Barrett`s Esophagus in Bariatric Surgery: Regression or Progression?

INTRODUCTION: Morbid obesity is well known as a risk factor for gastroesophageal reflux disease (GERD) and its related disorders such as Barrett's esophagus (BE). This study aimed to evaluate the development of BE in patients who underwent bariatric surgery. MATERIALS AND METHODS: Using a single-center prospectively established database of obese patients who underwent bariatric surgery from 01/2012 to 12/2019, we retrospectively compared the preoperative endoscopic findings of BE to those after 1-2 years and 3-5 years following bariatric surgery. The change of BE was detected endoscopically according to Prague classification and histologically according to the British guidelines of detecting columnar epithelium on the distal esophagus. RESULTS: Among 914 obese patients who underwent bariatric surgery and received a preoperative esophagogastroduodenoscopy (EGD), we found 119 patients (13%) with BE. A follow-up EGD was performed in 74 of the BE patients (62.2%). A total of 37 (50%) patients underwent a follow-up EGD after 1-2 years and 45 (60.8%) patients underwent it after 3-5 years. Among many clinical parameters, the surgical procedure was the only significant factor for the change of BE after bariatric surgery (p < 0.05). A regression of BE was found in 19 patients (n = 54, 35%) after laparoscopic Roux-en-Y- gastric bypass (LRYGB). Furthermore, a progression of BE was detected in six patients (n = 20, 30%) after laparoscopic sleeve gastrectomy (LSG). CONCLUSION: RYGB should be considered in obese patients with BE. Detecting BE prior to bariatric surgery may have an impact on decision-making regarding the suitable surgical bariatric procedure.

Endoscopic Bariatric Treatment with Duodenal-Jejunal Bypass Liner Improves Non-invasive Markers of Non-alcoholic Steatohepatitis.

PURPOSE: People with obesity often develop non-alcoholic fatty liver disease (NAFLD) and are at high risk of progression to non-alcoholic steatohepatitis (NASH). Few therapies are effective other than bariatric surgery. We therefore analyzed data from duodenal-jejunal bypass liner (DJBL) patients regarding steatosis, fibrosis, and NASH. METHODS: Consecutive DJBL patients with type 2 diabetes underwent standardized assessments up to device removal at 48 weeks. These included aspartate and alanine transaminase (AST, ALT), controlled attenuation parameter (CAP, for steatosis), and liver stiffness measurement (LSM, for fibrosis). The NAFLD fibrosis score (NFS), fibrosis-4 score (FIB4), and enhanced liver fibrosis (ELF) test were also used to assess fibrosis and the Fibroscan-AST (FAST) score to assess NASH. Mixed models were used and missing data were accounted for with multiple imputation. RESULTS: Thirty-two patients (18 female, mean age 55.1, mean BMI 40.2 kg/m2) were included. After 48 weeks, the change compared to baseline with 95% CI was a factor 0.74 (0.65 to 0.84) for AST, 0.63 (0.53 to 0.75) for ALT, and a difference of - 0.21 (- 0.28 to - 0.13) for FAST, all with p < 0.001. Fibrosis based on LSM, NFS, and ELF did not change whereas FIB4 exhibited slight improvement. Eight DJBL were explanted early due to device-related complications and eight complications led to hospitalization. CONCLUSIONS: One year of DJBL therapy is associated with relevant improvements in non-invasive markers of steatosis and NASH, but not fibrosis, and is accompanied by a substantial number of complications. Given the lack of alternatives, DJBL deserves further attention.

Correction to: Preoperative Upper-GI Endoscopy Prior to Bariatric Surgery: Essential or Optional?

In the original article the name of author Matthias Blüher was incorrect. It is correct here and the original article has been corrected.

Preoperative Upper-GI Endoscopy Prior to Bariatric Surgery: Essential or Optional?

