Health utility scores from EQ-5D and health-related quality of life in patients with esophageal cancer: a real-world cross-sectional study.

Esophageal cancer and its treatment can cause serious morbidity/toxicity. These effects on health-related quality of life (HRQOL) can be measured using disease-specific scales such as FACT-E, generic scales such as EQ-5D-3L, or through symptoms. In a two-year cross-sectional study, we compared HRQOL across esophageal cancer patients treated in an ambulatory clinic and across multiple disease states, among patients with all stages of esophageal cancer. Consenting patients completed FACT-E, EQ-5D, a visual analog scale, and patient reported (PR)-ECOG. Symptom complexes were constructed from FACT-E domains. Responses were categorized by disease state: pre-, during, and post-treatment, surveillance, progression, and palliative chemotherapy. Spearman correlation and multivariable linear regression characterized these associations. In total, 199 patients completed 317 questionnaires. Mean FACT-E and subscale scores dropped from baseline through treatment and recovered during post-treatment surveillance (P < 0.001); EQ-5D health utility scores (HUS) displayed a similar pattern but with smaller differences (P = 0.07), and with evidence of ceiling effect. Among patients with stage II/III esophageal cancer, mean EQ-5D HUS varied across disease states (P < 0.001), along with FACT-E and subscales (P < 0.001). Among patients with advanced disease, there was no significant difference between baseline and on-treatment total scores, but improved esophageal cancer-specific scales were noted (P = 0.003). Strong correlation was observed between EQ-5D and FACT-E (R = 0.73), along with physical and functional subscales. In addition, the association between FACT-E and EQ-5D HUS was maintained in a multivariable model (P < 0.001). We interpret these results to suggest that in a real-world clinic setting, FACT-E, EQ-5D HUS, and symptoms were strongly correlated. Most HRQOL and symptom parameters suggested that patients had worse HRQOL and symptoms during curative therapy, but recovered well afterwards. In contrast, palliative chemotherapy had a neutral to positive impact on HRQOL/symptoms when compared to their baseline pre-treatment state.

An increased CD25-positive intestinal regulatory T lymphocyte population is dependent upon Cox-2 activity in the Apcmin/+ model.

Only mismatch repair (MMR)-deficient colorectal cancer (CRC) appears to respond well to programmed death (PD)-1 inhibition at the present time. Emerging evidence suggests a role for micro-environmental factors such as CD25+ cells modulating response to PD-1 inhibition. In the ApcMin/+ model of familial adenomatous polyposis (MMR-proficient CRC), increased Cyclooxygenase-2 (Cox-2) expression by cells which include alternatively activated mononuclear phagocytes promotes intestinal tumorigenesis by mechanisms which may include immune suppression. To gain insight into this, we compared regulatory T cell (Treg ) populations between ApcMin/+ and wild-type mice prior to and after the phase of increased intestinal Cox-2-dependent prostaglandin E2 (PGE2 ) production. There was no difference in systemic Treg function or numbers between ApcMin/+ and wild-type mice. However, increased numbers of small intestinal CD25+ Tregs were observed with increased Cox-2 activity in the absence of any difference in the expression of Tgf-ß or Tslp between ApcMin/+ and wild-type mice. Cox-2 inhibitor therapy (Celecoxib) reversed the increase in ApcMin/+ intestinal CD25+ Treg numbers, without decreasing numbers of CD25+ systemic Tregs . Forkhead box protein 3 (FoxP3+ ) and Cox-2+ cells were co-localized to the interstitium of adenomas of Apcmin/+ mice. These results suggest selective dependence of an 'activated Treg ' phenotype on paracrine Cox-2 activity in ApcMin/+ small intestine. For therapeutic potential, further studies are required to evaluate the relevance of these findings to human cancer as well as the functional significance of CD25+ intestinal Tregs in cancer.

Accuracy of GFR estimation by the Cockroft and Gault, MDRD, and Wright equations in Oncology patients with renal impairment.

