ABSTRACT
Cholangiocarcinoma (CC) and hepatocellularcarcinoma (HCC) are two main forms of liver malignancies, which exhibit differences in drug response and prognosis. Immunohistotochemical staining for cytokeratin markers has been used to some success in the differential diagnosis of CC from HCC. However, there remains a need for additional markers for increased sensitivity and specificity of diagnosis. In this study, we have identified a p38 MAP kinase, p38delta (also known as MAPK13 or SAPK4) as a protein that is upregulated in CC relative to HCC and to normal biliary tract tissues. We performed microarray gene expression profiling on 17 cases of CC, 12 cases of adjacent normal liver tissue, and three case of normal bile duct tissue. p38delta was upregulated in 16 out of 17 cases of CC relative to normal tissue. We subsequently performed immunohistochemical staining of p38delta in 54 cases of CC and 54 cases of HCC. p38delta staining distinguished CC from HCC with a sensitivity of 92.6% and a specificity of 90.7%. To explore the possible functional significance of p38delta expression in CC, we examined the effects of overexpression and knockdown of p38delta expression in human CC cell lines. Our results indicate that p38delta is important for motility and invasion of CC cells, suggesting that p38delta may play an important role in CC metastasis. In summary, p38delta may serve as a novel diagnostic marker for CC and may also serve as a new target for molecular based therapy of this disease.
Subject(s)
Bile Duct Neoplasms/diagnosis , Bile Ducts, Intrahepatic , Biomarkers, Tumor/metabolism , Cholangiocarcinoma/diagnosis , Mitogen-Activated Protein Kinase 13/metabolism , Antigens, Neoplasm/metabolism , Bile Duct Neoplasms/metabolism , Bile Duct Neoplasms/pathology , Bile Ducts, Intrahepatic/metabolism , Bile Ducts, Intrahepatic/pathology , Blotting, Western , Cell Movement , Cholangiocarcinoma/metabolism , Cholangiocarcinoma/pathology , Collagen , Diagnosis, Differential , Drug Combinations , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Gene Silencing , Humans , Immunohistochemistry , Immunoprecipitation , Laminin , Mitogen-Activated Protein Kinase 13/genetics , Mitogen-Activated Protein Kinase 13/immunology , Neoplasm Invasiveness , Predictive Value of Tests , Proteoglycans , Sensitivity and Specificity , Up-RegulationABSTRACT
Sclerosing encapsulating peritonitis, or "abdominal cocoon," is a rare but serious complication of continuous ambulatory peritoneal dialysis. It is characterized by the diffuse appearance of marked sclerotic thickening of the peritoneal membrane resulting in intestinal obstruction. A 14-year-old adolescent boy with a history of end-stage renal failure on continuous ambulatory peritoneal dialysis presented with symptoms of acute intestinal obstruction. A computed tomography scan of the abdomen revealed distended small bowel loops clustered and displaced to the right upper quadrant. The overlying peritoneum was markedly thickened and calcified. Laparotomy confirmed the diagnosis of sclerosing encapsulating peritonitis and the patient was treated with excision of the fibrocollagenous membrane. Postoperatively, he had prolonged ileus requiring parenteral nutritional support and peritoneal dialysis was restarted on postoperative day 10. A high degree of cognizance is needed to facilitate diagnosis and treatment of this uncommon and potentially life-threatening condition.
Subject(s)
Peritoneal Dialysis, Continuous Ambulatory/adverse effects , Peritonitis/etiology , Adolescent , Calcinosis/etiology , Humans , Ileus/etiology , Intestinal Obstruction/diagnosis , Jejunal Diseases/etiology , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/therapy , Male , Peritonitis/pathology , Peritonitis/surgery , Postoperative Complications/etiology , Sclerosis , Tissue Adhesions/etiology , Tissue Adhesions/surgery , Torsion Abnormality/etiologyABSTRACT
BACKGROUND: The diagnosis of severe acute respiratory syndrome (SARS) in surgical patients can potentially be missed based on current World Health Organization (WHO) case definitions. METHOD: We report a retrospective case series of 10 surgical inpatients diagnosed with SARS following an outbreak in the surgical wards. Patients were included if they fulfilled the WHO case definition of probable SARS, had an active surgical problem and were admitted to the surgical wards during the outbreak period. Clinical histories, laboratory investigations and radiological findings were reviewed and analyzed. RESULTS: The mean age of the cohort was 57.6 years (range: 38-78 years). Nine patients had concomitant medical conditions. Three patients were in the early postoperative period, while the remaining seven were admitted for surgical related infections. All patients presented with fever, but only eight had accompanying respiratory symptoms. Lymphopenia and raised lactate dehydrogenase (LDH) was seen in seven patients. Eight patients had positive bacterial cultures. The primary abnormality on chest radiograph was air-space opacification. Rapid progression of radiological changes was seen in seven patients. Mortality rate for our cohort is 20%. CONCLUSION: The diagnosis of SARS in surgical patients differs from that previously described in normal patients. An apparent cause of fever and positive blood cultures cannot exclude a diagnosis of SARS. The current WHO case definition could result in delayed or even missed diagnosis. Early isolation of febrile patients with a positive contact history must be undertaken, even in the face of another identifiable cause.