Showing papers by "Adrian C Bateman published in 2008"

The desmoplastic reaction surrounding hepatic colorectal adenocarcinoma metastases aids tumor growth and survival via alphav integrin ligation

Abstract: Purpose: The treatment of metastatic colorectal carcinoma represents a major clinical challenge. We investigated the hypothesis that the desmoplastic reaction within the liver elicited by metastatic adenocarcinoma, characterized by collagen I deposition and altered collagen IV distribution, promotes the growth and survival of hepatic colorectal carcinoma metastases. Experimental Design: Partial hepatectomy specimens for metastatic colorectal adenocarcinoma were examined immunohistochemically for differential integrin expression. Human colorectal adenocarcinoma cell lines HT-29, KM12SM, and KM12c were grown on wild-type collagen I or IV, or cleavage-resistant r/r collagen I, and assessed for their growth, survival, and resistance to 5-fluorouracil. The effect of α v β 3 and α v β 5 integrin blockade by neutralizing antibodies was examined. Results: Collagen I, in contrast to collagen IV, significantly enhanced the growth, survival, and chemoresistance of colorectal carcinoma cells. Blockade of the α v β 3 and α v β 5 integrins significantly reduced colorectal carcinoma cell proliferation on collagen, especially in the cell line with the most metastatic potential. These in vitro findings correlated with the pattern of integrin expression identified within resected hepatic colorectal carcinoma metastases. Using matrix metalloproteinase-resistant r/r collagen I as a dominant negative ligand for α v integrins, we showed a key role for this integrin-ligand interaction in mediating the survival and proliferation of colorectal carcinoma cells. Conclusions: Desmoplasia has an important role in the development of hepatic colorectal carcinoma metastasis. The interaction between integrin and collagen I is identified as a potential therapeutic target.

Specialty-specific multi-source feedback: assuring validity, informing training.

Abstract: Context: The white paper 'Trust, Assurance and Safety: the Regulation of Health Professionals in the 21st Century' proposes a single, generic multi-source feedback (MSF) instrument in the UK. Multi-source feedback was proposed as part of the assessment programme for Year 1 specialty training in histopathology. Methods: An existing instrument was modified following blueprinting against the histopathology curriculum to establish content validity. Trainees were also assessed using an objective structured practical examination (OSPE). Factor analysis and correlation between trainees' OSPE performance and the MSF were used to explore validity. All 92 trainees participated and the assessor response rate was 93%. Reliability was acceptable with eight assessors (95% confidence interval 0.38). Factor analysis revealed two factors: 'generic' and 'histopathology'. Pearson correlation of MSF scores with OSPE performances was 0.48 (P = 0.001) and the histopathology factor correlated more highly (histopathology r = 0.54, generic r = 0.42; t = − 2.76, d.f. = 89, P < 0.01). Trainees scored least highly in relation to ability to use histopathology to solve clinical problems (mean = 4.39) and provision of good reports (mean = 4.39). Three of six doctors whose means were < 4.0 received free text comments about report writing. There were 83 forms with aggregate scores of < 4. Of these, 19.2% included comments about report writing. Results: Specialty-specific MSF is feasible and achieves satisfactory reliability. The higher correlation of the 'histopathology' factor with the OSPE supports validity. This paper highlights the importance of validating an MSF instrument within the specialty-specific context as, in addition to assuring content validity, the PATH–SPRAT (Histopathology–Sheffield Peer Review Assessment Tool) also demonstrates the potential to inform training as part of a quality improvement model.

Acute pancreatitis as the first presentation of Wegener's granulomatosis.

Abstract: Context Wegener’s granulomatosis is a systemic vasculitis with prominent involvement of the respiratory tract and kidney. An association between acute pancreatitis and Wegener's granulomatosis is rarely reported and is even rarer as the first presentation. This can result in diagnostic difficulty and may allow severe pancreatitis to develop with potentially poor outcome. Case report We report a rare case with fatal outcome of vasculitis consistent with Wegener’s granulomatosis presenting as acute pancreatitis in a 20-year-old female. The patient was admitted with worsening abdominal pain associated with nausea and loss of appetite. Accepted causes of acute pancreatitis were excluded and granulomatous vasculitis of the pancreas was confirmed from immunological profile, computed tomography and histology. As the disease progressed the patient experienced cutaneous, pulmonary, renal and severe gut involvement. Thirteen months from diagnosis the patient died of multi-organ failure despite appropriate surgical and immunosuppressive therapy. Conclusion Vasculitic disease of the pancreas is rare but should be considered when other causes have been appropriately ruled out. Careful radiological, immunological and histological diagnosis is necessary and early immunosuppressant therapy in conjunction with advice from immunologists is essential to avoid the poor outcome reported in this and other case reports.

CD117/KIT expression in pancreatic adenocarcinoma.

Abstract: Objective: CD117/KIT overexpression is common in neoplasms such as gastrointestinal stromal tumors and predicts clinical response to tyrosine kinase inhibitors Pancreatic adenocarcinoma has a poor prognosis, and therefore, targeted molecular therapymay be beneficial Marked differences in the incidence of CD117/KIT expression have been reported in pancreatic adenocarcinoma The aim of this study was to test the hypothesis that CD117/KIT expression is unusual in pancreatic adenocarcinoma Methods: CD117/KIT immunohistochemistry was performed on 23 archival pancreatic adenocarcinoma samples using 2 primary antibodies Results: Satisfactory internal and external positive control labeling was achieved for both primary antibodies No tumor cell labeling was identified using one primary antibody, whereas all cases showed cytoplasmic CD117/KIT staining with the second However, CD117/KIT expression was also identified using the latter within nuclei and benign pancreatic epithelium, suggesting that artifactual staining was occurring Conclusions: Pancreatic adenocarcinoma does not express CD117/KIT as assessed using the primary immunohistochemical antibody usually used in our laboratory for CD117/KIT detection The variation in reported incidence of CD117/KIT expression in pancreatic adenocarcinoma is because of methodological differences in immunohistochemical technique Ideally, immunohistochemical studies of this molecule should be combined with mutational status testing of the c-kit gene