Reviews
Critical signaling pathways governing colitis-associated colorectal cancer: Signaling, therapeutic implications, and challenges
Long-term colitis in people with inflammatory bowel disease (IBD) may lead to colon cancer called colitis-associated colorectal cancer (CAC). Since the advent of preclinical prototypes of CAC, various immunological messaging cascades have been identified as implicated in developing this disease. The toll-like receptor (TLR)s, Janus kinase (JAK)-signal transducer and activator of transcription (STAT), Nuclear factor-kappa B (NF-κB), mammalian target of rapamycin complex (mTOR), autophagy, and oxidative stress are only a few of the molecular mechanisms that have been recognized as major components to CAC progression.Impact of colorectal cancer screening on incidence, mortality and surgery rates: Evidences from programs based on the fecal immunochemical test in Italy
Fecal immunochemical tests (FIT) are among the most commonly used tests for colorectal cancer (CRC) screening programs worldwide. However, no randomised controlled trials have been carried out evaluating the impact of FIT-based screening programs (FIT-progr) on CRC incidence and mortality rates. Italian FIT-progr represent one of the most widespread and established experience worldwide. This paper reviews the evidence on the impact of FIT-progr on CRC incidence, tumor stage at diagnosis, mortality and surgery rates, deriving from Italian routine programs, i.e., outside the research setting.Application of histology-agnostic treatments in metastatic colorectal cancer
Cancer treatment is increasingly focused on targeting molecular alterations identified across different tumor histologies. While some oncogenic drivers such as microsatellite instability (MSI) and NTRK fusions are actionable with the very same approach regardless of tumor type (“histology-agnostic”), others require histology-specific therapeutic adjustment (“histology-tuned”) by means of adopting specific inhibitors and ad hoc combinations. Among histology-agnostic therapies, pembrolizumab or dostarlimab demonstrated comparable activity in MSI metastatic colorectal cancer (mCRC) as in other tumors with MSI status (ORR 38% vs 40% and 36% vs 39%, respectively), while entrectinib or larotrectinib proved effective in NTRK rearranged mCRC even though less dramatically than in the overall population (ORR 20% vs 57%, and 50% vs 78%, respectively).Metastatic colorectal cancer (mCRC): French intergroup clinical practice guidelines for diagnosis, treatments and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, SFR)
This document is a summary of the French intergroup guidelines regarding the management of metastatic colorectal cancer (mCRC) published in January 2019, and available on the French Society of Gastroenterology website (SNFGE) ( www.tncd.org ).Molecular imaging in gastroenterology: A route for personalized endoscopy
With the rapid expansion and diversification of the repertoire of biological agents utilized in inflammatory bowel diseases and cancer and the increase in oncological patients in gastroenterology, visualization of single receptor or molecular target expression and the subsequent initiation of expression tailored therapy are gaining increasing attention. Through the combination of utilizing fluorescently labeled probes with high specificity towards defined molecular targets and their subsequent detection and visualization with endoscopic devices, molecular imaging is a new emerging field focusing on the receptor expression within the mucosa on a cellular level rather than on macroscopic changes.Treatment sequence of synchronously (liver) metastasized colon cancer
No standards for staging, systemic therapy or the timing of an operation are defined for patients newly diagnosed with synchronous metastases and a primary in the colon. An expert group of radiologists, medical, radiation and surgical oncologists therefore came together to discuss staging and treatment sequence for these patients and came up with a recommendation based on current evidence of potential therapeutic options. The discussion was organized to debate recommendations centred on 5 topics and therefore the position paper is built upon these titles and their subtitles.Role of fluorine 18 fluorodeoxyglucose positron emission tomography/computed tomography in gastrointestinal cancers
Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) has become a routine imaging modality for many malignancies and its use is currently increasing. In the present review article, we will summarize the evidence for FDG-PET/CT use in digestive cancers (excluding neuroendocrine tumours), and review the existing recommendations. While PET/CT is nowadays considered to be an important tool in the initial workup of oesophageal and anal cancers, new data are emerging regarding its use in assessing therapeutic efficacy, radiotherapy treatment planning, and detection of recurrence in case of isolated tumour marker elevation.Sessile serrated adenoma: From identification to resection
Until the past two decades, almost all colorectal polyps were divided into two main groups: hyperplastic polyps and adenomas. Sessile serrated adenomas presented endoscopic, pathological and molecular profiles distinct from others polyps. Previously under-diagnosed, physicians now identified sessile serrated adenomas. The serrated neoplastic pathway is accounting for up to one-third of all sporadic colorectal cancers and sessile serrated adenomas have been identified as the main precursor lesions in serrated carcinogenesis.Role of microsatellite instability in the management of colorectal cancers
Microsatellite instability is the consequence of a deficient mismatch repair system. It has a key role in the diagnostic strategy of Lynch syndrome, where tumours are all characterized by the presence of this phenotype. Microsatellite instability is therefore essential in the selection of colorectal cancer patients in whom a germline analysis of Mismatch Repair genes is possibly indicated. Moreover, microsatellite instability tumours are associated with a good prognosis and a resistance to fluorouracil-based adjuvant chemotherapy, which has a clinical application mainly in stage II colon cancer patients in whom adjuvant chemotherapy has a less beneficial effect than in stage III and outcome in presence of microsatellite instability is excellent.Dysplasia in inflammatory bowel diseases
In both Crohn's disease and ulcerative colitis, the secondary prevention of colorectal cancer basically relies on the histological detection of dysplasia. In inflammatory bowel diseases, dysplasia identifies the subgroup of patients eligible for stricter surveillance (or prophylactic colectomy). In clinical practice, a number of issues may influence the benefits of clinico-pathological surveillance for inflammatory bowel disease patients with dysplasia, including: sampling errors, inconsistent biopsy assessments, patients’ compliance with follow-up requirements, and how heath care is organized.Screening for colorectal cancer with immunochemical faecal occult blood tests
Population-based studies have shown that guaiac faecal occult blood testing followed by colonoscopy in case of positivity can reduce colorectal cancer mortality. However these tests have been criticised for their fairly low sensitivity. For this reason attention has been given to alternative tests. The aim of this paper is to review the evidence for screening for colorectal cancer using qualitative immunochemical faecal occult blood tests. For the complete range of tested cut-off values, immunochemical faecal occult blood tests lead to higher diagnostic yield, improved sensitivity and greater participation.The intelligent, painless, “germ-free” colonoscopy: A Columbus’ egg for increasing population adherence to colorectal cancer screening?
Colorectal cancer (CRC) represents a major cause of morbidity and mortality. Although it is widely accepted that CRC screening in average risk populations lowers CRC incidence and mortality, a disappointedly low adherence rate to both faecal occult blood testing and colonoscopy-based screening programs has been observed in Italy and in other European countries. Main reasons for the low acceptance of colonoscopy-based CRC screening has been ascribed to lack of recommendations given by general practitioners, fear of discomfort or complications, embarrassment, and avoidance of unpleasant preparation.Targeted therapy in colorectal cancer: do we know enough?
The present paper is a critical review about the recent development of new agents that have revolutioned the therapeutical approach of solid tumours with a particular focus on colorectal cancer. Until a few years ago, chemotherapy has been considered the only medical treatment for advanced disease. At the moment, new drugs blocking some cell functions, such as monoclonal antibodies or tyrosin kinase inhibitors are available for many oncologists, but their efficacy should be debated for several reasons.
