Editorial article to: Animal experimental study on magnetic anchor technique-assisted endoscopic submucosal dissection of early gastric cancer.

In this editorial we comment on the article published in the recent issue of the World Journal of Gastrointestinal Endoscopy 2023; 15 (11): 634-680. Gastric cancer (GC) remains the fifth most common malignancy and the fourth leading cause of cancer-related death worldwide. The overall prevalence of GC has declined, although that of proximal GC has increased over time. Thus, a significant proportion of GC cases and deaths can be avoided if preventive interventions are taken. Early GC (EGC) is defined as GC confined to the mucosa or submucosa. Endoscopic resection is considered the most appropriate treatment for precancerous gastrointestinal lesions improving patient quality of life, with reduced rates of complications, shorter hospitalization period, and lower costs when compared to surgical resection. Endoscopic mucosal resection (EMR) and endoscopic sub-mucosal dissection (ESD) are representative endoscopic treatments for EGC and precancerous gastric lesions. Standard EMR implies injection of a saline solution into the sub-mucosal space, followed by excision of the lesion using a snare. Complete resection rates vary depending on the size and severity of the lesion. When using conventional EMR methods for lesions less than 1 cm in size, the complete resection rate is approximately 60%, whereas for lesions larger than 2 cm, the complete resection rate is low (20%-30%). ESD can be used to remove tumors exceeding 2 cm in diameter and lesions associated with ulcers or submucosal fibrosis. Compared with EMR, ESD has higher en bloc resection rates (90.2% vs 51.7%), higher complete resection rates (82.1 vs 42.2%), and lower recurrence rates (0.65% vs 6.05%). Thus, innovative techniques have been introduced.

Occurrence of Colorectal Cancer After a Negative Colonoscopy in Patients With Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.

BACKGROUND/AIM: Despite the application of colorectal cancer (CRC) surveillance guidelines, the detection of early neoplastic lesions might be difficult in patients with inflammatory bowel disease (IBD). To explore the risk of post-colonoscopy CRC (PCCRC) in patients with IBD we performed a systematic review and meta-analysis. PATIENTS AND METHODS: A systematic literature search was performed (PROSPERO; no. CRD42023453049). We included studies reporting the 3-year PCCRC (PCCRC-3y) prevalence, according to World Endoscopy Organization (WEO)-endorsed definition, in IBD and non-IBD patients. As primary outcome we evaluated the PCCRC-3y prevalence, according to WEO definitions, in IBD- and non-IBD patients and calculated the odds ratio (OR). The secondary outcome was to assess risk factors for PCCRC development in IBD patients. RESULTS: Three retrospective observational cohort studies were included. The pooled PCCRC-3y rate in patients with IBD was 30.8% [95% confidence interval (CI)=24.4-37.5%] and in non-IBD patients was 6.8% (95%CI=6.2-7.4%). The PCCRC-3y occurrence in IBD patients was significantly higher than that in non-IBD patients (OR=6.04; 95%CI=4.04-9.4; I2=95%), but a high heterogeneity among studies was noted. Furthermore, patients with ulcerative colitis (UC) had a significantly higher prevalence of PCCRC than patients with Crohn's Disease (CD): 30.9% (95%CI=27.8-34.2%) vs. 22.3% (95%CI=18-27%), respectively (OR=1.6, 95%CI=1.2-2.2; I2=0%). CONCLUSION: One-third of CRC in IBD patients were PCCRC, and these numbers were significantly higher when compared with those in non-IBD patients. Furthermore, the prevalence of PCCRC in patients with UC was higher compared to those with CD. However, prospective studies are required to better characterize risk factors for PCCRC development in patients with IBD.

Stricturing Crohn's disease: what is the role of endoscopic stenting? A systematic review.

