Endoscopic Gallbladder Drainage: A Comprehensive Review on Indications, Techniques, and Future Perspectives.

In recent years, therapeutic endoscopy has become a fundamental tool in the management of gallbladder diseases in light of its minimal invasiveness, high clinical efficacy, and good safety profile. Both endoscopic transpapillary gallbladder drainage (TGBD) and endoscopic ultrasound (EUS)-guided gallbladder drainage (EUS-GBD) provide effective internal drainage in patients with acute cholecystitis unfit for cholecystectomy, avoiding the drawbacks of external percutaneous gallbladder drainage (PGBD). The availability of dedicated lumen-apposing metal stents (LAMS) for EUS-guided transluminal interventions contributed to the expansion of endoscopic therapies for acute cholecystitis, making endoscopic gallbladder drainage easier, faster, and hence more widely available. Moreover, EUS-GBD with LAMS opened the possibility of several cholecystoscopy-guided interventions, such as gallstone lithotripsy and clearance. Finally, EUS-GBD has also been proposed as a rescue drainage modality in malignant biliary obstruction after failure of standard techniques, with encouraging results. In this review, we will describe the TBGD and EUS-GBD techniques, and we will discuss the available data on clinical efficacy in different settings in comparison with PGBD. Finally, we will comment on the future perspectives of EUS-GBD, discussing the areas of uncertainty in which new data are more strongly awaited.

Feasibility and safety of deep sedation with propofol and remifentanil in spontaneous breathing during endoscopic retrograde cholangiopancreatography: an observational prospective study.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is an interventional procedure that requires deep sedation or general anaesthesia. The purpose of this prospective observational study was to assess the feasibility and safety of deep sedation in ERCP to maintain spontaneous breathing. METHODS: This is a single-centre observational prospective cohort study conducted in a tertiary referral university hospital. All consecutive patients who needed sedation or general anaesthesia for ERCP were included from January 2021 to June 2021. Deep sedation was achieved and maintained by continuous infusion of an association of propofol and remifentanil. The primary endpoint was to assess the prevalence of major anaesthesia-related complications, such as arrhythmias, hypotension, gas exchange dysfunction, and vomiting (safety endpoint). Secondary endpoints were: (a) to assess the prevalence of signs of an insufficient level of sedation, such as movement, cough, and hiccups (feasibility endpoint): (b) time needed to achieve the target level of sedation and for recovery from anaesthesia. In order to do so we collect the following parameters: peripheral oxygen saturation, fraction of inspired oxygen, noninvasive systemic blood pressure, heart rate, number of breaths per minute, neurological functions with the use of the bispectral index to determine depth of anaesthesia, and partially exhaustive CO2 end pressure to continuously assess the ventilatory status. The collected data were analysed by several tests: Shapiro-Wilk, Student's t, Tuckey post-hoc, Wilcoxon rank-sum and Kruskall-Wallis ran. Statistical analysis was performed using Stata/BE 17.0 (StataCorp LLC). RESULTS: 114 patients were enroled. Eight patients were excluded because they did not meet the inclusion criteria. We found that all patients were hemodynamically stable: intraoperative mean systolic blood pressure was 139,23 mmHg, mean arterial pressure was on average 106,66 mmHg, mean heart rate was 74,471 bpm. The mean time to achieve the target level of sedation was 63 s, while the mean time for the awakening after having stopped drug infusion was 92 s. CONCLUSIONS: During ERCP, deep sedation and analgesia using the association of propofol and remifentanil and maintaining spontaneous breathing are safe and feasible, allowing for a safe and quick recovery from anaesthesia.

Hemostatic Powders in Non-Variceal Upper Gastrointestinal Bleeding: The Open Questions.