INTRODUCTION: The role of preoperative upper-gastrointestinal (GI) gastroscopy has been discussed with controversy in bariatric surgery. The aim of this study was to evaluate the incidence of upper-GI pathologies detected via endoscopy prior to bariatric surgery along with their clinical significance for patients' management. MATERIAL AND METHODS: In our single center prospectively established database of obese patients, who underwent bariatric surgery from January 2011 to December 2017, we retrospectively analyzed the perioperative endoscopic findings along with their influence on patients' management. RESULTS: In total, 636 obese patients with median BMI (body mass index) of 49 kg/m2 [range 31-92] received an upper-GI endoscopy prior to bariatric surgery. Among the surgical procedures, laparoscopic Roux-Y-gastric bypass (72.6%; n = 462) was the most frequent operation. Endoscopically detected pathological conditions were peptic ulcer 3.5% (22/636), Helicobacter pylori (Hp) gastritis 22.4% (143/636), and gastric or duodenal polyps 6.8% (43/636). Reflux esophagitis could be detected in 139/636 patients (21.9%). Barrett's esophagus (BE) was histologically diagnosed in 95 cases (15.0%), whereas BE was suspected endoscopically in 75 cases (11.3%) only. Esophageal adenocarcinomas were detected in 3 cases (0.5%). Change of the operative strategy due to endoscopically or histologically detected pathologic findings had to be performed in 10 cases (1.6%). CONCLUSION: Preoperative upper-GI endoscopy identifies a wide range of abnormal endoscopic findings in obese patients, which may have a significant impact on decision-making, particularly regarding the most suitable bariatric procedure and the appropriate follow-up. Therefore, preoperative upper-GI endoscopy should be considered in all obese patients prior to bariatric procedure.

Endoscopic findings and outcome in caustic ingestion of acidic and alkaline agents in adults: A retrospective analysis.

Caustic ingestion in adults is a rare but potentially life-threatening problem. It remains controversial whether endoscopic findings and mortality differ between acid and alkali ingestion. We compared ingestion of these agents and evaluated prediction parameters for survival and complications.Adult patients who presented with caustic ingestion were analyzed from 2005 to 2016. Mucosal injury was graded endoscopically by Zargar's score. Age, gender, intent of ingestion, caustic agents, comorbidities, management, complications, and mortality were examined.Thirty-one patients met inclusion criteria and were divided into acid (n = 10) and alkali group (n = 21). Ingestion of alkali resulted in higher grades (≥III) of esophageal (56% vs 24%, P = .01) and stomach injuries (43% vs 13%, P = .05) and was mostly done with suicidal intent (76% vs 30%, P = .003). Patients in the alkali group received more often surgical interventions, mechanical ventilation and tracheotomy. Overall complications including Zargar's-score ≥ grade III, mediastinitis, and aspiration pneumonia were higher in alkali group but all showed no statistical significance (P = .73). Mortality (acid: 1 (10%), alkali: 4 (19%), P = .52), age, gender, comorbidities, and intensive care management did not differ significantly between the groups. Chronic renal failure and mediastinitis were promising prediction parameters for mortality but did not reach statistical significance. No independent risk factors for the development of esophageal stenosis were identified.Alkaline agents caused a higher mucosal injury severity and were more often used in suicidal intent. Mediastinitis and chronic renal failure might be potential prediction parameters for survival but need to be evaluated in larger studies.

Endoscopic full-thickness transoral outlet reduction with semicircumferential endoscopic submucosal dissection.

BACKGROUND: Endoscopic full-thickness transoral outlet reduction (efTOR) is a therapeutic option to reduce a dilated gastrojejunal anastomosis (GJA) after Roux-en-Y gastric bypass (RYGB). Mucosal ablation with argon plasma coagulation (APC) is usually performed to achieve tissue adaptation. However, rupture of sutures before scarring can lead to recurrent dilatation of the GJA. Here, we describe efTOR with a semicircumferential endoscopic submucosal dissection (ESD-efTOR) as an alternative to APC-efTOR. METHODS: We enrolled 41 patients with comparable baseline characteristics (APC-efTOR 26; ESD-efTOR 15). The main objectives were reduction in the GJA diameter and in ruptured sutures. Technical success, complications, total weight loss (TWL), and percentage of total and excess weight loss (%TWL and %EWL) at 3 and 12 months, were assessed. RESULTS: ESD-efTOR resulted in significantly fewer ruptured sutures (20 % vs. 69 %; P = 0.004) and a greater reduction in the GJA (major 20 % vs. 0 %; minor 54 % vs. 37 %; no reduction 13 % vs. 58 %; P = 0.02) after 3 months. Technical efficacy, examination time, and rate of complications were comparable. CONCLUSIONS: ESD-efTOR resulted in a significantly greater reduction in the GJA diameter and a lower risk of ruptured sutures compared with APC-efTOR.

