Strategic analysis and recommendations of the Sociedad Española de Patología Digestiva (SEPD) regarding population-based screening programs for colorectal cancer in Spain.

INTRODUCTION: population-based screening programs are effective to reduce colorectal cancer-related mortality and incidence. However, given their complex development, sound organization and design do not warrant success. This study provides a strategic analysis of the Spanish programs, as well as recommendations in an attempt to contribute to their optimization. METHODS: a multidisciplinary panel of researchers, supported by the Sociedad Española de Patología Digestiva (SEPD), has performed a SWOT (strengths, weaknesses, opportunities and threats) analysis, from which a proposal of recommendations was developed; their adequacy was judged using an adapted version of the RAND/UCLA method. RESULTS: 5 weaknesses, 3 threats, 5 strengths and 5 opportunities were identified, and a total of 15 recommendations were developed emphasizing aspects with room for improvement in program orientation, particularly the need to increase participation, fight variability and inequities, improve information processes and systems quality, ensure specific, adequate funding, and evaluate health results. CONCLUSION: promoting an operational collaboration framework between all the public health and care levels involved should facilitate effective communication with society regarding the benefits of taking part in population screening programs while persuading decision and policy makers of the critical importance of taking an active, determined stance regarding its implementation.

Activity of Spanish gastroenterology units before and after the COVID-19 pandemic: an assessment using the EFIC_AD tool, developed by the Sociedad Española de Patología Digestiva (SEPD).

INTRODUCTION: the COVID-19 pandemic had a strong impact on the healthcare model. The Sociedad Española de Patología Digestiva (SEPD) offered gastroenterology care units (UAAD) an instrument (EFIC_AD) to record and analyze their efficacy and efficiency. Thus, the impact of the pandemic on the activity of UAAD was assessed. METHODS: A descriptive study, based on the EFIC_AD registry for the period 2019-2021, of activity regarding admissions, clinic visits, and endoscopic as well as non-endoscopic tests, and endoscopy room performance. RESULTS: data were collected from up to 42 hospitals (22 with ≥ 500 beds). Overall, activity during 2020 compared to 2019 decreased by 12.30 % for admissions and 40 % for pH-metries (16.70 % for new clinic visits; 14.34 % for referrals from primary care; 24.70 % for gastroscopies; 32.50 % for colonoscopies; 31.00 % for endoscopic ultrasounds; 18.20 % for endoscopic retrograde cholangiopancreatography (ERCPs); 38.00 % for manometries; 23.60 % for abdominal ultrasounds; 36.17 % for liver transient elastographies [Fibroscan®]). The levels achieved during 2019 were not fully recovered during 2021 except for digestive motility studies, and virtually for endoscopy room performance rate (88.15 % in 2019; 67.77 % in 2020; 85.93 % in 2021). CONCLUSIONS: during 2020 the COVID-19 pandemic led to a markedly decreased in specific activities at UAAD, which was not fully recovered in 2021 despite endoscopy room performance return to normal.

Detection of serrated lesions in proximal colon by simulated sigmoidoscopy vs faecal immunochemical testing in a multicentre, pragmatic, randomised controlled trial.

BACKGROUND: The diagnostic yield of the faecal immunochemical test and sigmoidoscopy in detecting proximal serrated polyps in a colorectal cancer screening programme has not been fully assessed. AIM: We determined the detection rate of proximal serrated polyps by simulated sigmoidoscopy and faecal immunochemical test compared with total colonoscopy in a population-based, multicentre, nationwide, randomised controlled trial (ColonPrev study). METHODS: Sigmoidoscopy yield was simulated based on the UK-Flexible Sigmoidoscopy Trial for total colonoscopy referral. Definitions were: proximal serrated polyp (proximal serrated polyp): sessile serrated polyp or hyperplastic polyp of any size and proximal at-risk serrated polyp (at-risk proximal serrated polyp): sessile serrated polyp of any size or hyperplastic polyp ≥ 10 mm, both located proximally to the splenic flexure. RESULTS: A total of 10,611 individuals underwent faecal immunochemical test and 5059 underwent total colonoscopy and were evaluated by simulated sigmoidoscopy. Sigmoidoscopy and faecal immunochemical test were less accurate in detecting proximal serrated polyps (odds ratio: 0.13; 95% confidence interval: 0.10-0.18 and 0.13; 0.09-0.18, p < 0.0001, respectively). Both tests were inferior to colonoscopy in detecting at-risk proximal serrated polyps, and sigmoidoscopy was inferior to faecal immunochemical test in detecting these lesions (odds ratio: 0.17; 95% confidence interval: 0.10-0.30 and 0.25; 0.17-0.37, p < 0.0001, respectively). CONCLUSION: Sigmoidoscopy and faecal immunochemical test are less accurate in detecting proximal serrated polyps than colonoscopy, particularly in women.

