Indocyanine Green Tattooing During Colonoscopy as a Guide to Laparoscopic Colorectal Cancer Surgery: A Literature Review.

BACKGROUND: Endoscopic tattooing of colorectal lesions has been performed employing several markers. The indocyanine green (ICG) that uses near infrared fluorescence technology, has been recently adopted in laparoscopic colorectal cancer surgery. This study aims to systematically review the international literature to validate the ICG in laparoscopic colorectal surgery, in order to include the ICG in the therapeutic protocol. METHODS: Following AMSTAR 2 criteria, we performed a systematic review to evaluate the use of green indocyanine as a marker for preoperative endoscopic tattooing and for lymph nodes mapping. The study selection was conducted using the PubMed database from January 1989 to July 2022. RESULTS: We identified 25 eligible studies. 13 based on fluorescent tumor localization in laparoscopic colorectal surgery using ICG while 12 of them reported the lymphatic road mapping and sentinel node identification by ICG using a near-infrared camera system. One study analyzed both topics. CONCLUSIONS: In laparoscopic colorectal cancer surgery indocyanine green can be used to localize fluorescent tumors and mapping fluorescence lymph node. The use of ICG appears to be a valid and safe technique that helps the surgeon to achieve a better oncological radicality. However, the protocols need to be clarified by further studies.

Sizzling Fat-Curative Endoscopic Resection of a Giant Lipoma Causing Colo-Colic Intussusception.

Giant colonic lipomas, tumors that infrequently occur in the gastrointestinal tract, can manifest as bleeding, abdominal pain and, in few cases, obstruction with intussusception. Surgery is usually the treatment of choice. We report the case of a 78 years-old woman with abdominal pain, constipation, and bleeding due to a giant lipoma of the sigmoid colon causing intussusception. After an initial diagnostic colonoscopy, the patient underwent an endoscopic mucosal resection (EMR) without complications. Even if surgery is traditionally the primary therapeutic approach for giant colonic lipomas, selected cases can be successfully treated with EMR.

Gerd symptoms after laparoscopic Roux-en-Y gastric bypass: an emerging scenario.

Laparoscopic Roux-en-Y gastric bypass (RYGB) is the second most performed bariatric procedure and it is considered the procedure of choice to treat patients with severe obesity and gastroesophageal reflux disease (GERD). However, some authors described the new onset or the recurrence of GERD symptoms after RYGB, and data at follow-up were scanty. In our center, we evaluated trend in weight, GERD symptoms and obesity-related comorbidities in 45 patients undergone RYGB at least 60 months before (mean follow-up 99.9 ± 22.9 months). At RYGB 51.1% patients referred preoperative GERD symptoms; among them, 47.8% showed an intraoperative hiatal hernia (HH). At medium-term follow-up mean BMI was significantly lower compared to baseline (p < 0.001). Among patients with preoperative GERD, 69.6% had GERD resolution and 30.4% reported postoperative GERD symptoms. Furthermore, 18.2% without preoperative GERD referred postoperative GERD new onset. We confirmed that RYGB as primary intervention provides satisfactory weight loss and a high percentage of GERD symptoms resolution. However, about 24.4% of patients complained of GERD symptoms at medium-term follow-up. The pathophysiology of GERD after RYGB, de novo or persistence, is not completely understood and several hypotheses could be drawn; however, further studies focusing the pathophysiology of these symptoms are needed.

Endoscopic suturing for GI applications: initial results from a prospective multicenter European registry.

BACKGROUND AND AIMS: OverStitch devices (OverStitch and OverStitch Sx; Apollo Endosurgery, Inc, Austin, Tex, USA) are used for a wide range of applications. A European registry was created to prospectively collect technical and clinical data regarding both systems to provide procedural outcomes and to find correlation between procedural characteristics and outcomes. This study shows the initial results of the first 3 years of the registry. METHODS: Patients who underwent endoscopic suturing from January 2018 to January 2021 at 9 centers were enrolled. Data regarding the disease treated,suturing pattern and outcomes were registered. Technical feasibility (success reaching the target area), technical success (success placing sutures), and clinical success (complete resolution of the clinical issue) were recorded and analyzed. RESULTS: During the study period, 137 patients (57.7% men) were enrolled with 100% technical feasibility rate. Endoscopic suturing was successfully performed in 136 cases (16.7% with OverStitch Sx), obtaining a technical success rate of 99.3%. No adverse events were recorded. Overall clinical success was 89%. Mucosal defects were sutured in 32 patients (100% clinical success). Leaks/fistulas were treated in 23 patients (64.7% clinical success). The clinical success of stent fixations (n = 38) was 85%. Perforations (n = 22) were repaired with a clinical success of 94.7%. No significant correlation between location, suture pattern or number, and the success was found, except in case of fistulas where fistulas <1 cm treated by a continuous suture were more likely to achieve clinical success in the follow-up (P < .001). CONCLUSIONS: OverStitch-based suturing is technically feasible regardless of site and method of suturing, with no cases of failure. The overall technical success rate of 99.3% and the clinical outcome success rate of 89% demonstrate that OverStitch technology provides reliable suturing with clinical advantages, especially with fistulas <1 cm.

