Gastrointestinal genetic reprogramming of vitamin A metabolic pathways in response of Roux-en-Y gastric bypass.

Roux-en-Y gastric bypass (RYGB) is one of the most performed bariatric surgical techniques. However, RYGB commonly results, as side effects, in nutritional deficiencies. This study aimed to examine changes in the expression of vitamin A pathway encoding genes in the gastrointestinal tract (GI) and to evaluate the potential mechanisms associated with hypovitaminosis A after RYGB. Intestinal biopsies were obtained through double-balloon endoscopy in 20 women with obesity (age 46.9±6.2 years; body mass index [BMI] 46.5±5.3 kg/m2 [mean±SD]) before and three months after RYGB (BMI, 38.2±4.2 kg/m2). Intestinal mucosal gene microarray analyses were performed in samples using a Human GeneChip 1.0 ST array (Affymetrix). Vitamin A intake was assessed from 7-day food records and serum retinol levels were evaluated by electrochemiluminescence immunoassay. Our results showed the following genes with significant downregulation (p≤0.05): LIPF (-0.60), NPC1L1 (-0.71), BCO1 (-0.45), and RBP4 (-0.13) in duodenum; CD36 (-0.33), and ISX (-0.43) in jejunum and BCO1 (-0.29) in ileum. No significant changes in vitamin A intake were found (784±694 retinol equivalents [RE] pre-operative vs. 809±753 RE post-operative [mean±SD]). Although patients were routinely supplemented with 3500 international units IU/day (equivalent to 1050 µg RE/day) of oral retinol palmitate, serum concentrations were lower in the post-operative when compared to pre-operative period (0.35±0.14 µg/L vs. 0.52±0.33 µg/L, respectively - P=0.07), both within the normal range. After RYGB, the simultaneous change in expression of GI genes, may impair carotenoid metabolism in the enterocytes, formation of nascent chylomicrons and transport of retinol, resulting in lower availability of vitamin A.

Risk factors for gastroesophageal reflux after POEM for achalasia: a systematic review and meta-analysis.

INTRODUCTION: Peroral endoscopic myotomy (POEM) demonstrated similar efficacy to surgical myotomy in the management of achalasia. However, gastroesophageal reflux disease (GERD) is common after POEM. The aim of this study is to identify factors associated with GERD after POEM. METHOD: After searching electronic databases, randomized trials and observational studies including patients with achalasia or other spastic esophageal disorders, treated by POEM, and providing GERD data were selected. GERD was evaluated by 3 methods: pH monitoring, endoscopic findings, and symptoms. For each method, an analysis was performed comparing the outcomes related to the following independent variables: full-thickness (FT) vs circular myotomy, anterior vs posterior, long myotomy vs short myotomy, naive vs previous treatment failure, previous Heller myotomy (HM) vs non-previous-HM, Type I vs II, Type I vs III, and Type II vs III. RESULTS: 2869 publications were identified, and 25 studies met criteria for inclusion in the qualitative analysis. Of these, 18 were included in the meta-analysis. According to the endoscopic findings, circular and anterior myotomy demonstrated a lower trend of GERD with borderline significance (p = 0.06; p = 0.07, respectively). In the pH monitoring and symptom analyses, circular myotomy, anterior myotomy, treatment naive, and non-HM patients were associated with a lower occurrence of GERD; however, no statistically significant difference was found. When comparing achalasia subtypes, no statistical difference was found in all analyses. CONCLUSION: This systematic review and meta-analysis suggest that a circular anterior approach may limit post-POEM GERD and should be considered in appropriate patients.

Comparative study of strategies to prevent esophageal and periesophageal injury during atrial fibrillation ablation.

