ABSTRACT Background: In the past decades, endoscopic ultrasound has developed from a diagnostic tool to a platform for many therapeutic interventions. Various technological advancements have emerged since the last Brazilian Consensus, demanding a review and update of the recommendations based on the best scientific evidence. Methods: A group of 32 renowned echoendoscopists selected eight relevant topics to be discussed to generate clinical questions. After that, a literature review was conducted to answer these questions based on the most updated evidence. Results: Thirty-three statements were formulated and voted on by the experts to reach a consensus. The Oxford System was used to grade the level of evidence. Conclusion: There is moderate evidence to support that the needle shape, gauge, or aspiration technique does not influence the yield of endoscopic ultrasound (EUS)-guided tissue sampling of pancreatic solid lesions. There is moderate evidence to support using EUS-TTNB of the cyst wall to differentiate between mucinous and non-mucinous cystic neoplasms. There is little evidence to support the EUS-guided treatment of gastric varices. There is a high level of evidence to support that EUS-guided biliary drainage and ERCP present similar outcomes in patients with distal malignant biliary obstruction. There is a high level of evidence for using EUS to diagnose neoplastic pancreatic cysts and detect necrosis before indicating drainage. There is moderate evidence to support EUS-GE over duodenal stent for malignant gastric outlet obstruction in patients with a life expectancy higher than 2 months. There is a high level of evidence to support the use of RFA in treating both functioning and non-functioning types of NET.

Squamous cell carcinoma is the main histological tumor type in the upper aerodigestive tract (UADT), including the esophagus (ESCC) and the head and neck sites, as well as the oral cavity (OCSCC), larynx (LSCC) and oropharynx (OPSCC). These tumors are induced by alcohol and tobacco exposure, with the exception of a subgroup of OPSCC linked to human papillomavirus (HPV) infection. Few genes are frequently mutated in UADT tumors, pointing to other molecular mechanisms being involved during carcinogenesis. The F-box and leucine-rich repeat protein 7 (FBXL7) is a potential tumor-suppressing gene, one that is frequently hypermethylated in pancreatic cancer and where the encoded protein promotes the degradation of AURKA, BIRC5 and c-SRC. Thus, the aim of this study was to evaluate the methylation and expression profile of FBXL7 in the UADT and the gene’s association with the clinical, etiological and pathological characteristics of patients, as well as the expression of its degradation targets. Here we show that the FBXL7 gene’s body is hypomethylated in the UADT, independently of histology, but not in virus-associated tumors. FBXL7 body methylation and gene expression levels were correlated in the ESCC, LSCC, OCSCC and OPSCC. Immunohistochemistry analysis showed that FBXL7 protein levels are not correlated with the levels of its degradation targets, AURKA and BIRC5, in the UADT. The high discriminatory potential of FBXL7 body hypomethylation between non-tumor and tumor tissues makes it a promising biomarker.

Esophageal squamous cell carcinoma (ESCC) ranks among the most lethal tumors worldwide, as a consequence of late detection and poor treatment response, evidencing the need for diagnosis anticipation and new therapeutic targets. First, we investigated the IL6 gene and protein expression in the esophagus of individuals without esophageal disorders (healthy), ESCC, and non-tumoral surrounding tissue (NTST). Our results showed that IL6 mRNA and protein expression is upregulated in tumor cells relative to NTST. In the TCGA dataset, we identified a set of genes whose expression was correlated with IL6 mRNA levels, including the antiapoptotic gene BCL3. By using an immortalized esophageal cell line, we confirmed that IL6 was capable of inducing BCL3 expression in esophageal cells. BCL3 mRNA and protein are overexpressed in ESCC and NTST compared to healthy esophagus, and BCL3 mRNA could distinguish the morphologically normal samples (healthy and NTST) with 100% sensitivity and 95.12% specificity. The spatial intratumoral heterogeneity of both IL6 and BCL3 expression was evaluated, corroborating IL6 upregulation throughout the tumor, while tumor and NTST showed a consistent increase of BCL3 expression relative to the healthy esophagus. Our study shows that IL6 overexpression seems to be a key event in ESCC carcinogenesis, contributing to ESCC through a homogeneous antiapoptotic signalling via BCL3 overexpression, thus suggesting anti-IL6 therapies to be further considered for ESCC treatment. Finally, our data support the use of BCL3 mRNA expression as a potential biomarker for ESCC detection.

Esophageal squamous cell carcinoma (ESCC) is among the ten most frequent and deadly cancers, without effective therapies for most patients. More recently, drugs targeting deregulated growth factor signaling receptors have been developed, such as HGF-MET targeted therapy. We assessed MET and HGF genetic alterations and gene and protein expression profiles in ESCC patients from the Brazilian National Cancer Institute and publicly available datasets, as well as the intratumor heterogeneity of the alterations found. Our analyses showed that HGF and MET genetic alterations, both copy number and mutations, are not common in ESCC, affecting 5 and 6% of the cases, respectively. HGF showed a variable mRNA expression profile between datasets, with no alterations (GSE20347), downregulation (GSE45670), and upregulation in ESCC (our dataset and GSE75241). On the other hand, MET was found consistently upregulated in ESCC compared to non-tumor surrounding tissue, with median fold-changes of 5.96 (GSE20347), 3.83 (GSE45670), 6.02 (GSE75241), and 5.0 (our dataset). Among our patients, 84% of the tumors showed at least a two-fold increase in MET expression. This observation was corroborated by protein levels, with 55% of cases exhibiting positivity in 100% of the tumor cells. Intratumor heterogeneity was evaluated in at least four tumor biopsies from five patients and two cases showed a consistent increase in MET expression (at least two-fold) in all tumor samples. Our data suggested that HGF-MET signaling pathway was likely to be overactivated in ESCC, representing a potential therapeutic target, but eligibility for this therapy should consider intratumor heterogeneity.