Gastric peroral endoscopic pyloromyotomy for refractory gastroparesis: a systematic review of early outcomes with pooled analysis.

BACKGROUND AND AIMS: Gastroparesis (GP) is a chronic debilitating condition. Prior pyloric-targeted procedures are either invasive or have questionable efficacy. Gastric peroral pyloromyotomy (G-POEM) has been proposed as a minimally invasive approach. We performed a pooled analysis to evaluate the efficacy and safety of G-POEM for GP. METHODS: Electronic databases (Medline, Scopus, EMBASE) were searched up to January 2019. Studies including patients who underwent G-POEM for GP were eligible. Procedural, clinical, and safety outcomes were assessed by pooling data with a random- or fixed-effect model according to the degree of heterogeneity to obtain a proportion with a 95% confidence interval. RESULTS: Ten studies were eligible for inclusion (292 patients), and 2 of the 10 studies were prospective. Seven studies were performed in the United States, 2 in France, and 1 in China. Endoscopic pyloromyotomy was feasible in all patients. Significant symptomatic improvement was achieved after 83.9% of procedures (mean follow-up, 7.8 ± 5.5 months). When comparing the mean values of pre- and postprocedural scintigraphic evolution, there was a significant decrease of the residual percentage at 2 and 4 hours. The overall adverse events rate was 6.8%. CONCLUSIONS: G-POEM appears to be a promising approach for GP in terms of safety and efficacy outcomes in the short term.

Sheep in Wolf's Clothing: Pedunculated Colonic Lipoma with Overlying Hyperplastic and Ulcerated Epithelium.

INTRODUCTION: Lipomas are the most common non-epithelial benign tumors of the gastrointestinal tract with a reported incidence in the colon of 0.2-4.4%. These lesions are usually asymptomatic with a typical endoscopic finding of a smooth, slightly yellow, circular, polyp that is sessile in most cases, covered with normal colonic mucosa. AREAS COVERED: There are rare reported cases of alterations of the overlying mucosa such as hyperplasia, atrophy, adenomatous changes, and necrosis. EXPERT COMMENTARY: We report a rare case of pedunculated colonic lipoma of the transverse colon covered with hyperplastic and ulcerated epithelium easily misdiagnosed as an adenomatous lesion.

Procedural Anxiety, Pain Catastrophizing, and Procedure-Related Pain during EGD and Colonoscopy.

OBJECTIVES: Although sedatives and analgesic drugs defuse anxiety and relieve pain, digestive endoscopy still is uncomfortable and painful for some patients. Identifying patients who tolerate digestive endoscopy less well remains difficult. The present study evaluated the relations between procedural anxiety, catastrophizing thoughts, and pain, using a prospective design and multimodal assessments of pain. METHODS: A total of 118 consecutive patients were assessed for procedural anxiety before endoscopy. During endoscopy, a doctor rated the patients' pain behavior. Before discharge, the patients retrospectively rated endoscopy pain and related catastrophizing thoughts. RESULTS: Notwithstanding sedation, our study revealed large between-subject variability in pain. Catastrophizing thoughts mediated the relation between procedure-related pain observed by the doctor and pain intensity reported by the patient. Catastrophizing thoughts also mediated the effect of procedural anxiety. Our study showed that anxiety exacerbates endoscopy pain when the patient engages in ruminative thinking and feels unable to cope with unpleasant bodily sensations. CONCLUSIONS: This study shows that catastrophizing thoughts account for between-subject differences in endoscopy pain. Rumination and helplessness but not magnification explain how procedural anxiety may evolve in a painful endoscopy experience. To the extent that one can address catastrophizing thoughts, endoscopy pain can be mitigated, especially for patients who are difficult to sedate.

Efficacy of Sedation by Midazolam in Association With Meperidine or Fentanyl and Role of Patient Distress During Elective Colonoscopy.