BACKGROUND/AIMS: Endoscopic stenting for stricturing Crohn's disease (CD) is an emerging treatment that achieves more persistent dilatation of the stricture over time than endoscopic balloon dilatation (EBD). We aimed to explore the efficacy and safety of stenting for the treatment of CD strictures. METHODS: A systematic electronic literature search was performed (PROSPERO; no. CRD42022308033). The primary outcomes were technical success, efficacy, complication rate, and the need for further interventions due to reobstruction. The outcomes of partially covered self-expanding metal stents (PCSEMS) with scheduled retrieval after seven days were also analyzed. RESULTS: Eleven eligible studies were included in the review. Overall, 173 patients with CD were included in this study. Mean percentage of technical success was 95% (range, 80%-100%), short-term efficacy was 100% in all studies, and long-term efficacy was 56% (range, 25%-90%). In patients with a scheduled PCSEMS retrieval, the long-term efficacy was 76% (range, 59%-90%), the mean complication rate was 35% (range, 15%-57%), and the major complication rate was 11% (range, 0%-29%). CONCLUSION: Endoscopic stenting with scheduled PCSEMS retrieval may be considered a feasible second-line treatment for short CD strictures to postpone surgery. However, larger head-to-head prospective studies are needed to understand the role of stenting as an alternative or additional treatment to EBD in CD.

Serotonin and Melatonin in Human Lower Gastrointestinal Tract.

BACKGROUND AND AIMS: Melatonin is a ubiquitous hormone produced not only by the pineal gland but also by other organs and tissues. It is involved in the regulation of several gastrointestinal functions. The main cells responsible for the production and release of extrapineal melatonin are the enterochromaffin (EC) cells that produce serotonin. They are involved in the pathogenesis of neuromotor disorders that characterize functional gastrointestinal disorders and in the pathophysiology of inflammatory intestinal diseases. Our aim was the immunohistochemical highlighting on biopsy samples of normal gastrointestinal mucosa and in ulcerative colitis (UC) of immunoreactive cells for melatonin and serotonin in order to identify any differences in their distribution. MATERIALS AND METHODS: Our prospective case-control study involves the highlighting on human mucosal biopsies of immunoreactive cells for melatonin and serotonin. All patients undergoing colonoscopy + ileoscopy were considered eligible for the study, divided into two groups: 1. patients with active ulcerative colitis (UC); 2. control group consisting of patients undergoing endoscopic examination for colorectal cancer screening. RESULTS: Twenty-one patients were enrolled. The controls had a higher concentration of EC cells containing 5HT particularly in the rectum (p value ≤ 0.05). In patients with active colitis the expression of 5-HT-iR was greater in all tracts of the colon. The correlation analysis in UC patients shows that a higher expression of 5-HT-iR+ cells corresponds to a lower extension of the disease and a greater severity of the same. CONCLUSIONS: 5HT+ cells decreased in the case of UC compared to healthy controls. In the severe disease, there was an increase in the expression of melatonin-secreting cells, probably as a compensatory response to the inflammation and oxidative stress. This increase is negatively correlated with the extent of the disease and positively with the severity of the same.

Eosinophilic Esophagitis: Cytokines Expression and Fibrotic Markers in Comparison to Celiac Disease.