More than ever, primum non nocere (first, do no harm) is the main thought we all should have in our minds at this particular moment of the human being! Jean Guillaume Auguste Lugol, the famous French physician who developed the "5% potassium iodide solution" (called Iodine) would never anticipate the importance of his once-known therapeutic substance when presenting his Mémoire sur l’émploi de l’iode dans les maladies scrofuleuses in 1829 at the Royal Academy of Sciences of Paris.1Powell J.L. Powell's pearls: Jean Guillaume Auguste Lugol, MD (1788-1851).Obstet Gynecol Surv. 2006; 61: 1Crossref Google Scholar Although Professor Lugol's original efforts to use iodine to stop the progress of tuberculosis proved to be unsuccessful in the following years, it was Walter Schiller's pioneer studies of early cervical cancer histogenesis,2Powell J.L. Biographic sketch: Powell's Pearls: Walter Schiller, MD (1887-1960).Obstet Gynecol Surv. 2004; 59: 319-320Crossref Scopus (3) Google Scholar, 3Brodmerkel Jr., G.J. Schiller's test: an aid in esophagostopic diagnosis.Gastroenterology. 1971; 60: 813-818Google Scholar, 4Schiller W. Early diagnosis of carcinoma of the cervix.Surg Gynecol Obstet. 1933; 56: 210-212Google Scholar after nearly 100 years, that built up a “noble” place for this solution among the medical diagnostic resources that were to come, especially for upper GI endoscopy. Back to chemistry lessons: Lugol's solution contains potassium iodide (KI) and a stoichiometric amount of elemental free iodine (I2), which confers to it varying strengths, the most commonly available from 1% to 5%. By reacting with the I2, iodine ion (I-) forms a triiodide ion (I3-), which is soluble in water and has its presence revealed by a yellow or brown color according to its low or high concentration in the solution, respectively.5Iodine Test https://en.wikipedia.org/wiki/Iodine_test. Available at: https://en.wikipedia.org/w/index.php?title=Iodine_test&oldid=961160990. Accessed June 6, 2020.Google Scholar Having the essential capability of reacting with glucose chains, a significant amounts of I3- is “ready to work” wherever the glucose chains are stored. In contrast to malignant nonkeratinized epithelial cells, the typical cells contain abundant glycogen, a polymeric biomolecule composed of thousands of linear chains of 8 to 12 glucose units, on average.6Glycogen.https://en.wikipedia.org/wiki/GlycogenDate: 2020Date accessed: June 7, 2020Google Scholar After Lugol’s solution is sprayed onto stratified squamous epithelium, the intracellular glucose chains coil up, fitting inside the I3-. This reaction soon turns into an absorbing deep dark brown light one, mimicking the “iodine clock reaction” phenomenon and indicating silently (and for a short time) the presence of a well-glycogenated normal epithelium: the longer the glucose chains are, the more intense the color reaction will be.7Cartwright H. Kinetics of the persulfate-iodide clock reaction 2006.http://cartwright.chem.ox.ac.uk/tlab/experiments/502.pdfDate accessed: June 8, 2020Google Scholar Evaluating a variety of patients with an insightful eye, Professor Walter Schiller registered areas of different shades of brown staining on cervical mucosa. Interpreted as Lugol positive, or Schiller negative, or simply, iodine represented either benign conditions (eg, columnar epithelium, atrophic squamous epithelium, ulcers, infection, hyperkeratosis, or traumatic desquamation) or the more relevant suggestive premalignant (eg, metaplastic epithelium, dysplastic epithelium) and malignant conditions. Although not pathognomonic, his work drove the attention of the scientific community to learn the boundaries of high energy-consuming epithelial lesions. “Pathologic epithelium, especially carcinomatous, does not take up the stain, but instead remains light, or at most slightly yellowish.” His words, published in 1933, remain effective today.8Schiller Walter (1887–1960): Schiller’s Test.in: Baskett T. Eponyms and Names in Obstetrics and Gynaecology. Cambridge University Press, Cambridge2019: 372Google Scholar Being the seventh most common cancer in the world (3.2% of all cases) and consisting essentially of the esophageal squamous cell carcinoma (ESCC) histiotype, esophageal cancer remains in the sixth position in mortality (5.3%) according to GLOBOCAN 2018.9Cancer fact sheets - Oesophagel cancer Cancer Today - IARC: GLOBOCAN 2018.https://gco.iarc.fr/today/data/factsheets/cancers/6-Oesophagus-fact-sheet.pdfDate: 2020Date accessed: June 8, 2020Google Scholar With a geographically uneven incidence (21-fold difference between the countries with the lowest and the highest incidence rates), a high lethality (89%), and a predominantly advanced staging at diagnosis, ESCC bears the burden of a poor overall 5-year survival rate (16.9%).10Zhang Y. Epidemiology of esophageal cancer.World J Gastroenterol. 2013; 19: 5598-5606Crossref PubMed Scopus (637) Google Scholar Harmful relationships connecting silent (often asymptomatic) superficial lesions to subtle changes in the mucosa and high tumor aggressiveness (cancer rapidly invades through the wall) are among the reasons why ESCC is easily overlooked during endoscopic examination or diagnosed late. Therefore, the detection of precursor lesions and/or ESCC at an earlier and potentially curable stage of the disease is critical (and desirable) to improve patient survival. The development of a flexible fiberoptic endoscope by Hirschowitz et al11Hirschowitz B.I. Peters C.W. Curtiss L.E. Preliminary report on a long fiberscope for examination of stomach and duodenum.Med Bull (Ann Arbor). 1957; 23: 178-180PubMed Google Scholar dramatically changed endoscopic practice in the late 1950s and allowed further conformable and direct inspection of the upper GI lumen. Soon, in 1966, Voegeli12Voegeli R. [Schiller's iodine test in the diagnosis of esophageal diseases. Preliminary report].Pract Otorhinolaryngol (Basel). 1966; 28: 230-239PubMed Google Scholar kicked off the era of enhanced imaging for endoscopic esophageal investigation by reporting the first use of Lugol’s solution on nonkeratinized epithelial mucosa. Subsequent findings by Rywlin and Ortega13Rywlin A.M. Ortega R. Glycogenic acanthosis of the esophagus.Arch Pathol. 1970; 90: 439-443PubMed Google Scholar in 1970 (glycogenic acanthosis), Brodmerkel3Brodmerkel Jr., G.J. Schiller's test: an aid in esophagostopic diagnosis.Gastroenterology. 1971; 60: 813-818Google Scholar in 1971 (diagnosis of esophageal diseases), Nothmann et al14Nothmann B.J. Wright J.R. Schuster M.M. In vivo vital staining as an aid to identification of esophagogastric mucosal junction in man.Am J Dig Dis. 1972; 17: 919-924Crossref PubMed Scopus (39) Google Scholar in 1972 (characterization of squamocolumnar junction limits), and Toriie et al15Toriie S. Akasaka Y. Yamaguchi K. et al.New trial for endoscopical observation of esophagus by dye spraying method.G E N. 1976; 30: 159-165PubMed Google Scholar in 1975 (diagnosis of esophageal diseases), to mention some workers, helped promote the use of vital chromoendoscopy in the differential diagnosis of esophageal diseases. As an example, some of the terms established by them (eg, glycogenic acanthosis) are still in use today. As a well-established concern, improved endoscopic detection and delineation of the limits of high-grade dysplasia and/or early cancerous lesions in the high-risk cancer population (eg, tobacco and alcohol users, patients with already diagnosed ESCC or head-and-neck carcinoma) should be pursued whenever optimal visualization of squamous mucosal abnormalities is required.16Dawsey S.M. Fleischer D.E. Wang G.Q. et al.Mucosal iodine staining improves endoscopic visualization of squamous dysplasia and squamous cell carcinoma of the esophagus in Linxian, China.Cancer. 1998; 83: 220-231Crossref PubMed Scopus (263) Google Scholar,17Bugter O. van de Ven S.E.M. Hardillo J.A. et al.Early detection of esophageal second primary tumors using Lugol chromoendoscopy in patients with head and neck cancer: a systematic review and meta-analysis.Head Neck. 2019; 41: 1122-1130Crossref Scopus (14) Google Scholar Widely (and also wisely) available today, Lugol’s staining turned into an invaluable tool in characterizing the esophageal epithelial surface as a simple and quick technique of progressively spraying the solution on the surface to stain the mucosa with a brown pattern, except for atypical lesions.15Toriie S. Akasaka Y. Yamaguchi K. et al.New trial for endoscopical observation of esophagus by dye spraying method.G E N. 1976; 30: 159-165PubMed Google Scholar For these lesions, the sensitivity for mild dysplasia, moderate dysplasia, severe dysplasia, and cancer was 45.9%, 55.3%, 87.0%, and 97.7%, respectively.18Li J. Xu R. Liu M. et al.Lugol chromoendoscopy detects esophageal dysplasia with low levels of sensitivity in a high-risk region of China.Clin Gastroenterol Hepatol. 2018; 16: 1585-1592Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar Given the fact that “hidden” esophagel cancer may continue evolving asymptomatically, especially in low-income populations, all efforts to prompting resection of these lesions or to better direct biopsies are worth it. That is one reason why the inexpensive Lugol’s solution became so important to the endoscopy family. On the other hand, despite the remarkable achievements and benefits of iodine staining in endoscopy, its routine use would not be without a “cost” to the patients, ie, without having adverse effects. Regardless of the concentration of the free corrosive iodine component in the solution, several studies mention mucosal irritation leading to acute and late adverse symptoms after Lugol’s staining: retrosternal and/or epigastric pain, chest discomfort, acute esophageal and gastric injury (eg, chemical esophagitis, ulcer), and possible allergic reactions are among a broad collection of the reported reactions.19Gotoda T. Kanzaki H. Okamoto Y. et al.Tolerability and efficacy of the concentration of iodine solution during esophageal chromoendoscopy: a double-blind randomized controlled trial.Gastrointest Endosc. 2020; 91: 763-770Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar, 20Park J.M. Seok Lee I. Young Kang J. et al.Acute esophageal and gastric injury: complication of Lugol's solution.Scand J Gastroenterol. 