Meperidine and fentanyl are opioids currently used in addition to midazolam for sedation and analgesia during colonoscopy in Italy. The aim of the study was to assess the impact of patients' psychological state before elective colonoscopy on the efficacy of the sedation regimens. Eighty outpatients who underwent an elective colonoscopy were included in our study. The Hospital Anxiety and Depression Scale questionnaire was self-administered to evaluate basal anxiety and depression state. The rate of baseline discomfort was evaluated by a standard 100-mm visual analog scale. Sedation was obtained alternatively with a midazolam-meperidine or midazolam-fentanyl combination. There were no statistically significant differences between the fentanyl and meperidine groups on body mass index, age, and gender composition. Patients in the meperidine group reported less pain during colonoscopy than patients in the fentanyl group. There were statistically significant positive correlations in the meperidine group with the distress, anxiety, and depression. Our study has pointed out greater effectiveness of the midazolam plus meperidine regimen, equal recovery times, and no significant differences in the duration of the endoscopic examinations. The evaluation of patients' psychological status seems to predict the efficacy of sedation when the nociceptive component of pain is well controlled.

Quality of life in patients with loco-regional rectal cancer after ELRR by TEM versus VLS TME after nChRT: long-term results.

BACKGROUND: Endoluminal loco-regional resection (ELRR) by transanal endoscopic microsurgery (TEM) may be an alternative treatment option to Laparoscopic total mesorectal excision (LTME), in selected patients with N0 rectal cancer. Post-operative quality of life (QoL) evaluation is an important parameter of outcomes related to high percentage of functional sequelae. We reported, in a previous paper, the short and medium term results of QoL in patients who underwent ELRR or LTME. The aim is to evaluate the 3 year QoL in patients with iT2-T3 N0/+ rectal cancer who underwent ELRR by TEM or LTME after neoadjuvant radio-chemotherapy (nChRT) in a retrospective analysis of prospectively collected data. METHODS: We enrolled in this study, 39 patients with iT2-T3 rectal cancer who underwent ELRR (n = 19) or LTME (n = 20), according to predefined criteria. QoL was evaluated by EORTC QLQ-C30 and QLQ-CR38 questionnaires at admission, after n-RCT and 1, 6, 12, and 36 months after surgery. RESULTS: No statistically significant differences in QoL evaluation were observed between the two groups, both at admission and after n-RCT. In short term (1-6 months) period, significantly better results were observed in ELRR group by QLQ-C30 in global health status (p = 0.03), physical functioning (p = 0.026), role functioning (p = 0.04), emotional functioning (p = 0.04), cognitive functioning, fatigue (p < 0.05), dyspnoea (p < 0.001), insomnia (p < 0.05), appetite loss (p < 0.05), constipation (≤ 0.05), and by QLQ-CR38 in: body image (p = 0.03) and defecation (p = 0.025). At 1 year, the two groups were homogenous as assessed by QLQ-C30, whereas the QLQCR38 still showed better results of ELRR versus LTME in body image (p = 0.006), defecation problems (p = 0.01), and weight loss (p = 0.005). At 3 years, no statistically significant differences were observed between the two groups. CONCLUSIONS: In selected patients with rectal cancer, who underwent ELRR by TEM or LTME, QoL tests at 3 years do not show any statistical differences on examined items.

Endoscopic mucosal resection in elderly patients.

BACKGROUND: Endoscopic mucosal resection (EMR) of early superficial colorectal carcinomas is nowadays accepted as the gold standard treatment for this type of neoplasia. AIM: This study aims to evaluate the efficacy and safety of mucosectomy in elderly patients considering the predictive value of submucosal infiltration. METHODS: A retrospective study of all patients referred for EMR of sessile colorectal polyps classified IIa by the Paris classification between April 2013 and April 2015. A total of 50 patients (30 males (60 %); age range = 44-86; mean age = 67.7) were enrolled. Patients were divided in two groups considering 65 years as cutoff to individuate the elderly patients. RESULTS: EMR was performed in 53 lesions: 39 were performed en bloc and 14 by piecemeal technique. 30 % of lesions were in the rectum; 11 % in the sigmoid colon; 15 % in the descending colon; 6 % in the transverse colon; 24 % in the ascendant colon; and 14 % in the cecum. The mean size of the resected specimens was 20 mm (range 8-80 mm). The rate of complete resection was 79.2 %, incomplete 13.2 %, not estimable 7 %. Ten patients underwent surgery because of an incomplete resection and/or histological evaluation. CONCLUSIONS: Colon EMR is safe and effective in elderly patients. Endoscopy is still helped in the correct indication for surgery in high-risk surgical patients.

IFSO Worldwide Survey 2020-2021: Current Trends for Bariatric and Metabolic Procedures.

