Chronic inflammation in patients with Inflammatory Bowel Disease (IBD) leads to an increased risk of colorectal cancer, small bowel cancer, intestinal lymphoma and cholangiocarcinoma. However, treatments for IBD have also been associated with an increased risk of neoplasms. Patients receiving Thiopurines (TPs) have an increased risk of hematologic malignancies, non-melanoma skin cancer, urinary tract neoplasms and cervical cancer. Anti-TNFs have been associated with a higher risk of neoplasms, mainly lymphomas and melanomas; however, the data are controversial, and some recent studies do not confirm the association. Nevertheless, other biologic agents, such as ustekinumab and vedolizumab, have not shown an increased risk of any neoplasm to date. The risk of malignancies with tofacitinib exists, but its magnitude and relationship with previous treatment with TPs is not defined, so more studies from daily clinical practice are needed. Although biologic therapy seems to be safe for patients with current cancer or a prior history of cancer, as has been demonstrated in other chronic inflammatory conditions, prospective studies in this specific population are needed. Until that time, it is crucial to manage such conditions via the combined clinical expertise of the gastroenterologist and oncologist.

First-degree relatives (FDR) of patients with colorectal cancer have a higher risk of developing colorectal cancer than the general population. For this reason, screening guidelines recommend colonoscopy every 5 or 10 y, starting at the age of 40, depending on whether colorectal cancer in the index-case is diagnosed at <60 or ≥60 y, respectively. However, studies on the risk of neoplastic lesions are inconclusive. The aim of this study was to determine the risk of advanced neoplasia (three or more non-advanced adenomas, advanced adenoma, or invasive cancer) in FDR of patients with colorectal cancer compared to average-risk individuals (i.e., asymptomatic adults 50 to 69 y of age with no family history of colorectal cancer). This cross-sectional analysis includes data from 8,498 individuals undergoing their first lifetime screening colonoscopy between 2006 and 2012 at six Spanish tertiary hospitals. Of these individuals, 3,015 were defined as asymptomatic FDR of patients with colorectal cancer (“familial-risk group”) and 3,038 as asymptomatic with average-risk for colorectal cancer (“average-risk group”). The familial-risk group was stratified as one FDR, with one family member diagnosed with colorectal cancer at ≥60 y (n = 1,884) or at <60 y (n = 831), and as two FDR, with two family members diagnosed with colorectal cancer at any age (n = 300). Multiple logistic regression analysis was used for between-group comparisons after adjusting for potential confounders (age, gender, and center). Compared with the average-risk group, advanced neoplasia was significantly more prevalent in individuals having two FDR with colorectal cancer (odds ratio [OR] 1.90; 95% confidence interval [CI] 1.36–2.66, p < 0.001), but not in those having one FDR with colorectal cancer diagnosed at ≥60 y (OR 1.03; 95% CI 0.83–1.27, p = 0.77) and <60 y (OR 1.19; 95% CI 0.90–1.58, p = 0.20). After the age of 50 y, men developed advanced neoplasia over two times more frequently than women and advanced neoplasia appeared at least ten y earlier. Fewer colonoscopies by 2-fold were required to detect one advanced neoplasia in men than in women. Major limitations of this study were first that although average-risk individuals were consecutively included in a randomized control trial, this was not the case for all individuals in the familial-risk cohort; and second, the difference in age between the average-risk and familial-risk cohorts. Individuals having two FDR with colorectal cancer showed an increased risk of advanced neoplasia compared to those with average-risk for colorectal cancer. Men had over 2-fold higher risk of advanced neoplasia than women, independent of family history. These data suggest that screening colonoscopy guidelines should be revised in the familial-risk population. Colorectal cancer kills about 700,000 people worldwide every year. This common cancer develops when one of the epithelial cells that lines the colon (the final part of the digestive system; also known as the large intestine or large bowel) or the rectum (the lower end of the colon) acquires genetic changes that allow it to divide uncontrollably to form a tumor (lump), to invade surrounding tissues, and to move around the body (metastasize). Symptoms of colorectal cancer include weight loss, blood in the stool, and changed bowel habits. Treatments for the condition include surgery, chemotherapy, and radiation. As with all types of cancer, these treatments are more likely to be successful if started when the tumor is small and before it has invaded surrounding tissues. Consequently, many countries run screening programs to detect the earliest signs of colorectal cancer in apparently