Estimation of renal function is crucial to guidance of systemic chemotherapy. With stable creatinine levels, the glomerular filtration rate (GFR) is often estimated from a single measurement of serum creatinine. We compared accuracy of the Cockroft and Gault (C&G), modifying diet in renal diseases (MDRD) and Wright estimates in Oncology patients with renal impairment. Analysis was carried out on the basis of monodentate platinum treatment as the nephrotoxic mechanism of these drugs may affect accuracy of these estimates. Sixty-two consecutive patients with stable creatinine levels who had isotopic GFR measurement of ≤ 60 ml min(-1) at a regional cancer center were reviewed. Twenty-nine were on monodentate platinum treatment. Isotopic GFR was compared with estimated GFR by the three equations. We defined three categories of estimate based on the fractional difference from isotopic GFR: 'perfect' (< 10%), 'reasonable' (≥ 10% but < 30%) and 'poor' (≥ 30%). There was a trend toward provision of more perfect estimates by the MDRD equation particularly in patients on monodentate platinum treatment. Similar numbers had poor estimates from either of these equations, particularly at extremes of body weight. The MDRD formula may be the most accurate of these equations in Oncology patients with renal impairment, particularly with monodentate platinum treatment.

Breast radiotherapy for occult breast cancer with axillary nodal metastases--does it reduce the local recurrence rate and increase overall survival?

AIMS: The optimal management of axillary lymph node metastases from occult breast cancer (TXN1-2M0) is uncertain and practice varies in the use of primary breast radiotherapy. We conducted a retrospective review to examine clinical outcomes for patients managed with or without primary breast radiotherapy. MATERIALS AND METHODS: Case records from the clinical oncology database were reviewed to identify patients presenting with axillary nodal metastases but no detectable primary tumour between 1974 and 2003. Fifty-three patients with TXN1-2M0 breast cancer were identified, representing 0.4% of patients managed for breast cancer during this period. Of those tested, 59% had oestrogen receptor-positive tumours. Seventy-seven per cent received ipsilateral breast radiotherapy. RESULTS: There was a trend towards reduced ipsilateral breast tumour recurrence in patients who received radiotherapy (16% at 5 years, 23% at 10 years) compared with those who did not (36% at 5 years, 52% at 10 years). Similarly, the locoregional recurrence rate was 28% at 5 years for patients who received radiotherapy compared with 53.7% at 5 years for non-irradiated patients. Breast cancer-specific survival was higher (P=0.0073; Log-rank test) in patients who received ipsilateral breast radiotherapy (72% at 5 years, 66% at 10 years) compared with those who did not (58% at 5 years, 15% at 10 years). CONCLUSION: Primary breast radiotherapy may reduce ipsilateral breast tumour recurrence and may increase survival in patients presenting with axillary lymph node metastases and occult breast primary (TXN1-2M0). Larger studies or prospective registration studies are needed to validate these findings.

Retrospective audit of the acute management of stroke in two district general hospitals in the uk.

BACKGROUND: There is some evidence to suggest that the standard of acute medical care provided to patients with cerebrovascular disease is a major determinant of the eventual outcome. Consequently, the Royal College of Physicians (RCP) of London issues periodic guidelines to assist healthcare providers in the management of patients presenting with stroke. OBJECTIVE: An audit of the acute management of stroke in two hospitals belonging to the same health care trust in the UK. METHOD: Retrospective review of 98 randomly selected case-notes of patients managed for cerebrovascular disease in two acute hospitals in the UK between April and June 2004. The pertinent guidelines of RCP (London) are highlighted while audit targets were set at 70%. RESULTS: 84% of patients presenting with cerebrovascular disease had a stroke rather than a TIA, anterior circulation strokes were commonest. All patients with stroke were admitted while those with TIAs were discharged on the same day but most patients with TIA were not followed up by Stroke specialists. Most CT-imaging of the head was done after 24 hours delaying the commencement of anti-platelets for patients with ischaemic stroke or neurosurgical referral for haemorrhagic stroke. Furthermore, there was a low rate of referral for carotid ultrasound in patients with anterior circulation strokes. Anti-platelets and statins were commenced for most patients with ischaemic stroke while diabetes was well controlled in most of them. However, ACE-inhibitors and diuretics such as indapamide were under-utilized for secondary prevention in such patients. Warfarin anti-coagulation was underutilized in patients with ischaemic stroke who had underlying chronic atrial fibrillation. While there was significant multi-disciplinary team input, dysphagia and physiotherapy assessments were delayed. Similarly, occupational therapy input and psychological assesment were omitted from the care of most patients. CONCLUSION: Hospital service provision for the management of cerebrovascular disease needs to provide appropriate specialist follow up for patients with TIA, prompt radiological imaging and multi-disciplinary team input for patients with stroke. Furthermore, physicians need to utilize appropriate antihypertensives and anti-coagulation more frequently in the secondary prevention of stroke.