Is CO2 insufflation an amelioration of routine colonoscopy?

BACKGROUND: The insufflation of gas during colonoscopy leads to distention of the colon with abdominal discomfort and pain for the patients. Use of CO2 during endoscopy is reported to minimize abdominal discomfort during and after endoscopy. Aim of this study was to find out whether this improvement leads to decreased dosage of sedation drugs in order to improve patient's safety and satisfaction. METHODS: In this double-blind, randomized and controlled study 150 Patients referred to colonoscopy were assigned to either CO2 or air insufflation. We recorded basic characteristics of colonoscopy and the amount of drugs used for sedation. Patients and investigators filled out questionnaires to record pain, abdominal bloating and flatulence. RESULTS: Seventy-two patients were randomized for examination with room air, 78 patients for use of CO2. We found no difference in basic characteristics of colonoscopy (cecal intubation time and procedure time). Both groups were administered the same amount of drugs for sedation. We found only slight improvement of pain, abdominal bloating and flatulence. CONCLUSIONS: The study revealed only moderate positive effects for use of CO2 during colonoscopy. We found only modest improvement of patient's comfort during and after colonoscopy. No reduced doses of drugs for sedation could be recorded.

Design of the Weight-loss Endoscopy Trial (WET): a multi-center, randomized, controlled trial comparing weight loss in endoscopically implanted duodenal-jejunal bypass liners vs. intragastric balloons vs. a sham procedure.

BACKGROUND: Obesity is a global problem leading to reduced life expectancy, cardiovascular diseases, diabetes and many types of cancer. Even people willing to accept treatment only achieve a mean weight loss of about 5 kg using commercial weight loss programs. Surgical interventions, e.g. sleeve gastrectomy or gastric bypass are effective but accompanied by risk of serious complications and side effects. Less invasive endoscopic procedures mainly comprise the intragastric balloon (IB) and the duodenal-jejunal bypass liner (DJBL). To date, a randomized comparison between these devices has not been undertaken or shown to be superior to a sham procedure. METHODS: We designed a multi-center, randomized, patient and assessor-blinded, controlled trial comparing weight loss in endoscopically implanted IB vs. DJBL vs. a sham procedure. A total of 150 patients with a BMI > 35 kg/m2 or > 30 with obesity-related comorbidities and indication for proton pump inhibitors are randomized to receive either IB, DJBL or a sham gastroscopy (2:2:1 ratio). All participants undergo regular dietary consultation. The IB will be removed after 6 months, whereas the DJBL will be explanted after 12 months. All patients will receive gastroscopies at implantation and explantation of the devices or sedation without gastroscopy to maintain blinding. Main exclusion criteria are malignant diseases, peptic ulcer or previous bariatric intervention. Weight loss 12 months after explantation of the devices, changes in comorbidities, quality of life, complication rates and safety will be evaluated. DISCUSSION: This trial could help to identify the most effective and safest endoscopic device, thus determining the new standard procedure for endoscopic bariatric treatment. TRIAL REGISTRATION: 16th January 2017. DRKS00011036. Funded by the German Research Foundation (DFG).

[Dysphagia from a gastroenterologist's perspective]. / Dysphagie aus gastroenterologischer Sicht.

