Pressure dynamics of the esophagogastric junction at rest and during inspiratory maneuvers after Nissen fundoplication.

Low sphincter pressure and inability of the crural diaphragm to elevate it at the esophagogastric junction are important pathophysiological mechanisms of gastroesophageal reflux disease (GERD). The object of this study was to depict how Nissen fundoplication changed the resting and inspiratory pressures of the anti-reflux barrier. We selected 14 patients (eight males; mean age 42.7 years; mean body mass index 27.8) for surgery. They answered symptoms questionnaires and underwent high-resolution manometry (HRM) before and 6 months after Nissen fundoplication. We used a standard manometric protocol (resting and liquid swallows) and assessment of esophagogastric junction (EGJ) pressure metrics during standardized forced inspiratory maneuvers against increasing loads (Threshold Maneuvers). We used the Wilcoxon test for comparison of pre and postoperative data. After fundoplication, heartburn and regurgitation scores diminished remarkably (from 4.5 and 2, respectively, to zero; P = 0.002 and P = 0.0005, respective medians). Also, the median expiratory EGJ pressure had a significant increase from 8.1 to 18.1 mmHg (P = 0.002), while mean respiratory pressure and EGJ contractility integral (EGJ-CI) increased without statistical significance (P = 0.064 and P = 0.06, respectively). Axial EGJ displacement was lower after fundoplication. The EGJ relaxation pressure (P = 0.001), the mean distal esophageal intrabolus pressure (P = 0.01) and the distal latency (P = 0.017) increased after fundoplication. There was a reduction in the contraction front velocity (P = 0.043). During evaluation with standardized inspiratory maneuvers, the inspiratory EGJ pressures (under loads of 12, 24, 36 and 48 cmH2O) were lower after surgery for all loads (median for load 12 cmH2O: 145.6 vs. 102.7 mmHg; P = 0.004). Fundoplication and hiatal closure increased the expiratory EGJ pressure and promoted a great GERD symptom relief. The surgery seemed to overcompensate a reduced EGJ mobility and inspiratory pressure.

BILIARY FISTULAS ASSOCIATED WITH LIVER TRANSPLANTATION VERSUS OTHER ETIOLOGIES: WHAT IS THE SUCCESS RATE OF THE ENDOSCOPIC TREATMENT?

BACKGROUND: Biliary fistulas typically occur as surgical complications after laparoscopic cholecystectomy, liver transplantation, or partial liver resection. AIMS: This study aimed to evaluate the efficacy of the endoscopic treatment of biliary fistulae secondary to liver transplantation compared to that of other etiologies. METHODS: A retrospective study of 25 patients undergoing endoscopic retrograde cholangiopancreatography for biliary fistula from 2015 to 2021 was conducted at the Endoscospy Unit of Walter Cantídio University Hospital. Clinical characteristics and endoscopic success rates of the post-liver transplantation group were analyzed in comparison with those of other etiologies. RESULTS: The main causes of biliary fistula were liver transplantation (44%) and cholecystectomy complications (44%). The post-liver transplantation group had a significantly higher proportion of male sex (liver transplantation=81.8%, others=28.6%) and older age (liver transplantation=54.1 years, others=42.0 years) and a higher incidence of biliary stenosis (liver transplantation=90.9%, others=14.3%) than those of the group with other etiologies (p<0.05). The two groups received similar treatment types, among which sphincterotomy associated with biliary stent placement was most commonly used. Endoscopic therapeutic success rates showed no significant difference between the post-liver transplantation group (63.6%) and the group with other etiologies (71.4%). CONCLUSIONS: The endoscopic treatment of biliary fistulae secondary to liver transplantation presented a recovery rate similar to that of other etiologies despite the patients older age and the presence of biliary stenosis.

Biliary fistulas associated with liver transplantation versus other etiologies: what is the success rate of the endoscopic treatment? / Fístulas biliares associadas com transplante hepático versus outras etiologias: qual a taxa de sucesso do tratamento endoscópico?