Correlation between adenoma detection rate in colonoscopy- and fecal immunochemical testing-based colorectal cancer screening programs.

BACKGROUND: The adenoma detection rate (ADR) is the main quality indicator of colonoscopy. The ADR recommended in fecal immunochemical testing (FIT)-based colorectal cancer screening programs is unknown. METHODS: Using the COLONPREV (NCT00906997) study dataset, we performed a post-hoc analysis to determine if there was a correlation between the ADR in primary and work-up colonoscopy, and the equivalent figure to the minimal 20% ADR recommended. Colonoscopy was performed in 5722 individuals: 5059 as primary strategy and 663 after a positive FIT result (OC-Sensor™; cut-off level 15 µg/g of feces). We developed a predictive model based on a multivariable lineal regression analysis including confounding variables. RESULTS: The median ADR was 31% (range, 14%-51%) in the colonoscopy group and 55% (range, 21%-83%) in the FIT group. There was a positive correlation in the ADR between primary and work-up colonoscopy (Pearson's coefficient 0.716; p < 0.001). ADR in the FIT group was independently related to ADR in the colonoscopy group: regression coefficient for colonoscopy ADR, 0.71 (p = 0.009); sex, 0.09 (p = 0.09); age, 0.3 (p = 0.5); and region 0.00 (p = 0.9). The equivalent figure to the 20% ADR was 45% (95% confidence interval, 35%-56%). CONCLUSIONS: ADR in primary and work-up colonoscopy of a FIT-positive result are positively and significantly correlated.

Incidence of advanced neoplasia during surveillance in high- and intermediate-risk groups of the European colorectal cancer screening guidelines.

Background and study aims: The European guidelines for quality assurance in colorectal cancer (CRC) screening have established high-risk (≥ 5 adenomas or an adenoma ≥ 20 mm) and intermediate-risk (3 - 4 adenomas or at least one adenoma 10 - 19 mm in size, or villous histology, or high grade dysplasia) groups with different endoscopic surveillance intervals. The aim of this study was to evaluate the difference in the incidence of advanced neoplasia (advanced adenoma or CRC) between the two risk groups. Patients and methods: This retrospective group study included patients meeting high- or intermediate-risk criteria for adenomas detected in CRC screening programs and the COLONPREV study before European guidelines were adopted in Spain (June 2011) with a 3-year surveillance recommendation according to Spanish guidelines. The primary outcome measure was the incidence of advanced neoplasia in patients undergoing surveillance. The secondary outcome measure was the CRC incidence. We used an adjusted proportional hazards regression model to control confounding variables. Results: The study included 5401 patients (3379 intermediate risk, 2022 high risk). Endoscopic surveillance was performed in 65.5 % of the patients (2.8 ±â€Š1 years). The incidence of advanced neoplasia in the high- and intermediate-risk groups was 16.0 % (59.0 cases/1000 patient-years) and 12.3 % (41.2 cases/1000 patient-years), respectively. The CRC incidence was 0.5 % (1.4 cases/1000 patient-years) and 0.4 % (1 case/1000 patient-years), respectively. The advanced neoplasia and CRC attributable risk to the high risk group was of 3.7 % and 0.1 %, respectively. In the proportional hazards analysis, the risk of advanced neoplasia was greater in the high-risk group (hazard ratio [HR] 1.5, 95 % confidence interval [CI] 1.2 - 1.8), with no significant differences in the CRC incidence (HR 1.6, 95 %CI 0.6 - 3.8). Conclusions: Patients meeting high-risk criteria have a higher incidence of advanced neoplasia during endoscopic surveillance. No differences were found in the CRC incidence at a 3-year surveillance recommendation.

