Background: Janus kinase-inhibitors (JAK-i) have recently been approved for treating patients with Ulcerative Colitis (UC); therefore, further information is needed, particularly regarding efficacy and safety. Objectives: To provide a comprehensive review regarding the efficacy and safety of currently available JAK-i in UC. Methods: The PubMed and Scopus databases were considered, searching for ‘JAK’, ‘JAK-inhibitor’, ‘Janus Kinases’, ‘Tofacitinib’, ‘Filgotinib’, ‘Upadacitinib’, individually or in combination with ‘IBD’, ‘Ulcerative Colitis’, ‘safety’, ‘efficacy’, ‘study’ and ‘trial’. The search was focused on full-text papers published in English, with no publication date restrictions. Results: The efficacy and safety of JAK-i approved for treating patients with UC have been summarized. These included Tofacitinib, Filgotinib and Upadacitinib. Findings from both clinical trials and real-life studies in UC were reported, with particular regard to their efficacy in inducing clinical response and remission, steroid-free remission and endoscopic and histological healing. Overall, JAK-i proved to be effective and safe in selected subgroups of patients with UC. The rapid onset of action and the oral route of administration represent the most relevant characteristics of these drugs. Safety concerns using Tofacitinib in subgroups of patients (infections, hypercholesterolemia, venous thromboembolism and cardiovascular events) were initially raised. More recently, all JAK-i for UC showed an overall satisfactory safety profile. However, indication should be carefully given. Conclusions: The use of JAK-i UC is promising, although no predictive markers of response are currently available. Optimizing their use, as monotherapy or combined with other immunomodulators, may increase their efficacy in appropriately selected subgroups of patients with UC.

Malignant bowel obstruction (MBO) is a critical complication occurring in patients with advanced malignancy. Current treatments are both surgical and non-surgical, the latter including medical, endoscopic, and percutaneous approaches. Surgery is still the treatment of choice for MBO. However, almost 50% of patients are unfit for surgery because of poor performance status. Given the high post-operative mortality rate and the frailty of MBO patients, the least invasive surgical intervention is recommended. Therefore, recent multidisciplinary recommendations have suggested considering less invasive interventions instead of palliative surgery. Medical therapy, aiming to alleviate symptoms, is usually only a part of the therapeutic strategy when managing patients with MBO. Percutaneous techniques, including both interventional radiology and endoscopic procedures, are safe and effective for symptom relief, but often do not allow oral diet resumption. Endoscopic techniques are achieving a more relevant role for MBO treatment, as supported by the widening of the indication to colonic intraluminal stenting in the latest update of the European guidelines. Current data support the use of colonic stenting as both a bridge to surgery and the definitive treatment of malignant colonic obstruction. The development of endoscopic ultrasound-guided anastomotic techniques may offer the possibility of widening its applications to endoscopic treatment of MBO, allowing stenosis to be overcome, and reestablishing the continuity of the gastrointestinal tract in small bowel obstructions as well. The introduction of new interventional endoscopic techniques and their progressive diffusion will add the possibility to adopt minimally invasive solutions to treat a critical condition such as MBO.

Background/Objectives: Endometriosis and inflammatory bowel disease (IBD) share some epidemiological, clinical and pathogenetic features. A differential diagnosis between pelvic endometriosis and IBD may be challenging, even for expert clinicians. In the present review, we aimed to summarize the currently available data regarding the relationship between endometriosis and IBD and their possible association. Methods: The PubMed and Scopus database were considered, by searching the following terms: “Crohn’s Disease”, “Ulcerative Colitis”, “Endometriosis”, “Adenomyosis”, and “Inflammatory Bowel Disease”, individually or combined. Full-text papers published in English with no date restriction were considered. Results: Few studies have researched the possible association between endometriosis and IBD. Both conditions are characterized by chronic recurrent symptoms, which may be shared (abdominal pain, fatigue, infertility, menstrual irregularities, diarrhea, constipation). Deep infiltrating endometriosis (DIE) can cause bowel symptoms. In a large Danish study, a 50% increased risk of IBD was observed in women with endometriosis. A missed diagnosis of endometriosis and an increased risk of endometriosis has been reported in IBD. Current evidence does not support an association between endometriosis and IBD characteristics. However, IBD may be associated with DIE, characterized by pelvic symptoms (dyschezia, dyspareunia). Preliminary observations suggest an increased IBD risk in patients with endometriosis treated with hormonal therapy. Conclusions: Current findings suggest that a careful search is needed for concomitant endometriosis in subgroups of patients with IBD showing compatible symptoms and vice versa. A multidisciplinary approach including dedicated gastroenterologists and gynecologists is required for a proper search for IBD and endometriosis in subgroups of patients. This approach may avoid diagnostic delays or overtreatments for these conditions.