healthy people. One of the methods used to screen for colorectal cancer is colonoscopy—visual examination of the colonic lining using a tube-like instrument that is inserted through the rectum into the colon. Colonoscopy also detects adenomas (polyps), benign tumors that lack the ability to invade or metastasize. It is important to find and remove adenomas because these growths can develop into colorectal cancers. In the United States, colonoscopy is recommended every 10 y for everyone in the general population over 50 y old. However, the first-degree relatives (parents, siblings, or child) of patients with colorectal cancer have a higher risk of developing colorectal cancer than people in the general population. So, current screening guidelines in the US and elsewhere recommend colonoscopy every 5 or 10 y from age 40 for people who have a first-degree relative diagnosed with colorectal cancer, depending on whether the relative’s colorectal cancer was diagnosed before or after the age of 60, respectively. Notably, no large-scale studies have compared the risk of adenomas in symptom-free people with first-degree relatives with colorectal cancer with the risk in symptom-free average-risk people. This large multicenter cross-sectional study (a study that looks at a single time point) aims to remedy this deficit in the evidence base. The researchers enrolled 3,015 first-degree relatives of patients with colorectal cancer and 3,038 average-risk individuals, all of whom were undergoing their first screening colonoscopy in Spain. They divided the familial-risk cohort into two groups. The 1-FDR group comprised people with one first-degree relative diagnosed with colorectal cancer at ≥60 y or at <60 y. The 2-FDR group comprised individuals with two first-degree relatives diagnosed with colorectal cancer at any age. They then compared the risk of advanced neoplasia (three or more non-advanced adenomas, advanced adenoma, or invasive cancer) in the different groups after adjusting for age and sex (confounding factors that affect an individual’s risk of colorectal cancer). Advanced neoplasia was more prevalent (present in a higher proportion of the population) in the 2-FDR group than in average-risk individuals; individuals in the 2-FDR group were nearly twice as likely to have advanced neoplasia as average-risk individuals. Compared to average-risk individuals, individuals with 1-FDR diagnosed at ≥60 y and at <60 y had no increased risk of advanced neoplasias. Notably, after age 50, men developed advanced neoplasias over 2-fold more frequently than women, and advanced neoplasias appeared at least 10 y earlier in men than in women. These findings suggest that the risk of advanced neoplasia is markedly increased in individuals having two first-degree relatives with colorectal cancer compared to average-risk individuals but not in individuals having only one affected first-degree relative. They also suggest that men have a 2-fold higher risk of advanced neoplasia than women, independent of family history. Several aspects of the study design may affect the accuracy of these findings. For example, the average-risk study participants were older than the participants with first-degree relatives with colorectal cancer, and different approaches were used to enroll the two sets of participants, which may have introduced some bias. Nevertheless, these findings suggest that the guidelines for screening for colorectal cancer should be revised. Specifically, they suggest that men with two first-degree relatives with colorectal cancer may benefit from early screening colonoscopy but that the screening strategy recommended for the average-risk population may be appropriate for individuals with only one first-degree relative with colorectal cancer. This list of resources contains links that can be accessed when viewing the PDF on a device or via the online version of the article at http://dx.doi.org/10.1371/journal.pmed.1002008.

The small intestine is key in the digestion and absorption of macro and micronutrients. The large intestine is essential for the absorption of water, to allow adequate defecation, and to harbor intestinal microbiota, for which their nutritional role is as important as it is unknown. This article will describe the causes and consequences of malnutrition in patients with inflammatory bowel diseases, the importance of screening and replacement of micronutrient deficits, and the main indications for enteral and parenteral nutrition in these patients. We will also discuss the causes of short bowel syndrome, a complex entity due to anatomical or functional loss of part of the small bowel, which can cause insufficient absorption of liquid, electrolytes, and nutrients and lead to complex management. Finally, we will review the causes, consequences, and management of malnutrition in patients with malignant and benign digestive tumors, including neuroendocrine tumors (present not only in the intestine but also in the pancreas).