Impact of age- and gender-specific cut-off values for the fecal immunochemical test for hemoglobin in colorectal cancer screening.

BACKGROUND: There is no information on the impact of age and gender on the diagnostic yield of different positivity thresholds for the fecal immunochemical test for hemoglobin (FIT). OBJECTIVES: To evaluate the performance of this test at distinct positivity cut-offs in a population-based colorectal cancer (CRC) screening program. METHODS: CRC detection rate (DR), and analysis of resources were evaluated retrospectively, at different cut-offs of FIT (20, 25, 30, 35 and 40µg Hb/g) respect to a reference value (15µg Hb/g), according to age and gender, in a screening population of 10,611 participants of the ColonPrev study (Quintero. NEJM 2013). RESULTS: At the reference cut-off value, 36 CRC and 252 advanced adenomas (AA) were diagnosed. Increasing the cut-off in women ≤60 years decreases colonoscopies performed by 44.5% without modifying the CRC (DR). Same CRC DR was observed in men ≤60 years and women >60 years increasing cut-off at 25-30µg Hb/g. In men >60 years, all increases in the cut-off affected the CRC DR, especially when the cut-off was increased from 35 to 40µg Hb/g (CRC miss rate 25%). CONCLUSIONS: To improve the performance of FIT in CRC screening programs, FIT cut-offs could be individualized by age and gender.

A randomized trial to compare the efficacy and tolerability of sodium picosulfate-magnesium citrate solution vs. 4 L polyethylene glycol solution as a bowel preparation for colonoscopy.

PURPOSE: The purpose of this study is to compare the efficacy and acceptability of an evening-before regimens of sodium picosulfate/magnesium citrate (SPMC) and polyethylene glycol (PEG) as bowel cleansers and to explore the results of a same-day regimen of SPMC. METHODS: Multicenter, randomized, observer-blinded, parallel study carried out in subjects who were 18-80 years old and were undergoing diagnostic colonoscopy for the first time. The primary outcome was treatment success, which was a composite outcome defined by (1) the evaluation of the overall preparation quality as "excellent" or "good" by two blinded independent evaluators with the Fleet(®) Grading Scale for Bowel Cleansing and (2) a subject's acceptability rating of "easy to take" or "tolerable." The primary outcome was analyzed using a logistic regression with site, gender, and age group (age ≥65 years and <65 years) as factors. RESULTS: Four hundred ninety subjects were included in the efficacy evaluation. Although treatment success was significantly higher in subjects assigned to the evening-before regimen of SPMC vs. subjects assigned to the evening-before PEG, when evaluating the two individual components for treatment success, there were significant differences in the ease of completion but not in the quality of preparation. The same-day SPMC regimen was superior to both the evening-before regimen of SPMC and PEG in terms of the quality of preparation, especially regarding the proximal colon. CONCLUSIONS: An evening-before regimen of SPMC is superior to an evening-before regimen of PEG in terms of subject's acceptability. The same-day SPMC regimen provides better cleansing levels in the proximal colon.

Association of a characteristic membrane pattern of annexin A2 with high invasiveness and nodal status in colon adenocarcinoma.

