Subcutaneous Infliximab in Refractory Crohn's Disease Patients: A Possible Biobetter?

Background: A subcutaneous formulation of infliximab (IFX-SC) approved to treat patients with inflammatory bowel disease may offer improved efficacy versus intravenous infliximab. Methods: Patients with refractory Crohn's disease (CD, n = 32) previously treated unsuccessfully with at least 2 biologics were treated with IFX-SC and followed from baseline at Week 0 (W0) to Week 30 (W30). The study's primary endpoint was the treatment's persistence at W30, while secondary goals included the analysis of serum infliximab trough levels (TL IFX), dynamics of anti-IFX antibodies (ATIs), and clinical, serum and fecal markers of CD activity during IFX-SC treatment. Results: Midterm treatment persistence with the continuation of treatment after W30 was 53%. TL IFX median values showed rapid, significant upward dynamics and exceeded 15.5 µg/mL at W30, whereas median ATI levels significantly declined. Among ATI-negative patients at W0 (n = 15), only one showed IFX immunogenicity with newly developed ATIs at W30. Among ATI-positive patients at W0, ATI seroconversion from ATI-positive to ATI-negative status was observed in 10 of 17 patients (58.8%). Patients who had continued IFX-SC treatment at W30 showed significant decreases in C-reactive protein (P = .0341), fecal calprotectin (P = .0002), and Harvey-Bradshaw index (P = .0029) since W0. Conclusions: Patients with refractory CD previously treated with at least 2 biologics exhibited clinically relevant improvement with IFX-SC, which showed less immunogenic potential than IFX-IV and highly stable TL IFX.

Comparison of Four Bowel Cleansing Agents for Colonoscopy and the Factors Affecting their Efficacy. A Prospective, Randomized Study.

BACKGROUND AND AIMS: Adequate bowel preparation is essential for successful and effective colonoscopy. Several types of cleansing agents are currently available including low-volume solutions. The aim of this study was to compare the efficacy of four different bowel cleansing agents. METHODS: A single-center, prospective, randomized, and single-blind study was performed. Consecutive patients referred for colonoscopy were enrolled and randomized into one of the following types of laxatives: polyethylenglycol 4L (PEG), oral sulfate solution (OSS), 2L polyethylenglycol + ascorbate (2L-PEG/Asc), or magnesium citrate + sodium picosulfate (MCSP). The primary outcome was quality of bowel cleansing evaluated according to the Boston Bowel Preparation Scale (BBPS). Secondary outcomes were polyp detection rate (PDR) and tolerability. RESULTS: Final analysis was performed on 431 patients. The number of patients with adequate bowel preparation (BBPS total scores ≥6 and sub scores ≥2 in each segment) was not significantly different throughout all groups (95.4% PEG; 94.6% OSS; 96.3% 2L-PEG/Asc; 96.2% MCSP; p=0.955). Excellent bowel preparation (BBPS total scores ≥ 8) was associated with younger age (p=0.007). The groups did not have significantly different PDRs (49.5% PEG; 49.1% OSS; 38% 2L-PEG/Asc; 40.4% MCSP; p=0.201). The strongest predictors of pathology identification were age and male gender. The best-tolerated solution was MCSP (palatability: p<0.001; nausea: p=0.024).

The conversion factor for predicting adenoma detection rate from polyp detection rate varies according to colonoscopy indication and patient sex.

The adenoma detection rate (ADR) is the primary quality indicator for colonoscopies. The polyp detection rate (PDR) is available from administrative data and does not depend on histology verification. The correlation between PDR and ADR and the ADR/PDR conversion factor in preventive colonoscopies were evaluated. In the prospective study, asymptomatic individuals aged 45-75 years with preventive colonoscopy in 2012-2016 were included. Spearman's correlation coefficient was used to assess PDR/ADR for each endoscopist. Conversion factor predicting ADR from PDR was obtained by linear regression and subsequently compared with adenoma to polyp detection rate quotient. One thousand six hundred fourteen preventive colonoscopies performed by 16 endoscopists in 8 screening colonoscopy centres in the Czech Republic were analysed. Correlation between PDR and ADR in all preventive colonoscopies was high and statistically significant (Rs 0.82; P < 0.001). There was a strong correlation between PDR and ADR in men (Rs 0.74; P = 0.002) and in screening colonoscopies (Rs 0.85; P < 0.001). The conversion factor to convert ADR from PDR was 0.72 in all preventive colonoscopies, 0.76 in FOBT+ colonoscopies and 0.67 in screening colonoscopies. ADR may be replaced by PDR in the assessment of colonoscopy quality. The value of the conversion factor varies according to colonoscopy indication and gender of examined individuals; in this Czech study, it was 0.72 in all preventive colonoscopies. The minimum requested ADR of 25 % corresponds to a PDR of 35 %, when converted with the appropriate conversion factor.

