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ObjectiveIt is difficult to predict the presence of histological risk factors for lymph node metastasis (LNM) before endoscopic treatment of T1 colorectal cancer (CRC). Therefore, endoscopic therapy is propagated to obtain adequate histological staging. We examined whether secondary surgery following endoscopic resection of high-risk T1 CRC does not have a negative effect on patients' outcomes compared with primary surgery.DesignPatients with T1 CRC with one or more histological risk factors for LNM (high risk) and treated with primary or secondary surgery between 2000 and 2014 in 13 hospitals were identified in the Netherlands Cancer Registry. Additional data were collected from hospital records, endoscopy, radiology and pathology reports. A propensity score analysis was performed using inverse probability weighting (IPW) to correct for confounding by indication.Results602 patients were eligible for analysis (263 primary; 339 secondary surgery). Overall, 34 recurrences were observed (5.6%). After adjusting with IPW, no differences were observed between primary and secondary surgery for the presence of LNM (OR 0.97; 95% CI 0.49 to 1.93; p=0.940) and recurrence during follow-up (HR 0.97; 95% CI 0.41 to 2.34; p=0.954). Further adjusting for lymphovascular invasion, depth of invasion and number of retrieved lymph nodes did not alter this outcome.ConclusionsOur data do not support an increased risk of LNM or recurrence after secondary surgery compared with primary surgery. Therefore, an attempt for an en-bloc resection of a possible T1 CRC without evident signs of deep invasion seems justified in order to prevent surgery of low-risk T1 CRC in a significant proportion of patients.

Objectives:The decision to perform secondary surgery after endoscopic resection of T1 colorectal cancer (CRC) depends on the risk of lymph node metastasis and the risk of incomplete resection. We aimed to examine the incidence and risk factors for incomplete endoscopic resection of T1 CRC after a macroscopic radical endoscopic resection.Methods:Data from patients treated between 2000 and 2014 with macroscopic complete endoscopic resection of T1 CRC were collected from 13 hospitals. Incomplete resection was defined as local recurrence at the polypectomy site during follow-up or malignant tissue in the surgically resected specimen in case secondary surgery was performed. Multivariate regression analysis was performed to analyze factors associated with incomplete resection.Results:In total, 877 patients with a median follow-up time of 36.5 months (interquartile range 16.0–68.3) were included, in whom secondary surgery was performed in 358 patients (40.8%). Incomplete resection was observed in 30 patients (3.4%; 95% confidence interval (CI) 2.3–4.6%). Incomplete resection rate was 0.7% (95% CI 0–2.1%) in low-risk T1 CRC vs. 4.4% (95% CI 2.7–6.5%) in high-risk T1 CRC (P=0.04). Overall adverse outcome rate (incomplete resection or metastasis) was 2.1% (95% CI 0–5.0%) in low-risk T1 CRC vs. 11.7% (95% CI 8.8–14.6%) in high-risk T1 CRC (P=0.001). Piecemeal resection (adjusted odds ratio 2.60; 95% CI 1.20–5.61, P=0.02) and non-pedunculated morphology (adjusted odds ratio 2.18; 95% CI 1.01–4.70, P=0.05) were independent risk factors for incomplete resection. Among patients in whom no additional surgery was performed, who developed recurrent cancer, 41.7% (95% CI 20.8–62.5%) died as a result of recurrent cancer.Conclusions:In the absence of histological high-risk factors, a ‘wait-and-see’ policy with limited follow-up is justified. Piecemeal resection and non-pedunculated morphology are independent risk factors for incomplete endoscopic resection of T1 CRC.