OBJECTIVE: To compare the prevalence of esophageal and periesophageal thermal injury in patients undergoing radiofrequency (RF) atrial fibrillation (AF) ablation using 8 mm tip catheters during three different esophageal protection strategies. METHODS: Forty-five consecutive patients with paroxysmal or persistent AF underwent first ablation procedure, besides esophagogastroduodenoscopy (EGD) combined with radial endosonography (EUS) performed before and after the pulmonary vein (PV) isolation. Before the procedure, patients were randomly assigned to one of three esophageal lesion protection strategies: group I-without any protective or monitoring dispositive and limiting RF applications to 30 W for 20 seconds, in left atrium posterior wall (LAPW); group II-power and time of RF delivery, up to 50 W for 20 seconds at LAPW, limited by esophageal temperature monitoring; group III-applications of RF in LAPW with fixed power application of 50 W for 20 seconds during continuous esophageal cooling. RESULTS: Baseline characteristics of patients were similar in all groups. The four PVs were isolated in 14 (93.3%), 13 (86.7%), and 15 (100%) patients, respectively in groups I, II, and III. The mean RF power was significantly higher (P < .001) in the posterior side of PVs in group III. Post-AF ablation EGD and EUS revealed two esophageal wall ulcerations and two periesophageal mediastinal edemas only in the esophageal cooling group (P = .008). CONCLUSION: Esophageal cooling balloon strategy resulted in a higher RF power energy delivery when ablating at the LA posterior wall, using 8 mm nonirrigated tip catheters under temperature mode control. Despite that, patients presented a relatively low incidence of esophageal and periesophaeal injuries.

Randomized controlled trial of hemostatic powder versus endoscopic clipping for non-variceal upper gastrointestinal bleeding.

BACKGROUND AND AIMS: Despite advances in pharmacological and endoscopic management of non-variceal upper gastrointestinal bleeding (NVUGIB), mortality is still relevant. TC-325 (Hemospray-Cook Medical) is a mineral powder with adsorptive properties, designed for endoscopic hemostasis. There are still no comparative trials studying this new hemostatic modality. The objective of this research was to compare the use of TC-325 (associated with epinephrine injection) with the combined technique of endoscopic clipping and epinephrine injection for the treatment of patients with NVUGIB. METHODS: We conducted a pilot randomized controlled trial with patients that presented NVUGIB with an actively bleeding lesion at the endoscopic evaluation. Patients were randomized either to the Hemospray or Hemoclip group. The randomization list was generated by a computer program and remained unknown throughout the entire trial. All patients underwent second-look endoscopy. RESULTS: Thirty-nine patients were enrolled. Peptic ulcer was the most frequent etiology. Primary hemostasis was achieved in all Hemospray cases and in 90% of Hemoclip group (p = 0.487). Five patients in Hemospray group underwent an additional hemostatic procedure during second-look endoscopy, while no patient in the Hemoclip group needed it (p = 0.04). Rebleeding, emergency surgery and mortality rates were similar in both groups. No toxicity, allergy events, or gastrointestinal obstruction signs were observed in Hemospray group. CONCLUSIONS: TC-325 presents similar hemostatic results when compared with conventional dual therapy for patients with NVUGIB. Hemospray's excellent primary hemostasis rate certifies it as a valuable tool in arduous situations of severe bleeding or difficult location site.

Peroral endoscopic myotomy in pediatric jackhammer esophagus.

The jackhammer esophagus is a rare hypercontractile disorder and diagnosis is based on high-resolution manometry. Peroral endoscopic myotomy (POEM) of the spastic esophagus segments has been described. We report a pediatric patient with jackhammer esophagus that was treated endoscopically.

Narrow band imaging versus lugol chromoendoscopy to diagnose squamous cell carcinoma of the esophagus: a systematic review and meta-analysis.

