Screen-detected colorectal cancers are associated with an improved outcome compared with stage-matched interval cancers.

BACKGROUND: Colorectal cancers (CRCs) detected through the NHS Bowel Cancer Screening Programme (BCSP) have been shown to have a more favourable outcome compared to non-screen-detected cancers. The aim was to identify whether this was solely due to the earlier stage shift of these cancers, or whether other factors were involved. METHODS: A combination of a regional CRC registry (Northern Colorectal Cancer Audit Group) and the BCSP database were used to identify screen-detected and interval cancers (diagnosed after a negative faecal occult blood test, before the next screening round), diagnosed between April 2007 and March 2010, within the North East of England. For each Dukes' stage, patient demographics, tumour characteristics, and survival rates were compared between these two groups. RESULTS: Overall, 322 screen-detected cancers were compared against 192 interval cancers. Screen-detected Dukes' C and D CRCs had a superior survival rate compared with interval cancers (P=0.014 and P=0.04, respectively). Cox proportional hazards regression showed that Dukes' stage, tumour location, and diagnostic group (HR 0.45, 95% CI 0.29-0.69, P<0.001 for screen-detected CRCs) were all found to have a significant impact on the survival of patients. CONCLUSIONS: The improved survival of screen-detected over interval cancers for stages C and D suggest that there may be a biological difference in the cancers in each group. Although lead-time bias may have a role, this may be related to a tumour's propensity to bleed and therefore may reflect detection through current screening tests.

Management and short-term outcome of malignant colorectal polyps in the north of England(1).

AIM: Management of malignant colorectal polyps (MCP) is contentious, with no randomized controlled trials comparing endoscopic with surgical management. This study reviews the management and outcomes of MCPs across a UK region. METHOD: Patients with a malignant polyp were identified using the NORCCAG (NORthern Colorectal Cancer Audit Group) database between April 2006 and July 2010. All histopathology reports and follow-up procedures were reviewed. RESULTS: Of 386 patients identified, 165 (42.7%) had the polyp biopsied and 221 (57.3%) had an endoscopic local excision (37 piecemeal excision, 184 polypectomy). All patients having an endoscopic biopsy underwent surgery. 103 (46.6%) having a local excision had follow-up surgery, of whom 79 (76.7%) had no residual cancer. Of the 118 patients managed endoscopically, none had residual cancer on follow-up endoscopy. The 21 (5.4%) Dukes C cancers were associated with Kikuchi SM3/Haggitt 4 lesions (χ(2) =10.85, P=0.005) and lesions with an involved/unsure excision margin (χ(2) =7.44, P=0.017). Predictors of finding residual tumour at surgery after local excision were Kikuchi SM3/Haggitt Level 4 (χ(2) =17.07, P<0.001) and an involved/unsure excision margin (χ(2) =20.45, P<0.001). An excision margin >0 mm was associated with the finding of no residual tumour (χ(2) =25.21, P<0.001). There was no difference in survival between surgical and endoscopic management (χ(2) =0.634, P=0.426) after a mean follow-up of 25.1 months. CONCLUSION: Endoscopic management of a subgroup of MCPs appears safe. A clear resection margin (>0 mm) appears sufficient to avoid surgery, except in locally advanced lesions (Kikuchi 3/Haggitt 4) which have a greater risk of residual cancer at surgery and lymph node metastasis.

Comparison of screen-detected and interval colorectal cancers in the Bowel Cancer Screening Programme.

BACKGROUND: The NHS Bowel Cancer Screening Programme (BCSP) offers biennial faecal occult blood testing (FOBt) followed by colonoscopy after positive results. Colorectal cancers (CRCs) registered with the Northern Colorectal Cancer Audit Group database were cross-referenced with the BCSP database to analyse their screening history. METHODS: The CRCs in the screening population between April 2007 and March 2010 were identified and classified into four groups: control (diagnosed before first screening invite), screen-detected, interval (diagnosed between screening rounds after a negative FOBt), and non-uptake (declined screening). Patient demographics, tumour characteristics and survival were compared between groups. RESULTS: In all, 511 out of 1336 (38.2%) CRCs were controls; 825 (61.8%) were in individuals invited for screening of which 322 (39.0%) were screen detected, 311 (37.7%) were in the non-uptake group, and 192 (23.3%) were interval cancers. Compared with the control and interval cancer group, the screen-detected group had a higher proportion of men (P=0.002, P=0.003 respectively), left colon tumours (P=0.007, P=0.003), and superior survival (both P<0.001). There was no difference in demographics, tumour location/stage, or survival between control and interval groups. CONCLUSION: The FOBt is better at detecting cancers in the left colon and in men. The significant numbers of interval cancers weren't found to have an improved outcome compared with the non-screened population.