The identification of tumor cells in lymph nodes is essential for the correct classification of patients with colorectal cancer who may benefit from adjuvant treatments. Proper classification of tumor stage becomes entangled by variables such as an insufficient number of lymph nodes examined, which can result in erroneous or missed diagnosis. The determination of pathologic factors in the primary tumor associated with positive lymph nodes is an area of research that has attempted to provide variables to solve this problem. In the present study, we observed that the localization of annexin A2 (AnxA2) in a cell membrane is the characteristic that distinguishes tumor cells with high invasiveness. Localization of AnxA2 expression was also studied in tissue specimens from 58 patients with invasive colorectal carcinoma (T3-T4), who had undergone colectomy with radical lymph node dissection. Interestingly, the membrane pattern observed in tumor cell lines was also identified in patient's tissue samples and allowed us to distinguish among different cell populations with the tumor. Univariate analysis showed that tumor deposits in pericolic fat, extramural vascular invasion, and amount of cells with AnxA2 membrane pattern in the tumor invasive edge had a significant influence on lymph node metastasis. On the contrary, multivariate analysis revealed that the number of cells with AnxA2 membrane pattern (P < 0.05) and tumor deposits (P < 0.05) was significantly associated with lymph node metastasis. Furthermore, AnxA2 cellular localization was observed in cell clusters that define tumor budding, and a significant association between both variables was detected.

Resistance to Selumetinib (AZD6244) in colorectal cancer cell lines is mediated by p70S6K and RPS6 activation.

Selumetinib (AZD6244, ARRY-142886) is a MEK1/2 inhibitor that has gained interest as an anti-tumour agent. We have determined the degree of sensitivity/resistance to Selumetinib in a panel of colorectal cancer cell lines using cell proliferation and soft agar assays. Sensitive cell lines underwent G1 arrest, whereas Selumetinib had no effect on the cell cycle of resistant cells. Some of the resistant cell lines showed high levels of ERK1/2 phosphorylation in the absence of serum. Selumetinib inhibited phosphorylation of ERK1/2 and RSK and had no effect on AKT phosphorylation in both sensitive and resistant cells. Furthermore, mutations in KRAS, BRAF, or PIK3CA were not clearly associated with Selumetinib resistance. Surprisingly, Selumetinib was able to inhibit phosphorylation of p70 S6 kinase (p70S6K) and its downstream target ribosomal protein S6 (RPS6) in sensitive cell lines. However, p70S6K and RPS6 phosphorylation remained unaffected or even increased in resistant cells. Moreover, in some of the resistant cell lines p70S6K and RPS6 were phosphorylated in the absence of serum. Interestingly, colorectal primary cultures derived from tumours excised to patients exhibited the same behaviour than established cell lines. Pharmacological inhibition of p70S6K using the PI3K/mTOR inhibitor NVP-BEZ235, the specific mTOR inhibitor Rapamycin and the specific p70S6K inhibitor PF-4708671 potentiated Selumetinib effects in resistant cells. In addition, biological inhibition of p70S6K using siRNA rendered responsiveness to Selumetinib in resistant cell lines. Furthermore, combination of p70S6K silencing and PF-47086714 was even more effective. We can conclude that p70S6K and its downstream target RPS6 are potential biomarkers of resistance to Selumetinib in colorectal cancer.

Comparative Study of 17-AAG and NVP-AUY922 in Pancreatic and Colorectal Cancer Cells: Are There Common Determinants of Sensitivity?

The use of heat shock protein 90 (Hsp90) inhibitors is an attractive antineoplastic therapy. We wanted to compare the effects of the benzoquinone 17-allylamino-17-demethoxygeldanamycin (17-AAG, tanespimycin) and the novel isoxazole resorcinol-based Hsp90 inhibitor NVP-AUY922 in a panel of pancreatic and colorectal carcinoma cell lines and in colorectal primary cultures derived from tumors excised to patients. PANC-1, CFPAC-1, and Caco-2 cells were intrinsically resistant to 17-AAG but sensitive to NVP-AUY922. Other cellular models were sensitive to both inhibitors. Human epidermal growth factor receptor receptors and their downstream signaling pathways were downregulated in susceptible cellular models, and concurrently, Hsp70 was induced. Intrinsic resistance to 17-AAG did not correlate with expression of ATP-binding cassette transporters involved in multidrug resistance. Some 17-AAG-resistant, NVP-AUY922-sensitive cell lines lacked NAD(P)H: quinone oxidoreductase 1 (NQO1) enzyme and activity. However, colorectal LoVo cells still responded to both drugs in spite of having undetectable levels and activity of NQO1. Pharmacological and biologic inhibition of NQO1 did not confer resistance to 17-AAG in sensitive cell lines. Therefore, even though 17-AAG sensitivity is related to NQO1 protein levels and enzymatic activity, the absence of NQO1 does not necessarily convey resistance to 17-AAG in these cellular models. Moreover, NVP-AUY922 does not require NQO1 for its action and is a more potent inhibitor than 17-AAG in these cells. More importantly, we show in this report that NVP-AUY922 potentiates the inhibitory effects of chemotherapeutic agents, such as gemcitabine or oxaliplatin, and other drugs that are currently being evaluated in clinical trials as antitumor agents.