PURPOSE: This IFSO survey aims to describe the current trends of metabolic and bariatric surgery (MBS) reporting on the number and types of surgical and endoluminal procedures performed in 2020 and 2021, in the world and within each IFSO chapter. METHODS: All national societies belonging to IFSO were asked to complete the survey form. The number and types of procedures performed (surgical and endoluminal interventions) from 2020 to 2021 were documented. A special section focused on the impact of COVID-19, the existence of national protocols for MBS, the use of telemedicine, and any mortality related to MBS. A trend analysis of the data, both worldwide and within each IFSO chapter, was also performed for the period between 2018 and 2021. RESULTS: Fifty-seven of the 74 (77%) IFSO national societies submitted the survey. Twenty-four of the 57 (42.1%) reported data from their national registries. The total number of surgical and endoluminal procedures performed in 2020 was 507,806 and in 2021 was 598,834. Sleeve gastrectomy (SG) remained the most performed bariatric procedure. Thirty national societies (52%) had regional protocols for MBS during COVID-19, 61.4% supported the use of telemedicine, and only 47.3% collected data on mortality after MBS in 2020. These percentages did not significantly change in 2021 (p > 0.05). CONCLUSIONS: The number of MBS markedly decreased worldwide during 2020. Although there was a positive trend in 2021, it did not reach the values obtained before the COVID-19 pandemic. SG continued to be the most performed operation. Adjustable gastric banding (AGB) continues to decrease worldwide.

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.

Novel Impedance-pH Parameters in Pre-Bariatric Assessment of Patients: A Pilot Study.

Novel impedance-pH parameters, Mean Nocturnal Baseline Impedance (MNBI) and Post-Reflux Swallow-Induced Peristaltic Wave (PSPW) index, have been proposed to improve the gastro-esophageal reflux disease (GERD) diagnostic yield. This study aims to determine the integrity of the esophageal epithelial barrier and chemical clearance using these novel parameters and to correlate them with acid exposure time (AET) and acid clearance time (ACT) in obese patients who are candidates for bariatric surgery (BS). Twenty impedance-pHmetry tracings of patients prior to BS were reviewed. Nine (45%) patients with a conclusive diagnosis of GERD had significantly higher ACT, lower MNBI in the distal esophagus and lower PSPW indexes compared to obese patients without GERD. Moreover, 100% of obese patients with GERD had a pathological ACT compared to obese patients without GERD (p = 0.003). However, the percentage of pathological MNBI and PSPW index did not differ between obese patients with and without GERD. The PSPW index and MNBI of the distal channel significantly correlated with ACT and AET. Further studies are needed to assess the role of time-consuming novel parameters in the routine evaluation of morbidly obese patients candidates for BS. The value of acid clearance time is confirmed as a relevant impedance-pH parameter in these patients.

Case report: Laparoscopic nissen-sleeve gastrectomy in a young adult with incidental finding of Morgagni-Larrey hernia.

Laparoscopic sleeve Gastrectomy (LSG) is the most performed bariatric procedure worldwide but it is associated with an increased incidence of de-novo or recurrent GERD. Recently a new technique consisting in LSG with associated fundoplication has been described. Morgagni-Larrey hernia is very rare and there is a lack of evidences on its correct surgical treatment. There are only rare cases of a MLH incidental diagnosis in patients submitted to bariatric surgery. We present our experience of Morgagni-Larrey Hernia (MLH) incidentally found intraoperatively in a patient with Gastroesophageal Reflux Disease (GERD) with Hiatal Hernia (HH) undergoing a bariatric surgical procedure.

Endocuff Vision-Assisted Resection for Difficult Colonic Lesions-Preliminary Results of a Multicenter, Prospective Randomized Pilot Study.

Background-Screening programs for colorectal cancer are implemented due to their ability to reduce mortality. The Endocuff Vision is a new endoscopic device that significantly improves the adenoma detection rate. The primary outcome was to assess the efficacy of ECV in improving stability and reducing operation time during difficult colon polypectomies in a multicenter randomized prospective study. Methods-In a randomized multicenter pilot study, two groups of patients who underwent difficult polypectomies with and without the assistance of Endocuff Vision were compared. Demographics and clinical characteristics of patients were obtained, and polyps' size, morphology, site, and access (SMSA); polypectomy time; and endoscope stability were evaluated. Results-From October 2016 to April 2020, 32 patients were enrolled. In total, 12 patients underwent Endocuff Vision polypectomy, and 20 patients underwent standard polypectomy by using a computer-generated random number table. No statistical differences were found in clinical characteristics, SMSA, and polypectomy time. The most interesting findings were the positive correlations between shaking and SMSA (r = 0.55, p = 0.005) and shaking and polypectomy time (r = 0.745, p < 0.0001). Conclusion-Endocuff Vision seems to be adequately stable during difficult endoscopic resection procedures. The new parameter proposed that shaking is strongly correlated to the stability of the endoscope, the difficulty of the resection (SMSA), and the polypectomy time.