Hemostatic powder (HP) is a relatively recent addition to the arsenal of hemostatic endoscopic procedures (HEPs) for gastrointestinal bleeding (GIB) due to benign and malignant lesions. Five types of HP are currently available: TC-325 (Hemospray™), EndoClot™, Ankaferd Blood Stopper®, and, more recently, UI-EWD (NexpowderTM) and CEGP-003 (CGBio™). HP acts as a mechanical barrier and/or promotes platelet activation and coagulation cascade. HP may be used in combination with or as rescue therapy in case of failure of conventional HEPs (CHEPs) and also as monotherapy in large, poorly accessible lesions with multiple bleeding sources. Although the literature on HP is abundant, randomized controlled trials are scant, and some questions remain open. While HP is highly effective in inducing immediate hemostasis in GIB, the rates of rebleeding reported in different studies are very variable, and conditions affecting the stability of hemostasis have not yet been fully elucidated. It is not established whether HP as monotherapy is appropriate in severe GIB, such as spurting peptic ulcers, or should be used only as rescue or adjunctive therapy. Finally, as it can be sprayed on large areas, HP could become the gold standard in malignancy-related GIB, which is often nonresponsive or not amenable to treatment with CHEPs as a result of multiple bleeding points and friable surfaces. This is a narrative review that provides an overview of currently available data and the open questions regarding the use of HP in the management of non-variceal upper GIB due to benign and malignant diseases.

Efficacy of hemostatic powders as monotherapy or rescue therapy in gastrointestinal bleeding related to neoplastic or non-neoplastic lesions.

BACKGROUND: Hemostatic powder (HP) in gastrointestinal bleeding (GIB) is mainly used as rescue therapy after failure of conventional hemostatic procedures (CHP). AIM: To define the best field of application and the efficacy of HP as first choice monotherapy or rescue therapy. METHODS: We compared the efficacy of HP monotherapy, HP rescue therapy, and CHP in the management of active GIB due to neoplastic and non-neoplastic lesions. RESULTS: A total of 108 patients, 43 treated with HP as either first choice or rescue therapy and 65 with CHP, were included in the study. The most frequent sources of bleeding were peptic ulcer and malignancy. Immediate hemostasis rates were: HP monotherapy = 100% in peptic ulcer and 100% in malignancy; HP rescue therapy = 93.2% in peptic ulcer and 85.7% in malignancy; CHP = 77.9% in peptic ulcer and 41.7 in malignancy. Definitive hemostasis rates were: HP monotherapy = 50% in peptic ulcer and 45.5% in malignancy; HP rescue therapy = 73.3% in peptic ulcer and 85.7% in malignancy; CHP = 69.1% in peptic ulcer and 33.3% in malignancy. No difference was found in terms of additional intervention between the three groups. CONCLUSIONS: HP is highly effective as monotherapy and rescue therapy in GIB. GIB related to malignancy may be the best field of application of HP, but confirmatory studies are necessary.

Factors influencing diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in pancreatic and biliary tumors.

BACKGROUND AND AIM: Diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is influenced by several factors, primarily operator expertise. Formal training in EUS-FNA, as suggested by the European Society of Gastrointestinal Endoscopy and the American Society for Gastrointestinal Endoscopy guidelines, is not always available and is often expensive and time-consuming. In this study we evaluate factors influencing the diagnostic accuracy of pancreatic EUS-FNA. METHODS: In a retrospective study, 557 consecutive EUS-FNAs were evaluated. Several variables relating to the procedures were considered to calculate the EUS-FNA performance over eight years. RESULTS: A total of 308 out of 557 EUS-FNAs were selected. Overall sensitivity of EUS-FNA was 66% (95% CI: 60.8-71.8), specificity 100%, and diagnostic accuracy 69% (95% CI: 64.0-74.4). An increase in diagnostic accuracy was observed to >90% using a new fine-needle biopsy (FNB) needle and in the case of simultaneous sampling of primary and metastatic lesions. Diagnostic accuracy >80% was observed after 250 procedures, in the absence of rapid on-site cytopathological examination (ROSE). Multivariate logistic regression analysis confirmed that the FNB needle, operator skill, and double EUS-FNA sampling are associated with high diagnostic accuracy. CONCLUSIONS: The learning curve for EUS-FNA may be longer and a considerable number of procedures are needed to achieve high diagnostic accuracy in the absence of ROSE. However, the use of FNB needles and the simultaneous sampling of primary and metastatic lesions can rapidly improve the diagnostic accuracy of the procedure.

The impact of COVID-19 pandemic in the colorectal cancer prevention.