ABSTRACT - BACKGROUND: Biliary fistulas typically occur as surgical complications after laparoscopic cholecystectomy, liver transplantation, or partial liver resection. AIMS: This study aimed to evaluate the efficacy of the endoscopic treatment of biliary fistulae secondary to liver transplantation compared to that of other etiologies. METHODS: A retrospective study of 25 patients undergoing endoscopic retrograde cholangiopancreatography for biliary fistula from 2015 to 2021 was conducted at the Endoscospy Unit of Walter Cantídio University Hospital. Clinical characteristics and endoscopic success rates of the post-liver transplantation group were analyzed in comparison with those of other etiologies. RESULTS: The main causes of biliary fistula were liver transplantation (44%) and cholecystectomy complications (44%). The post-liver transplantation group had a significantly higher proportion of male sex (liver transplantation=81.8%, others=28.6%) and older age (liver transplantation=54.1 years, others=42.0 years) and a higher incidence of biliary stenosis (liver transplantation=90.9%, others=14.3%) than those of the group with other etiologies (p<0.05). The two groups received similar treatment types, among which sphincterotomy associated with biliary stent placement was most commonly used. Endoscopic therapeutic success rates showed no significant difference between the post-liver transplantation group (63.6%) and the group with other etiologies (71.4%). CONCLUSIONS: The endoscopic treatment of biliary fistulae secondary to liver transplantation presented a recovery rate similar to that of other etiologies despite the patients older age and the presence of biliary stenosis

RESUMO - RACIONAL: As fístulas biliares geralmente ocorrem como complicações cirúrgicas, especialmente após colecistectomia laparoscópica, transplante hepático ou ressecção hepática parcial. OBJETIVOS: Avaliar a eficácia do tratamento endoscópico das fístulas biliares secundária ao transplante hepático em comparação com outras etiologias. MÉTODOS: Estudo retrospectivo de 25 pacientes submetidos a Colangiopancreatografia Retrógada Endoscópica por fístula biliar entre 2015 e 2021 no Serviço de Endoscopia do Hospital Universitário Walter Cantídeo. As características clínicas e as taxas de sucesso endoscópico do grupo pós-transplante hepático foram analisadas em comparação com as de outras etiologias. RESULTADOS: As principais causas de fístula biliar foram pós-transplante hepático (44%) e complicações da pós-colecistectomia (44%). O grupo pós-transplante hepático apresentou proporção significativamente maior de sexo masculino (pós-transplante hepático=81,8%, outros=28,6%) e idade mais avançada (pós-transplante hepático=54,1 anos, outros=42,0 anos) e maior incidência de estenose biliar (pós-transplante hepático=90,9%, outros=14,3%) do que o grupo com outras etiologias (p<0,05). Os dois grupos receberam tipos de tratamento semelhantes, dentre os quais a esfincterotomia associada à aposição de prótese biliar foi a mais utilizada. As taxas de sucesso terapêutico endoscópico não mostraram diferença significativa entre o grupo pós-transplante hepático (63,6%) e o grupo com outras etiologias (71,4%). CONCLUSÕES: O tratamento endoscópico das fístulas biliares secundária ao transplante hepático apresentou taxa de recuperação semelhante à de outras etiologias, apesar da idade avançada dos pacientes e da presença de estenose biliar.

TanP: A Multifunctional Anionic Peptide From Tityus stigmurus Scorpion Venom.