Antagonistic effects of phentolamine and octopamine on rhythmic motor output of crayfish thoracic ganglia.

Spontaneous rhythmic motor output of crayfish thoracic ganglia consists of bursts of activity in antagonistic leg motor neurons (MNs), alternating with a rather slow cycle period (typically > or = 20 s). The most common pattern (77% of preparations) consists of long coxal promotor bursts, the duration of which was correlated strongly with cycle period, and relatively short remotor bursts independent of cycle period. Octopamine, at a concentration of 2-30 microM reversibly retarded this rhythm, increasing both cycle period and promotor burst duration. Higher concentrations of octopamine inhibited promotor nerve activity and abolished rhythmic bursting. Phentolamine (10-50 microM) had the opposite effect of decreasing cycle period, mainly by decreasing promotor burst duration. Whereas in the presence of octopamine promotor bursts were lengthened and became even more strongly related to cycle period, phentolamine promoted a more symmetrical rhythm with shorter promotor bursts that were less dependent on cycle period. When octopamine was applied in the presence of phentolamine, there was no significant increase in cycle period or burst duration, although high octopamine concentrations (100 microM) were still capable of inhibiting promotor nerve activity. To our knowledge, pharmacological modulation of a spontaneous locomotor rhythm by an amine antagonist (applied by itself) has not been reported previously. The results raise the testable possibility that phentolamine exerts its modulatory effects by acting as an octopamine antagonist in crayfish thoracic ganglia.

Modulation of spontaneous and reflex activity of crayfish leg motor neurons by octopamine and serotonin.

1. We compared the effects of octopamine and serotonin on the activity of crayfish leg motor neurons in an isolated preparation of the 4th thoracic ganglion. Spontaneous activity of leg promotor (swing phase in a forward walking crayfish) and remotor (stance phase) motor neurons consisted either of continuous promotor activity (with the remotor nerve silent) or alternating bursts of promotor and remotor activity. Octopamine and serotonin, at high concentrations (< or = 100 and < or = 20 microM, respectively), abolished spontaneous promotor activity and rhythmic bursting (if ongoing). Both amines induced tonic remotor nerve activity, but each amine activated different identified remotor motor neurons. 2. Reflex responses of remotor motor neurons to stimulation of thoracocoxal (TC) joint proprioceptors were modulated by octopamine and serotonin in characteristic ways. The muscle receptor (TCMRO) that signals joint remotion excited a subset of remotor motor neurons in an assistance reflex. The chordotonal organ (TCCO) that signals joint promotion excited different remotor motor neurons in a resistance reflex. Octopamine abolished assistance reflexes and facilitated resistance reflexes. One assistance group unit was inhibited, whereas reflex reversal was induced in another: this unit was now excited in a resistance reflex, rather than in an assistance reflex. The responses of resistance group remotor units were enhanced. Serotonin had the opposite effect on assistance group remotors: one unit was excited and generated a stronger assistance reflex. The effect of serotonin on resistance group remotor units was similar (but quantitatively different) to that of octopamine. 3. Both octopamine and serotonin modulated spontaneous motor output at concentrations below those required to inhibit promotor nerve activity. Rhythmic promotor and remotor bursting was abolished, and replaced with continuous promotor activity, by serotonin at 1 microM and octopamine at 1-10 microM. In nonbursting preparations, promotor activity could be excited (instead of inhibited) by either amine at lower concentrations. 4. Octopaminergic inhibition of spontaneous promotor activity was antagonized by mianserin (10 microM). Phentolamine at the same concentration was less effective as an antagonist. Serotonergic inhibition of promotor activity was not blocked by mianserin. Mianserin also antagonized inhibitory, but not excitatory, effects of octopamine on remotor reflex responses. Serotonergic modulation of these reflexes was not affected. 5. An intersegmental difference was found in aminergic inhibition of promotor nerve activity. Whereas the effect (at the higher concentrations used) was inhibition of promotor activity from T4, simultaneous recordings from promotor nerves of the more rostral ganglia T3 and T2 showed either promotor excitation, or inhibition that was significantly weaker than in T4. This may relate to the known postural effects of these amines in intact crayfish and lobsters. 6. We conclude that octopamine and serotonin are modulators of segmental reflexes in the crayfish walking system. Each amine "assembles" a unique remotor nerve reflex response from different combinations of remotor units. In the case of octopamine, inhibitory effects are mediated by a mianserin-sensitive receptor, whereas excitatory effects are mediated by a mianserin-insensitive receptor.