INTRODUCTION: Eosinophilic esophagitis (EoE) is now recognized as the main inflammatory condition that leads to fibrosis, unlike other chronic inflammatory gastrointestinal diseases, such as celiac disease. The aim of our study is to characterize the collagen deposition and cytokine expression involved in the fibrogenic response in patients affected by EoE in comparison to celiac disease. MATERIALS AND METHODS: Consecutive patients with a clinical suspicion of untreated EoE or active celiac disease were enrolled. In the control group, patients with negative upper endoscopy were included. Total RNA was isolated from biopsy specimens using a commercial kit (SV Total RNA Isolation System, Promega Italia Srl). Quantitative real-time PCR (qRT-PCR) was performed in triplicate using a StepOne™ Real-Time PCR instrument (Thermo Fisher Scientific, Monza, Italy). mRNA encoding for inflammatory molecules: interleukin 4 (IL-4), interleukin 5 (IL-5), interleukin 13 (IL-13), and fibrotic markers: transforming growth factor beta 1 (TGF-ß), mitogen-activated protein kinase kinase kinase 7 (MAP3K7), serpin family E member 1 (SERPINE1), were quantified using TaqMan Gene Expression Assays (Applied Biosystems). RESULTS: In EoE, the qPCR analysis showed an increase in all the inflammatory cytokines. Both IL-5 and Il-3 mRNA expression resulted in a statistically significant increase in oesophageal mucosa with respect to the celiac duodenum, while no differences were present in IL-4 expression. TGF-ß expression was similar to the controls in the mid esophagus but reduced in the distal EoE esophagus (RQ: 0.46 ± 0.1). MAP3K7 expression was reduced in the mid esophagus (RQ: 0.59 ± 0.3) and increased in the distal esophagus (RQ: 1.75 ± 0.6). In turn, the expression of SERPINE1 was increased in both segments and was higher in the mid than in the distal esophagus (RQ: 5.25 ± 3.9, 1.92 ± 0.9, respectively). Collagen deposition was greater in the distal esophagus compared to the mid esophagus [18.1% ± 8 vs. 1.3% ± 1; p = 0.008]. CONCLUSIONS: The present study confirms the esophageal fibrotic involution involving the distal esophagus and shows that the inflammatory pathway in EoE is peculiar to this disease and different from other chronic inflammatory gastrointestinal disorders such as celiac disease.

The Role of Insulin Resistance in Fueling NAFLD Pathogenesis: From Molecular Mechanisms to Clinical Implications.

Non-alcoholic fatty liver disease (NAFLD) represents a predominant hepatopathy that is rapidly becoming the most common cause of hepatocellular carcinoma worldwide. The close association with metabolic syndrome's extrahepatic components has suggested the nature of the systemic metabolic-related disorder based on the interplay between genetic, nutritional, and environmental factors, creating a complex network of yet-unclarified pathogenetic mechanisms in which the role of insulin resistance (IR) could be crucial. This review detailed the clinical and pathogenetic evidence involved in the NAFLD-IR relationship, presenting both the classic and more innovative models. In particular, we focused on the reciprocal effects of IR, oxidative stress, and systemic inflammation on insulin-sensitivity disruption in critical regions such as the hepatic and the adipose tissue, while considering the impact of genetics/epigenetics on the regulation of IR mechanisms as well as nutrients on specific insulin-related gene expression (nutrigenetics and nutrigenomics). In addition, we discussed the emerging capability of the gut microbiota to interfere with physiological signaling of the hormonal pathways responsible for maintaining metabolic homeostasis and by inducing an abnormal activation of the immune system. The translation of these novel findings into clinical practice could promote the expansion of accurate diagnostic/prognostic stratification tools and tailored pharmacological approaches.

Adherence to European Society of Gastrointestinal Endoscopy Quality Performance Measures for Upper and Lower Gastrointestinal Endoscopy: A Nationwide Survey From the Italian Society of Digestive Endoscopy.