Anionic peptides of scorpions are molecules rich in aspartic and/or glutamic acid residues and correspond to a class of peptides without disulfide bonds that are still little explored. TanP is a linear anionic peptide (50 amino acid residues and net charge -20) present in the venom gland of the scorpion, Tityus stigmurus, with chelating properties for Cu2+ ion and immunomodulatory properties. The therapeutic application of chelating molecules is related to cases of acute or chronic intoxication by metals, neurodegenerative diseases, hematological diseases, healing of skin wounds, cardiovascular diseases, and cancer. In this approach, the chelating activity of TanP was evaluated in relation to new metal ions (Fe2+ and Zn2+) of biological importance, as well as its antioxidant, hemostatic, immunomodulatory, and healing potential, aiming to expand the biological and biotechnological potential of this peptide. TanP (25 µM) was able to form stable complexes with Fe2+ in a ratio of 1:5 (TanP: Fe2+). Theoretical results suggest that TanP can work as a sensor to identify and quantify Fe2+ ions. The fluorescence intensity of TanP (1.12 µM) decreased significantly after the addition of Fe2+, obtaining the highest ratio 1: 7.4 (TanP: Fe2+) that led to the lowest fluorescence intensity. For Zn2+, no relevant spectral change was noted. TanP (50 µM) showed a maximum of 3% of hemolytic activity, demonstrating biocompatibility, as well as exhibiting a 1,1-diphenyl-2-picrylhydrazyl radical-scavenging activity of above 70% at all the concentrations tested (1-25 µM), and 89.7% iron-chelating activity at 25 µM and 96% hydroxyl radical-scavenging activity at 73.6 µM. In addition, TanP (12.5 and 25 µM) revealed an anticoagulant effect, prolonging the clotting time in prothrombin time and activated partial thromboplastin time assays, with no fibrinogenolytic activity. TanP (12.5 and 25 µM) induced the release of TNF-α by murine macrophages, in the absence of lipopolysaccharides, with a concentration-dependent increase and also stimulated the migration of 3T3 cells in the in vitro healing assay. Thus, TanP revealed a multifunctional potential, being useful as a prototype for the development of new therapeutic and biotechnological agents.

Valores normais da manometria de alta resolução de esôfago: estudo multicêntrico brasileiro / Normal values of esophageal high-resolution manometry: a brazilian multicenter study

ABSTRACT BACKGROUND: The high-resolution manometry has been a significant advance in esophageal diagnostics. There are different types of catheter and systems devices to capture esophageal pressures that generate variable data related to Chicago Classification (CC) and consequently influence normal values results. There are not normative data for the 24-channel water-perfused high-resolution manometry system most used in Brazil with healthy volunteers in supine posture. OBJECTIVE: To determine manometric esophageal normative values for a 24-channel water-perfused high-resolution manometry catheter in supine posture using healthy volunteers according to CC 3.0 parameters. METHODS: A total of 92 volunteers with no gastrointestinal symptoms or medications affecting GI motility underwent esophageal high-resolution manometry by standard protocol. Age, gender and manometry parameters analyzed using Alacer software were collected. The median, range, and 5th and 95th percentiles (where applicable) were obtained for all high-resolution manometry metrics. Normal value percentiles were defined as 95th integrated relaxation pressure, 5th-100th distal contractile integral, and 5th distal latency. RESULTS: The mean age was 40.5±13.2 years. Our normative metrics were integrated relaxation pressure <16 mmHg and distal contractile integral (708-4111 mmHg.cm.s) distal latency was <6 s and peristaltic break size (>4 cm). For EGJ-CI the range 5th-95th was 21.7-86.9 mmHg.cm.s. CONCLUSION: This is the first report of normative data for the 24-channel water-perfused system in supine posture. It revealed higher integrated relaxation pressure and distal latency duration which suggest the need to change CC 3.0 cutoffs for this system. It is observed that there is a tendency that DCI >7000 mmHg.cm.s may represent the lower limit of hypercontractility, and when <700 mmHg.cm.s (<5% percentile) interpreted as ineffective esophageal motility or failcontraction. Also compared to Chicago 3.0, higher integrated relaxation pressure and duration of distal latency were found. We emphasize that these data must be confirmed by future studies.

