Risk stratification of symptomatic patients suspected of colorectal cancer using faecal and urinary markers.

AIM: Faecal markers, such as the faecal immunochemical test for haemoglobin (FIT) and faecal calprotectin (FCP), have been increasingly used to exclude colorectal cancer (CRC) and colonic inflammation. However, in those with lower gastrointestinal symptoms there are considerable numbers who have cancer but have a negative FIT test (i.e. false negative), which has impeded its use in clinical practice. We undertook a study of diagnostic accuracy CRC using FIT, FCP and urinary volatile organic compounds (VOCs) in patients with lower gastrointestinal symptoms. METHOD: One thousand and sixteen symptomatic patients with suspected CRC referred by family physicians were recruited prospectively in accordance with national referring protocol. A total of 562 patients who completed colonic investigations, in addition to providing stool for FIT and FCP as well as urine samples for urinary VOC measurements, were included in the final outcome measures. RESULTS: The sensitivity and specificity for CRC using FIT was 0.80 [95% confidence interval (CI) 0.66-0.93] and 0.93 (CI 0.91-0.95), respectively. For urinary VOCs, the sensitivity and specificity for CRC was 0.63 (CI 0.46-0.79) and 0.63 (CI 0.59-0.67), respectively. However, for those who were FIT-negative CRC (i.e. false negatives), the addition of urinary VOCs resulted in a sensitivity of 0.97 (CI 0.90-1.0) and specificity of 0.72 (CI 0.68-0.76). CONCLUSIONS: When applied to the FIT-negative group, urinary VOCs improve CRC detection (sensitivity rises from 0.80 to 0.97), thus showing promise as a second-stage test to complement FIT in the detection of CRC.

Systematic review with meta-analysis: the efficacy of faecal microbiota transplantation for the treatment of recurrent and refractory Clostridium difficile infection.

BACKGROUND: Clostridium difficile infection (CDI) is the commonest nosocomial cause of diarrhoea. Faecal microbiota transplantation (FMT) is an approved treatment for recurrent or refractory CDI but there is uncertainty about its use. AIM: To evaluate the efficacy of FMT in treating recurrent and refractory CDI and investigate outcomes from modes of delivery and preparation. METHODS: A systematic review and meta-analysis was performed. MEDLINE, EMBASE, CINAHL, Cochrane Library, trial registers and conference proceedings were searched. Studies on FMT in recurrent and refractory CDI were included. The primary outcome was clinical resolution with subgroup analyses of modes of delivery and preparation. Random effects meta-analyses were used to combine data. RESULTS: Thirty seven studies were included; seven randomised controlled trials and 30 case series. FMT was more effective than vancomycin (RR: 0.23 95%CI 0.07-0.80) in resolving recurrent and refractory CDI. Clinical resolution across all studies was 92% (95%CI 89%-94%). A significant difference was observed between lower GI and upper GI delivery of FMT 95% (95%CI 92%-97%) vs 88% (95%CI 82%-94%) respectively (P=.02). There was no difference between fresh and frozen FMT 92% (95%CI 89%-95%) vs 93% (95%CI 87%-97%) respectively (P=.84). Administering consecutive courses of FMT following failure of first FMT resulted in an incremental effect. Donor screening was consistent but variability existed in recipient preparation and volume of FMT. Serious adverse events were uncommon. CONCLUSION: Faecal microbiota transplantation is an effective treatment for recurrent and refractory Clostridium difficile infection, independent of preparation and route of delivery.

Diagnostic accuracy of faecal biomarkers in detecting colorectal cancer and adenoma in symptomatic patients.

BACKGROUND: The diagnosis of colorectal cancer (CRC) can be difficult as symptoms are variable with poor specificity. Thus, there is a quest for simple, non-invasive testing that can help streamline those with significant colonic pathology. AIM: To assess using faecal immunochemical test for haemoglobin (FIT) or faecal calprotectin (FCP) to detect CRC and adenoma in symptomatic patients referred from primary care. METHODS: A total of 799 referred for urgent lower gastrointestinal investigations were prospectively recruited. Of these, 430 completed colonic investigations and returned stool samples, and were included in the final statistical analysis. Faecal immunochemical test for haemoglobin was performed on HM-JACKarc analyser (Kyowa Medex, Tokyo, Japan), and FCP by the EliA Calprotectin immunoassay (Thermo Fisher Scientific, Waltham, United States). RESULTS: The negative predictive value (NPV) using FIT alone or both markers (FIT and FCP) in combination was similar at 99% for CRC, with a sensitivity and specificity of 84% and 93%, respectively. FIT measurements were significantly higher in left-sided colonic lesions compared with the right side; 713 vs. 94; P = 0.0203). For adenoma, the NPV using FIT alone, or both markers (FIT and FCP) in combination, was similar at 94% with a sensitivity and specificity of 69% and 56%, respectively. CONCLUSIONS: Undetectable faecal immunochemical test for haemoglobin is sufficiently sensitive to exclude colorectal cancer, with higher values in left-sided lesions. FCP in combination does not appear to provide additional diagnostic information. Further studies to determine the health economic benefits of implementing faecal immunochemical test for haemoglobin in primary care are required.