Swallowing disorders (dysphagia) comprise a common cause of medical consultation and are defined as a subjective sensation of difficulty or abnormality of swallowing. In the initial step, a clear differentiation of dysphagia from odynophagia and globus sensation for further diagnostic procedures is mandatory. The careful questioning of patients symptoms and complaints is often helpful for the differentiation of oropharyngeal and esophageal dysphagia. Oropharyngeal dysphagia is mainly caused by neurological disorders (cerebral ischemia, Parkinson's disease, dementia) or local compression of malignancies, thyroid gland or lymph nodes. In contrast, stenosis of the tubular esophagus (peptic stricture, rings and webs, diverticula, malignancies, infections) can lead to esophageal dysphagia, mostly only after ingestion of solids. Esophageal dysphagia after ingestion of solids and liquids is often caused by motility disorders of the esophagus (achalasia, hypertensive or hypercontractile esophagus). Important diagnostic procedures comprise endoscopy, barium swallow and high-resolution manometry. Overlap syndromes are frequent and need to be supervised interdisciplinary. The diagnostic algorithm and interpretation of exam results is complex. If the results are ambiguous, a reevaluation and, when appropriate, repetition of diagnostics are recommended. Whereas oropharyngeal dysphagia is treated by neurologists or ENT physicians, diagnostic and treatment of esophageal dysphagia is a challenging role for gastroenterologists.

Epidemiology and Resistance Patterns of Bacterial and Fungal Colonization of Biliary Plastic Stents: A Prospective Cohort Study.

BACKGROUND: Plastic stents used for the treatment of biliary obstruction will become occluded over time due to microbial colonization and formation of biofilms. Treatment of stent-associated cholangitis is often not effective because of inappropriate use of antimicrobial agents or antimicrobial resistance. We aimed to assess the current bacterial and fungal etiology of stent-associated biofilms, with particular emphasis on antimicrobial resistance. METHODS: Patients with biliary strictures requiring endoscopic stent placement were prospectively enrolled. After the retrieval of stents, biofilms were disrupted by sonication, microorganisms were cultured, and isolates were identified by matrix-associated laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry and/or biochemical typing. Finally, minimum inhibitory concentrations (MICs) were determined for various antimicrobial agents. Selected stents were further analyzed by fluorescence in situ hybridization (FISH). RESULTS: Among 120 patients (62.5% males, median age 64 years) with biliary strictures (35% malignant, 65% benign), 113 double pigtail polyurethane and 100 straight polyethylene stents were analyzed after a median indwelling time of 63 days (range, 1-1274 days). The stent occlusion rate was 11.5% and 13%, respectively, being associated with a significantly increased risk of cholangitis (38.5% vs. 9.1%, P<0.001). Ninety-five different bacterial and 13 fungal species were detected; polymicrobial colonization predominated (95.8% vs. 4.2%, P<0.001). Enterococci (79.3%), Enterobacteriaceae (73.7%), and Candida spp. (55.9%) were the leading pathogens. Candida species were more frequent in patients previously receiving prolonged antibiotic therapy (63% vs. 46.7%, P = 0.023). Vancomycin-resistant enterococci accounted for 13.7%, extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae with co-resistance to ciprofloxacin accounted for 13.9%, and azole-resistant Candida spp. accounted for 32.9% of the respective isolates. CONCLUSIONS: Enterococci and Candida species play an important role in the microbial colonization of biliary stents. Therefore, empirical antimicrobial treatment of stent-associated cholangitis should be guided toward enterococci, Enterobacteriaceae, streptococci, anaerobes, and Candida. To determine causative pathogens, an accurate microbiological analysis of the extracted stent(s) may be helpful.

Palliative Endoscopic Treatment Options in Malignancies of the Biliopancreatic System.

In most of the cases, pancreatic cancer and malignancies of the bile tract can only be treated palliatively. Endoscopy offers several methods for effective control of the symptoms in those situations. In pancreatic cancer, stenting of bile ducts enables a control of jaundice most of the time. Stenting of an obstructed duodenum can relieve symptoms of gastric outlet obstruction without the need for major surgery. In biliary tract cancer, stenting of the bile ducts can provide effective drainage of the biliary system. Photodynamic therapy and radiofrequency ablation can sometimes be a valuable tool in symptom control. This review tries to provide an overview on endoscopic palliative treatment options in pancreatic cancer and biliary tract cancer.

Irinotecan with 5-FU/FA in advanced biliary tract adenocarcinomas: a multicenter phase II trial.