RESUMO CONTEXTO: A manometria de alta resolução tem sido um avanço significativo nos diagnósticos esofágicos. Existem diferentes tipos de cateteres e sistemas dispositivos para capturar pressões esofágicas que geram dados variáveis relacionados à Classificação de Chicago (CC) e, consequentemente, podem influenciar os resultados de valores da normalidade. Não há dados normativos com voluntários saudáveis na postura supina, para o sistema manométrico sob perfusão em água de 24 canais, o mais utilizado no Brasil. OBJETIVO: Determinar os valores normativos manométricos do esôfago para um cateter sob perfusão de alta resolução de 24 canais na postura supina utilizando-se voluntários saudáveis assintomáticos de acordo com os parâmetros CC. MÉTODOS: Um total de 92 voluntários sem sintomas gastrointestinais ou medicamentos que afetassem a motilidade gastrointestinal foram submetidos à manometria de alta resolução do esôfago por protocolo padrão (Sistema Alacer Multiplex). Foram coletados parâmetros de idade, sexo e os da manometria analisados pelo software Alacer versão 6.2. A mediana, os limites, e 5% e 95% percentis (quando aplicável) foram obtidos para todas as métricas de alta resolução. Os valores normais foram definidos como percentis de 95% da integral da pressão de relaxamento (IRP), 5%-100% da integral contrátil distal (DCI), e 5% latência distal. RESULTADOS: A média de idade foi de 40,5±13,2 anos. As métricas normativas foram definidas como IRP <16 mmHg) e DCI (708-4111 mmHg.cm.s). Para a latência distal foi de 5,8-9,9 s (faixa: 5,3-10,7s). O comprimento total de quebra na contração esofágica foi de 4,0 cm (faixa: 0,1-6,8 cm). Para a EGJ-CI a faixa 5%-95% percentis foi de 21,7-86,9 mmHg.cm.s. CONCLUSÃO: Este é o primeiro relatório de dados normativos para o sistema de 24 canais perfundido por água na postura supina. A partir dos dados encontrados observa-se a possibilidade de alterar os cortes CC 3.0 para este sistema. Observa-se que há uma tendência que DCI >7000 mmHg.cm.s possa representar o limite inferior da hipercontratilidade e quando <700 mmHg.cm.s (<5% percentil) interpretada como motilidade esofágica ineficaz ou contração falha. Também em comparação com Chicago 3.0, foi encontrada maior pressão de relaxamento integrado e duração da latência distal. Ressaltamos que esses dados devem ser confirmados por estudos futuros.

NORMAL VALUES OF ESOPHAGEAL HIGH-RESOLUTION MANOMETRY: A BRAZILIAN MULTICENTER STUDY.

BACKGROUND: The high-resolution manometry has been a significant advance in esophageal diagnostics. There are different types of catheter and systems devices to capture esophageal pressures that generate variable data related to Chicago Classification (CC) and consequently influence normal values results. There are not normative data for the 24-channel water-perfused high-resolution manometry system most used in Brazil with healthy volunteers in supine posture. OBJECTIVE: To determine manometric esophageal normative values for a 24-channel water-perfused high-resolution manometry catheter in supine posture using healthy volunteers according to CC 3.0 parameters. METHODS: A total of 92 volunteers with no gastrointestinal symptoms or medications affecting GI motility underwent esophageal high-resolution manometry by standard protocol. Age, gender and manometry parameters analyzed using Alacer software were collected. The median, range, and 5th and 95th percentiles (where applicable) were obtained for all high-resolution manometry metrics. Normal value percentiles were defined as 95th integrated relaxation pressure, 5th-100th distal contractile integral, and 5th distal latency. RESULTS: The mean age was 40.5±13.2 years. Our normative metrics were integrated relaxation pressure <16 mmHg and distal contractile integral (708-4111 mmHg.cm.s) distal latency was <6 s and peristaltic break size (>4 cm). For EGJ-CI the range 5th-95th was 21.7-86.9 mmHg.cm.s. CONCLUSION: This is the first report of normative data for the 24-channel water-perfused system in supine posture. It revealed higher integrated relaxation pressure and distal latency duration which suggest the need to change CC 3.0 cutoffs for this system. It is observed that there is a tendency that DCI >7000 mmHg.cm.s may represent the lower limit of hypercontractility, and when <700 mmHg.cm.s (<5% percentile) interpreted as ineffective esophageal motility or failcontraction. Also compared to Chicago 3.0, higher integrated relaxation pressure and duration of distal latency were found. We emphasize that these data must be confirmed by future studies.

Polysaccharide from Gracilaria caudata protects the human esophageal mucosal barrier: A differential topical effect and structural dependence.

