Butyrate is a short-chain fatty acid that plays a key role in maintaining gut homeostasis as well as the integrity of the intestinal barrier. In the present study, we investigated the effect of oral microencapsulated sodium butyrate (BLM) administration in maintaining remission and improving residual symptoms and inflammatory markers in a population of patients with ulcerative colitis (UC). Forty-two patients with UC in clinical remission were enrolled in the study. Three patients were lost to follow up; 39 patients (18 treated with BLM add-on therapy and 21 with standard mesalamine only) that reached 12 months of follow up were included in the final analysis. Therapeutic success (defined as Mayo partial score ≤ 2 and faecal calprotectin (FC) < 250 µg/g at 12 months of follow up) was achieved in 25 patients (64.1%); 15/18 (83.3%) in BLM group and 10/21 (47.6%) in control group (p = 0.022). Consistently, 13/18 patients (72.2%) receiving BLM improved residual symptoms compared to 5/21 patients (23.8%) in control group (p = 0.003). FC values significantly diminished from the baseline to the end of follow up in patients that received BLM, while FC values remained almost stable in the control group. In conclusion, oral BLM supplementation appears to be a valid add-on therapy in order to maintain remission in patients with UC. Further randomized, placebo-controlled, double-blind clinical trials are needed to validate our results on a larger population or cohort of patients.

Cholangiocarcinoma (CCA) is an aggressive neoplasia with an increasing incidence and mortality. It is characterized by a strong desmoplastic stroma surrounding cancer cells. Cancer-associated fibroblasts (CAFs) are the main cell type of CCA stroma and they have an important role in modulating cancer microenvironments. CAFs originate from multiple lines of cells and mainly consist of fibroblasts and alpha-smooth muscle actin (α-SMA) positive myofibroblast-like cells. The continuous cross-talking between CCA cells and desmoplastic stroma is permitted by CAF biochemical signals, which modulate a number of pathways. Stromal cell-derived factor-1 expression increases CAF recruitment to the tumor reactive stroma and influences apoptotic pathways. The Bcl-2 family protein enhances susceptibility to CAF apoptosis and PDGFRβ induces fibroblast migration and stimulates tumor lymphangiogenesis. Many factors related to CAFs may influence CCA prognosis. For instance, a better prognosis is associated with IL-33 expression and low stromal IL-6 (whose secretion is stimulated by microRNA). In contrast, a worst prognosis is given by the expression of PDGF-D, podoplanin, SDF-1, α-SMA high expression, and periostin. The maturity phenotype has a prognostic relevance too. New therapeutic strategies involving CAFs are currently under study. Promising results are obtained with anti-PlGF therapy, nintedanib (BIBF1120), navitoclax, IPI-926, resveratrol, and controlled hyperthermia.

One of the major procedural risks of third space endoscopy techniques is represented by intraprocedural bleeding.1 A clear strategy to reduce the risk of intraprocedural bleeding remains elusive, since current guidelines do not suggest a standardised approach, and existing practice consists of the direct coagulation of the designed vessels during submucosal dissection.2 Bleeding episodes can lengthen or complicate these procedures, by obstructing clear visualisation of the structures or resulting in the application of excessive electrocoagulation current.3 In some of these cases, complete haemostasis is not achievable, and the use of additional haemostatic devices, such as coagulation forceps, is required. However, these forceps present with some limitations, requiring the exchange of the device, slowing procedures and increasing the costs. In addition, by applying soft coagulation current, it may result in an unpredictable risk of deep mural injuries.4