BACKGROUND: The coronavirus disease 2019 (COVID-19) has led to a policy of severe restrictions in almost all countries strongly involved by the pandemic. National Health System is among activities suffering from the COVID-19 and the lockdown. AIM: To evaluate the impact of COVID-19 in colorectal cancer (CRC) prevention. METHODS: We report the change in the hospital organization to meet the growing healthcare needs determined by COVID-19. The limitations of CRC prevention secondary to COVID-19 and their effects on the healthcare are analyzed considering the features of the CRC screening programs in the average-risk population and endoscopic surveillance in patients with inflammatory bowel diseases (IBD). RESULTS: The interruption of CRC prevention may lead to a delayed diagnosis of CRC, possibly in a more advanced stage. The economic burden and the impact on workload for gastroenterologists, surgeons, and oncologists will be greater as long as the CRC prevention remains suspended. To respond to the increased demand for colonoscopy once COVID-19 will be under control, we should optimize the resources. It will be necessary to stratify the CRC risk and reach an order of priority. It should be implemented the number of health workers, equipment, and spaces dedicated to performing colonoscopy for screening purpose and in subjects with alarm symptoms in the shortest time. To this aim, the funds earmarked for healthcare should be increased. CONCLUSION: The economic impact will be dramatic, but COVID-19 is the demonstration that healthcare has to be the primary goal of humans.

High Smad7 sustains inflammatory cytokine response in refractory coeliac disease.

Refractory coeliac disease (RCD) is a form of coeliac disease (CD) resistant to gluten-free diet and associated with elevated risk of complications. Many effector cytokines over-produced in the gut of patients with RCD are supposed to amplify the tissue-destructive immune response, but it remains unclear if the RCD-associated mucosal inflammation is sustained by defects in counter-regulatory mechanisms. The aim of the present study was to determine whether RCD-related inflammation is marked by high Smad7, an intracellular inhibitor of transforming growth factor-ß1 (TGF-ß1 ) activity. Smad7 was evaluated in duodenal biopsy samples of patients with RCD, patients with active CD, patients with inactive CD and healthy controls by Western blotting, immunohistochemistry and real-time PCR. In the same samples, TGF-ß1 and phosphorylated (p)-Smad2/3 were evaluated by ELISA and immunohistochemistry, respectively. Pro-inflammatory cytokine expression was evaluated in RCD samples cultured with Smad7 sense or antisense oligonucleotide. Smad7 protein, but not RNA, expression was increased in RCD compared with active and inactive CD patients and healthy controls and this was associated with defective TGF-ß1 signalling, as marked by diminished p-Smad2/3 expression. TGF-ß1 protein content did not differ among groups. Knockdown of Smad7 in RCD biopsy samples reduced interleukin-6 and tumour necrosis factor-α expression. In conclusion, in RCD, high Smad7 associates with defective TGF-ß1 signalling and sustains inflammatory cytokine production. These results indicate a novel mechanism by which the mucosal cytokine response is amplified in RCD and suggest that targeting Smad7 can be therapeutically useful in RCD.

Indications, Techniques and Future Perspectives of Walled-off Necrosis Management.

Necrotizing pancreatitis is a complex clinical condition burdened with significant morbidity and mortality. In recent years, the huge progress of interventional endoscopic ultrasound (EUS) has allowed a shift in the management of pancreatic necrotic collections from surgical/percutaneous approaches to mini-invasive endoscopic internal drainage and debridement procedures. The development of lumen-apposing metal stents (LAMSs), devices specifically dedicated to transmural EUS interventions, further prompted the diffusion of such techniques. Several studies have reported excellent outcomes of endoscopic interventions, in terms of technical success, clinical efficacy and safety compared to surgical interventions, and thus endoscopic drainage of walled-off necrosis (WON) has become a fundamental tool for the management of such conditions. Despite these advancements, some critical unresolved issues remain. Endoscopic therapeutic approaches to WON are still heterogeneous among different centers and experts. A standardized protocol on indication, timing and technique of endoscopic necrosectomy is still lacking, and experts often adopt a strategy based on personal experience more than robust data from well-conducted studies. In this review, we will summarize the available evidence on endoscopic management of WON and will discuss some unanswered questions in this rapidly evolving field.

