. With these findings, the patient was admitted for surgery. Physical examination, laboratory work-ups, and pulmonary function tests revealed normal results. The patient underwent thoracotomy of the right hemithorax. Intraoperatively, an elongated, pulsatile, fixed mass measuring 10 x 12 x 12 cm occupying the middle and posterior mediastinum extending from the azygous vein down to the diaphragm was noted. Microscopic examination of the resected tissues showed fibrocollagenous and adipose tissue fragments with several variably sized vascular channels with no evidence of malignancy. Large caliber arteries and veins were encountered and there was excessive bleeding hence, total excision of the mass was aborted. Results: Histopathologic examination revealed fibrocollagenous and adipose tissue with several irregular thick-walled vascular channels, nerve bundles, lymphocytic infiltrates, and hemorrhagic areas. The final anatomic diagnosis was: Fibrocollagenous tissue with proliferating blood vessels. A hemangioma and/or arteriovenous malformation is considered. Elastic stain and immunohistochemical staining were done. Thick-walled blood vessels were highlighted by elastic stain. The endothelial cells were immunoreactive to Factor VIII. S100 stained a nerve bundle and isolated neural cells. Positivity to CD31 was also observed on the cells lining the vessels. The immunohistochemical staining result supported the diagnosis of arteriovenous malformation. Conclusion:We report a rare case of posterior mediastinal arteriovenous malformation in a 27-year-old male. This is a case of an uncommon tumor in a very unusual location. The advent of immunohistochemistry has aided in classifying proliferating vascular tumors. The need to identify markers for the prognostic significance was emphasized, providing the opportunity to better inform our clinical colleagues. Due to the rarity of the disease, it posed a great dilemma which required a multidisciplinary approach. It provided a diagnostic and surgical challenge to our clinicians, radiologists, pathologists, and thoracovascular surgeons as well.

BackgroundProstate stem cell antigen (PSCA) has been implicated in the pathogenesis of several solid tumours, either due to changes in protein expression, or through association with the rs2294008 polymorphism in the PSCA gene. To our knowledge, the role of PSCA in the development of colorectal neoplasia has not been explored. We performed a genotyping study to assess for associations between the rs2294008 polymorphism and risk of adenomatous polyps and colorectal cancer. DNA samples were available from 388 individuals with colorectal neoplasia and 496 controls, all of whom had undergone screening colonoscopy. In addition, we performed immunohistochemical staining for PSCA in colonic tissue representing all stages of the adenoma-carcinoma sequence.ResultsNo genotypic associations were found between the rs2294008 polymorphism and the risk of colorectal adenomata or cancer. Immunohistochemical staining did not reveal any alteration in PSCA expression accompanying the adenoma-carcinoma sequence.ConclusionFrom these data it seems unlikely that PSCA has a role in the initiation or progression of colorectal neoplasia.

Background:Neutrophil gelatinase-associated lipocalin (NGAL) has a diverse functional repertoire, involved in the innate immune response as well as cell growth and differentiation. Expression has been linked to malignant disease development and progression.Methods:Neutrophil gelatinase-associated lipocalin expression was assessed immunohistochemically in 98 colorectal neoplastic lesions (52 cancer polyps (CaPs) and 46 sporadic adenoma/adjacent normal mucosa paired specimens) to investigate association with adenoma progression and early colorectal carcinogenesis.Results:Within CaPs, all adenomatous and carcinomatous epithelium expressed NGAL, with 92% (43 out of 47) and 58% (19 out of 33) epithelial positivity, respectively, as well as positive stromal cell expression. This was significantly increased compared with normal mucosal epithelium (P=0.0001). Neutrophil gelatinase-associated lipocalin positivity was also identified in sporadic low-grade adenomas, in both the epithelial and stromal compartments as compared with adjacent normal mucosa (P=0.0001 and 0.0002), and this increased along with adenoma size >1 cm (P=0.03).Conclusion:Neutrophil gelatinase-associated lipocalin is expressed by the majority of human neoplastic colorectal lesions. This phenotypic switch occurs at an early stage in neoplastic progression with clear differential expression between normal mucosa and adenomatous polyps, rather than further downstream in disease progression at the adenoma–carcinoma transformation. Thus, NGAL expression is not a useful biomarker for determining disease progression from adenomatous to malignant colorectal neoplasia.