BACKGROUND: In the early stage esophageal cancer, changes in the mucosa are subtle and pass unnoticed in endoscopic examinations using white light. To increase sensitivity, chromoscopy with Lugol's solution has been used. Technological advancements have led to the emergence of virtual methods of endoscopic chromoscopy, including narrow band imaging (NBI). NBI enhances the relief of the mucosa and the underlying vascular pattern, providing greater convenience without the risks inherent to the use of vital dye. The purpose of this systematic review and meta-analysis was to evaluate the ability of NBI to diagnose squamous cell carcinoma of the esophagus and to compare it to chromoscopy with Lugol's solution. METHODS: This systematic review included all studies comparing the diagnostic accuracy of NBI and Lugol chromoendoscopy performed to identify high-grade dysplasia and/or squamous cell carcinoma in the esophagus. In the meta-analysis, we calculated and demonstrated sensitivity, specificity, and positive and negative likelihood values in forest plots. We also determined summary receiver operating characteristic (sROC) curves and estimates of the areas under the curves for both per-patient and per-lesion analysis. RESULTS: The initial search identified 7079 articles. Of these, 18 studies were included in the systematic review and 12 were used in the meta-analysis, for a total of 1911 patients. In per-patient and per-lesion analysis, the sensitivity, specificity, and positive and negative likelihood values for Lugol chromoendoscopy were 92% and 98, 82 and 37%, 5.42 and 1.4, and 0.13 and 0.39, respectively, and for NBI were 88 and 94%, 88 and 65%, 8.32 and 2.62, and 0.16 and 0.12, respectively. There was a statistically significant difference in only specificity values, in which case NBI was superior to Lugol chromoendoscopy in both analyses. In the per-patient analysis, the area under the sROC curve for Lugol chromoendoscopy was 0.9559. In the case of NBI, this value was 0.9611; in the per-lesion analysis, this number was 0.9685 and 0.9587, respectively. CONCLUSIONS: NBI was adequate in evaluating the esophagus in order to diagnose high-grade dysplasia and squamous cell carcinoma. In the differentiation of those disorders from other esophageal mucosa alterations, the NBI was shown to be superior than Lugol.

Endoscopic colostomy with percutaneous colopexy: an animal feasibility study.

BACKGROUND: Indications for colostomy in colorectal diseases are obstruction of the large bowel, such as in cancer, diverticular disease in the acute phase, post-radiotherapy enteritis, complex perirectal fistulas, anorectal trauma and severe anal incontinence. Some critically ill patients cannot tolerate an exploratory laparotomy, and laparoscopic assisted colostomy also requires general anesthesia. OBJECTIVE: To evaluate the feasibility, safety and efficacy of performing colostomy assisted by colonoscopy and percutaneous colopexy. MATERIALS AND METHODS: Five pigs underwent endoscopic assisted colostomy with percutaneous colopexy. Animals were evaluated in post-operative days 1, 2, 5 and 7 for feeding acceptance and colostomy characteristics. On day 7 full colonoscopy was performed on animals followed by exploratory laparotomy. RESULTS: Average procedure time was 27 minutes (21-54 min). Postoperative mobility and feeding of animals were immediate after anesthesia recovery. Position of the colostomy, edges color, appearance of periostomal area, as well as its function was satisfactory in four animals. Retraction of colostomy was present in one pig. The colonoscopy and laparotomy control on the seventh day were considered as normal. A bladder perforation that was successfully repaired through the colostomy incision occurred in one pig. The main limitation of this study is its experimental nature. CONCLUSION: Endoscopic assisted colostomy with percutaneous colopexy proves to be a safe and effective method with low morbidity for performing colostomy in experimental animals, with possible clinical application in humans.

[Submucosal endoscopic dissection in the treatment of early esophageal cancer]. / Disección endoscópica submucosa en el tratamiento del cáncer precoz deesófago.

We report the case of a male patient, 80 years old, with a history of dyspepsia and no family history of neoplasias. In the upper digestive endoscopy in the distal esophagus, a flat depressed lesion with the appearance of early carcinoma, type IIC of Paris classification, was diagnosed by biopsy as a squamous carcinoma in situ, infiltrating, moderately differentiated non-keratinizing grade II carcinoma. He underwent submucosal endoscopic dissection without complications. Histopathology concluded: carcinoma of squamous cells, predominantly in situ of distal esophagus, measuring 0.6 cm, with focus of 0.1 cm of infiltration in the own lamina; absence of angiolymphatic or perineural invasion. The histopathology specimen had margins of surgical resection free of neoplasia. Stage pT1a. Three months later, in the endoscopy control with biopsy of the area, there was no evidence of carcinoma. We present the case because it is still a challenge to establish the diagnosis of esophageal cancer at an early stage, especially in patients without symptoms, highlighting the importance of chromoendoscopy and a good endoscopic examination to reach the diagnosis. Submucosal endoscopy dissection could be considered as a safe and effective alternative treatment to radical surgery.

Role of EUS evaluation after endoscopic eradication of esophageal varices with band ligation.