Helicobacter pylori infection associates with a mucosal downregulation of ghrelin, negative regulator of Th1-cell responses.

BACKGROUND: Helicobacter pylori (Hp)-related gastritis is characterized by a predominant T helper (Th)1/Th17 cell immunity. Ghrelin (GR) has immunoregulatory properties and inhibits experimental Th cell-dependent pathology. AIMS: To evaluate whether Hp infection associates with changes in GR expression and whether GR negatively regulates Th1/Th17 cytokines during Hp infection. METHODS: GR expression was evaluated by real-time PCR in gastric biopsies taken from Hp-infected and Hp-uninfected patients and in gastric biopsies of Hp-negative subjects cultured with or without H. pylori culture supernatant. To examine whether GR regulates Hp-induced cytokine production, H. pylori-infected gastric biopsies were stimulated with GR, and interleukin (IL)-12, interferon (IFN)-γ and IL-4 transcripts were evaluated by real-time PCR. IL-12 and IFN-γ were also analyzed in lamina propria mononuclear cells (LPMCs) extracted from Hp-infected gastric biopsies and cultured with GR. RESULTS: GR RNA transcripts were reduced in biopsies from Hp-infected patients. Treatment of Hp-negative gastric biopsies with Hp culture supernatant reduced GR RNA expression. GR dose-dependently inhibited RNA expression of IL-12 and IFN-γ but not IL-4 in ex vivo cultures of mucosal explants and in cultures of gastric LPMCs from Hp-positive patients. CONCLUSIONS: GR is downregulated in the gastric mucosa of H. pylori-infected patients. Such a defect could contribute to sustain the ongoing Th1-cell response.

Corrigendum: An essential role of adenosine deaminase acting on RNA 1 in coeliac disease mucosa.

[This corrects the article DOI: 10.3389/fimmu.2023.1175348.].

An essential role of adenosine deaminase acting on RNA 1 in coeliac disease mucosa.

Background and aim: Type I interferons (IFNs) are highly expressed in the gut mucosa of celiac disease (CD) gut mucosa and stimulates immune response prompted by gluten ingestion, but the processes that maintain the production of these inflammatory molecules are not well understood. Adenosine deaminase acting on RNA 1 (ADAR1), an RNA-editing enzyme, plays a crucial role in inhibiting self or viral RNAs from activating auto-immune mediated responses, most notably within the type-I IFN production pathway. The aim of this study was to assess whether ADAR1 could contribute to the induction and/or progression of gut inflammation in patients with celiac disease. Material and methods: ADAR1 expression was assessed by Real time PCR and Western blotting in duodenal biopsy taken from inactive and active celiac disease (CD) patients and normal controls (CTR). To analyze the role of ADAR1 in inflamed CD mucosa, lamina propria mononuclear cells (LPMC) were isolated from inactive CD and ADAR1 was silenced in with a specific antisense oligonucleotide (AS) and then incubated with a synthetic analogue of viral dsRNA (poly I:C). IFN-inducing pathways (IRF3, IRF7) in these cells were evaluated with Western blotting and inflammatory cytokines were evaluated with flow cytometry. Lastly, the role of ADAR1 was investigated in a mouse model of poly I:C-driven small intestine atrophy. Results: Reduced ADAR1 expression was seen in duodenal biopsies compared to inactive CD and normal controls. Ex vivo organ cultures of duodenal mucosal biopsies, taken from inactive CD patients, stimulated with a peptic-tryptic digest of gliadin displayed a decreased expression of ADAR1. ADAR1 silencing in LPMC stimulated with a synthetic analogue of viral dsRNA strongly boosted the activation of IRF3 and IRF7 and the production of type-I IFN, TNF-α and IFN-γ. Administration of ADAR1 antisense but not sense oligonucleotide to mice with poly I:C-induced intestinal atrophy, significantly increased gut damage and inflammatory cytokines production. Conclusions: These data show that ADAR1 is an important regulator of intestinal immune homeostasis and demonstrate that defective ADAR1 expression could provide to amplifying pathogenic responses in CD intestinal mucosa.

Characterization of IL-17A-producing cells in celiac disease mucosa.

