Successful treatment of fulminant postoperative bleeding due to acquired haemophilia.

Acquired haemophilia is a rare but life-threatening phenomenon in patients who have undergone surgical treatment. We describe a patient with a history of pancreatic cancer and a conventional pancreaticoduodenectomy, who underwent elective resection of an enterocutaneous fistula, complicated by fulminant haemorrhagic shock, caused by acquired haemophilia A. Eventually, the bleeding was controlled by a combination of aggressive haemostatic and immunosuppressive therapy. Prompt diagnosis of acquired haemophilia is crucial to allow early and appropriate haemostatic treatment and reduce the period of increased bleeding risk by eradicating the inhibitor with immunosuppressive therapy.

MicroRNA expression in formalin-fixed paraffin embedded tissue using real time quantitative PCR: the strengths and pitfalls.

MicroRNAs (miRNAs) are a group of small non-coding RNAs with a huge impact in a wide range of biological processes, including cancer. The evidence collected to date demonstrates that miRNAs represent valid diagnostic, prognostic and predictive markers in cancer. The identification of these miRNA biomarkers in archived tissues has been facilitated by novel development and refinement of detection methodologies. Quantitative real-time reverse-transcription PCR (qRT-PCR) is one of the most common methods used to detect low levels of miRNAs with high sensitivity and specificity. However, several technical parameters should be identified and optimized in order to obtain meaningful and reproducible results. The purpose of this review is to describe some of these technical parameters and improve the validity and reliability of miRNA expression studies.

KRAS mutation analysis: a comparison between primary tumours and matched liver metastases in 305 colorectal cancer patients.

BACKGROUND: KRAS mutation is a negative predictive factor for treatment with anti-epidermal growth factor receptor antibody in metastatic colorectal cancer (CRC). KRAS mutation analysis is usually performed on primary tumour tissue because metastatic tissue is often not available. However, controversial data are available on the concordance of test results between primary tumours and corresponding metastases. We assessed the concordance of KRAS mutation status in a study of 305 primary colorectal tumours and their corresponding liver metastases. METHODS: Patients with histologically confirmed CRC who underwent surgical resection of the primary tumour and biopsy or surgical resection of the corresponding liver metastasis were included. KRAS mutation analysis was performed for codons 12 and 13. RESULTS: KRAS mutation was detected in 108 out of 305 primary tumours (35.4%). In 11 cases (3.6%), we found a discordance between primary tumour and metastasis: 5 primary tumours had a KRAS mutation with a wild-type metastasis, 1 primary tumour was wild type with a KRAS mutation in the metastasis, and in 5 cases the primary tumour and the metastasis had a different KRAS mutation. CONCLUSION: We observed a high concordance of KRAS mutation status of 96.4% (95% CI 93.6-98.2%) between primary colorectal tumours and their corresponding liver metastases. In only six patients (2.0%; 95% CI 0.7-4.2%), the discordance was clinically relevant. In this largest and most homogenous study to date, we conclude that both primary tumours and liver metastases can be used for KRAS mutation analysis.

Clinicopathological features and outcome in advanced colorectal cancer patients with synchronous vs metachronous metastases.

BACKGROUND: Synchronous metastases of colorectal cancer (CRC) are considered to be of worse prognostic value compared with metachronous metastases, but only few and conflicting data have been reported on this issue. METHODS: We retrospectively investigated patient demographics, primary tumour characteristics and overall survival (OS) in 550 advanced CRC patients with metachronous vs synchronous metastases, who participated in the phase III CAIRO study. For this purpose only patients with a prior resection of the primary tumour were considered. RESULTS: The clinical and pathological characteristics associated with poor prognosis that we observed more often in patients with synchronous metastases (n=280) concerned an abnormal serum lactate dehydrogenase (LDH) concentration (P=0.01), a worse WHO performance status (P=0.02), primary tumour localisation in the colon (P=0.002) and a higher T stage (P=0.0006). No significant difference in median OS was observed between patients with synchronous metastases and metachronous metastases (17.6 vs 18.5 months, respectively, P=0.24). CONCLUSION: Despite unfavourable clinicopathological features in patients with synchronous metastases with a resected primary tumour compared to patients with metachronous metastases, no difference in the median OS was observed. Possible explanations include a (partial) chemoresistance in patients with metachronous disease because of previous adjuvant treatment, whereas differences between the two groups in screening procedures resulting in a lead time bias to diagnosis or in prognostic molecular markers remain speculative.