BACKGROUND AND AIMS: Variceal recurrence after endoscopic band ligation (EBL) for secondary prophylaxis is a frequent event. Some studies have reported a correlation between variceal recurrence and variceal rebleeding with the EUS features of paraesophageal vessels. A prospective observational study was conducted to correlate EUS evaluation of paraesophageal varices, azygos vein, and thoracic duct with variceal recurrence after EBL variceal eradication in patients with cirrhosis. METHODS: EUS was performed before and 1 month after EBL variceal eradication. Paraesophageal varices, azygos vein, and thoracic duct maximum diameters were evaluated in predetermined anatomic stations. After EBL variceal eradication, patients were submitted to endoscopic examinations every 3 months for 1 year. We looked for EUS features that could predict variceal recurrence. RESULTS: Thirty patients completed a 1-year endoscopic follow-up. Seventeen patients (57%) presented variceal recurrence. There was no correlation between azygos vein and thoracic duct diameter with variceal recurrence. Larger paraesophageal varices predicted variceal recurrence in both evaluation periods. Paraesophageal varices diameters that best correlated with variceal recurrence were 6.3 mm before EBL (52.9% sensitivity, 92.3% specificity, and .749 area under the receiver operating characteristic curve [AUROC]) and 4 mm after EBL (70.6% sensitivity, 84.6% specificity, and .801 AUROC). CONCLUSIONS: We conclude that paraesophageal varices diameter measured by EUS predicts variceal recurrence within 1 year after EBL variceal eradication. Paraesophageal diameter after variceal eradication is a better recurrence predictor, because it has a lower cut-off parameter, higher sensitivity, and higher AUROC.

Comparison of electrical current and ultrasonic device for incision of the septum of the pharyngoesophageal diverticulum in a pig model.

BACKGROUND: Complications of endoscopic treatment of pharyngoesophageal diverticulum (PED) such as bleeding and perforation occur in up to 15 % of cases. Our objective was to compare incision of the PED septum using the ultrasonic device (group H) with incision using electrical current (group M) in a pig model. METHODS: Twenty domestic pigs were divided into groups H and M. The incision of the PED septum was performed using the ultrasonic device or using electrical current, respectively. The procedural time, complication rate, length of the border of the incised septum, and thermal tissue damage were compared between groups. RESULTS: Mean time to divide the septum and total procedure time were significantly shorter in group H. Mean length of the border of the incised septum was significantly higher in group H. The lateral thermal spread caused by electrical current (group M) was more intense. Hemorrhage was exclusively observed in group M. CONCLUSION: Experimental endoscopic diverticulotomy using ultrasonic device was faster and caused less tissue damage when compared to electrical current.

Hemostatic effect of oxidized regenerated cellulose in an experimental gastric mucosal resection model.

BACKGROUND AND STUDY AIM: The endoscopic hemostatic therapies currently available do not always result in hemostasis of gastrointestinal bleeding. Oxidized regenerated cellulose (ORC) mesh is a widely available surgical hemostatic material. The aim of this study was to evaluate the hemostatic efficacy of ORC in experimental gastric hemorrhage after endoscopic resection. METHODS: This was a prospective, two-stage experimental, Phase I, proof-of-concept study. In Stage 1, eight gastric mucosal lesions were created in anticoagulated rabbits and treated with ORC (closed or open pores). In Stage 2, the endoscopic introduction and application of ORC mesh pieces were evaluated in a porcine model of endoscopic submucosal dissection (ESD). RESULTS: In Stage 1, hemostasis was achieved in all lesions. Hemostasis was achieved more rapidly with closed-pore than open-pore ORC (24.5 vs. 66.5 seconds) (P < 0.01). At 24 hours, all lesions showed persistent hemostasis. There were no episodes of rebleeding, complications, or mortality. In Stage 2, the endoscopic introduction of ORC pieces and application with a biopsy forceps were feasible in all ESD lesions. CONCLUSIONS: ORC was an effective hemostatic agent for bleeding lesions following mucosal resection in anticoagulated rabbits. Closed-pore ORC achieved hemostasis faster than open-pore ORC. Endoscopic introduction and release of ORC were feasible.

Evolving endoscopic surgery.