Participation and detection rates by age and sex for colonoscopy versus fecal immunochemical testing in colorectal cancer screening.

PURPOSE: To compare two strategies for colorectal cancer screening: one-time colonoscopy versus fecal immunochemical testing (FIT) (and colonoscopy for positive) every 2 years, in order to determine which strategy provides the highest participation and detection rates in groups of sex and age. METHODS: This analysis was performed with data from the first screening round within the COLONPREV study, a population-based, multicenter, nationwide trial carried out in Spain. Several logistic regression models were applied to identify the influence of the screening test on participation rates and detection of proximal and distal neoplasms, as well to identify the influence of age and sex: women aged 50-59 years, women aged 60-69 years, men aged 50-59 years, and men aged 60-69 years. RESULTS: Participation was higher in women than in men, especially among women aged 50-59 years (25.91 % for colonoscopy and 35.81 % for FIT). Crossover from colonoscopy to FIT was higher among women than men, especially among those aged 60-69 years (30.37 %). In general, detection of any neoplasm and advanced adenoma was higher with colonoscopy than with FIT, but no significant differences were found between the two strategies for colorectal cancer detection. Detection of advanced adenoma in both arms was lower in women [specifically in women aged 50-59 years (OR 0.31; 95 % CI 0.25-0.38) than in men aged 60-69 years]. Women aged 50-59 years in the colonoscopy arm had a higher probability of detection of advanced adenoma (OR 4.49; 95 % CI 3.18-6.35), as well as of detection of neoplasms in proximal and distal locations (proximal OR 19.34; 95 % CI 12.07-31.00; distal OR 11.04; 95 % CI 8.13-15.01) than women of the same age in the FIT arm. These differences were also observed in the remaining groups but to a lesser extent. CONCLUSION: Women were more likely to participate in a FIT-based strategy, especially those aged 50-59 years. The likelihood of detection of any neoplasm was higher in the colonoscopy arm for all the population groups studied, especially in women aged 50-59 years. Distinct population groups should be informed of the benefits of each screening strategy so that they may take informed decisions.

Rate of detection of advanced neoplasms in proximal colon by simulated sigmoidoscopy vs fecal immunochemical tests.