This study aimed to evaluate the in vitro protective effect of topical treatment with a native sulfated polysaccharide of G. caudata (SP-Gc), hydrolyzed (H-SP-Gc), or desulfated (D-SP-Gc) polysaccharide of Gracilaria caudata in esophageal biopsies obtained from GERD patients. Biopsies were obtained from nonerosive reflux disease (NERD) patients and from erosive esophagitis patients. Then, the biopsies were mounted in an Ussing chamber to measure the basal transepithelial electrical resistance (TEER). The effect of mucosal exposure to an acid solution on TEER was analyzed with or without different concentrations (1, 0.3 or 1%) of SP-Gc, H-SP-Gc, or D-SP-Gc, precoated on the mucosa. Basal esophageal mucosal electrical resistance was significantly lower in erosive esophagitis than from NERD. Mucosal samples precoated with native SP-Gc (1%) significantly prevented TEER drop induced by an acidic solution in NERD, but this effect was not observed in erosive esophagitis. Topical application of D-SP-Gc showed no difference compared to native SP-Gc. However, when treated with chemically-modified SP-Gc, the protective effect observed with native SP-Gc was lost. The present study indicated that SP-Gc protects the human esophageal mucosal barrier in NERD patients. This effect is dependent on the structure but is independent of the presence of sulfate.

Association between endoscopic findings and histopathological confirmation in patients with suspicion of eosinophilic esophagitis.

BACKGROUND: The diagnosis of eosinophilic esophagitis (EoE) is performed by the detection of 15 or more eosinophils per field in an esophageal biopsy sample, but the endoscopic findings alone are not validated for a diagnosis of the disease. OBJECTIVE: To evaluate the association between the endoscopic findings and histopathological diagnosis in patients with suspected EoE in endoscopy. METHODS: A retrospective study of 24 patients with suspicion of EoE during endoscopy was held. The information was collected from databases of Endoscopy and Pathology services of the Hospital Universitário Walter Cantídio, Universidade Federal do Ceará, from March 2012 to April 2018. The patients were divided into a group with positive biopsy (>15 Eosinophils/field, N=8) and a group with negative biopsy (<15 Eosinophils/field, N=16), and the endoscopic findings were compared between the two groups. RESULTS: From a total of 24 patients, 79.1% had longitudinal grooves, 20.8% white exudates, 33.3% mucosal pallor or loss of vascularity and 45.8% had more than one endoscopic finding. There was a significant difference (P<0.05) in the evaluation of the finding of mucosal pallor or decreased vasculature alone among the groups. The positive predictive value and negative predictive value of the presence of more than one endoscopic findings for the diagnosis of EoE was 54% and 84%, respectively. CONCLUSION: There was a low association between the presence of endoscopic findings and histopathological confirmation of the disease, which indicates that endoscopic findings alone are not reliable for the diagnosis of EoE.

Association between endoscopic findings and histopathological confirmation in patients with suspicion of eosinophilic esophagitis / Associação entre achados endoscópicos e confirmação histopatológica em pacientes com suspeita de esofagite eosinofílica

ABSTRACT BACKGROUND: The diagnosis of eosinophilic esophagitis (EoE) is performed by the detection of 15 or more eosinophils per field in an esophageal biopsy sample, but the endoscopic findings alone are not validated for a diagnosis of the disease. OBJECTIVE: To evaluate the association between the endoscopic findings and histopathological diagnosis in patients with suspected EoE in endoscopy. METHODS: A retrospective study of 24 patients with suspicion of EoE during endoscopy was held. The information was collected from databases of Endoscopy and Pathology services of the Hospital Universitário Walter Cantídio, Universidade Federal do Ceará, from March 2012 to April 2018. The patients were divided into a group with positive biopsy (>15 Eosinophils/field, N=8) and a group with negative biopsy (<15 Eosinophils/field, N=16), and the endoscopic findings were compared between the two groups. RESULTS: From a total of 24 patients, 79.1% had longitudinal grooves, 20.8% white exudates, 33.3% mucosal pallor or loss of vascularity and 45.8% had more than one endoscopic finding. There was a significant difference (P<0.05) in the evaluation of the finding of mucosal pallor or decreased vasculature alone among the groups. The positive predictive value and negative predictive value of the presence of more than one endoscopic findings for the diagnosis of EoE was 54% and 84%, respectively. CONCLUSION: There was a low association between the presence of endoscopic findings and histopathological confirmation of the disease, which indicates that endoscopic findings alone are not reliable for the diagnosis of EoE.