Since the days of Albukasim in medieval Spain, natural orifices have been regarded not only as a rather repugnant source of bodily odors, fluids and excreta, but also as a convenient invitation to explore and treat the inner passages of the organism. However, surgical ingenuity needed to be matched by appropriate tools and devices. Lack of technologically advanced instrumentation was a strong deterrent during almost a millennium until recent decades when a quantum jump materialized. Endoscopic surgery is currently a vibrant and growing subspecialty, which successfully handles millions of patients every year. Additional opportunities lie ahead which might benefit millions more, however, requiring even more sophisticated apparatuses, particularly in the field of robotics, artificial intelligence, and tissue repair (surgical suturing). This is a particularly exciting and worthwhile challenge, namely of larger and safer endoscopic interventions, followed by seamless and scarless recovery. In synthesis, the future is widely open for those who use together intelligence and creativity to develop new prototypes, new accessories and new techniques. Yet there are many challenges in the path of endoscopic surgery. In this new era of robotic endoscopy, one will likely need a virtual simulator to train and assess the performance of younger doctors. More evidence will be essential in multiple evolving fields, particularly to elucidate whether more ambitious and complex pathways, such as intrathoracic and intraperitoneal surgery via natural orifice transluminal endoscopic surgery (NOTES), are superior or not to conventional techniques.

Endoscopic ultrasound-guided choledochoduodenostomy and duodenal stenting in patients with unresectable periampullary cancer: one-step procedure by using linear echoendoscope.

OBJECTIVE: Describe a case series of endoscopic ultrasound (EUS)-guided choledochoduodenostomy (EUS-CD) associated with duodenal self-expandable metal stents (SEMS) placement using solely the linear echoendoscope in seven patients with obstructive jaundice and duodenal obstruction due to unresectable periampullary cancer. MATERIAL AND METHODS: EUS-CD in the first portion of the duodenum, associated with duodenal SEMS placement was performed in seven patients with unresectable periampullary cancer with obstructive jaundice and invasive duodenal obstruction. Laboratory tests and clinical follow-up were performed until patient's death. The procedure was performed by an experienced endoscopist under conscious sedation. The puncture position was chosen based on EUS evaluation, at the common bile duct (CBD) above the tumor, through the distal part of the duodenal bulb. After that, the needle was withdrawn and a wire-guided needle knife was used to enlarge the site puncture in the duodenal wall. Then, a partially covered SEMS was passed over the guide, through the choledochoduodenal fistula. Duodenal SEMS placement was performed during the same endoscopic procedure. RESULTS: The procedure was performed in seven patients, ranging between 34 and 86 years. Technical success of EUS-CD, by the stent placement, occurred in 100% of the cases. There were no early complications. Duodenal SEMS placement was effective in 100% of the cases that remained alive after a follow-up of 7 and 30 days. CONCLUSION: The results suggest therapeutic EUS one-step procedure drainage as an alternative for these patients, with good clinical success, feasible technique and safety.

Roux-en-Y gastric bypass affects the expression of genes related to the intestinal folate metabolism pathway in obese women.

OBJECTIVES: Roux-en-Y gastric bypass (RYGB) promotes sustained weight loss, and the resulting new gastrointestinal anatomy can contribute to nutritional depletions. Folate deficiency is one of the most frequently observed nutritional deficiencies after RYGB. The aim of this study was to assess whether RYGB affects the expression of genes related to the intestinal folate metabolism pathway as an additional molecular mechanism contributing to its postoperative deficiency. METHODS: Biopsies from the duodenum, jejunum, and ileum of 20 obese women were collected before and 3 mo after RYGB. The expression of genes involved in intestinal folate metabolism was assessed by microarray and reverse transcriptase polymerase chain reaction (RT-qPCR). Folate intake (7-d food record) and plasma levels (electrochemiluminescence) also were measured. RESULTS: Compared with the preoperative phase, transcriptomic alterations were observed in all intestinal segments studied after RYBG, mainly marked by decreased expression of genes encoding folate transporters/receptors and increased expression of genes involved in folate biosynthesis (P < 0.05). Reduced folate intake and plasma folate levels were also observed simultaneously (P < 0.05). Plasma folate concentrations correlated inversely with intestinal FOLR2 and SHMT2 genes (P < 0.001). CONCLUSION: The present findings suggested that impaired expression of genes related to intestinal folate metabolism may contribute to the early systemic deficiency after RYGB and highlight a potential transcriptomic reprogramming of the intestine in response to RYGB to compensate for folate depletion induced by this surgical technique.