OBJECTIVES:Optical diagnosis of T1 colorectal cancer (CRC) and T1 CRC with deep submucosal invasion is important in guiding the treatment strategy. The use of advanced imaging is not standard clinical practice in Western countries. A systematic review and meta-analysis were conducted comparing the accuracy of narrow band imaging (NBI), magnifying chromoendoscopy (MCE), and gross morphological features (GMF) seen with conventional view for the optical diagnosis of T1 CRC and deep submucosal invasion.METHODS:A literature search identified studies on the optical diagnosis of T1 CRC and deep invasion using NBI, MCE, or GMF. Pooled estimates (PE) of sensitivity and specificity across studies reporting on NBI or MCE were compared using a random effects bivariate meta-regression approach, and a paired analysis focusing on studies that performed both techniques within the same patient was performed.RESULTS:Thirty-three studies with 31,568 polyps were included. For the optical diagnosis of T1 CRC, both NBI (4 studies; PE 0.85, 95% confidence interval (CI) 0.75–0.91) and MCE (5 studies; PE 0.90, 95% CI 0.83–0.94) yielded higher sensitivity as compared with GMF (3 studies; range 0.21–0.46). No significant preference for NBI or MCE was found (sensitivity relative risk (RR) 0.93, 95% CI 0.79–1.09, P=0.37; specificity RR 0.98, 95% CI 0.86–1.11, P=0.74). Similarly, for the optical diagnosis of deep invasion, both NBI (13 studies; PE 0.77, 95% CI 0.68–0.84) and MCE (17 studies; PE 0.81, 95% 0.75–0.87) yielded higher sensitivity as compared with GMF (6 studies; range 0.18–0.88), and no significant preference for either NBI or MCE was found (sensitivity RR 0.92, 95% CI 0.76–1.11, P=0.36; specificity RR 1.00, 95% CI 0.96–1.04, P=0.92).CONCLUSIONS:This review supports the use of advanced imaging techniques in preference to GMF to reduce the risk of performing piecemeal resection for T1 CRCs or unnecessary surgical referral for lesions amendable to endoscopic resection. A preference for either NBI or MCE could not be observed.

Homozygous plasminogen-deficient (Plg-/-) mice had a significantly reduced thrombolytic capacity toward intravenously injected 125I-fibrin labeled plasma clots prepared from Plg-/- murine plasma (9% +/- 3% lysis after 8 hours; (mean +/- SEM, n = 6), as compared with 82% +/- 8% in wild-type mice; P < .0001). Bolus injection of 1 mg purified murine plasminogen in 10- to 17-week-old Plg-/- mice increased the plasminogen antigen and activity levels at 8 hours to normal levels (130 +/- 5 micrograms/mL). Plasminogen administration was associated with significant restoration of thrombolytic potential (64% +/- 7% spontaneous clot lysis; P < .0001 versus lysis without plasminogen injection). Bolus injection of 1 mg plasminogen in homozygous tissue- type plasminogen activator-deficient (t-PA-/-) mice doubled the plasminogen antigen and activity levels after 8 hours and increased 125I-fibrin clot lysis at 8 hours from 13% +/- 3% to 34% +/- 5% (P = .008). Fibrinogen, t-PA antigen and alpha 2-antiplasmin activity levels after 8 hours were not significantly different in the groups with or without plasminogen injection. Injection of plasminogen induced a variable increase (on average 7- to 10-fold) of PAI-1, but no correlation with the extent of spontaneous clot lysis was observed. Histopathologic examination at the end of the experiments revealed that fibrin deposition in the liver of Plg-/- mice was slightly reduced 8 hours after bolus plasminogen injection (P = .007) and markedly reduced after 24 hours (P < .0001). Plasminogen antigen levels in liver extracts were comparable with those found in wild-type mice at 8 hours (130 +/- 20 versus 110 +/- 15 ng/mg protein) and decreased to 25 +/- 3.2 ng/mg protein at 24 hours. Thus, restoration of normal plasminogen levels in Plg-/- mice normalized the thrombolytic potential toward experimentally induced pulmonary emboli, and resulted in removal of endogenous fibrin deposits within 24 hours.

In a double-masked group comparative study, 20 patients received 2% nedocromil sodium four times daily and 23 placebo eye drops, for treatment of perennial allergic conjunctivitis (PAC). All had at least a one-year diagnosis of bilateral PAC and remained symptomatic despite using 2% sodium cromoglycate eye drops four times daily for at least 14 days Symptom severity (0-4) during sodium cromoglycate monotherapy was then recorded in a one-week baseline prior to randomisation, a minimum total score of 11 being mandatory. During the trial, no eye medication was allowed other than the test treatment. Clinic examinations were made before and after baseline and after one, three and six weeks' treatment, and patients kept daily diary cards of eye symptom severity. Compared to placebo, nedocromil sodium significantly (p<0.05) improved diary scores for itching (weeks 3, 4, 5, 6), total symptoms (weeks 5, 6) and general eye condition (week 6). Mean scores over the final four weeks, allowing a two-week washout, showed similar improvements in itching (p = 0.01), total symptoms (p = 0.05) and general eye condition (p = 0.04). Clinical assessments again favoured nedocromil sodium, which improved itching (week 3, p = 0.002), burning (week 6, p = 0.007), overall eye condition (weeks 3-6, p<0.05). and conjunctival thickening and hyperaemia (weeks 3-6, p<0.05). Finally, both patient (p = 0.02) and clinician (p = 0.0015) opinions of efficacy favoured nedocromil sodium over placebo.These results show nedocromil sodium to be effective in controlling symptoms of perennial allergic conjunctivitis which persisted during treatment with sodium cromoglycate.