Hypersecretion of proinflammatory cytokines and dysregulated activation of the IL-23/Th17 axis in response to intestinal microbiota dysbiosis are key factors in the pathogenesis of inflammatory bowel ...diseases (IBD). In this work, we studied how
and
strains affect AIEC-LF82 virulence mechanisms and the consequent inflammatory response linked to the CCR6-CCL20 and IL-23/Th17 axes in Crohn's disease (CD) and ulcerative colitis (UC) patients. All
and
strains significantly reduced the LF82 adhesion and persistence within HT29 intestinal epithelial cells, inhibiting IL-8 secretion while not affecting the CCR6-CCL20 axis. Moreover, they significantly reduced LF82 survival within macrophages and dendritic cells, reducing the secretion of polarizing cytokines related to the IL-23/Th17 axis, both in healthy donors (HD) and UC patients. In CD patients, however, only
Bbr8 strain was able to slightly reduce the LF82 persistence within dendritic cells, thus hampering the IL-23/Th17 axis. In addition, probiotic strains were able to modulate the AIEC-induced inflammation in HD, reducing TNF-α and increasing IL-10 secretion by macrophages, but failed to do so in IBD patients. Interestingly, the probiotic strains studied in this work were all able to interfere with the IL-23/Th17 axis in UC patients, but not in CD patients. The different interaction mechanisms of probiotic strains with innate immune cells from UC and CD patients compared to HD suggest that testing on CD-derived immune cells may be pivotal for the identification of novel probiotic strains that could be effective also for CD patients.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abstract Purpose To evaluate the PSA response, local control, progression free survival (PFS) and toxicity of stereotactic body radiotherapy (SBRT) for nodal (LN) oligorecurrent prostate cancer. ...Material and Methods Between 05/2012 and 10/2015, 124 lesions were treated in 94 patients with a median dose of 24Gy/3 fractions. 70 patients were treated for a single lesion, 25 for >1 lesion. In 34 patients androgen deprivation (AD) was added to SBRT. We evaluated biochemical response with PSA dosage every three months after SBRT: a three months’ PSA decreased pre-SBRT PSA of more than 10% identified responder patient. In case of PSA increase, imaging was performed to evaluate clinical progression. Toxicity was assessed every 6-9 months after SBRT. Results Median follow-up was 18.5 months. In 13 patients (14%) grade 1-2 toxicity were reported without any grade 3-4. Biochemical response, stabilization and progression were observed in 64 (68%), 10 (11%) and 20 (21%) out of 94 evaluable patients. Clinical progression was observed in 31 (33%) patients after a median time of 8.1 months. In-field progression occurred in 12 lesions (9.7%). 2-year local control and PFS rates were 84% and 30%, respectively. Age>75years correlated with better biochemical response rate. Age>75years, concomitant AD administered up to 12 months and pelvic LN involvement correlated with longer PFS. Conclusions SBRT is safe and offers good in-field control. At two years after SBRT, 1 out of 3 patients is progression-free. Further investigation is warranted to identify patients that benefit most from SBRT and to define the optimal combination with AD.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
In the last decades, Endoscopic ultrasound (EUS) has rapidly grown and evolved from being mainly a diagnostic procedure, to being an interventional and therapeutic tool in several pathological ...clinical scenarios. With the progressive growth in technical expertise and dedicated devices, interventional endoscopic ultrasound procedures (IEUSP) have shown high rates of technical and clinical success, together with a relatively safe profile. However, the description and the standardization of different and specific types of adverse events (AEs) are still scarce in literature, and, consequently, even less the management of AEs. The aim of this study is to critical review and to describe AEs related to each of the main IEUSP, and to provide an overview on the possible management strategies of endoscopic complications. Future studies and guidelines are surely required to reach a better standardization of different AEs and their best management.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Patients presenting with acute colonic obstruction are usually evaluated in the emergency department and multiple specialties are involved in the patients' management. Pre-treatment evaluation is ...essential in order to establish the correct endoscopic indication for stent implantation. Contrast-enhanced imaging could allow the exclusion of benign causes of colonic obstruction and evaluation of the length of malignant stricture. Endoscopic stenting is the gold standard of treatment for palliative indications whereas there are still concerns about its use as a bridge to surgery. Different meta-analyses showed that stenting as a bridge to surgery improves short-term surgical outcomes but has no role in improving long-term outcomes. Multidisciplinary evaluation is also essential in patients that may be started on or are currently receiving antiangiogenic agents because endoscopic stenting may increase the risk of perforation. Evidence in the literature is weak and based on retrospective data. Here we report on how to correctly evaluate a patient with acute colonic malignant obstruction in collaboration with other essential specialists including a radiologist, surgeon and oncologist, and how to optimize the technique of endoscopic stenting.