Background: The quality of gastrointestinal (GI) endoscopy has been recently identified as a major priority being associated with many outcomes and patient's experience. Objective: To assess adherence of endoscopists to the European Society of Gastrointestinal Endoscopy (ESGE) quality performance measures for upper and lower GI endoscopy in Italy. Methods: All endoscopist members of the Italian Society of Digestive Endoscopy (SIED) were invited from October 2018 to December 2018 to participate to a self-administered questionnaire-based survey. The questionnaire included questions on demographics and professional characteristics, and the recent ESGE quality performance measures for upper and lower GI endoscopy. Results: A total of 392 endoscopists participated in the study. Only a minority (18.2%) of participants recorded the duration of esophagogastroduodenoscopy (EGD) and 51% provided accurate photo documentation in the minimum standard of 90% of cases. Almost all endoscopists correctly used Prague and Los Angeles classifications (87.8% and 98.2%, respectively), as well as Seattle and Management of precancerous conditions and lesions in the stomach (MAPS) biopsy protocols (86.5% and 91.4%, respectively). However, only 52.8% of participants monitored complications after therapeutic EGD, and 40.8% recorded patients with a diagnosis of Barrett's esophagus (BE). With regard to colonoscopy, almost all endoscopists (93.9%) used the Boston Bowel Preparation Scale for measuring bowel preparation quality and reported a cecal intubation rate ≥90%. However, about a quarter (26.2%) of participants reported an adenoma detection rate of <25%, only 52.8% applied an appropriate polypectomy technique, 48% monitored complications after the procedure, and 12.4% measured patient's experience. Conclusion: The adherence of endoscopists to ESGE performance measures for GI endoscopy is sub-optimal in Italy. There is a need to disseminate and implement performance measures and endorse educational and scientific interventions on the quality of endoscopy.

Role of New Anatomy, Biliopancreatic Reflux, and Helicobacter Pylori Status in Postgastrectomy Stump Cancer.

Distal gastrectomy for benign gastroduodenal peptic disease has become rare, but it still represents a widely adopted procedure for advanced and, in some countries, even for early distal gastric cancer. Survival rates following surgery for gastric malignancy are constantly improving, hence the residual mucosa of the gastric stump is exposed for a prolonged period to biliopancreatic reflux and, possibly, to Helicobacter pylori (HP) infection. Biliopancreatic reflux and HP infection are considered responsible for gastritis and metachronous carcinoma in the gastric stump after oncologic surgery. For gastrectomy patients, in addition to eradication treatment for cases that are already HP positive, endoscopic surveillance should also be recommended, for prompt surveillance and detection in the residual mucosa of any metaplastic-atrophic-dysplastic features following surgery.

Solitary Fibrous Tumor of the Seminal Vesicle: A Systematic Literature Review and Case Presentation.

BACKGROUND/AIM: Solitary fibrous tumors (SFTs) are ubiquitous mesenchymal neoplasms that have an unpredictable biological behavior. Histological criteria for this type of malignancy are uncertain. Clinical characteristics, diagnostic and treatment options of SFTs originating in the seminal vesicle are presented in this review article. MATERIALS AND METHODS: A systematic review including the following databases: Scopus, Embase and Medline from 1960 until the end of March 2021 was performed according to the Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines. RESULTS: We found seven patients affected with SFTs of seminal vesicle, in which we added our own case, making a total of 8 patients. Mean age at presentation was 55±7 years. Mean size of the SFTs was 9±2 cm and the right seminal vesicle was preferentially involved. The majority of patients were symptomatic and presenting symptoms were hematuria, dysuria, hematospermia, urinary increased frequency and urgency. Abdominal ultrasonography, computed tomography (CT) scan, and magnetic resonance (MRI) were the diagnostic tools. Trans-rectal ultrasound-guided core biopsy was also used. Seven (87%) patients had open surgery. Adjuvant radiotherapy after R0 resection was used in 1 patient. CONCLUSION: The treatment of SFTs located in the seminal vesicle necessitates a radical surgical resection to obtain acceptable results in terms of local recurrence and distant metastases.

Short-term outcomes of stents in obstructive rectal cancer: A systematic review and meta-analysis.