2007; 42: 135-137Crossref PubMed Scopus (31) Google Scholar, 21Thuler F.P. de Paulo G.A. Ferrari A.P. Chemical esophagitis after chromoendoscopy with Lugol's solution for esophageal cancer: case report.Gastrointest Endosc. 2004; 59: 925-926Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar All these “friendly fire” clinical symptoms may further discourage the clinical use of the iodine substance and decrease early identification of premalignant and malignant lesions. Like a re-entry mechanism, in the end, they may prevent early diagnosis of esophageal cancer. It is already known that sodium thiosulfate solution (STS) eases the symptoms induced by mucosal staining with Lugol's solution. Therefore, it has been recommended for routine use after Lugol's staining.22Kondo H. Fukuda H. Ono H. et al.Sodium thiosulfate solution spray for relief of irritation caused by Lugol's stain in chromoendoscopy.Gastrointest Endosc. 2001; 53: 199-202Abstract Full Text Full Text PDF PubMed Scopus (83) Google Scholar However, not diffusely used, it has been suggested to neutralize just the iodine on the surface of the squamous epithelium. At this point, would the use of the iodine solution to clarify our “endoscopic myopia” justify the risk of promoting patients’ retrosternal pain and/or chest discomfort and leaving these symptoms unpunished? Or would it be possible to step outside the box, as Keith Ferrazzi suggests, and “act the way into a new way of thinking”? Is there any hidden solution waiting to be found? The nonmaleficence precept, derived from the maxim primum non nocere (do no harm) principle, is one of the principal precepts of bioethics. It reminds healthcare personnel to (re)consider the possible harm that any intervention might do. In this issue of Gastrointestinal Endoscopy, the study by Jin et al,23Jin D. Wang J. Zhan Q. et al.The safety and efficacy of 2% vitamin C solution spray for relief of mucosal irritation caused by Lugol chromoendoscopy: a multicenter, randomized, double-blind, parallel trial.Gastrointest Endosc. 2020; 92: 554-564Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar “The safety and efficacy of 2% vitamin C solution (VCS) spray for relief of mucosal irritation caused by Lugol chromoendoscopy: a multicenter, randomized, double-blind, parallel trial,” may shed light on relieving the discomfort of symptoms from the topical application of Lugol’s solution. Following an old statement that says “to have something new, somebody needs to do something never tried before,” the authors tested spraying VCS on mucosal surface after iodine solution and proved that it also neutralizes free iodine, relieving the subsequent adverse symptoms. Commended on having first tested the effect of different concentrations of vitamin C both in vitro and ex vivo (experiments on pig esophageal specimens), the authors observed that a 2% VCS had an optimal discoloration effect on the esophageal brown iodine-stained mucosa without histologic damage.23Jin D. Wang J. Zhan Q. et al.The safety and efficacy of 2% vitamin C solution spray for relief of mucosal irritation caused by Lugol chromoendoscopy: a multicenter, randomized, double-blind, parallel trial.Gastrointest Endosc. 2020; 92: 554-564Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar Only then did they translate the results of these bench studies into a noninferiority randomized translational trial. Washing the esophageal mucosa of patients undergoing Lugol chromoendoscopy (10 mL 2% Lugol iodine solution) with a different solution, and evaluating patients’ descriptions of their clinical symptoms after 5 and 35 minutes of ending the examinations, they compared the improving symptoms in 3 distinct groups of 80 patients each, using in the normal saline (NS) group an NS solution (20 mL), in the STS group a 5% STS, and, finally, in the VCS group, a 2% VCS.23Jin D. Wang J. Zhan Q. et al.The safety and efficacy of 2% vitamin C solution spray for relief of mucosal irritation caused by Lugol chromoendoscopy: a multicenter, randomized, double-blind, parallel trial.Gastrointest Endosc. 2020; 92: 554-564Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar With the reduction of acute and late adverse symptom severity scores as primary endpoints and the discoloration effect of esophageal brown iodine-stained mucosa as a secondary endpoint, they found no difference between the STS and VCS groups regarding the reduction of both acute and late adverse symptom scores except when they were determined against NS, where both were superior.23Jin D. Wang J. Zhan Q. et al.The safety and efficacy of 2% vitamin C solution spray for relief of mucosal irritation caused by Lugol chromoendoscopy: a multicenter, randomized, double-blind, parallel trial.Gastrointest Endosc. 2020; 92: 554-564Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar Interestingly, the authors also found that VCS better alleviated acute acid regurgitation and late retrosternal discomfort or pain when compared with STS. VCS and STS quickly discolored the iodine-stained mucosa in a similar way, performing better than NS.23Jin D. Wang J. Zhan Q. et al.The safety and efficacy of 2% vitamin C solution spray for relief of mucosal irritation caused by Lugol chromoendoscopy: a multicenter, randomized, double-blind, parallel trial.Gastrointest Endosc. 2020; 92: 554-564Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar Despite the encouraging results obtained with VCS, one must remember that this trial was designed as a noninferiority comparison, ie, the study aimed to demonstrate that an experimental treatment is not substantially worse than a control treatment (placebo or active control). Noninferiority trials may be performed in situations where conducting a placebo control trial is unethical.22Kondo H. Fukuda H. Ono H. et al.Sodium thiosulfate solution spray for relief of irritation caused by Lugol's stain in chromoendoscopy.Gastrointest Endosc. 2001; 53: 199-202Abstract Full Text Full Text PDF PubMed Scopus (83) Google Scholar Moreover, in favor of the authors’ choice of protocol design, the noninferiority trials may also be used in the investigation of important advantages of the new treatment over the standard ones, especially in terms of improved safety, convenience, better compliance, or cost. Currently considered the best experimental design to assess issues related to treatment and prevention, noninferiority trials have gained popularity within the past decades and are more complex to design, conduct, and interpret than conventional superiority trials. There are some complicated issues with trials of this type that make them less reliable than typical superiority trials.24Hahn S. Understanding noninferiority trials.Korean J Pediatr. 2012; 55: 403-407Crossref PubMed Scopus (73) Google Scholar Among others, noninferiority margin (the maximum acceptable extent of clinical noninferiority of an experimental treatment), assay sensitivity (the ability to distinguish effective treatments from those that are less effective or ineffective), and sample size are important factors to consider.24Hahn S. Understanding noninferiority trials.Korean J Pediatr. 2012; 55: 403-407Crossref PubMed Scopus (73) Google Scholar As for the study by Jin et al,23Jin D. Wang J. Zhan Q. et al.The safety and efficacy of 2% vitamin C solution spray for relief of mucosal irritation caused by Lugol chromoendoscopy: a multicenter, randomized, double-blind, parallel trial.Gastrointest Endosc. 2020; 92: 554-564Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar the authors found that acid regurgitation/heartburn was experienced by 33% and 15% of the patients in the STS and VCS groups, respectively, generating statistical significance (P = .017).23Jin D. Wang J. Zhan Q. et al.The safety and efficacy of 2% vitamin C solution spray for relief of mucosal irritation caused by Lugol chromoendoscopy: a multicenter, randomized, double-blind, parallel trial.Gastrointest Endosc. 2020; 92: 554-564Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar Digging into this result, it should be interpreted with caution because it could be a false positive result, representing a complicated issue as mentioned above. Accordingly, in a superiority trial, a sample size of 120 patients in each group would be needed to detect this same difference (ie, 33% vs 15% in a dichotomous endpoint). Therefore, the fair conclusion (along with the take-home message) is that VCS is noninferior compared with STS in preventing the adverse events related to Lugol spraying of the esophageal mucosa. On the basis of the results obtained by Jin et al23Jin D. Wang J. Zhan Q. et al.The safety and efficacy of 2% vitamin C solution spray for relief of mucosal irritation caused by Lugol chromoendoscopy: a multicenter, randomized, double-blind, parallel trial.Gastrointest Endosc. 2020; 92: 554-564Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar with the use of NS, it is also noteworthy that an “antidote” solution, either VCS or STS, should be used as an integral part of Lugol chromoendoscopy for the sake of our patients’ comfort. Not less important, availability and costs will certainly influence the choice of VCS or STS solutions in the different endoscopy services worldwide. Finally, keeping alive the principle of the primum non nocere in their research, we thank the authors for expanding our arsenal of drugs to mitigate patient discomfort caused by Lugol's chromoendoscopy. Dr Maluf-Filho is a consultant for Apollo, Boston Scientific, Cook Medical, and Olympus. The other author disclosed no financial relationships. The safety and efficacy of 2% vitamin C solution spray for relief of mucosal irritation caused by Lugol chromoendoscopy: a multicenter, randomized, double-blind, parallel trialGastrointestinal EndoscopyVol. 92Issue 3PreviewLugol chromoendoscopy facilitates endoscopic visualization of esophageal dysplasia and carcinoma. Vitamin C solution (VCS) can theoretically neutralize free iodine, which causes mucosal irritation. The aim was to assess the safety and efficacy of VCS for relieving adverse symptoms caused by Lugol iodine staining. Full-Text PDF