BACKGROUND & AIMS: We compared the ability of biennial fecal immunochemical testing (FIT) and one-time sigmoidoscopy to detect colon side-specific advanced neoplasms in a population-based, multicenter, nationwide, randomized controlled trial. METHODS: We identified asymptomatic men and women, 50-69 years old, through community health registries and randomly assigned them to groups that received a single colonoscopy examination or biennial FIT. Sigmoidoscopy yield was simulated from results obtained from the colonoscopy group, according to the criteria proposed in the UK Flexible Sigmoidoscopy Trial for colonoscopy referral. Patients who underwent FIT and were found to have ≥75 ng hemoglobin/mL were referred for colonoscopy. Data were analyzed from 5059 subjects in the colonoscopy group and 10,507 in the FIT group. The main outcome was rate of detection of any advanced neoplasm proximal to the splenic flexure. RESULTS: Advanced neoplasms were detected in 317 subjects (6.3%) in the sigmoidoscopy simulation group compared with 288 (2.7%) in the FIT group (odds ratio for sigmoidoscopy, 2.29; 95% confidence interval, 1.93-2.70; P = .0001). Sigmoidoscopy also detected advanced distal neoplasia in a higher percentage of patients than FIT (odds ratio, 2.61; 95% confidence interval, 2.20-3.10; P = .0001). The methods did not differ significantly in identifying patients with advanced proximal neoplasms (odds ratio, 1.17; 95% confidence interval, 0.78-1.76; P = .44). This was probably due to the lower performance of both strategies in detecting patients with proximal lesions (sigmoidoscopy detected these in 19.1% of patients and FIT in 14.9% of patients) vs distal ones (sigmoidoscopy detected these in 86.8% of patients and FIT in 33.5% of patients). Sigmoidoscopy, but not FIT, detected proximal lesions in lower percentages of women (especially those 50-59 years old) than men. CONCLUSIONS: Sigmoidoscopy and FIT have similar limitations in detecting advanced proximal neoplasms, which depend on patients' characteristics; sigmoidoscopy underperforms for women 50-59 years old. Screening strategies should be designed on the basis of target population to increase effectiveness and cost-effectiveness. ClinicalTrials.gov number: NCT00906997.

Economic evaluation of colorectal cancer (CRC) screening.

Because of its incidence and mortality colorectal cancer represents a serious public health issue in industrial countries. In order to reduce its social impact a number of screening strategies have been implemented, which allow an early diagnosis and treatment. These basically include faecal tests and studies that directly explore the colon and rectum. No strategy, whether alone or combined, has proven definitively more effective than the rest, but any such strategy is better than no screening at all. Selecting the most efficient strategy for inclusion in a population-wide program is an uncertain choice. Here we review the evidence available on the various economic evaluations, and conclude that no single method has been clearly identified as most cost-effective; further research in this setting is needed once common economic evaluation standards are established in order to alleviate the methodological heterogeneity prevailing in study results.

Linaclotide in the treatment of patients with irritable bowel syndrome and constipation - analysis of an opportunity.

Linaclotide is a secretagogue that provides a combined effect on visceral pain. The European Medicines Agency has authorized its indication for the symptomatic treatment of moderate to severe irritable bowel syndrome with constipation in adults. The purpose of this review is to discuss the clinical framework for linaclotide use in our setting, the drug´s characteristics and pre-clinical development, and the clinical studies supporting its use in order to establish relevant views regarding its validity and clinical applicability. The results suggest that the only -non-severe- adverse effect associated with this drug is diarrhea. As regards effectiveness, linaclotide consistently shows favorable, significant differences in absolute risk versus placebo for all objective outcome variables described by regulatory agencies, with a combined pain and constipation response between 12.6% and 22.8% according to the variable and trial under consideration. This response is sustained and drug-related, as it goes away upon discontinuation. To conclude, linaclotide has a safety and efficacy profile that, from a clinical perspective, warrants its use for patients meeting irritable bowel syndrome and constipation criteria, with significant symptoms that cannot be relieved with other less specific measures. In the absence of predictive rules for response, it is recommended that, should the patient fail to respond, he or she should be considered not eligible for linaclotide therapy, and both indication and treatment continuity should be reserved for objective responders alone.

Effect of aspirin and antiplatelet drugs on the outcome of the fecal immunochemical test.