Perception of the COVID-19 pandemic in patients with achalasia and its impact on gastrointestinal symptoms: a proof-of-concept study.

Background: Currently, no data are available on COVID-19 pandemic perception in patients with achalasia. We evaluated how the COVID-19 lockdown was perceived by these patients and its impact on their upper gastrointestinal symptoms. Methods: COVID-19 perception was assessed in 64 patients with achalasia using a previously published survey. Upper gastrointestinal symptoms were assessed using a standardized questionnaire and the results were compared to those obtained before the COVID-19 pandemic. All questionnaires were administered by telephone/video calls during the second Italian lockdown. Results: Fifty-one patients (79.7%) responded to the survey. For the question "On a 0-100 scale, how worried are you about the COVID-19 pandemic?" the mean score was 72.8±27.1, and 64.7% of patients with achalasia gave a score >60 on a visual analog scale of 0-100. In addition, those who considered themselves more vulnerable or anxious about contracting the infection than the general population, showed a significantly higher score for COVID-19 fear compared to those who felt less vulnerable or anxious (79.7±27.6 vs. 62.5±23.6, P=0.027; 80.9±19.6 vs. 57.1±33.1, P=0.002, respectively). The selected patients (n=29), who had not undergone any change in medical/surgical treatment for at least one year before the COVID-19 pandemic, had a significant worsening of the intensity-frequency score of regurgitation, heartburn, odynophagia, water brash, and epigastric burning during the lockdown (P<0.05). Finally, 75% of the patients were very interested in using Telemedicine. Conclusions: The COVID-19 lockdown had a significant impact on the psychological aspects and upper gastrointestinal symptoms of patients with achalasia. Telemedicine might represent a follow-up strategy.

Do difficulties in emotional processing predict procedure pain and shape the patient's colonoscopy experience?

OBJECTIVES: Pain and fear of colonoscopy are inter-related; they make the colonoscopy experience unpleasant and impede adherence to colorectal cancer screening and prevention campaigns. According to previous research, fear and pain have been found to depend on patients' maladaptive cognitions and exaggerated emotional responses. The present study investigated whether emotional processing difficulties predicted colonoscopy pain and the associated catastrophising thoughts. DESIGN: Prospective, observational, blinded. METHOD: A sample of 123 patients was assessed for specific emotional processing difficulties (ie, suppression of emotions, unprocessed emotions, failure to control emotions, avoidance of emotional triggers and impoverished emotional experience) and anxiety-related variables (ie, worry, anxiety and depression) before colonoscopy. A trained medical doctor rated patients' behavioural manifestations of pain during colonoscopy. After complete recovery from sedation, the patients rated the endoscopy experience using perceived pain and situation-specific pain catastrophising scales. RESULTS: About half of the patients were above the cut-off for anxiety before the procedure. Notwithstanding sedation, behavioural manifestations of pain during colonoscopy indicated probable or moderate pain for about one-third of the patients. Failure to control emotions, poor emotional experience and avoiding emotional triggers were positively correlated with behavioural manifestations of pain, self-reported pain and pain catastrophising. Regression analyses, controlling for gender, age, colonoscopy experience and sedation, revealed that avoidance of emotional triggers uniquely contributed to predicting pain outcomes. CONCLUSIONS: Early identification of emotional processing difficulties associated with pain catastrophising can help define personalised psychological preparation paths to manage negative emotions in patients who fear colonoscopy pain.

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.

Mesenchymal Stem Cells for Cryptoglandular Anal Fistula: Current State of Art.

Anal fistula is a common disease that needs surgical treatment to be resolved. Despite a variety of surgical options, the major problem is still to cure complex fistulas without any recurrence in the long-term follow-up but, at the same time, to avoid an impairment of continence. In recent years, one solution has been the application of mesenchymal stem cells derived from adipose tissue, especially in association with other treatments, such as the use of fibrin glue or the previous application of a seton. Their initial use in fistulas associated with Crohn's disease has shown encouraging results. In this non-systematic review our aim is to analyze the use in cryptoglandular fistulas: the rate of healing is not so high, and the number of studies is limited. Therefore, further randomized controlled trials are needed to establish their efficacy in the case of complex cryptoglandular anal fistulas and their possible complications.

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.