A higher frequency of mucinous and signet-ring cell colonic adenocarcinoma has been reported in inflammatory bowel disease (IBD). The primary aim was to investigate the frequency of mucinous and signet-ring cell colorectal adenocarcinoma in patients with IBD (Cases) versus age-matched non-IBD Controls. The secondary aims were to compare the characteristics of these two histotypes of colorectal cancer (CRC) in IBD patients vs. Controls and to search for specific risk factors in IBD. In a case–control study, all IBD patients with CRC diagnosed from 2000 to 2022 were enrolled and matched for age (1:2) with non-IBD Controls with CRC. The study population included 120 CRC patients (40 IBD, 80 Controls). In IBD, CRC included standard adenocarcinoma in 23 (57.5%) patients mucinous/signet-ring cell adenocarcinoma in 17 (42.5%) patients. The proportion of mucinous/signet-ring cell adenocarcinoma was higher in IBD than in Controls (17 [42.5%] vs. 18 [22.5%]; p = 0.03). In rectal CRC, the proportion of mucinous/signet-ring cell adenocarcinoma was higher than standard adenocarcinoma in IBD (8 [47.1%] vs. 4 [17.4%]; p = 0.04) but not in Controls (4 [22.2%] vs. 20 [32.2%]; p = 0.59). In rectal CRC, the proportion of these two histotypes was higher in Cases than in Controls (8/12 [66.6%] vs. 4/24 [16.6%]; p = 0.008), with no risk factors identified in IBD. CRC was more frequently represented by mucinous/signet-ring cell adenocarcinoma in IBD than in age-matched non-IBD Controls. In IBD, these two CRC histotypes were more frequent in the rectum.

Patients with long-standing inflammatory bowel disease (IBD) involving the colon are at higher risk of developing colorectal dysplastic or neoplastic lesions. While from sporadic colorectal cancer follows an “adenoma-carcinoma” sequence, IBD colitis-associated carcinogenesis is mainly related to an “inflammation-dysplasia-carcinoma” sequence. Currently, specific endoscopic surveillance strategies involving dye spray and virtual chromoendoscopy have been standardized, aiming for early CRC diagnosis. When detected, colitis-associated dysplasia should be classified according to standard classification, thus allowing for better treatment. Indeed, most IBD-associated dysplastic lesions can be treated with endoscopic resection, even though available procedures are usually more challenging than those in the general population. The higher frequency of severe submucosal fibrosis and the difficulty in the definition of lesions’ margins account for this issue. Current endoscopic resection techniques include polypectomy, endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). Recent evidence suggests the relevance of en bloc resection, as this may be associated with lower rates of recurrence. Therefore, particularly for larger (>20 mm) lesions, ESD should be preferred, even though it is considered the most difficult technique due to frequent severe submucosal fibrosis. Considering the growing number of new endoscopic resective techniques, including underwater EMR or ESD, which in the general population have been suggested to lower procedure-related risks and may also allow a larger spread of advanced endoscopic resection in IBD. However, additional data are needed to assess the medium- and long-term efficacy of endoscopic resection of visible dysplasia in IBD patients, which are burdened by a high risk of local and, more importantly, metachronous recurrence.

Introduction: The risk of new or recurrent cancer in inflammatory bowel disease (IBD) patients with a history of cancer treated with immunomodulators (IMMs), including conventional immunosuppressors (ISSs), biologics or small molecules is undefined. The primary aim was to assess the frequency of new or recurrent cancer in IBD patients treated with IMMs after first cancer. The secondary aim was to evaluate risk factors for new/recurrent cancer in the same IBD population. Methods: In a retrospective multicenter study, all IBD patients using any IMM after first (index) cancer were enrolled. Inclusion criteria: Crohn’s disease (CD) or ulcerative colitis (UC), history of any cancer, detailed clinical history, and follow-up after cancer of ≥6 months. Exclusion criteria: IMM use for ≤3 months. Results: In total, 122 IBD patients (84 CD, 38 UC) treated with IMMs after first cancer were enrolled (age 59.5 [26–89] years). Index cancer included (n = [%]) genitourinary tract cancer (18 [14.8]), non-melanotic skin cancer (NMSC) (17 [13.9]), breast cancer (15 [12.3]), thyroid cancer (13 [10.7]), melanoma (14 [11.4]), colorectal cancer (CRC) (11 [9.0]), hematopoietic cancer (9 [7.4]), prostatic cancer (8 [6.6]), neuroendocrine cancer (4 [3.3]), head and neck cancer (3 [2.5]), liver cancer (3 [2.5]), endometrium cancer (2 [1.6]), lung cancer (1 [0.8]) and others (3 [2.5]). ISSs after cancer included (n = [%]) thiopurines (10 [37]), methotrexate (MTX) (14 [51.9]) and others (3 [11.1]) Biologics included (n = [%]) TNF-inhibitors (36 [32.4]), vedolizumab (60 [53.6]), ustekinumab (45 [40.2]), small molecules (9 [7.3]) and others (6 [5.4]). In a median follow-up of 8 [1–45] years after index cancer, 12/122 (9.8%) patients using IMMs after cancer developed new or recurrent cancer. No risk factors for new/recurrent cancer (i.e., age at diagnosis of cancer, smoke, gender, IBD type, IMM use, duration before or after cancer) were identified. Conclusions: In a multicenter study, ISSs or biologics after cancer were not identified as risk factors for new or recurrent cancer in IBD. However, IMMs were used after a long-term interval from index cancer.