OBJECTIVE: To evaluate the effect of aspirin and nonaspirin antiplatelet agents (NAAAs) on the performance of the fecal immunochemical test (FIT). PARTICIPANTS AND METHODS: We performed a post hoc analysis of results from a clinical trial that involved 28,696 asymptomatic average-risk men and women aged 50 to 69 years invited to participate in a colorectal cancer screening program with FIT between November 1, 2008, and June 31, 2011. RESULTS: The test was returned by 6390 individuals (22.3%), of whom 5821 (91.1%) reported not using antiplatelet drugs (nonusers group) and 569 (8.9%) reported using these drugs at the time of testing (users group). The FIT result was positive in 48 of 569 users (8.4%) and 365 of 5821 nonusers (6.3%) (P=.05). A positive FIT result was found in 7.3% (28/384) of aspirin users, 7.1% (10/140) of NAAA users, and 22.2% (10/45) of those undergoing dual antiplatelet therapy (DAPT) (aspirin plus an NAAA). The DAPT subgroup had a significantly higher positive FIT rate than the nonuser group (odds ratio, 3.5; 95% CI, 1.7-7.3; P<.05). The positive predictive value (PPV) for advanced neoplasia (AN) in nonusers was 50.4% vs 50.0% in users (P = .40). The PPV for AN was 57.0% in aspirin users, 30.0% in NAAA users, and 50.0% in DAPT users, without statistically significant differences between the user and nonuser groups. CONCLUSION: The use of DAPT increased the rate of positive FIT results. Use of aspirin, NAAAs, or both did not modify the PPV for AN in this population-based colorectal screening program.

An endoscopic technique for treating symptomatic distal jejunum obstruction by leaving the overtube in place.

Double balloon enteroscopy has a limitation for positioning an enteral stent in the distal jejunum through its long, narrow biopsy channel. When the distal end of its overtube is left in place close to the neoplasia with the enteroscope removed, if we push an enteral stent introduction system, it tends to form loops so the techniquecannot be performed with this instrument. However, the double balloon colonoscope has a shorter overtube length and using the same push-and-pull technique we can reach the distal jejunum with this instrument by inserting the delivery stent system without loops through its overtube. We present a patient with neoplastic obstruction in the distal jejunum with resolution of his symptoms after positioning an enteral stent.

Risk of advanced proximal neoplasms according to distal colorectal findings: comparison of sigmoidoscopy-based strategies.

BACKGROUND: Screening for colorectal cancer with sigmoidoscopy benefits from the fact that distal findings predict the risk of advanced proximal neoplasms (APNs). This study was aimed at comparing the existing strategies of postsigmoidoscopy referral to colonoscopy in terms of accuracy and resources needed. METHODS: Asymptomatic individuals aged 50-69 years were eligible for a randomized controlled trial designed to compare colonoscopy and fecal immunochemical test. Sigmoidoscopy yield was estimated from results obtained in the colonoscopy arm according to three sets of criteria of colonoscopy referral (from those proposed in the UK Flexible Sigmoidoscopy, Screening for COlon REctum [SCORE], and Norwegian Colorectal Cancer Prevention [NORCCAP] trials). Advanced neoplasm detection rate, sensitivity, specificity, and number of individuals needed to refer for colonoscopy to detect one APN were calculated. Logistic regression analysis was performed to identify distal findings associated with APN. All statistical tests were two-sided. RESULTS: APN was found in 255 of 5059 (5.0%) individuals. Fulfillment of UK (6.2%), SCORE (12.0%), and NORCCAP (17.9%) criteria varied statistically significantly (P < .001). The NORCCAP strategy obtained the highest sensitivity for APN detection (36.9%), and the UK approach reached the highest specificity (94.6%). The number of individuals needed to refer for colonoscopy to detect one APN was 6 (95% confidence interval [CI] = 4 to 7), 8 (95% CI = 6 to 9), and 10 (95% CI = 8 to 12) when the UK, SCORE, and NORCCAP criteria were used, respectively. The logistic regression analysis identified distal adenoma ≥10 mm (odds ratio = 3.77; 95% CI = 2.52 to 5.65) as the strongest independent predictor of APN. CONCLUSIONS: Whereas the NORCCAP criteria achieved the highest sensitivity for APN detection, the UK recommendations benefited from the lowest number of individuals needed to refer for colonoscopy.

Relationship of colonoscopy-detected serrated polyps with synchronous advanced neoplasia in average-risk individuals.