Celiac disease (CD) is a gluten-sensitive enteropathy associated with a marked infiltration of the mucosa with IFN-gamma-secreting Th1 cells. Recent studies have shown that a novel subset of T cells characterized by expression of high levels of IL-17A, termed Th17 cells, may be responsible for pathogenic effects previously attributed to Th1 cells. In this study, we characterized the expression of IL-17A-producing cells in CD. By real-time PCR and ELISA, it was shown that expression of IL-17A RNA and protein is more pronounced in active CD biopsy specimens in comparison with inactive CD and normal mucosal biopsy specimens. Flow cytometry confirmed that IL-17A is overproduced in CD mucosa and that CD4(+) and CD4(+)CD8(+) cells were major sources. The majority of IL-17A-producing CD4(+) and CD4(+)CD8(+) cells coexpressed IFN-gamma but not CD161. The addition of a peptic-tryptic digest of gliadin to ex vivo organ cultures of duodenal biopsy specimens taken from inactive CD patients enhanced IL-17A production by both CD4(+) and CD4(+)CD8(+) cells. Because we previously showed that IL-21, a T cell-derived cytokine involved in the control of Th17 cell responses, is overproduced in CD, we next assessed whether IL-17A expression is regulated by IL-21. Blockade of IL-21 activity by a neutralizing IL-21 Ab reduced IL-17A expression in cultures of active CD and peptic-tryptic digest of gliadin-treated CD biopsy specimens. In conclusion, our data show that IL-17A is increased in CD and is produced by cells that also make IFN-gamma.

The impact of COVID-19 on elective and urgent digestive endoscopic procedures: a report on a year of pandemic in a gastroenterology centre in Italy.

Introduction: The COVID-19 pandemic (COVID-19) affected digestive endoscopic activity worldwide. Resumption and maintenance of elective endoscopic activity are crucial to containing the impact of COVID-19 on mortality and prognosis of gastrointestinal disorders, primarily cancers. Aim: To assess the impact of COVID-19 during and after the lockdown period on endoscopic activity. Material and methods: The endoscopic activity undertaken during the COVID-19-related lockdown (March 2020-May 2020) and in the post-lockdown period (June 2020-March 2021) was compared with that in the corresponding periods of the year before COVID-19 in a gastroenterology centre in Italy. Results: During the lockdown period, there was a reduction in esophagogastroduodenoscopy (EGD), colonoscopy (CSPY), endoscopic ultrasound (EUS), and endoscopic-retrograde cholangiopancreatography (ERCP) of 75.8%, 74.8%, 60%, and 42%, respectively, compared with the corresponding period of the year before COVID-19. During the post-lockdown period to date, EGD, CSPY, EUS, and ERCP increased as compared to the lockdown period (30.6%, 50.6%, 33.6%, and 65.4%, respectively), but only ERCP showed a full recovery when compared with the corresponding period of the year before COVID-19. Conclusions: Endoscopic activity decreased significantly during the COVID-19 lockdown, and only ERCP had a full recovery in the post-lockdown period. The pandemic-related limitations and the backlog of endoscopic procedures represent important reasons for the increased risk or delayed diagnosis of GI cancers.

Endoscopic Ultrasound Plus Endoscopic Retrograde Cholangiopancreatography Based Tissue Sampling for Diagnosis of Proximal and Distal Biliary Stenosis Due to Cholangiocarcinoma: Results from a Retrospective Single-Center Study.

Differentiating between benign and malignant biliary stenosis (BS) is challenging, where tissue diagnosis plays a crucial role. Endoscopic retrograde cholangiopancreatography (ERCP)-based tissue sampling and endoscopic ultrasound (EUS) with fine-needle aspiration (FNA) or biopsy (FNB) are used to obtain tissue specimens from BS. The aim of this retrospective study was to evaluate the diagnostic yield of EUS-FNA/B plus ERCP with brushing or forceps biopsy in BS. All endoscopic procedures performed in patients with BS at our gastroenterology unit were reviewed. The gold standard for diagnosis was histopathology of surgical specimens or the progression of the malignancy at radiological or clinical follow-up. A total of 70 endoscopic procedures were performed in 51 patients with BS. Final endoscopic diagnosis was reached in 96% of the patients and was malignant in 61.7% and benign in 38.3% of cases. Sensitivity, specificity, and diagnostic accuracy were 73.9%, 100%, and 80%, respectively, for EUS-FNA/B; 66.7%, 100%, and 82.5% for ERCP; and 83.3%, 100%, and 87.5% for both procedures carried out in the same session. The combination of EUS and ERCP tissue sampling seems to increase diagnostic accuracy in defining the etiology of BS. Performing both procedures in a single session reduces the time required for diagnostic work-up and optimizes resources.