RESUMO CONTEXTO: O diagnóstico da esofagite eosinofílica é realizado através da detecção, em amostra de biópsia esofágica, de 15 ou mais eosinófilos por campo, sendo que os achados endoscópicos isolados não são validados para o diagnóstico da doença. OBJETIVO: Avaliar a associação entre os achados endoscópicos com o diagnóstico histopatológico em pacientes com suspeita de esofagite eosinofílica na endoscopia. MÉTODOS: Estudo retrospectivo de 24 pacientes com suspeita de esofagite eosinofílica durante endoscopia digestiva alta. As informações foram colhidas de bancos de dados dos serviços de Endoscopia e Patologia do Hospital Universitário Walter Cantídio da Universidade Federal do Ceará, no período de março de 2012 a abril de 2018. Os pacientes foram divididos em grupo com biópsia positiva (>15 eosinófilos/campo, N=8) e grupo com biópsia negativa (<15 eosinófilos/campo, N=16), sendo comparados os achados endoscópicos entre os dois grupos. RESULTADOS: Do total de 24 pacientes, 79,1% tinham a presença de sulcos longitudinais, 20,8% exsudatos brancos, 33,3% palidez de mucosa ou perda da vascularização e 45,8% apresentaram mais de um achado endoscópico. Houve diferença significativa (P<0,05) na avaliação do achado de palidez ou perda da vascularização, isoladamente, entre os grupos. O valor preditivo positivo e valor preditivo negativo da presença de mais de um achado endoscópico para o diagnóstico de esofagite eosinofílica foi de 54% e 84%, respectivamente. CONCLUSÃO: Houve uma baixa associação entre a presença de achados endoscópicos e a confirmação histopatológica da doença, o que faz com que os achados endoscópicos isolados não sejam confiáveis para o diagnóstico de esofagite eosinofílica.

Gastroduodenal Symptoms in Inflammatory Bowel Disease Are Correlated with Gastric Emptying and Serum Levels of Active Ghrelin.

BACKGROUND: Inflammatory bowel disease (IBD) is associated with delay in gastric emptying, increase in ghrelin, and decrease in leptin. The aim was to investigate the correlation between gastroduodenal (GD) symptoms, gastric emptying, and serum levels of active ghrelin and leptin in IBD. Twenty-seven IBD patients and 26 healthy volunteers were asked to complete the Porto Alegre Dyspeptic Symptoms Questionnaire. A gastric emptying test for solids was performed using a C13 octanoic acid breath test. During this test, serum samples were collected for measuring active ghrelin and leptin concentrations by radioimmunoassay. SUMMARY: Patients with IBD demonstrated delayed gastric emptying compared with healthy volunteers. In patients with GD symptoms, the delay in gastric emptying was more pronounced, and there were significant correlations of satiety and vomiting with gastric emptying. Basal leptin, but not active ghrelin, increased in patients with GD symptoms compared with patients without these symptoms. There were negative correlations between basal active ghrelin with total Porto Alegre score and epigastric pain in IBD patients with GD symptoms. Key Messages: In IBD, satiety and vomiting were associated with delay in gastric emptying. Conversely, epigastric pain had a negative correlation with active ghrelin. Our results suggest that different pathophysiological mechanisms contribute to GD symptoms in IBD.

Concordância entre diferentes patologistas no diagnóstico anatomopatológico de uma série de 128 pólipos gástricos / Agreement between different pathologists in histopathologic diagnosis of 128 gastric polyps

ABSTRACT BACKGROUND - Gastric polyps are elevated mucosal lesions. Most of them are less than 1 cm and when larger than 2 cm, has a high malignancy probability. The histopathological types are mainly fundic gland polyps, hyperplastic polyps and adenomatous polyps. OBJECTIVE - To evaluate the agreement between three different pathologists in the histopathological diagnosis of 128 biopsied gastric polyps in Digestive Endoscopy Unit from Walter Cantídeo University Hospital, between May 2010 to May 2012. METHODS - To describe the intensity of agreement between observers, we use kappa index that is based on the number of concordant measures between them. RESULTS - There was substantial agreement in the diagnosis of adenoma (kappa=0.799, CI: 0.899-0.698) and fundic glands (kappa=0.655, CI: 0.755-0.555). Regarding to hyperplastic polyps (kappa=0.415, CI: 0.515-0.315) and inflammatory (kappa=0.401, CI: 0.501-0.301), we obtained a moderate agreement. Regarding the presence of Helicobacter pylori in biopsy of the polyp, there was a low agreement (kappa=0.219, CI: 0.319-0.119). CONCLUSION - It is clear that the agreement between pathologists depends on the histological type of the biopsied polyp and this agreement is more substantial in adenoma, or fundic gland polyps.