Regulation of stromal cell cyclooxygenase-2 in the ApcMin/+ mouse model of intestinal tumorigenesis.

Cyclooxygenase-2 (Cox-2) is expressed predominantly by stromal cells in intestinal adenomas from the Apc(Min/+) mouse model of familial adenomatous polyposis. We investigated the mechanistic basis of stromal cell Cox-2 expression in Apc(Min/+) mouse adenomas, as well as Cox-2 expression and activity in histologically normal (HN) Apc(Min/+) mouse intestine, in order to gain further insights into regulation of Cox-2 as a potential chemoprevention target. Upregulation of Cox-2 in intestinal tumours is not an intrinsic feature of Apc(Min/+) macrophages as bone marrow-derived Apc(Min/+) macrophages did not exhibit an abnormality in Cox-2 expression or activity. Intestinal permeability to lactulose or mannitol was similar in Apc(Min/+) mice and wild-type littermates, implying that macrophage activation by luminal antigen is unlikely to explain stromal cell Cox-2 induction. Moreover, stromal cells exhibited differential expression of Cox-2 and inducible nitric oxide synthase, suggesting 'alternative' (M2) rather than 'classical' (M1) macrophage activation. Flow cytometric sorting of isolated stromal mononuclear cells (SMNCs), on the basis of M-lysozyme and specific macrophage marker expression, demonstrated that macrophages, neutrophils and non-myelomonocytic cells all contributed to lamina propria prostaglandin (PG) E(2) synthesis. However, the majority of PGE(2) synthesis by macrophages was via a Cox-2-dependent pathway compared with predominant Cox-1-derived PGE(2) production by non-myelomonocytic cells. SMNCs from HN Apc(Min/+) intestinal mucosa exhibited similar levels of Cox-2 mRNA and protein, but produced more Cox-2-derived PGE(2) than wild-type cells at 70 days of age. There was an age-dependent decline in PGE(2) synthesis by Apc(Min/+) SMNCs, despite tumour progression. These data suggest that other Cox-2-independent factors also control PGE(2) levels during Apc(Min/+) mouse intestinal tumorigenesis. Regulation of macrophage Cox-2 expression and other steps in PGE(2) synthesis (e.g. PGE synthase) are valid targets for novel chemoprevention strategies that could minimize or avoid systemic COX-2 inhibition.

Molecular biology and medicine: a review of developments.

BACKGROUND: The human genome-sequencing project was completed in April 2003, in the same year that marks the 50th anniversary of the discovery of the double helical structure of DNA. Much of the knowledge derived from the huge number of discoveries in molecular biology research over the past five decades and the genome project has the potential to be of immense benefit world-wide. Such knowledge is already of widespread application in the developed world and much more potential in the future. METHODS & RESULTS: This article briefly reviews the literature of research works on molecular biology in English language and discusses some of the findings and highlights recent developments and future trends. CONCLUSIONS: The advancement in molecular biology presents huge opportunities and potentials for improved health services worldwide. The article also proposes an approach whereby benefits could be reaped from the application of molecular biology techniques and the information derived from the human genome project in sub-Saharan Africa.