Tips and tricks for the diagnosis and management of biliary stenosis-state of the art review.

Biliary stenosis may represent a diagnostic and therapeutic challenge resulting in a delay in diagnosis and initiation of therapy due to the frequent difficulty in distinguishing a benign from a malignant stricture. In such cases, the diagnostic flowchart includes the sequential execution of imaging techniques, such as magnetic resonance, magnetic resonance cholangiopancreatography, and endoscopic ultrasound, while endoscopic retrograde cholangiopancreatography is performed to collect tissue for histopathological/cytological diagnosis or to treat the stenosis by insertion of stent. The execution of percutaneous transhepatic drainage with subsequent biopsy has been shown to increase the possibility of tissue diagnosis after failure of the above techniques. Although the diagnostic yield of histopathology and imaging has increased with improvements in endoscopic ultrasound and peroral cholangioscopy, differential diagnosis between malignant and benign stenosis may not be easy in some patients, and strictures are classified as indeterminate. In these cases, a multidisciplinary workup including biochemical marker assays and advanced technologies available may speed up a diagnosis of malignancy or avoid unnecessary surgery in the event of a benign stricture. Here, we review recent advancements in the diagnosis and management of biliary strictures and describe tips and tricks to increase diagnostic yields in clinical routine.

Idiopathic acute pancreatitis: a single-center investigation of clinical and biochemical features.

Acute pancreatitis (AP) is termed as idiopathic (IAP) when the underlying conditions of pancreatic inflammation remain unknown. The aim of this study was to identify different clinical features in patients with IAP and AP of known aetiology. All patients hospitalized in our Gastroenterology Unit with an initial diagnosis of AP were recruited. AP was classified as of known aetiology or idiopathic according to clinical examination, serum biochemistry testing, and radiological imaging investigations, and clinical data in both patient groups were compared. A total of 127 patients (80 males, mean age: 57 years) were eligible for the analysis, 92 of which (73%) with AP of known aetiology and 35 (27%) with IAP. The major causes of AP were biliary obstruction (65%) or alcohol abuse (25%). Previous cholecystectomy was more frequent in patients with AP of known aetiology than in patients with IAP (14% versus 0%); patients with IAP showed lower gamma-glutamyl transpeptidase levels, lower daily alcohol intake, and higher frequency of gastroenteritis than patients with AP of known aetiology (34.3% versus 15.2%). Previous intake of nonsteroidal anti-inflammatory drugs was more frequent in patients with IAP than in patients with AP of known aetiology (23% versus 0%). No further differences in clinical features were found between the two patient groups. IAP accounts for almost 20% of cases of AP. An association of AP with gastroenteritis or the use of NSAIDs should be considered if time-related with disease onset, especially in patients with no recurrent attacks.

A Pharmacological Batch of Mongersen that Downregulates Smad7 is Effective as Induction Therapy in Active Crohn's Disease: A Phase II, Open-Label Study.