RESUMO CONTEXTO - Os pólipos gástricos são lesões elevadas da mucosa. A maioria são menores que 1 cm (60%-82%) e quando maiores do que 2 cm, tem alta probabilidade de malignidade. Os tipos histopatológicos são principalmente pólipos de glândulas fúndicas, pólipos hiperplásicos e pólipos adenomatosos. OBJETIVO - Avaliar a concordância entre três diferentes patologistas no diagnóstico histopatológico de 128 pólipos gástricos biopsiados na Unidade de Endoscopia Digestiva do Hospital Universitário Walter Cantídeo no período de maio de 2010 a maio de 2012. MÉTODOS - Para descrevermos a intensidade de concordância entre os avaliadores, utilizamos o índice kappa que é baseado no número de medidas concordantes entre eles. RESULTADOS - Houve uma substancial concordância no diagnóstico de adenoma (kappa=0,799, IC: 0,899-0,698) e glândulas fúndicas (kappa=0,655, IC: 0,755-0,555). Em relação aos pólipos hiperplásicos (kappa=0,415, IC: 0,515-0,315) e inflamatórios (kappa=0,401, IC: 0,501-0,301), obtivemos uma concordância moderada. Em relação à presença do Helicobacter pylori na biópsia do pólipo, houve uma baixa concordância (kappa=0,219, IC: 0,319-0,119). CONCLUSÃO - Em vista do que foi observado, torna-se claro que a concordância entre observadores depende do tipo histológico do pólipo biopsiado, sendo essa mais alcançada no diagnóstico de adenoma e pólipos de glândulas fúndicas.

AGREEMENT BETWEEN DIFFERENT PATHOLOGISTS IN HISTOPATHOLOGIC DIAGNOSIS OF 128 GASTRIC POLYPS.

BACKGROUND: - Gastric polyps are elevated mucosal lesions. Most of them are less than 1 cm and when larger than 2 cm, has a high malignancy probability. The histopathological types are mainly fundic gland polyps, hyperplastic polyps and adenomatous polyps. OBJECTIVE: - To evaluate the agreement between three different pathologists in the histopathological diagnosis of 128 biopsied gastric polyps in Digestive Endoscopy Unit from Walter Cantídeo University Hospital, between May 2010 to May 2012. METHODS: - To describe the intensity of agreement between observers, we use kappa index that is based on the number of concordant measures between them. RESULTS: - There was substantial agreement in the diagnosis of adenoma (kappa=0.799, CI: 0.899-0.698) and fundic glands (kappa=0.655, CI: 0.755-0.555). Regarding to hyperplastic polyps (kappa=0.415, CI: 0.515-0.315) and inflammatory (kappa=0.401, CI: 0.501-0.301), we obtained a moderate agreement. Regarding the presence of Helicobacter pylori in biopsy of the polyp, there was a low agreement (kappa=0.219, CI: 0.319-0.119). CONCLUSION: - It is clear that the agreement between pathologists depends on the histological type of the biopsied polyp and this agreement is more substantial in adenoma, or fundic gland polyps.

Lower esophageal sphincter pressure measurement under standardized inspiratory maneuveurs.

BACKGROUND: Through rhythmic variations, the diaphragm influence lower esophageal sphincter (LES) pressure acting as an external sphincter. LES pressure recording is characterized by increased pressure in inspiration due to contraction of the diaphragmatic crura that involves the sphincter. AIM: To describe a method of measuring LES pressure during standardized inspiratory maneuvers with increasing loads. METHODS: The study population comprised of eight healthy female volunteers (average age of 31.5 years). An esophageal high-resolution manometry and impedance system was used for measuring the LES pressure during 3-second inspiratory efforts under 12, 24 and 48 cm H2O loads (Threshold maneuvers). RESULTS: There was a significant difference between the average maximum LES pressure and the average maximum basal LES pressure during the first (76.19±17.92 difference, p=0.0008), second (86.92±19.01 difference, p=0.0004), and third seconds of the maneuver (90.86±17.93 difference, p=0.0002), with 12, 24 and 48 cmH2O loads. CONCLUSION: This maneuver is a standardization of the inspiratory LES pressure and may better differentiate patients with reflux disease from healthy individuals, and may also be useful for monitoring the treatment of these patients through inspiratory muscle training.