Introduction :Neoadjuvant chemoradiotherapy (neoCRT) followed by surgery is the standard of care for locally advanced rectal cancer (LARC), and sphincter preservation is a desirable endpoint, but quality of life (QOL) is often impaired after treatment. Objective To evaluate QOL in five different moments of treatment in a randomized trial comparing two different neoadjuvant regimens. Methods Stage II and III rectal cancer patients were randomized to receive neoCRT with either capecitabine (Group 1) or 5-Fu and leucovorin (Group 2) concomitant to long course radiotherapy. EORTCs QLQ C30 and CR38 were applied before treatment (T0), after neoCRT (T1), after rectal resection (T2), early after adjuvant chemotherapy (T3), and one year after end of treatment or stoma closure (T4). Wexner scale was used for continence evaluation at T4. A C30 summary score (Geisinger et cols) was calculated to compare QOL results.Results 32 patients were assigned to Group 1and 31 to Group 2. QOL was improved comparing T0 to T1 (mean 80.5 vs 88.0, p<0.001), and decreased comparing T1 to T2 (mean 88.0 vs 80.4, p<0.001). No difference in QOL summary was detected comparing T2 to T3 (79.8 vs 82.4, p=0.194) or T3 to T4 (83.0 vs 83.0, p=0.993). No difference in QOL was detected comparing the two treatment groups as clinical response was comparable. Mean Wexner scale score was 9.2, and a score ≥10 correlated with symptoms of diarrhea and defecation problems at T4. Conclusion : QOL improved after neoCRT but worsened following rectal resection, with no significant recovery during follow-up. Capecitabine and 5-Fu/Lv were equivalent in neoadjuvant regimen. Incontinence was high after sphincter preservation. C30 summary score was useful to detect differences in overall Quality of Life in addition to C30 multiple item questionnaire.