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death. Abdominal ultrasound (US) is by far the most widely used first-level exam for the diagnosis of HCC. We aimed to ...assess whether different ultrasound patterns were related to tumor prognosis. Methods: We retrospectively reviewed all patients with a new diagnosis of HCC (single nodule) and undergoing radiofrequency thermal ablation (RFTA) at our clinic between January 2009 and December 2021. Patients were classified according to four HCC ultrasound patterns: 1A, single capsulated nodule; 1B, well capsulated intra-node nodule; 1C, cluster consisting of capsulated nodules; and 2, non-capsulated nodule. Results: 149 patients were analysed; median follow-up time was 43 months. US patterns 1A (32.9%) and 1B (61.1%) were the most commonly seen. Median overall survival (OS) and recurrence-free survival (RFS) from RFTA were 54 months (95% CI, 42–66) and 22 months (95% CI, 12–32), respectively. Pattern 1A showed the best OS. Compared to pattern 1A, 1B was independently associated with worse OS (51 months (95% CI, 34–68) vs. 46 months (95% CI, 18–62)) and RFS (34 months (95% CI, 27–41) vs. 18 months (95% CI, 12–24)). Patterns 1C and 2 were associated with worse RFS compared to 1A, while no difference was seen for OS. Among baseline clinical variables, pattern 1B exhibited higher histological grade (p = 0.048) and tumor dimension (p = 0.034) compared to pattern 1A. Conclusions: Our findings demonstrate that different US patterns correlate with different survival outcomes and tumor behavior in patients with HCC. Prospective studies are needed to confirm these results.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The environmental issue has become central in the public debate, but the new scenario of the infosphere within which it takes place with its informal formation, does not seem to increase awareness ...but rather confusion and cognitive difficulty that holds citizens back from participating in public decisions on the environment. An alarm for pedagogy, ecopedagogy and science in general that should foster a dialogue based on a different approach to the co-construction of knowledge between expert and lay knowledge and new education.
Anti-TNF therapies infliximab (IFX), adalimumab (ADA), and golimumab (GOL) are approved for treating moderate to severe ulcerative colitis (UC). In UC, only the switch from IFX to ADA has been ...investigated, reaching no more than 10–43% remission rates at 12 months.
Of the present study was to investigate disease outcome after a switch from subcutaneous (SC) agents to the intravenous (IV) agent (IFX).
In this retrospective multicentre study, we analysed the charts of UC patients unresponsive/intolerant or with secondary loss of response (LOR) to ADA or GOL who were switched to IFX. We evaluated clinical response and remission together with adverse events at 3, 6, and 12 months follow-up.
Seventy-six patients were included; 38 patients started ADA and 38 started GOL for a mean therapy duration of 6 ± 6 months. Indications for switch were adverse events in 3%, primary failure in 79%, and LOR in 18% of patients. Clinical remission was reached by 47%, 50%, and 77% of patients, respectively. Patients that switched for LOR did numerically, but not statistically, better than patients who switched for primary failure.
Our data show a superior remission rate in SC to IV anti-TNF switch in UC compared to the IV to SC switch reported in literature.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
: Biliary drainage (BD) in patients with surgically altered anatomy (SAA) could be obtained endoscopically with different techniques or with a percutaneous approach. Every endoscopic technique could ...be challenging and not clearly superior over another. The aim of this survey is to explore which is the standard BD approach in patients with SAA.
: A 34-question online survey was sent to different Italian tertiary and non-tertiary endoscopic centers performing interventional biliopancreatic endoscopy. The core of the survey was focused on the first-line and alternative BD approaches to SAA patients with benign or malignant obstruction.
: Out of 70 centers, 39 answered the survey (response rate: 56%). Only 48.7% of them declared themselves to be reference centers for endoscopic BD in SAA. The total number of procedures performed per year is usually low, especially in non-tertiary centers; however, they have a low tendency to refer to more experienced centers. In the case of Billroth-II reconstruction, the majority of centers declared that they use a duodenoscope or forward-viewing scope in both benign and malignant diseases as a first approach. However, in the case of failure, the BD approach becomes extremely heterogeneous among centers without any technique prevailing over the others. Interestingly, in the case of Roux-en-Y, a significant proportion of centers declared that they choose the percutaneous approach in both benign (35.1%) and malignant obstruction (32.4%) as a first option. In the case of a previous failed attempt at BD in Roux-en-Y, the subsequent most used approach is the EUS-guided intervention in both benign and malignant indications.
