Effects of neo-adjuvant chemotherapy for oesophago-gastric cancer on neuro-muscular gastric function.

Delayed gastric emptying symptoms are often reported after chemotherapy. This study aims to characterise the effects of chemotherapy on gastric neuro-muscular function. Patients undergoing elective surgery for oesophago-gastric cancer were recruited. Acetylcholinesterase, nNOS, ghrelin receptor and motilin expressions were studied in gastric sections from patients receiving no chemotherapy (n = 3) or oesophageal (n = 2) or gastric (n = 2) chemotherapy. A scoring system quantified staining intensity (0-3; no staining to strong). Stomach sections were separately suspended in tissue baths for electrical field stimulation (EFS) and exposure to erythromycin or carbachol; three patients had no chemotherapy; four completed cisplatin-based chemotherapy within 6 weeks prior to surgery. AChE expression was markedly decreased after chemotherapy (scores 2.3 ± 0.7, 0.5 ± 0.2 and 0 ± 0 in non-chemotherapy, oesophageal- and gastric-chemotherapy groups (p < 0.03 each) respectively. Ghrelin receptor and motilin expression tended to increase (ghrelin: 0.7 ± 0.4 vs 2.0 ± 0.4 and 1.2 ± 0.2 respectively; p = 0.04 and p = 0.2; motilin: 0.7 ± 0.5 vs 2.2 ± 0.5 and 2.0 ± 0.7; p = 0.06 and p = 0.16). Maximal contraction to carbachol was 3.7 ± 0.7 g and 1.9 ± 0.8 g (longitudinal muscle) and 3.4 ± 0.4 g and 1.6 ± 0.6 (circular) in non-chemotherapy and chemotherapy tissues respectively (p < 0.05 each). There were loss of AChE and reduction in contractility to carbachol. The tendency for ghrelin receptors to increase suggests an attempt to upregulate compensating systems. Our study offers a mechanism by which chemotherapy markedly alters neuro-muscular gastric function.

Ghrelin promotes nuclear factor kappa-B activation in a human B-lymphocyte cell line.

Ghrelin, an orexigenic hormone of gastric origin that stimulates growth hormone secretion, may modulate inflammation. This experimental study examines the effect of ghrelin on NFκB (p65 subunit), a transcriptional factor involved in inflammation on a human B-lymphocyte cell (WILCL). After confirming the expression of ghrelin receptor protein using western blotting the cells were transferred to wells maintaining a density of 1 × 10(6) cells per ml and a proportion activated with phytohaemagluttinin. Activated and resting cells were exposed to octanoyl-, desoctanoyl ghrelin and a non-peptide ghrelin agonist (Pfizer CP-464709) in increasing concentrations for 6 h. Cell protein extracts were analyzed for NFκB activation using Trans AM NFκB p65 assay. IL-6, IL-8, IL-10, IL-13 and TNFα were measured in the media using Lincoplex human cytokine assay. In octanoyl ghrelin treated resting cells, NFκB activity (Optical Density OD(450 nm)) (mean ± SEM) in control cells was 0.42 ± 0.10 and increased to 0.61 ± 0.20 (P = 0.044), 0.54 ± 0.10 (P = 0.043), 0.52 ± 0.08 at 1, 10 and 100 nM concentrations respectively. No effect was detected with desoctanoyl ghrelin or ghrelin agonist and no specific change in cytokine production. In conclusion, Octanoyl ghrelin increased NFκB activation by up to 50% in a B-lymphocyte cell line suggesting an effect on the inflammatory process.

Local impact of the English arm of the UK Bowel Cancer Screening Pilot study.

BACKGROUND: The English arm of the UK Bowel Cancer Screening Pilot study recently concluded its third round. The primary aim was to assess the impact of faecal occult blood test (FOBT) screening on the detection of symptomatic (non-screen-detected) cancers within the target age group (50-69 years). The secondary aim was to assess differences between screened and non-screened cohorts in Dukes' classification at diagnosis. METHODS: This population-based study utilized retrospective analysis of existing validated colorectal cancer (CRC) data over 5 years (April 2000 to March 2005), encompassing rounds one and two of screening. RESULTS: There was a 23 per cent (P = 0.011) reduction in the diagnosis of over the 5 years. Presentations with symptomatic cancer reduced by 49 per cent (P = 0.049), with a proportionate (2.6-fold) rise in the detection of screened (asymptomatic) malignancy. Cancers were diagnosed at an earlier stage in the screened population, with significantly more Dukes' A tumours than in the non-screen-detected cohort (P < 0.001) and an estimated odds ratio of 0.27 (95 per cent confidence interval 0.08 to 0.91) (P = 0.035) for Dukes' 'D' cancers. CONCLUSION: FOBT screening resulted in a significant reduction in the number of symptomatic cancers detected within the target age group. Tumours detected by screening were diagnosed at an earlier pathological stage.

The effects of population-based faecal occult blood test screening upon emergency colorectal cancer admissions in Coventry and north Warwickshire.

OBJECTIVE: The English arm of the UK Bowel Cancer Screening Pilot has recently concluded its third round. The primary aim of this study was to assess the effects of this programme on the emergency and elective cancer workload at University Hospitals Coventry and Warwickshire NHS Trust; the largest trust within the screened region. The secondary aim was to assess its effect upon Dukes staging, mortality and stoma formation for emergency colorectal cancer (CRC) admissions. DESIGN: A retrospective analysis of validated data for CRC admissions over a period of 6 years from 1999 to 2004 was performed. The first year, 1999, represented the pre-screening year (PSY) which was taken as a baseline. Data for the next 5 years, screening years 1-5 (SY1-SY5), were recorded for the mode of admission, occurrence of emergency surgery, 30-day mortality and Dukes staging. RESULTS: In the PSY (1999), 29.4% of CRCs were admitted as an emergency, decreasing to 15.8% by 2004 (p = 0.001). As a consequence, there was a significant decrease in the number of emergency CRC procedures performed over the same period (p<0.05). There was also a significant reduction in the 30-day mortality from 48% in 1999 to 13% in 2004 (p<0.05). Dukes stage C carcinomas, however, remained the predominant stage presenting as emergencies throughout the studied period (SY3, 53%; SY4, 38%; SY5, 50%). CONCLUSION: Following commencement of the UK Bowel Cancer Screening Pilot, there has been a significant decline in emergency CRC workload with a marked improvement in 30-day mortality and decreased stoma formation, in Coventry and North Warwickshire. It is postulated that the witnessed and notable positive impact over such a short time period is the result of increased detection of asymptomatic malignancies within the screening programme, increased public awareness of the symptoms of CRC, together with a change in attitudes and referral patterns of general practitioners within Coventry and North Warwickshire.