Often unexpectedly detected during a routine endoscopy, subepithelial lesions (SELs) are protruding lesions arising from the muscularis mucosa, submucosa, or muscularis propria covered with a normal mucosal surface. The differential diagnosis of such protruding lesions includes a broad range of entities, including stromal tumors, duplication cyst, lipoma, varix, pancreatic rest, and extrinsic compression from normal and abnormal structures.1 Most commonly found in the stomach, SELs, for a long time, seemed to be innocent and harmless findings.

Background and Objectives: Currently, pancreatic cystic lesions (PCLs) are recognized with increasing frequency and have become a more common finding in clinical practice. EUS is challenging in the diagnosis of PCLs and evidence-based decisions are lacking in its application. This study aimed to develop strong recommendations for the use of EUS in the diagnosis of PCLs, based on the experience of experts in the field. Methods: A survey regarding the practice of EUS in the evaluation of PCLs was drafted by the committee member of the International Society of EUS Task Force (ISEUS-TF). It was disseminated to experts of EUS who were also members of the ISEUS-TF. In some cases, percentage agreement with some statements was calculated; in others, the options with the greatest numbers of responses were summarized. Results: Fifteen questions were extracted and disseminated among 60 experts for the survey. Fifty-three experts completed the survey within the specified time frame. The average volume of EUS cases at the experts' institutions is 988.5 cases per year. Conclusion: Despite the limitations of EUS alone in the morphologic diagnosis of PCLs, the results of the survey indicate that EUS-guided fine-needle aspiration is widely expected to become a more valuable method.