Accuracy of Colon Capsule Endoscopy for Colorectal Neoplasia Detection in Individuals Referred for a Screening Colonoscopy.

BACKROUND: Capsule colonoscopy might present an alternative to colonoscopy for colorectal neoplasia screening. AIM: To assess the accuracy of second-generation capsule colonoscopy (CCE2) for colorectal neoplasia detection compared with conventional colonoscopy (CC). METHODS: From 2011-2015, we performed a multicenter, prospective, cross-over study evaluating the use of CCE2 as a possible colorectal cancer (CRC) screening test based on the assessment of the method's characteristics (accuracy) and safety and patient acceptance of the routine. Enrolled participants fulfilled the CRC screening population criteria if they were asymptomatic, were older than 50, and had no personal or familial history of colorectal neoplasia. The primary outcome was accuracy for the detection of polyps ≥ 6 mm. Secondary outcomes were accuracy for all polyps, polyps ≥ 10 mm, adenomas ≥ 10 mm, and cancers, the quality of bowel cleansing, safety, and CCE2 acceptability by the screening population. RESULTS: A total of 236 individuals were examined; 11 patients (5%) were excluded. Therefore, 225 subjects (95%) were considered in the intention-to-screen (ITS) group. A total of 201 patients (89%) completed both examinations successfully (per protocol group). In the ITS group, polyps were diagnosed during CC in 114 subjects (51%); polyps ≥ 6 mm, polyps ≥ 10 mm, and adenomas ≥ 10 mm were diagnosed in 34 (15%), 16 (7%), and 11 (5%) patients, respectively. The sensitivity of CCE2 for polyps ≥ 6 mm, polyps ≥ 10 mm, and adenomas ≥ 10 mm was 79% (95% confidence interval (CI): 62-91%), 88% (95% CI: 62-98%), and 100% (95% CI: 72-100%), respectively. CONCLUSION: Second-generation capsule colonoscopy is a safe, noninvasive, and sensitive method for colorectal neoplasia detection although CC remains the preferred method for considerable proportion of subjects. CCE2 may therefore be accepted as the primary screening test for colorectal cancer screening.

Monitoring of Circulating Tumor Cells by a Combination of Immunomagnetic Enrichment and RT-PCR in Colorectal Cancer Patients Undergoing Surgery.

BACKGROUND: The presence of circulating tumor cells (CTC) has been reported in patients with advanced colorectal cancer. Monitoring CTC (also known as a liquid-biopsy) has recently become the center of interest for low-invasive monitoring of cancer progression and predictive biomarkers testing. Along with high-cost technology and a complex methodology, a straightforward method based on magnetic beads enrichment followed by RT-PCR is set to allow for routine CTC analysis in colorectal cancer patients. OBJECTIVES: The main purpose of this study was to evaluate the possibility of CTC detection in routine monitoring of patients starting before and continuing after surgery. MATERIAL AND METHODS: The investigated group consisted of 30 patients mainly in advanced stages of colorectal cancer. In all patients, CTC detection was performed prior to surgery, in a subset of 14 patients additional sampling was done during and after surgery. In all cases, peripheral blood was processed using AdnaTest ColonCancer kit, which relies on enriching CTCs using EpCAM-functionalized magnetic beads and subsequently identifying tumorspecific CEA, EGFR and GA733-2 mRNA transcripts. RESULTS: Out of all the tested samples, CTC were found in one patient suffering from advanced disease with lung and liver metastases. There, however, the positive finding was confirmed in 3 consecutive samples acquired before, during and shortly after palliative R2 resection. CONCLUSIONS: The presence of CTC may be used to observe post-operative disease development. Due to the overall low CTC detection, further technology development may be necessary before its universal applicability to manage colorectal cancer patients.