BACKGROUND: A recent phase III trial did not confirm the previous clinical and endoscopic improvements seen in patients with Crohn's disease (CD) receiving Mongersen, an oral Smad7 antisense oligonucleotide. Factors accounting for such a discrepancy are unknown. OBJECTIVE: Our objective was to further assess whether Mongersen was effective as induction therapy in active CD and evaluate the in vitro inhibitory effect of various batches of Mongersen used in the previous and present trials on Smad7 expression. METHODS: In a phase II, open-label study, 18 patients with active CD (Crohn's Disease Activity Index [CDAI] score > 220 and evidence of endoscopic lesions) received Mongersen 160 mg/day for 12 weeks. The rates of clinical remission, defined as CDAI < 150, and clinical response, defined as a CDAI score decrease ≥ 100, were evaluated at week 4, 8, and 12. The fraction of circulating CCR9-expressing leukocytes was assessed by flow cytometry. Smad7 expression was evaluated in the human colorectal cancer cell line HCT-116 transfected with different batches of Mongersen using real-time polymerase chain reaction (PCR) and Western blotting, RESULTS: The proportions of patients experiencing clinical remission were 38.9%, 55.6%, and 50.0% at week 4, 8, and 12, respectively. At the same time points, the rates of clinical response were 72.2%, 77.8%, and 77.8%, respectively. Mongersen reduced the percentages of CCR9-expressing CD45+ cells. The batch of Mongersen used in this study, but not two batches used in the phase III study, inhibited Smad7 expression in HCT-116 cells. CONCLUSIONS: The present findings support the clinical benefit of Mongersen in active CD and show that various batches manufactured during the GED0301 program differ in their ability to inhibit in vitro Smad7. TRIAL REGISTRATION NUMBER: NCT02685683; EudraCT 2015-001693-18.

Efficacy and tolerability of very low-volume bowel preparation in patients with inflammatory bowel diseases.

OBJECTIVES: An adequate bowel preparation is essential for a quality colonoscopy. Patients with inflammatory bowel disease (IBD) show low compliance with bowel preparation due to the large volume of lavage solution to be ingested, especially if active symptoms are present, and the frequency of having a colonoscopy. We evaluated the efficacy and tolerability of a very low-volume (VLV) polyethylene glycol (PEG)-based solution in patients with IBD. METHODS: A cohort of 103 consecutive patients, 56 with Crohn's disease and 47 with ulcerative colitis, received a 1-L PEG-based bowel preparation divided into two 500-mL doses taken the evening before and the morning of the colonoscopy, each dose followed by at least another 500-mL of clear fluids. Colon cleansing was scored according to the Boston Bowel Preparation Scale (BBPS) and evaluated in relation to influencing variables. RESULTS: Bowel cleansing was adequate (BBPS ≥ 6) in 88 patients (85.4%). The time interval between the end of bowel preparation and the beginning of colonoscopy and the disease activity significantly affected colon cleansing. Most patients declared a complete intake of lavage solution (99%), the willingness to repeat the same bowel preparation in a future colonoscopy (86.4%), and a good taste assessment. CONCLUSION: The VLV PEG-based bowel preparation is effective and well accepted by IBD patients. As minimizing the volume of lavage solution required, the VLV-bowel preparation here tested could be of choice in subjects who perform periodically colonoscopy or in those who do not tolerate a larger amount of liquids.

Clinical care pathway program versus open-access system: a study on appropriateness, quality, and efficiency in the delivery of colonoscopy in the colorectal cancer.

Open-access colonoscopy (OAC), whereby the colonoscopy is performed without a prior office visit with a gastroenterologist, is affected by inappropriateness which leads to overprescription and reduced availability of the procedure in case of alarming symptoms. The clinical care pathway (CCP) is a healthcare management tool promoted by national health systems to organize work-up of various morbidities. Recently, we started a CCP dedicated to colorectal cancer (CRC), including a colonoscopy session for CRC diagnosis and prevention. We aimed to evaluate the appropriateness, the quality, and the efficiency in the delivery of colonoscopy with the open-access system and a CCP program in the CRC. Quality indicators for colonoscopy in subjects in the CCP were compared to referrals by general practitioners (OAC) or by non-gastroenterologist physicians (non-gastroenterologist physician colonoscopy, NGPC). Attendance rate to colonoscopy was greater in the CCP group and NGPC group than in the OAC group (99%, 99%, and 86%, respectively). Waiting time in the CCP group was shorter than in the OAC group (3.88 ± 2.27 vs. 32 ± 22.31 weeks, respectively). Appropriateness of colonoscopy prescription was better in the CCP group than in the OAC group (92 vs. 50%, respectively). OAC is affected by the lack of timeliness and low appropriateness of prescription. A CCP reduces the number of inappropriate colonoscopies, especially for post-polypectomy surveillance, and improves the delivery of colonoscopy in patients requiring a fast-track examination. The high rate of inappropriate OAC suggests that this modality of healthcare should be widely reviewed.