BACKGROUND: Serrated cancers account for 10% to 20% of all colorectal cancers (CRC) and more than 30% of interval cancers. The presence of proximal serrated polyps and large (≥10 mm) serrated polyps (LSP) has been correlated with colorectal neoplasia. OBJECTIVE: To evaluate the prevalence of serrated polyps and their association with synchronous advanced neoplasia in a cohort of average-risk population and to assess the efficacy of one-time colonoscopy and a biennial fecal immunochemical test for reducing CRC-related mortality. This study focused on the sample of 5059 individuals belonging to the colonoscopy arm. DESIGN: Multicenter, randomized, controlled trial. SETTING: The ColonPrev study, a population-based, multicenter, nationwide, randomized, controlled trial. PATIENTS: A total of 5059 asymptomatic men and women aged 50 to 69 years. INTERVENTION: Colonoscopy. MAIN OUTCOME MEASUREMENTS: Prevalence of serrated polyps and their association with synchronous advanced neoplasia. RESULTS: Advanced neoplasia was detected in 520 individuals (10.3%) (CRC was detected in 27 [0.5%] and advanced adenomas in 493 [9.7%]). Serrated polyps were found in 1054 individuals (20.8%). A total of 329 individuals (6.5%) had proximal serrated polyps, and 90 (1.8%) had LSPs. Proximal serrated polyps or LSPs were associated with male sex (odds ratio [OR] 2.08, 95% confidence interval [CI], 1.76-4.45 and OR 1.65, 95% CI, 1.31-2.07, respectively). Also, LSPs were associated with advanced neoplasia (OR 2.49, 95% CI, 1.47-4.198), regardless of their proximal (OR 4.15, 95% CI, 1.69-10.15) or distal (OR 2.61, 95% CI, 1.48-4.58) locations. When we analyzed subtypes of serrated polyps, proximal hyperplasic polyps were related to advanced neoplasia (OR 1.61, 95% CI, 1.13-2.28), although no correlation with the location of the advanced neoplasia was observed. LIMITATIONS: Pathology criteria for the diagnosis of serrated polyps were not centrally reviewed. The morphology of the hyperplasic polyps (protruded or flat) was not recorded. Finally, because of the characteristics of a population-based study carried out in average-risk patients, the proportion of patients with CRC was relatively small. CONCLUSION: LSPs, but not proximal serrated polyps, are associated with the presence of synchronous advanced neoplasia. Further studies are needed to determine the risk of proximal hyperplastic polyps.

Joint position statement by "Sociedad Española de Patología Digestiva" (Spanish Society of Gastroenterology) and "Sociedad Española de Farmacología" (Spanish Society of Pharmacology) on biosimilar therapy for inflammatory bowel disease.

Biological drugs or biopharmaceutical products, manufactured with or from living organisms using biotechnology, have represented a therapeutic revolution for the control of inflammatory bowel disease (IBD). At present, in this indication and in our country, only two biological are approved, infliximab (IFX) and adalimumab (ADA), both of them monoclonal antibodies against tumor necrosis factor alpha. Effectiveness data are strong for both therapies, with maximum levels of scientific evidence.The upcoming expiry date for these biologicals´ patents has allowed the potential marketing of so-called biosimilar agents for the IBD indication. While biosimilars are conceptually for biological what generics are for chemical drugs, the structural complexity of biosimilars and their biological and manufacturing variability lead to consider validation processes for these two types in humans as highly differential. Thus, in our setting, under the coverage of "Agencia Española del Medicamento y Productos Sanitarios (AEMPS)" (Spanish Agency of Medicines and Medical Devices), guidelines issued by the European Medicines Agency (EMA) are to be applied, which states that a number of stages or steps must be overcome in order to obtain approval for a biosimilar agent.However, despite the presence of these recommendations by EMA, which must be met by a biosimilar in order to be licensed in our marketplace, relevant uncertainties persist that only future decisions by EMA and AEMPS may clarify. The present stance by our task force is that biosimilar development should be undertaken according to established regulations, thus certifying their efficacy and safety. Similarly, this task force considers that results obtained from studies in rheumatoid arthritis (RA) should not be extrapolated to IBD since the biological variability of these complex structures will not ensure a lack of noticeable changes in efficacy and safety.