Esophageal squamous cell carcinoma (ESCC) presents poor prognosis, and patients diagnosed with this tumor currently lack target treatments. Therefore, in order to identify potential targets for ESCC treatment, we carried out a transcriptome analysis with ESCC and paired nonmalignant surrounding mucosa samples, followed by a master regulator analysis, and further explored the role of the identified central regulatory genes through in vivo and in vitro assays. Among the transcription factors deregulated/enriched in ESCC, we focused on FOXM1 because of its involvement in the regulation of critical biological processes. A new transcriptome analysis performed with ESCC cell lineage TE-1 showed that the modulation of FOXM1 expression resulted in PIK3R3 expression changes, whereas chromatin immunoprecipitation assay revealed that FOXM1 was capable of binding onto PIK3R3 promoter, thus demonstrating that PIK3R3 is a new FOXM1 target. Furthermore, FOXM1 overexpression resulted in the activation of PIK3/AKT signaling pathway through PIK3R3-mediated AKT phosphorylation. Finally, the analysis of the clinic-pathological data of ESCC patients revealed that overexpression of both FOXM1 and PIK3R3 was associated with poor prognosis, but only the latter was an independent prognosis factor for ESCC patients. In conclusion, our results show that FOXM1 seems to play a central role in ESCC carcinogenesis by upregulating many oncogenes found overexpressed in this tumor. Furthermore, PIK3R3 is a novel FOXM1 target that triggers the activation of the PI3K/AKT pathway in ESCC cells.

Abstract Background Anastomotic leaks after esophagectomy can lead to severe complications and account for 40% of postoperative deaths. During the last decades, several types of endoscopic treatments have became available, such as the use of esophageal stent and the use of vacuum therapy. In this paper we report one case of cervical anastomotic fistulas after esophagectomy treated with vacuum therapy and two cases treated with stent. Methods Three cases of cervical anastomotic fistulas after esophagectomy treated with an endoscopic aproach (stent and vacuum therapy) are reported. Results Case 1 61-year-old male with an mid-esophagus adenocarcinoma was treated with neoadjuvant chemotherapy and minimally invasve esophagectomy. On the 10th post-operative day (POD) a partial dehiscence of the anastomosis with communication with the mediastinum was identified, forming a cavity with a large amount of purulent secretion. A sponge attached to a nelaton probe, similar to the VAC device, was positioned inside the mentioned cavity and coupled to a continuous aspiration system. There was a gradual clinical improvement and on the 30th POD the sponge was finally removed. The patient was discharged on the 50th POD. Case 2: A 62-year-old male with a adenocarcinoma in the thoracic esophagus received neoadjuvant chemoradiotherapy and a minimally invasive esophagectomy. On the 7th POD, an anastomotic fistula draining by the chest tube was diagnosed. A stent that was positioned over the fistula area. The patient was discharged on the 28th POD with the stent, that was removed six weeks later. Case 3: 58 years old male patient presented with a superficial squamous cell carcinoma of the mid-thoracic esophagus. A minimally invasive esophagectomy was performed.On the 7th POD, a EGD was performed and showed a fistulous orifice in the esophagogastric anastomosis. A metal stent that was positioned over the fistula area. The patient evolved with empyema and a pulmonary decortication was performed by on the 17th POD. After progressive clinical improvement he was discharged on the 34th POD. Conclusion Esophageal stent has been successful used in treating this surgical complication. Recently, VAC therapy, is becoming an promising therapy for this complication, with lower morbidity and mortality rates and greater success in the closure of the anastomotic fistula when compared to the esophageal stent. Disclosure All authors have declared no conflicts of interest.

BACKGROUND AND OBJECTIVES:At the time of its introduction in the early 80s, endoscopic ultrasonography (EUS) was indicated for diagnostic purposes. Recently, EUS has been employed to assist or to be the main platform of complex therapeutic interventions.METHODS:From a series of relevant new topics in the literature and based on the need to complement the I Brazilian consensus on EUS, twenty experienced endosonographers identified and reviewed the pertinent literature in databases. The quality of evidence, strength of recommendations, and level of consensus were graded and voted on.RESULTS:Consensus was reached for eight relevant topics: treatment of gastric varices, staging of nonsmall cell lung cancer, biliary drainage, tissue sampling of subepithelial lesions (SELs), treatment of pancreatic fluid collections, tissue sampling of pancreatic solid lesions, celiac neurolysis, and evaluation of the incidental pancreatic cysts.CONCLUSIONS:There is a high level of evidence for staging of nonsmall cell lung cancer; biopsy of SELs as the safest method; unilateral and bilateral injection techniques are equivalent for EUS-guided celiac neurolysis, and in patients with visible ganglia, celiac ganglia neurolysis appears to lead to better results. There is a moderate level of evidence for: yield of tissue sampling of pancreatic solid lesions is not influenced by the needle shape, gauge, or employed aspiration technique; EUS-guided and percutaneous biliary drainage present similar clinical success and adverse event rates; plastic and metallic stents are equivalent in the EUS-guided treatment of pancreatic pseudocyst. There is a low level of evidence in the routine use of EUS-guided treatment of gastric varices.