OBJECTIVES: Biliary cancer has a poor prognosis and lacks a standard palliative chemotherapy. The purpose of this prospective single-arm phase II study was to determine the activity and tolerability of irinotecan, 5-fluorouracil, and folinic acid in advanced biliary cancer. PATIENTS AND METHODS: Patients with inoperable intrahepatic cholangiocarcinoma (ICC) or gallbladder cancer (GBC) and no prior chemotherapy were eligible. Irinotecan 80 mg/m2, followed by folinic acid 500 mg/m2 and 5-FU 2000 mg/m2 infused over 24 hours (Fufiri) were administered weekly 6 times, every 8 weeks. The primary endpoint was response rate, and secondary endpoints were overall survival (OS), progression-free survival (PFS), and toxicity. RESULTS: Seventeen patients with ICC and 13 patients with GBC were enrolled. All patients were evaluable for safety. WHO grade 3/4 drug-related adverse events occurred in 8 patients (27%), consisting of diarrhea and leukopenia in 5 and 3 patients, respectively. One patient with diarrhea grade 4 finally succumbed to sepsis. Objective response rate was 10% (95% confidence interval, 2.1%-26.5%), with an additional 10% of patients showing stable disease. Median overall survival was 166 days and 273 days, and median progression-free survival was 84 days and 159 days for ICC and GBC, respectively. CONCLUSIONS: Fufiri is a well-tolerated regimen in patients with ICC and GBC but has only modest activity in advanced biliary tract cancer.

Novel targeted approaches to treating biliary tract cancer: the dual epidermal growth factor receptor and ErbB-2 tyrosine kinase inhibitor NVP-AEE788 is more efficient than the epidermal growth factor receptor inhibitors gefitinib and erlotinib.

Aberrant activation of the epidermal growth factor receptor is frequently observed in neoplasia, notably in tumors of epithelial origin. Attempts to treat such tumors with epidermal growth factor receptor antagonists resulted in remarkable success in recent studies. Little is known, however, about the efficacy of this therapy in biliary tract cancer. Protein expression of epidermal growth factor receptor, ErbB-2, and vascular endothelial growth factor receptor-2 was assessed in seven human biliary tract cancer cell lines by immunoblotting. In addition, histological sections from 19 patients with extrahepatic cholangiocarcinoma were analyzed for epidermal growth factor receptor, ErbB-2 and vascular endothelial growth factor receptor-2 expression by immunohistochemistry. Moreover, we sequenced the cDNA products representing the entire epidermal growth factor receptor coding region of the seven cell lines, and searched for genomic epidermal growth factor receptor amplifications and polysomy by fluorescence in-situ hybridization. Cell growth inhibition by gefitinib erlotinib and NVP-AEE788 was studied in vitro by automated cell counting. In addition, the anti-tumoral effect of erlotinib and NVP-AEE788 was studied in a chimeric mouse model. The anti-tumoral drug mechanism in this model was assessed by MIB-1 antibody staining, terminal deoxynucleotidyl transfer-mediated dUTP nick end-labelling assay, von Willebrand factor staining, and immunoblotting for p-p42/44 (p-Erk1/2, p-MAPK) and p-AKT. Immunoblotting revealed expression of epidermal growth factor receptor, ErbB-2, and vascular endothelial growth factor receptor-2 in all biliary tract cancer cell lines. EGFR was detectable in six of 19 (32%) extrahepatic human cholangiocarcinoma tissue samples, ErbB-2 in 16 of 19 (84%), and vascular endothelial growth factor receptor-2 in nine of 19 (47%). Neither epidermal growth factor receptor mutations nor amplifications or polysomy were found in the seven biliary tract cancer cell lines. Gefitinib, erlotinib and NVP-AEE788 caused a significant growth inhibition in vitro; however, there was a significant difference in efficacy (NVP-AEE788>erlotinib>gefitinib). After 14 days of in-vivo treatment, using the chimeric mouse model, tumors had a significantly reduced volume and mass after NVP-AEE788, but not after erlotinib treatment, as compared with placebo. Reduction of proliferation (signalling via the mitogen-activated protein kinase pathway), induction of apoptosis and inhibition of angiogenesis were the main mechanisms of drug action. No significant reduction of anti-apoptotic AKT phosphorylation, however, occurred, which may be a possible counter mechanism of the tumor. Epidermal growth factor receptor, ErbB-2, and vascular endothelial growth factor receptor-2 expression was detectable in biliary tract cancer, and receptor inhibition exerts marked effects on tumor growth in vitro and in vivo, which was strongest for the dual EGFR/ErbB-2 inhibitor NVP-AEE788. Therefore, further clinical evaluation of this new drug for the treatment of biliary tract cancer is recommended.

