Frank A. Carey

Prognostic indicators for gastrointestinal stromal tumours: a clinicopathological and immunohistochemical study of 108 resected cases of the stomach

Aims:  Whether immunohistochemical markers increase accuracy in predicting prognosis for gastrointestinal stromal tumours (GISTs) remains uncertain. However, past studies have used only small, heterogeneous patient groups. Our aim was to test previously studied and more novel morphological features as well as four immunohistochemical markers as prognostic indicators amongst a large cohort of surgically resected, gastric GISTs.

Results from the first three rounds of the Scottish demonstration pilot of FOBT screening for colorectal cancer

Objectives: To assess the effects of the first three rounds of a pilot colorectal screening programme based on guaiac faecal occult blood testing (gFOBT) and their implications for a national population-based programme. Methods: A demonstration pilot programme was conducted in three Scottish NHS Boards. Residents aged between 50 and 69 years registered on the Community Health Index were included in the study. Results: In the first round, the uptake was 55.0%, the positivity rate was 2.07% and the cancer detection rate was 2.1/1000 screened. In the second round, these were 53.0%, 1.90% and 1.2/1000, respectively, and in the third round, 55.3%, 1.16% and 0.7/1000, respectively. In the first round, the positive predictive value of the gFOBT was 12.0% for cancer and 36.5% for adenoma; these fell to 7.0% and 30.3% in the second round and were maintained at 7.5% and 29.1% in the third round. The percentage of screen-detected cancers diagnosed at Dukes’ stage A was 49.2% in the first round, 40.1% in the second round and 36.3% in the third round. Conclusions: These results are compatible with those of previous randomised trials done in research settings, demonstrating that population-based colorectal cancer screening is feasible in Scotland and should lead to a comparable reduction in disease-specific mortality.

Interval cancers in a FOBT-based colorectal cancer population screening programme: implications for stage, gender and tumour site

Background Between 2000 and 2007, a demonstration pilot of biennial guaiac faecal occult blood test (GFOBT) screening was carried out in Scotland. Methods Interval cancers were defined as cancers diagnosed within 2 years (ie, a complete screening round) of a negative GFOBT. The stage and outcome of the interval cancers were compared with those arising contemporaneously in the non-screened Scottish population. In addition, the gender and site distributions of the interval cancers were compared with those in the screen-detected group and the non-screened population. Results Of the cancers diagnosed in the screened population, interval cancers comprised 31.2% in the first round, 47.7% in the second, and 58.9% in the third, although this was due to a decline in the numbers of screen-detected cancers rather than an increase in interval cancers. There were no consistent differences in the stage distribution of interval cancers and cancers from the non-screened population, and, in all three rounds, both overall and cancer-specific survival were significantly better for patients diagnosed with interval cancers (p<0.01). The percentage of cancers arising in women was significantly higher in the interval cancer group (50.2%) than in either the screen-detected group (35.3%, p<0.001) or the non-screened group (40.6%, p<0.001). In addition, the proportion of both right-sided and rectal cancers was significantly higher in the interval cancer group than in either the screen-detected (p<0.001) or non-screened (p<0.004) groups. Conclusions Although GFOBT screening is associated with substantial interval cancer rates that increase with screening round, the absolute numbers do not. Interval cancers are associated with a better prognosis than cancers arising in a non-screened population, and GFOBT appears to preferentially detect cancers in men and the left side of the colon at the expense of cancers in women and in the right colon and rectum.

Effect of gender, age and deprivation on key performance indicators in a FOBT-based colorectal screening programme

Objectives To assess the effect of gender, age and deprivation on key performance indicators in a colorectal cancer screening programme. Setting Between March 2000 and May 2006 a demonstration pilot of biennial guaiac faecal occult blood test (gFOBT) colorectal screening was carried out in North-East Scotland for all individuals aged 50-69 years. Methods The relevant populations were subdivided, by gender, into four age groups and into five deprivation categories according to the Scottish Index of Multiple Deprivation (SIMD), and key performance indicators analysed within these groups. Results In all rounds, uptake of the gFOBT increased with age (P < 0.001), decreased with increasing deprivation in both genders (P < 0.001), and was consistently higher in women than in men in all age and all SIMD groups. In addition, increasing deprivation was negatively associated with uptake of colonoscopy in men with a positive gFOBT (P < 0.001) although this effect was not observed in women. Positivity rates increased with age (P< 0.001) and increasing deprivation (P > 0.001) in both genders in all rounds, although they were higher in men than in women for all age and SIMD categories. Cancer detection rates increased with age (P < 0.001), were higher in men than in women in all age and SIMD categories, but were not consistently related to deprivation. In both genders, the positive predictive value (PPV) for cancer increased with age (P < 0.001) and decreased with increasing deprivation (P < 0.001) in all rounds and was consistently higher in men than in women in all age and SIMD categories. Conclusions In this population-based colorectal screening programme gender, age, and deprivation had marked effects on key performance indicators, and this has implications both for the evaluation of screening programmes and for strategies designed to reduce inequalities.