Background and study aims Performing a percutaneous endoscopic gastrostomy (PEG) in head and neck cancer (HNC) patients can be challenging because of the presence of trismus, pharyngeal obstruction by tumor, and pharyn-goesophageal strictures or fistula. Pharyngocutaneous fistula (PCF) is a major postoperative concern in patients submitted to total laryngectomy (TL). In the medical literature to date, the cervical fistula has been used as an access to PEG in only four reports. The aim of this study was to evaluate the safety of cervical fistula for insertion of a PEG tube. Patients and methods Retrospective study at a single tertiary referral center, regarding the technical feasibility, safety and outcomes of a PEG tube introduced by a cervical fistula in HNC patients with obstructive lesions of the oropharynx. Results The procedure was technically successful in all 21 patients. A PEG tube was used for a minimum of 1 month and a maximum of 120 months. Twelve patients died while using the PEG tube, 8 had it taken out because it was no longer needed, and only 1 had the tube still in use. Adverse events occurred in 8 patients: granuloma (19 %), dermatitis (9.5 %), accidental late removal of the tube (9.5%), periprocedural gastric wall hematoma (9.5 %), peristomal wound infection (4.7%), buried bumper syndrome (4.7 %), and traumatic gastric ulcer (4.7%). Conclusion A postoperative cervical fistula can successfully work as a reliable and safe access for a PEG tube procedure in HNC patients, avoiding unnecessary surgery and reducing costs.

The insertion of percutaneous endoscopic gastrostomy (PEG) through an alternative access route (pharyngoesophagostomies or cervical fistulas) is rarely described in the literature.

BACKGROUND:In the last 20 years, several papers have focused on demonstrating the impact of endoscopic ultrasonography findings on the management of different clinical scenarios in digestive disease. This fact is an indirect evidence of the difficulty of popularization of the method. On other hand, the limited availability of endoscopic ultrasonography in Brazil is a direct evidence of this limitation. This was the rationale for the organization of a consensus meeting on endoscopic ultrasonography. It was aimed to identify the best evidence that support the use of endoscopic ultrasonography in gastroenterology.METHODS:A panel of experts on endoscopic ultrasonography was selected based on the files of the Gastroenterology and Endoscopy Societies and on the registries of endoscope manufacturers. Two members of the meeting selected the relevant topics that were transformed into questions. The topics and the questions were debated among the experts five months before the consensus meeting. The experts were asked to perform systematic reviews in order to answer the questions so it could be possible to grade the answers based on the strength of the evidence. During the two days of the meeting the answers were presented, debated and voted. Consensus was reached when a minimum of 70% of the voters were in agreement. The final consensus report was submitted to the experts' evaluation and approval.RESULTS:Seventy nine questions were debated by the experts at the pre-Consensus meeting. As the result of this debate 85 questions came out and were assigned to the members of the panel. During the Consensus meeting 22 experts debated and voted 85 answers. Consensus was reached for several clinical scenarios for which the impact of endoscopic ultrasonography findings were supported by level 1 evidences: differential diagnosis of subepithelial lesions and thickening of gastric folds, staging and diagnosis of unresectable esophageal cancer, indirect signs of peritoneal involvement of gastric cancer, MALT gastric lymphoma and rectal cancer staging, diagnosis of common bile duct and gallbladder stones, diagnosis of chronic pancreatitis and differential diagnosis of a solid mass in chronic pancreatitis, differential diagnosis of the pancreatic cyst, prediction of the results of the endoscopic treatment of esophageal varices and diagnosis and staging of non-small cell lung cancer.CONCLUSIONS:There are the highest levels of evidences that support the indication of endoscopic ultrasonography for several digestive diseases and even for non-small cell lung cancer.

RACIONAL: Ainda que se reconheça a eficiência da ecoendoscopia para o diagnóstico e até mesmo para o tratamento de várias doenças do aparelho digestivo, a sua inclusão nos algoritmos de decisão clínica em gastroenterologia tem sofrido restrições. Este fato é comprovado indiretamente através da existência de vários estudos que se preocuparam em demonstrar o impacto do exame ecoendoscópio na mudança de condutas e na redução de custos. Outra evidência, esta direta e identificável em nosso meio, é a disponibilidade bastante limitada da ecoendoscopia no Brasil. Neste sentido, quiseram-se identificar as situações clínicas em que o exame ecoendoscópico é eficiente, através de revisões sistemáticas, graduando-se o grau da evidência e a força da recomendação, realizadas pelo grupo envolvido com o método em nosso país, apresentadas e votadas na forma de consenso. MÉTODO: O grupo de médicos que realiza ecoendoscopia foi formado a partir de informações obtidas junto às sociedades de especialidades e aos fabricantes de equipamentos. A lista de tópicos e perguntas relevantes foi formulada por dois membros do consenso (FMF, CMD), discutida com e distribuída aos consensualistas 5 meses antes da reunião de consenso. Foi solicitado que se realizassem, na medida do possível, revisões sistemáticas e que as respostas fossem apresentadas para a votação com o grau de evidência e a força da recomendação. Nos 2 dias da reunião de consenso, as respostas foram apresentadas, debatidas e votadas. Quando, no mínimo, 70% dos votantes concordaram com o texto da resposta, houve consenso. O relatório final foi submetido a apreciação e aprovado por todos os consensualistas. RESULTADOS: Setenta e nove questões foram debatidas na pré-reunião do consenso, resultando 85 questões que foram então distribuídas. Nos 2 dias da reunião do consenso, 22 participantes debateram e votaram as 85 respostas. O impacto causado pelo exame ecoendoscópico foi comprovado por evidências do nível 1, gerando recomendações grau A e consenso entre os participantes nas seguintes situações: diagnóstico diferencial da lesão subepitelial do tubo digestivo e do espessamento de pregas gástricas, estádio e identificação de lesão irressecável no câncer do esôfago, sinais indiretos de carcinomatose peritonial no câncer gástrico avançado, estádio de linfoma gástrico tipo Malt e estádio do câncer de reto, diagnóstico da litíase da vesícula biliar e do colédoco, diagnóstico da pancreatite crônica, diagnóstico diferencial do nódulo sólido da pancreatite crônica, diagnóstico diferencial do cisto pancreático, resultados do tratamento endoscópico das varizes esofágicas, diagnóstico e estádio do câncer de pulmão não-pequenas células. CONCLUSÃO: Já há evidências do melhor nível na literatura médica justificando a utilização do exame ecoendoscópico em várias doenças do sistema digestório e, até mesmo, no câncer do pulmão.