Imatinib mesylate (STI571; Glivec)--a new approach in the treatment of biliary tract cancer?

Non-resectable biliary tract cancer is associated with poor prognosis due to widespread resistance to chemotherapeutic agents and radiotherapy. It is therefore essential to explore new therapeutic approaches like the inhibition of tyrosine kinases. The aim of this study was to determine the expression of c-kit and platelet-derived growth factor (PDGF) receptors (PDGFRs) and the effects of the tyrosine kinase inhibitor imatinib +/- 5-fluorouracil (5-FU) on proliferation and apoptosis in biliary tract cancer cell lines. The expression of c-kit and PDGFR mRNA was examined in 12 biliary tract cancer cell lines using RT-PCR. Cells were treated with imatinib (1, 10, 20 and 50 micromol/l) +/- 5-FU (0.1 microg/ml) for 6 days and inhibition of cell growth was assessed by manual cell counting. Cell proliferation and apoptosis were analyzed by flow cytometry of BrdU and Annexin-V/propidium iodide-stained cells. c-kit and PDGF mRNA expression was detected in 50 and 75%, respectively. Imatinib (10 and 20 micromol/l) alone inhibited cell growth significantly higher in c-kit+ cell lines (p<0.02) and inhibition was independent of PDGFR status. The combination with 5-FU increased the effect of imatinib mesylate in all cell lines. Treatment of cells with imatinib +/- 5-FU was associated with a significant induction of apoptosis, but no inhibition of proliferation. We conclude that imatinib alone exerts marked effects on c-kit+ biliary tract cancer cell lines only at intermediate and high concentrations, but there is a potential role of low-dose imatinib in combination with 5-FU for the treatment of biliary tract cancers.

Inactivation of the INK4a/ARF locus and p53 in sporadic extrahepatic bile duct cancers and bile tract cancer cell lines.

The tumor-suppressor genes p14(ARF), p16(INK4a) and Tp53 are commonly inactivated in many tumors. We investigated their role in the pathogenesis of 9 bile tract cancer cell lines and 21 primary sporadic extrahepatic bile duct carcinomas. p53 and p16 protein expression was examined by Western blot analysis and immunohistochemistry. Mutation screening of p53 was done by SSCP and direct sequencing. Inactivating mechanisms of p14 and p16 were addressed by screening for mutations, homozygous deletions, chromosomal loss of 9p21 (loss of heterozygosity [LOH] analysis) and promoter hypermethylation of the p14/p16 genes. p53 overexpression could be detected in 7 of 9 cell lines and 7 of 21 primary tumors, but mutations were found in 3 cell lines only. p16 expression was absent in all cell lines, due to homozygous deletion of the gene in 8 of 9 cell lines and hypermethylation of the p16 promoter in one cell line (CC-LP-1). p14 exon 1beta was homozygously deleted in 6 of 9 cell lines, while retained in CC-LP-1 and 2 additional lines. No p14 promoter hypermethylation could be detected. p16 expression was lost in 11 of 21 primary tumors. p16 promoter hypermethylation was present in 9 of 21 primary tumors, all with lost p16 expression. Allelic loss at 9p21 was detected in 13 of 21 primary tumors, 10 of 11 with lost p16 expression and 8 of 9 with methylated p16 promoter. No p14 promoter hypermethylation or p14/p16 mutations could be detected. Neither Tp53 nor p16 alterations showed obvious association with histopathologic or clinical characteristics. In conclusion, inactivation of the p16 gene is a frequent event in primary sporadic extrahepatic bile duct cancers, 9p21 LOH and promoter hypermethylation being the principal inactivating mechanisms. Therefore, p16, but not p14, seems to be the primary target of inactivation at the INK4a locus in bile duct cancers. Other mechanisms than Tp53 mutations seems to be predominantly responsible for stabilization of nuclear p53 protein in bile duct cancers.