How significant is the association between metabolic syndrome and prevalence of colorectal neoplasia?

The incidence and prevalence of metabolic syndrome (MS) and colorectal cancer (CRC) has been rising in developed countries. The association between these two diseases has been widely studied and reported. Less evidence is available about the relationship between MS and CRC precancerous lesions (adenomatous polyps, adenomas). The aim of this paper is to present an overview of our scientific understanding of that topic and its implication in clinical practice. One of the principal goals of current CRC secondary prevention efforts is to detect and remove the precancerous lesions in individuals with an average CRC risk to prevent the development of invasive cancer. MS is not currently considered a high-risk CRC factor and is therefore not included in the guidelines of organized screening programs. However, in light of growing scientific evidence, the approach to patients with MS should be changed. Metabolic risk factors for the development of adenomas and cancers are the same - obesity, impaired glucose tolerance, dyslipidemia, hypertension, cardiovascular diseases and diabetes mellitus type 2. Therefore, the key issue in the near future is the development of a simple scoring system, easy to use in clinical practice, which would identify individuals with high metabolic risk of colorectal neoplasia and would be used for individual CRC secondary prevention strategies. Currently, such scoring systems have been published based on Asian (Asia-Pacific Colorectal Screening Score; APCS) and Polish populations.

[Population colorectal cancer screening in the Czech Republic]. / Populacní screening kolorektálního karcinomu v Ceské republice.

UNLABELLED: Colorectal cancer (CRC) is the third most common malignant disease in developed countries and its incidence is steadily growing. This trend has a stable character despite the fact that CRC is among the best prevention influenced malignancies. National CRC screening program in the Czech Republic, which was established in year 2000, follows the world trends resulting from evidence based medicine. Currently, the basic tools of screening program are immunochemical fecal occult blood tests and colonoscopy in case of their positivity or screening colonoscopy. Stagnation of participating population resulted to initiation of address invitation of the target population in January 2014, in which citizens are regularly invited to attend the screening program and their response is subsequently evaluated. Screening that impacts whole target group is called population screening. KEY WORDS: colorectal cancer, population screening program, colonoscopy, fecal occult blood tests, address invitation.

[Endoscopic classification of colon and rectal neoplasias]. / Endoskopická klasifikace neoplazií tlustého streva a konecníku.

Along with the dynamic evolution of the new field of digestive endoscopy, the need of unified and unambiguous terms for endoscopic findings arose in the second half of the 20th century. In collaboration with the OMED members, professor Zdenek Maratka drew up the first internationally acknowledged terminology for digestive endoscopy which was used in the full range for a period of almost 20 years. The technical progress later brought with it endoscopes which made it possible to view flat lesions, frequently overlooked until then. The classification of the surface lesions was further specified by the Paris Classification which drew from the experience of Japanese endoscopists. Thanks to the new endoscopic methods of imaging mucosa in vivo and the pit-pattern and vascular-pattern classification, we can currently estimate the biological nature of lesion with great accuracy and therefore choose the best therapeutic procedure.

Colorectal cancer prevention in the Czech Republic: time trends in performance indicators and current situation after 10 years of screening.

The incidence and mortality of colorectal cancer (CRC) in the Czech Republic is significant. The National CRC Screening Program started in 2000 and was further enhanced in 2009. In 2010, the European Guidelines were introduced. The aim of the present trend study was to evaluate the quality of the Czech National Colorectal Cancer Screening Program using early performance and long-term impact indicators. The screening program has been assessed using data from three sources: the Czech National Cancer Registry, the Czech National Reference Centre, and the Czech CRC Screening Registry. The data were compared with a set of recommended quality control indicators. Between 2006 and 2010, a total of 1 881 299 fecal occult blood tests were performed, of which 87 397 were positive (4.6%). Until 2011, a total of 68 527 fecal occult blood test follow-up colonoscopies were performed. In addition, between 2009 and 2011, a total of 10 309 screening colonoscopies were performed. As a result, a total of 25 255 adenomas (32.0% rate) and 3379 CRCs (4.3% rate) were detected. A trend of cancer detection in earlier stages has been observed. The overall program coverage has increased to 22.7% of the target population in 2010. The majority of European guidelines' quality indicators for nonpopulation-based programs were implemented in the Czech National CRC Screening program. An improvement in program management was accompanied by an increase in coverage as well as other performance indicators.