: This survey shows that the endoscopic BD approach is extremely heterogeneous, especially in patients with Roux-en-Y reconstruction or after ERCP failure in Billroth-II reconstruction. Percutaneous BD is still taken into account by a significant proportion of centers in the case of Roux-en-Y anatomy. The total number of endoscopic BD procedures performed in non-tertiary centers is usually low, but this result does not correspond to an adequate rate of referral to more experienced centers.
: Serum alpha-fetoprotein (AFP) is a recognized affordable oncological marker in patients with hepatocellular carcinoma (HCC). However, AFP's prognostic role has been assessed mainly after specific ...treatments, and no unanimously recognized cut-offs have been identified. The aim of this study is to investigate the prognostic role of different basal AFP cut-offs on survival and HCC course.
: In this single-center, retrospective study, all patients newly diagnosed with HCC between January 2009 and December 2021 were prospectively enrolled. Only patients suitable for curative HCC treatments were included in the analyses. Patients were stratified according to AFP cut-offs of 20, 200, 400, and 1000 ng/mL, which were correlated with survival outcomes and clinical parameters.
: A total of 266 patients were analyzed, with a median follow-up time of 41.5 months. Median overall survival (OS) of all cohort was 43 months. At the multivariate Cox-regression analysis, AFP value ≥ 1000 ng/mL correlated with impaired OS (1-year OS: 67% vs. 88%, 5-year OS: 1% vs. 43%;
= 0.005); other risk factors were tumor dimension ≥ 5 cm (HR 1.73;
= 0.002), Child-Pugh class B-C (HR 1.72;
= 0.002), BCLC stage A (vs. 0) (HR 2.4;
= 0.011), and malignant portal vein thrombosis (HR 2.57;
= 0.007). AFP ≥ 1000 ng/mL was also associated with a reduced recurrence-free survival (HR 2.0;
= 0.038), while starting from AFP ≥ 20 ng/mL, a correlation with development of HCC metastases over time (HR 3.5;
= 0.002) was seen. AFP values ≥ 20 ng/mL significantly correlated with tumor size and higher histological grading; starting from AFP values ≥ 400 ng/mL, a significant correlation with Child-Pugh class B-C and female gender was also observed.
: Basal AFP correlates with relevant outcomes in patients with HCC. It could help identify patients at a higher risk of worse prognosis who might benefit from personalized surveillance and treatment programs. Prospective studies are needed to confirm these results.
Obesity is a chronic disease that impairs quality of life and leads to several comorbidities. When conservative therapies fail, bariatric surgical options such as Roux-en-Y gastric bypass (RYGB) and ...sleeve gastrectomy (SG) are the most effective therapies to induce persistent weight loss. Over the last two decades, bariatric endoscopy has become a valid alternative to surgery in specific settings.
Restrictive gastric procedures, such as intragastric balloons (IGBs) and endoscopic gastroplasty, have been shown to be effective in inducing weight loss compared to diet modifications alone. Endoscopic gastroplasty is usually superior to IGBs in maintaining weight loss in the long-term period, whereas IGBs have an established role as a bridge-to-surgery approach in severely obese patients. IGBs in a minority of patients could be poorly tolerated and require early removal. More recently, novel endoscopic systems have been developed with the combined purpose of inducing weight loss and improving metabolic conditions. Duodenal mucosal resurfacing demonstrated efficacy in this field in its early trials: significant reduction from baseline of HbA1c values and a modest reduction of body weight were observed. Other endoscopic malabsorptive have been developed but need more evidence. For example, a pivotal trial on duodenojejunal bypasses was stopped due to the high rate of severe adverse events (hepatic abscesses). Optimization of these more recent malabsorptive endoscopic procedures could expand the plethora of bariatric patients that could be treated with the intention of improving their metabolic conditions.
Weight regain may occur in up to one third of patients after bariatric surgery. Different endoscopic procedures are currently performed after both RYGB and SG in order to modulate post-surgical anatomy. The application of argon plasma coagulation associated with endoscopic full-thickness suturing systems (APC-TORe) and Re-EndoSleeve have shown to be the most effective endoscopic treatments after RYGB and SG, respectively. Both procedures are usually well tolerated and have a very low risk of stricture. However, APC-TORe may sometimes require more than one session to obtain adequate final results. The aim of this review is to explore all the currently available primary and revisional endoscopic bariatric therapies focusing on their efficacy and safety and their potential application in clinical practice.
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