Thiopurines have been a cornerstone in the treatment of inflammatory bowel disease (IBD). Although they have been used for more than 50 years, there are still some unsolved issues about their efficacy and, also, some safety concerns, mainly the risk of myelosuppression and life-threatening lymphoproliferative disorders. Furthermore, the development of biological therapy raises the question whether there is still a role for thiopurines in the IBD treatment algorithm. On the other hand, limited cost and wide availability make thiopurines a reasonable option in settings of limited resources and increasing prevalence of IBD. In fact, there is a growing interest in optimizing thiopurine therapy, since pharmacogenomic findings suggest that a personalized approach based on the genotyping of some molecules involved in its metabolism could be useful to prevent side effects. Polymorphisms of thiopurine methyltransferase enzyme (TPMT) that result in low enzymatic activity have been associated with an increased risk of myelotoxicity, especially in Caucasians; however, in Asians it is assumed that the variants of nudix hydrolase 15 (NUDT15) are more relevant in the development of toxicity. Age is also important, since in elderly patients the risk of complications seems to be increased. Moreover, the primo-infection of Epstein Barr virus and cytomegalovirus under thiopurine treatment has been associated with severe lymphoproliferative disorders. In addition to assessing individual characteristics that may influence thiopurines treatment outcomes, this review also discusses other strategies to optimize the therapy. Low-dose thiopurines combined with allopurinol can be used in hypermethylators and in thiopurine-related hepatotoxicity. The measurement of metabolites could be useful to assess compliance, identify patients at risk of adverse events and also facilitating the management of refractory patients. Thioguanine is also a rescue therapy in patients with toxicity related to conventional thiopurine therapy. Finally, the current indications for thiopurines in monotherapy or in combination with biologics, as well as the optimal duration of treatment, are also reviewed.

Iron plays a key role in many physiological processes; cells need a very exact quantity of iron. In patients with inflammatory bowel disease, anaemia is a unique example of multifactorial origins, frequently being the result of a combination of iron deficiency and anaemia of chronic disease. The main cause of iron deficiency is the activity of the disease. Therefore, the first aim should be to reach complete clinical remission. The iron supplementation route should be determined according to symptoms, severity of anaemia and taking into account comorbidities and individual risks. Oral iron can only be used in patients with mild anaemia, whose disease is inactive and who have not been previously intolerant to oral iron. Intravenous iron should be the first line treatment in patients with moderate-severe anaemia, in patients with active disease, in patients with poor tolerance to oral iron and when erythropoietin agents or a fast response is needed. Erythropoietin is used in a few patients with anaemia to overcome functional iron deficiency, and blood transfusion is being restricted to refractory cases or acute life-threatening situations.

The availability of biologic therapies in inflammatory bowel disease (IBD) is increasing significantly. This represents more options to treat patients, but also more difficulties in choosing the therapies, especially in the context of bio-naïve patients. Most evidence of safety and efficacy came from clinical trials comparing biologics with placebo, with a lack of head-to-head studies. Network meta-analysis of biologics and real-world studies have been developed to solve this problem. Despite the results of these studies, there are also other important factors to consider before choosing the biologic, such as patient preferences, comorbidities, genetics, and inflammatory markers. Given that resources are limited, another important aspect is the cost of biologic therapy, since biosimilars are widely available and have been demonstrated to be effective with a significant decrease in costs. In this review, we summarize the evidence comparing biologic therapy in both Crohn´s disease (CD) and ulcerative colitis (UC) in different clinical situations. We also briefly synthesize the evidence related to predictors of biologic response, as well as the biologic use in extraintestinal manifestations and the importance of the drug-related costs.