Several compounds based on short chain fatty acids and/or probiotics/prebiotics have shown promising results in the therapy of ulcerative colitis (UC), possibly due to its key role in restoring gut homeostasis as well as intestinal barrier integrity. Here, we investigated the efficacy of a patented preparation based on calcium butyrate, Bifidobacterium bifidum, Bifidobacterium lactis, and fructooligosaccharides (FEEDColon^®, Princeps, Cuneo, Italy) in maintaining remission and improving subjective symptoms and inflammatory indices in patients with UC receiving 5-ASA therapy. A total of 42 patients were prospectively recruited and randomized in 21 patients receiving combination therapy with mesalamine (5-ASA) plus FEEDColon^® and 21 patients treated with standard 5-ASA therapy. Patients were assessed at baseline, at 6-month, and 12-month follow-up (FU). Therapeutic success (defined as Mayo partial score ≤ 2 and faecal calprotectin (FC) < 250 µg/g at 12-month FU) was reached by 32 (76%) patients: 20 (95%) among those treated with 5-ASA + FeedColon^®, and 12 (57%) among those treated with 5-ASA only (p = 0.009). Consistently, patients treated with combination therapy improved subjective symptoms (quality of life, abdominal pain, and stool consistency) and reduced FC values, while those treated with 5-ASA alone, improved neither subjective symptoms nor FC during the FU. In conclusion, FEEDColon^® supplementation appears to be a valid add-on therapy for the maintenance of remission in patients with UC. Further multicentre, placebo-controlled, double-blind clinical trials are needed to validate our results on larger cohorts of patients with UC.

Endoluminal biliary radiofrequency ablation (RFA) has been proposed as a palliative treatment for patients with malignant biliary obstruction (MBO) in order to improve stent patency and survival. However, the existing data on patients with inoperable extrahepatic cholangiocarcinoma (eCCA) are conflicting. We performed a meta-analysis of randomized trials comparing RFA plus stenting versus stenting alone in patients with inoperable eCCA. We searched for trials published in the PubMed/MEDLINE, Scopus, and Cochrane databases up to November 2023. Data extraction was conducted from published studies, and a quality assessment was carried out in accordance with the guidelines recommended by the Cochrane Collaboration. Hazard ratios (HRs) with 95% CI were estimated from the trials. The primary endpoints of interest were overall survival and stent patency. Out of 275 results, 5 randomized trials and 370 patients were included. While overall survival was not different between the groups (HR 0.62; 95% CI 0.36–1.07; p = 0.09; I² = 80%;), the subgroup analysis of studies employing plastic stents showed a trend toward better survival in the RFA-treated group (HR 0.42; 95% CI 0.22–0.80; p = 0.009; I² = 72%). Stent patency was improved in patients receiving RFA (HR 0.64; 95% CI 0.45–0.90; p = 0.01; I² = 23%). Adverse events were not different between the groups (OR 1.21; 95% CI 0.69–2.12; p = 0.50; I² = 0%). Despite the promising results, high heterogeneity and potential biases in the included studies suggest the need for further high-quality randomized trials to explore the potential cumulative effects of RFA on CCA treatment outcomes.

Liver cancer is very frequent, and hepatocellular carcinoma (HCC) accounts for the majority of liver cancer cases. Its growing incidence has been greatly affected by the increasing prevalence of metabolic-associated fatty liver disease (MAFLD). The latter is a new epidemic in our era. In fact, HCC is often generated from noncirrhotic liver and its treatment benefits from surgical and nonsurgical approaches, potentially bridged by transjugular intrahepatic portosystemic shunt (TIPS) use. TIPS use is an effective treatment for portal hypertension complications, but its application in patients with HCC and clinically significant portal hypertension (CSPH) remains controversial due to concerns about tumor rupture, dissemination, and increased toxicity. The technical feasibility and safety of TIPS use in HCC patients have been evaluated in several studies. Despite concerns about intraprocedural complications, retrospective studies have shown high success rates and low complication rates in TIPS placement for HCC patients. TIPS use in combination with locoregional treatments, such as transarterial chemoembolization (TACE) or transarterial radioembolization (TARE), has been explored as a treatment option for HCC patients with portal hypertension. These studies have shown improved survival rates in patients undergoing TIPS in combination with locoregional treatments. However, the efficacy and toxicity of TACE in combination with TIPS use require careful evaluation, as changes in venous and arterial flow can affect treatment outcomes and complications. The results from studies evaluating the impact of TIPS on systemic therapy and surgical options are also promising. In conclusion, the TIPS is a sufficiently safe, useful item available for physicians treating complications of portal hypertension. Moreover, a TIPS can be used in combination with locoregional therapy in HCC patients. Systemic chemotherapy can also benefit of the use of TIPS placement. A complex interplay affects TIPS use with surgery. The latter needs further data. The TIPS is a useful and safe add-on treatment, changing the natural course of HCC progression. Its use is regulated by a sophisticated physiologic and pathophysiologic flow of evidence.