Socioeconomic status and stage at presentation of colorectal cancer

The stage at which colorectal cancer presents varies by district of residence 1 , but the reasons for this are not clear. We correlated stage at presentation with socioeconomic status in a stable UK population. The pathology reports of 905 consecutive patients with colorectal cancer who had undergone transabdominal resection in Tayside between Jan 1, 1991, and Sept 30, 1997, were reviewed. Dukes’ staging was derived from the reports. Socioeconomic status was determined with the Carstairs score, a deprivation index based on the postal-code areas from the 1991 census. 2 Of the 905 patients, 128 were excluded due to absence of pathology reports on lymph-node involvement, and/or no record of postal code. 15% (n=120) of cases were stage A at diagnosis, 43% (n=330) stage B, and 42% (n=327) stage C. Patients with distant metastases were not considered because local registry data could not be relied upon to identify the primary lesion in all patients presenting with advanced cancer. Patients were stratified in ascending order of social deprivation into four groups, according to the quartiles of Carstairs score. Group 4 was the highest score, and comprised people with the greatest socioeconomic disadvantage. The distribution of Dukes’ stages in each of these four groups is shown in the table. From group 1 to group 4, there was a diminishing proportion of stage A, and an increasing proportion of stages B and C; the only exception was in group 2, where there was a slightly higher percentage of stage A, and a lower percentage of stage C than in group 1. The differences were significant (

The impact of population-based faecal occult blood test screening on colorectal cancer mortality: a matched cohort study

Background:Randomised trials show reduced colorectal cancer (CRC) mortality with faecal occult blood testing (FOBT). This outcome is now examined in a routine, population-based, screening programme.Methods:Three biennial rounds of the UK CRC screening pilot were completed in Scotland (2000–2007) before the roll out of a national programme. All residents (50–69 years) in the three pilot Health Boards were invited for screening. They received a FOBT test by post to complete at home and return for analysis. Positive tests were followed up with colonoscopy. Controls, selected from non-pilot Health Boards, were matched by age, gender, and deprivation and assigned the invitation date of matched invitee. Follow-up was from invitation date to 31 December 2009 or date of death if earlier.Results:There were 379 655 people in each group (median age 55.6 years, 51.6% male). Participation was 60.6%. There were 961 (0.25%) CRC deaths in invitees, 1056 (0.28%) in controls, rate ratio (RR) 0.90 (95% confidence interval (CI) 0.83–0.99) overall and 0.73 (95% CI 0.65–0.82) for participants. Non-participants had increased CRC mortality compared with controls, RR 1.21 (95% CI 1.06–1.38).Conclusion:There was a 10% relative reduction in CRC mortality in a routine screening programme, rising to 27% in participants.

Treatment of grade III anal intraepithelial neoplasia with photodynamic therapy: report of a case.

AbstractPURPOSE: We report the use of photodynamic therapy to treat a 53-year-old female with Grade III anal intraepithelial neoplasia. METHODS: Topical 5-aminolevulinic acid cream was applied to the affected area five hours before light treatment. The distribution of 5-aminolevulinic acid–induced protoporphyrin IX was identified by its characteristic red fluorescence. The lesion was treated by illumination with a 630-nm red laser light that used a total energy of 125 J/cm2 for approximately 17 minutes. RESULTS: Complete symptomatic relief was achieved after the first photodynamic therapy session, and macroscopic and microscopic ablation of dysplasia was achieved after a second session of photodynamic therapy. Healing was excellent, with no residual scarring or functional loss. CONCLUSION: Photodynamic therapy offers a simple, noninvasive method for treatment of anal intraepithelial neoplasia.

Low faecal haemoglobin concentration potentially rules out significant colorectal disease

The study aimed to determine whether faecal haemoglobin (Hb) concentration can assist in deciding who with lower abdominal symptoms will benefit from endoscopy.

Evaluation of a card collection-based faecal immunochemical test in screening for colorectal cancer using a two-tier reflex approach

Background: The guaiac faecal occult blood test (gFOBT) has been proved as a screening investigation for colorectal cancer, but has disadvantages. Newer faecal immunochemical tests (FITs) have many advantages, but yield higher positivity rates and are expensive. A two-tier reflex follow-up of gFOBT-positive individuals with a FIT before colonoscopy has been advocated as an efficient and effective approach. Methods: A new simple and stable card collection FIT was evaluated. Results: 1124 individuals who were gFOBT positive were asked to provide samples. 558 individuals participated, 320 refused and 246 did not return samples. No evidence of sampling bias was found. 302 individuals tested FIT negative and 256 tested positive. In the 302 FIT-negative individuals, 2 (0.7%) had cancer and 12 (4.0%) had large or multiple (high-risk) adenomatous polyps. In contrast, of 254 positive individuals, 47 (18.5%) had cancer and 54 (21.3%) had high-risk polyps. 93 (30.8%) of the FIT-negative individuals had a normal colonoscopy, but only 34 (13.4%) of the FIT-positive individuals had no pathology. Sensitivity, specificity, and positive and negative likelihood ratios (and 95% CIs) for cancer were 95.9% (84.8 to 99.3), 59.2% (54.7 to 63.5), 2.35 (2.08 to 2.65) and 0.07 (0.02 to 0.27), and for cancer and high-risk polyps were 87.8% (80.1 to 92.9), 65.3% (60.6 to 69.7), 2.53 (2.19 to 2.93) and 0.19 (0.11 to 0.31), respectively. Conclusions: A two-tier reflex screening algorithm, in which gFOBT-positive participants are tested with a FIT, is effective in identifying individuals at high risk of significant colorectal neoplasia. This strategy is transferable across different FIT formats. This approach has been adopted for the Scottish Bowel Screening Programme.

Gene expression in colorectal neoplasia: modifications induced by tissue ischaemic time and tissue handling protocol

Bray S E, Paulin F E M, Fong S C, Baker L, Carey F A, Levison D A, Steele R J C & Kernohan N M
(2010) Histopathology56, 240–250