BACKGROUND: With acute obstruction due to rectal or recto-sigmoid cancer, the safety and success of deploying self-expandable metal stents has been controversial. The aim of this systematic review was to synthesize the existing evidence on the outcomes and complication rates of stent placement in these patients. METHODS: We performed a literature search of PubMed by using appropriate keywords, and manual reference screening of included articles was done. The article screening, data extraction, and quality assessment was done by four independent reviewers. A meta analyses was performed for the main outcome measures: technical and clinical success and complication rates. RESULTS: We identified 962 articles in the search. After applying inclusion and exclusion criteria, we included 32 articles in the meta-analysis. The pooled technical success rate across 26 studies that reported it was 97% [95% confidence interval (CI): 95%-99%] without evidence of significant heterogeneity (I2 = 0.0%, P = 0.84), and the clinical success rate across 26 studies that reported it was 69% (95% CI: 58%-79%) with evidence of significant heterogeneity (I2 = 81.7%, P < 0.001). The pooled overall complication rate across the 32 studies was 28% (95% CI: 20%-37%) with evidence of significant heterogeneity (I2 = 79.3%, P < 0.001). CONCLUSION: The use of rectal stents in obstructing rectal or recto-sigmoid tumors seems to be technically feasible. A high rate of technical success, however, does not always translate into clinical success. A considerable complication rate is associated with this approach. Randomized controlled trials are needed to compare the outcomes of rectal stent placement with those of surgery.

Colon or Rectal Stent Positioning for Advanced Cancer Influences Quality of Life: A Critical Point of View.

BACKGROUND/AIM: Endoluminal self-expanding metallic stents (SEMS) may overcome the risk of mortality and morbidity of acute intestinal obstruction because of stage IV colon (CC) or rectal (RC) cancer. We evaluated the QoL in these groups of patients. PATIENTS AND METHODS: Forty-eight patients were enrolled in a prospective longitudinal cohort single-center trial to undergo SEMS positioning. Twenty-five patients had a CC and 23 RC. Karnofsky performance scale, Visual Analogue Scale and the EQ-5D- 5L™ questionnaire were administered before treatment and at 1, 3 and 6 months. RESULTS: Harmonized to the Italian population, the index values showed a statistically significant deterioration of the QoL in patients with RC when compared to those with CC at 1-, 3- and 6-months (1 month: p=0.001; 3- month: p=0.001; 6-month: p=0.045). Similarly, Visual Analogue Scale showed variations at 1- (p=0.008), 3- (p=0.001) and 6-months (p=0.020). Rectal stent deployment was the only independent predictor for a worse QoL in all domains (p<0.017; OR=0.196; 95%CI=0.51-0.749). CONCLUSION: Patients affected with stage IV CC had a better QoL after SEMS placement when compared to those affected with RC. The persistency of the primary tumor at the rectal level, even if irradiated, might negatively affect QoL.

Palliative Surgery or Metallic Stent Positioning for Advanced Gastric Cancer: Differences in QOL.

BACKGROUND AND OBJECTIVES: Twenty percent of the patients affected with stage IV antropyloric stomach cancer are hospitalized with a gastric outlet obstruction syndrome (GOOS) requiring its resolution to improve the quality of life (QoL). We present our preliminary short- and mid-term results regarding the influence of endoscopic placement of self-expandable metal stent (SEMS) or open stomach-partitioning gastrojejunostomy in QoL. MATERIALS AND METHODS: In this prospective randomized longitudinal cohort trial, we randomly assigned 27 patients affected with stage IV antropyloric stomach cancer into two groups: Group 1 (13 patients) who underwent SEMS positioning and Group 2 (14 patients) in whom open stomach-partitioning gastrojejunostomy was performed. The Karnofsky performance scale and QoL assessment using the EQ-5D-5L™ questionnaire was administered before treatment and thereafter at 1, 3, and 6 months. Results: At 1-month, index values showed a statistically significant deterioration of the QoL in patients of Group 2 when compared to those of Group 1 (p = 0.004; CI: 0.04 to 0.21). No differences among the groups were recorded at 3-month; whereas, at 6-month, the index values showed a statistically significant deterioration of the QoL in patients of Group 1 (p = 0.009; CI: -0.25 to -0.043). CONCLUSIONS: Early QoL of patients affected with stage IV antropyloric cancer and symptoms of GOOS is significantly better in patients treated with SEMS positioning but at 6-month the QoL significantly decrease in this group of patients. We explained the reasons of this fluctuation with the higher risk of re-hospital admission in the SEMS group.