Extrahepatic anterograde covered self-expandable metallic stent placement across malignant biliary obstruction passed by endoscopic ultrasound guidance access: a challenging technique.

The authors report the case of a female patient submitted to endoscopic cholangiography intending to drain the biliary tree due to jaundice. The patient had gastrointestinal deviation due to an advanced gastric cancer that evolved with a distal extrahepatic mass. Abdominal CT scan demonstrated a distal mass, extrahepatic biliary dilation and a normal intra-hepatic tree. In this condition and after a multidisciplinary discussion, an endoscopic ultrasound guided extrahepatic access with the deployment of a partially covered self-expandable metallic stent was performed. The patient normalized her bilirubin levels after a successful procedure.

Systematic review and meta-analysis of colon capsule endoscopy accuracy for colorectal cancer screening. An alternative during the Covid-19 pandemic?

AIM: To determine the diagnostic accuracy of colon capsule endoscopy for colorectal cancer screening. METHODS: Studies that compared the diagnostic performance of colonoscopy and second-generation colon capsule endoscopy (CCE-2) for screening of asymptomatic patients aged 50-75 years were included. The primary outcomes were sensitivity, specificity, and positive and negative likelihood ratios for polyps and adenomas measuring at least 6 mm or 10 mm. RESULTS: Eight full-text studies that evaluated 1602 patients were included for systematic review. Of these, 840 (52.43%) patients participated in an opportunistic screening program. The pooled outcomes of CCE-2 for polyps at least 6 mm / 10 mm were (CI = confidence interval): sensitivity: 88% (95% CI: 0.84-0.91) / 88% (95% CI: 0.82-0.93), specificity: 94% (95% CI: 0.92-0.95) / 95.5% (95% CI: 0.94-0.97); positive likelihood ratio: 11.86 (95% CI: 5.53-25.46) / 23.07 (95% CI: 6.163-86.36); negative likelihood ratio: 0.14 (95% CI: 0.1-0.21) / 0.14 (95% CI: 0.09-0.21). The area under the summary receiver operating characteristic curve for polyps at least 6 and 10 mm was 96.3% and 96.7%, respectively. The only cancer missed by complete CCE-2 was shown at multiple frames in the unblinded review. In total, 125 (7.8%) patients presented mild adverse events mostly related to bowel preparation. CONCLUSION: CCE-2 is demonstrated to be an effective and safe alternative method for colorectal cancer screening. Diagnostic performance of CCE-2 for polyps of at least 6 and 10 mm was similar. Completion rates still need to be improved.

Genetic reprogramming of remnant duodenum may contribute to type 2 diabetes improvement after Roux-en-Y gastric bypass.

OBJECTIVES: Type 2 diabetes control occurs within a few days after Roux-en-Y gastric bypass (RYGB) and might be related to intestinal adaptation to the new anatomic arrangement. The aim of this study was to evaluate the intestinal transcriptome response to RYGB and its correlation with markers of glycemic homeostasis. METHODS: Global transcriptomic analyses performed by microarray technique were conducted in intestinal biopsies collected from adult women with obesity (N = 20) and T2D before and 3 mo after RYGB. Clinical and biochemical markers of glycemic homeostasis were also evaluated. At 1-y postoperative, patients were classified as responsive (R) or non-responsive (NR) to complete T2D remission according to the American Diabetes Association criteria. Intestinal differentially expressed genes (DEGs) were analyzed separately in the two groups, validated by reverse transcription quantitative polymerase chain reaction, and applied in functional enrichment and canonical pathway analysis. Spearman correlations between clinical and biochemical variables with DEGs were conducted. Twelve patients were classified as R and displayed 62 (duodenum), 241 (jejunum), and 63 (ileum) DEGs. RESULTS: Eight of the patients with DEGs presented very strong or strong positive correlations with glycemia or glycated hemoglobin. Duodenal changes of genes involved in the LXR/RXR pathway were more likely to be associated with T2D. CONCLUSION: In obese women, complete remission of T2D after RYGB might include intestinal transcriptomic changes that suggest a potential role of intracellular cholesterol and lipid homeostasis on glucose control.