Safety, cost-effectiveness and feasibility of daycase paracentesis in the management of malignant ascites with a focus on ovarian cancer.

BACKGROUND: Paracentesis for malignant ascites is usually performed as an in-patient procedure, with a median length of stay (LoS) of 3-5 days, with intermittent clamping of the drain due to a perceived risk of hypotension. In this study, we assessed the safety of free drainage and the feasibility and cost-effectiveness of daycase paracentesis. METHOD: Ovarian cancer admissions at Hammersmith Hospital between July and October 2009 were audited (Stage 1). A total of 21 patients (Stage 2) subsequently underwent paracentesis with free drainage of ascites without intermittent clamping (October 2010-January 2011). Finally, 13 patients (19 paracenteses, Stage 3), were drained as a daycase (May-December 2011). RESULTS: Of 67 patients (Stage 1), 22% of admissions and 18% of bed-days were for paracentesis, with a median LoS of 4 days. In all, 81% of patients (Stage 2) drained completely without hypotension. Of four patients with hypotension, none was tachycardic or symptomatic. Daycase paracentesis achieved complete ascites drainage without complications, or the need for in-patient admission in 94.7% of cases (Stage 3), and cost £954 compared with £1473 for in-patient drainage. CONCLUSIONS: Free drainage of malignant ascites is safe. Daycase paracentesis is feasible, cost-effective and reduces hospital admissions, and potentially represents the standard of care for patients with malignant ascites.

DUSP16 is an epigenetically regulated determinant of JNK signalling in Burkitt's lymphoma.

BACKGROUND: The mitogen-activated protein kinase (MAPK) phosphatases or dual specificity phosphatases (DUSPs) are a family of proteins that catalyse the inactivation of MAPK in eukaryotic cells. Little is known of the expression, regulation or function of the DUSPs in human neoplasia. METHODS: We used RT-PCR and quantitative PCR (qPCR) to examine the expression of DUSP16 mRNA. The methylation in the DUSP16 CpG island was analysed using bisulphite sequencing and methylation-specific PCR. The activation of MAPK was determined using western blotting with phospho-specific antibodies for extra-cellular signal-related kinase (ERK), p38 and c-Jun N-terminal kinase (JNK). The proliferation of cell lines was assessed using the CellTiter 96 Aqueous One assay. RESULTS: The expression of DUSP16, which inactivates MAPK, is subject to methylation-dependent transcriptional silencing in Burkitt's Lymphoma (BL) cell lines and in primary BL. The silencing is associated with aberrant methylation in the CpG island in the 5' regulatory sequences of the gene blocking its constitutive expression. In contrast to BL, the CpG island of DUSP16 is unmethylated in other non-Hodgkin's lymphomas (NHLs) and epithelial malignancies. In BL cell lines, neither constitutive nor inducible ERK or p38 activity varied significantly with DUSP16 status. However, activation of JNK was increased in lines with DUSP16 methylation. Furthermore, methylation in the DUSP16 CpG island blocked transcriptional induction of DUSP16, thereby abrogating a normal physiological negative feedback loop that limits JNK activity, and conferred increased cellular sensitivity to agents, such as sorbitol and anthracycline chemotherapeutic agents that activate JNK. CONCLUSION: DUSP16 is a new epigenetically regulated determinant of JNK activation in BL.

No longer any role for routine follow-up chest x-rays in men with stage I germ cell cancer.

Following radical orchidectomy for testicular cancer, most patients undergo protocolled surveillance to detect tumour recurrences rather than receive adjuvant chemotherapy. Current United Kingdom national and most international guidelines recommend that patients require a chest x-ray (CXR) and serum tumour markers at each follow-up visit as well as regular CT scans; there is however, variation among cancer centres with follow-up protocols. Seminomas often do not cause tumour marker elevation; therefore, CT scans are the main diagnostic tool for detecting relapse. For non-seminomatous tumours, serum beta-HCG (HCG) and AFP levels are a very sensitive harbinger of relapse, but this only occurs in 50% of patients [1], and therefore, imaging remains as important. CXRs are meant to aid in the detection of lung recurrences and before the introduction of modern cross-sectional imaging in the early 1980s, CXRs would have been the only method of identifying lung metastasis. We examined the Thames Valley and Mount Vernon Cancer Centre databases to evaluate the role of CXRs in the 21st century for the follow-up of men with stage I testicular cancer between 2003 and 2015 to assess its value in diagnosing relapsed germ cell tumours. From a total of 1447 patients, we identified 159 relapses. All relapses were detected either by rising tumour markers or planned follow-up CT scans. Not a single relapse was identified on CXR. We conclude that with timely and appropriate modern cross-sectional imaging and tumour marker assays, the CXR no longer has any value in the routine surveillance of stage I testicular cancer and should be removed from follow-up guidelines and clinical practice. Omitting routine CXR from follow-up schedules will reduce anxiety as well as time that patients spend at hospitals and result in significant cost savings.

The cost of a QALY.

BACKGROUND: Current regulation of drug approvals has caused considerable controversy as entrusted to the National Institute of Clinical Excellence, and has led to a lack of availability of modern medicines on the basis of calculations made of 'value'. AIM: We have examined the assessment tool used by National Institute of Clinical Excellence (NICE) to establish the cost of drugs in order to assess whether it is a reasonable and objective evaluation methodology. DESIGN: A review of the methods of analysis. METHODS: An objective assessment of the value of the Quality Adjusted Life Year (QALY). RESULTS: We conclude that current methods used by NICE to assess drug costs are arbitrary, subjective and fail to reflect the true costs for patients, which are grossly overestimated. CONCLUSION: NICE needs to look again at the evaluation methods for calculating drug costs, and change their methodology from a subjective to an objective measure of true cost.