RACIONAL: Ainda que se reconheça a eficiência da ecoendoscopia para o diagnóstico e até mesmo para o tratamento de várias doenças do aparelho digestivo, a sua inclusão nos algoritmos de decisão clínica em gastroenterologia tem sofrido restrições. Este fato é comprovado indiretamente através da existência de vários estudos que se preocuparam em demonstrar o impacto do exame ecoendoscópio na mudança de condutas e na redução de custos. Outra evidência, esta direta e identificável em nosso meio, é a disponibilidade bastante limitada da ecoendoscopia no Brasil. Neste sentido, quiseram-se identificar as situações clínicas em que o exame ecoendoscópico é eficiente, através de revisões sistemáticas, graduando-se o grau da evidência e a força da recomendação, realizadas pelo grupo envolvido com o método em nosso país, apresentadas e votadas na forma de consenso. MÉTODO: O grupo de médicos que realiza ecoendoscopia foi formado a partir de informações obtidas junto às sociedades de especialidades e aos fabricantes de equipamentos. A lista de tópicos e perguntas relevantes foi formulada por dois membros do consenso (FMF, CMD), discutida com e distribuída aos consensualistas 5 meses antes da reunião de consenso. Foi solicitado que se realizassem, na medida do possível, revisões sistemáticas e que as respostas fossem apresentadas para a votação com o grau de evidência e a força da recomendação. Nos 2 dias da reunião de consenso, as respostas foram apresentadas, debatidas e votadas. Quando, no mínimo, 70% dos votantes concordaram com o texto da resposta, houve consenso. O relatório final foi submetido a apreciação e aprovado por todos os consensualistas. RESULTADOS: Setenta e nove questões foram debatidas na pré-reunião do consenso, resultando 85 questões que foram então distribuídas. Nos 2 dias da reunião do consenso, 22 participantes debateram e votaram as 85 respostas. O impacto causado pelo exame ecoendoscópico foi comprovado por evidências do nível 1, gerando recomendações grau A e consenso entre os participantes nas seguintes situações: diagnóstico diferencial da lesão subepitelial do tubo digestivo e do espessamento de pregas gástricas, estádio e identificação de lesão irressecável no câncer do esôfago, sinais indiretos de carcinomatose peritonial no câncer gástrico avançado, estádio de linfoma gástrico tipo Malt e estádio do câncer de reto, diagnóstico da litíase da vesícula biliar e do colédoco, diagnóstico da pancreatite crônica, diagnóstico diferencial do nódulo sólido da pancreatite crônica, diagnóstico diferencial do cisto pancreático, resultados do tratamento endoscópico das varizes esofágicas, diagnóstico e estádio do câncer de pulmão não-pequenas células. CONCLUSÃO: Já há evidências do melhor nível na literatura médica justificando a utilização do exame ecoendoscópico em várias doenças do sistema digestório e, até mesmo, no câncer do pulmão.BACKGROUND: In the last 20 years, several papers have focused on demonstrating the impact of endoscopic ultrasonography findings on the management of different clinical scenarios in digestive disease. This fact is an indirect evidence of the difficulty of popularization of the method. On other hand, the limited availability of endoscopic ultrasonography in Brazil is a direct evidence of this limitation. This was the rationale for the organization of a consensus meeting on endoscopic ultrasonography. It was aimed to identify the best evidence that support the use of endoscopic ultrasonography in gastroenterology. METHODS: A panel of experts on endoscopic ultrasonography was selected based on the files of the Gastroenterology and Endoscopy Societies and on the registries of endoscope manufacturers. Two members of the meeting selected the relevant topics that were transformed into questions. The topics and the questions were debated among the experts five months before the consensus meeting. The experts were asked to perform systematic reviews in order to answer the questions so it could be possible to grade the answers based on the strength of the evidence. During the two days of the meeting the answers were presented, debated and voted. Consensus was reached when a minimum of 70% of the voters were in agreement. The final consensus report was submitted to the experts' evaluation and approval. RESULTS: Seventy nine questions were debated by the experts at the pre-Consensus meeting. As the result of this debate 85 questions came out and were assigned to the members of the panel. During the Consensus meeting 22 experts debated and voted 85 answers. Consensus was reached for several clinical scenarios for which the impact of endoscopic ultrasonography findings were supported by level 1 evidences: differential diagnosis of subepithelial lesions and thickening of gastric folds, staging and diagnosis of unresectable esophageal cancer, indirect signs of peritoneal involvement of gastric cancer, MALT gastric lymphoma and rectal cancer staging, diagnosis of common bile duct and gallbladder stones, diagnosis of chronic pancreatitis and differential diagnosis of a solid mass in chronic pancreatitis, differential diagnosis of the pancreatic cyst, prediction of the results of the endoscopic treatment of esophageal varices and diagnosis and staging of non-small cell lung cancer. CONCLUSIONS: There are the highest levels of evidences that support the indication of endoscopic ultrasonography for several digestive diseases and even for non-small cell lung cancer.

Le but de cette étude multicentrique a été de savoir quel était le rendement de la ponction guidée par échoendoscopie (PGEE) de petites masses pancréatiques (<3cm). 7 centres (2 au Brésil, 1 en Belgique, 1 au Venezuela, 1 en Italie, 1 en Grèce et 1 en France) ont participé à cette étude.