Self-Expandable Metal Stents for Left Sided Colon Obstruction from Diverticulitis. A Single Center Retrospective Series.

Background and Objectives: The incidence of diverticulitis is increasing in western countries. Complicated diverticulitis is defined as diverticulitis associated with localized or generalized perforation, localized or distant abscess, fistula, stricture or obstruction. Colonic symptomatic strictures are often treated with segmental colectomy. The aim of our study is to report our experience with Self Expandable Metal Stents (SEMS) placement to relieve sigmoid obstruction secondary to diverticulitis, either as a permanent solution or as a bridge to elective colectomy. Material and Methods: From January 2016 to December 2018, 21 patients underwent SEMS placement for sigmoid obstruction secondary to diverticulitis at our institution. In four patients with poor general conditions, SEMS was considered the definitive form of treatment. In 17 patients, the stent was placed as bridge to elective colectomy. Data were prospectively collected and retrospectively analyzed. Primary outcomes were postoperative mortality and morbidity after SEMS and subsequent elective colectomy. Results: There was no mortality or major morbidity after SEMS placement or subsequent elective colectomy. No stoma was performed. Conclusions: Placement of Colorectal Self Expandable Stent represents a useful tool to relieve obstruction in patients with left-sided colonic diverticulitis. SEMS placement makes it possible to transform an emergency clinical condition into an elective condition, giving time to resolve the inflammation and the infection inevitably associated with complicated diverticulitis.

Improved results for left-sided malignant colorectal obstruction with a proper selection for self expandable metal stent placement, surgical resection or diverting stoma.

AIMS: Endoscopic placement of Self Expandable Metal Stents to relieve malignant colorectal obstruction has become a common therapeutic advancement in clinical practice. METHODS: In a 16 year period 145 patients had endoscopic placement of a Self-Expandable Metal Stent for acute/subacute left sided malignant colorectal obstruction in a center where gastroenterologists and surgeons cooperate in a daily basis, discussing indications. RESULTS: There was no operative mortality and no major complication in placement of the stent. Technical and clinical success was respectively 94.5% and 91.8%. Consultation among specialists changed the preoperative indication in 60 patients. CONCLUSIONS: Self-Expandable Metal Stents placement represents an important tool to treat patients with obstructing colorectal cancer. Surgical resection, diverting stoma or endoscopic stent placement should be chosen according to the clinical characteristics of each single patient. In this scenario, a close collaboration among specialists in selecting the most appropriate operative procedure is essential and brings to better results.

Is Low Inferior Mesenteric Artery Ligation Worthwhile to Prevent Urinary and Sexual Dysfunction After Total Mesorectal Excision for Rectal Cancer?

BACKGROUND/AIM: We studied the role of high or low inferior mesenteric artery (IMA) tie on defecatory, sexual and urinary dysfunctions in patients who underwent laparoscopic TME for early rectal cancer. PATIENTS AND METHODS: Forty-six consecutive patients undergoing curative laparoscopic resection for pT2N0M0, rectal adenocarcinoma from February 2013 to March 2019 were enrolled into this prospective randomized open label parallel trial to have a laparoscopic TME with a high (Group 1) or low IMA ligation (Group 2). Demographic data and information on symptoms and comorbidity, intra- and post-operative outcomes and defecatory, sexual and urinary functions before and after surgery according to the validated International quality of life questionnaires. RESULTS: A significant difference in postoperative total score of FIQL scale, Jorge-Wexner incontinence score and Agachan-Wexner constipation score were observed between the high and low tie groups at 1, 6, and 12 months after surgery. ICIQ-UI short form, FSFI, and IIEF demonstrated at 1, 6 and 12 months, the scores were significantly higher for patients of Group 1 as compared to those of Group 2. CONCLUSION: A low IMA ligation permits a better fecal continence, less abdominal pain, and less genito-urinary and sexual dysfunctions in patients submitted to TME for rectal cancer.