LOWER ESOPHAGEAL SPHINCTER PRESSURE MEASUREMENT UNDER STANDARDIZED INSPIRATORY MANEUVEURS / MEDIDAS DAS PRESSÕES DO ESFÍNCTER ESOFÁGICO INFERIOR POR MANOBRAS INSPIRATÓRIAS PADRONIZADAS

Background:Through rhythmic variations, the diaphragm influence lower esophageal sphincter (LES) pressure acting as an external sphincter. LES pressure recording is characterized by increased pressure in inspiration due to contraction of the diaphragmatic crura that involves the sphincter.Aim:To describe a method of measuring LES pressure during standardized inspiratory maneuvers with increasing loads.Methods:The study population comprised of eight healthy female volunteers (average age of 31.5 years). An esophageal high-resolution manometry and impedance system was used for measuring the LES pressure during 3-second inspiratory efforts under 12, 24 and 48 cm H2O loads (Threshold maneuvers).Results:There was a significant difference between the average maximum LES pressure and the average maximum basal LES pressure during the first (76.19±17.92 difference, p=0.0008), second (86.92±19.01 difference, p=0.0004), and third seconds of the maneuver (90.86±17.93 difference, p=0.0002), with 12, 24 and 48 cmH2O loads.Conclusion:This maneuver is a standardization of the inspiratory LES pressure and may better differentiate patients with reflux disease from healthy individuals, and may also be useful for monitoring the treatment of these patients through inspiratory muscle training.

Racional:Através de variações rítmicas, o diafragma influencia a pressão do EEI, atuando como um esfíncter externo. O registro manométrico da sua pressão caracteriza-se por aumento de pressão na inspiração resultante da contração da crura diafragmática que envolve o esfíncter. Objetivo:Descrever um método de medida da pressão do esfíncter esofágico inferior (EEI) durante manobras inspiratórias padronizadas, com cargas crescentes.Métodos:Oito voluntários sadios (sexo feminino, média de idade de 31,5 anos) participaram do estudo. Uma manometria esofágica de alta resolução e impedanciometria mediram a pressão do EEI durante manobras inspiratórias com o Threshold sob cargas de 12, 24 e 48 cm H2O. Resultados:Comparando-se as médias houve diferença significativa entre a pressão máxima do EEI e a sua pressão basal máxima durante o primeiro (diferença de 76,19±17,92, p=0,0008), segundo (diferença 86,92±19,01, p=0,0004) e terceiro segundos da manobra (diferença 90,86±17,93, p=0,0002), tanto com carga de 12 cm de H2O, quanto com 24 e 48 cm. Conclusão:Esta manobra é uma padronização da pressão inspiratória do EEI e pode diferenciar melhor pacientes com doença do refluxo de indivíduos sadios, podendo também ser útil na monitorização do tratamento desses pacientes por meio do treinamento muscular inspiratório.

Effect of methylation on relative energies of tautomers and on the intramolecular proton transfer barriers of protonated nitrosamine: A MR-CISD study.

MR-CISD, MR-CISD+Q, and MR-AQCC calculations have been performed on the minima and transition states (corresponding to intramolecular proton transfer between the protonation sites) of the ground state of protonated nitrosamine and N,N-dimethylnitrosamine. Our highest level results (MR-AQCC/cc-pVTZ) for the smaller system indicate that protonation on the N amino (2a) is practically as favorable as the most favorable protonation on the O atom (1a). They also suggest that protonation on the nitroso N atom (2c) is ∼14.5 kcal/mol less favorable than 1a. Results obtained at the MR-CISD+Q/cc-pVTZ level indicate that the effect of methylation on the relative energies of the tautomers is, in order of importance, 2a > 2c and increases their energies by ∼17.5 and 4.8 kcal/mol, respectively. They also indicate that methylation alters significantly the intramolecular proton transfer barriers. The largest differences between the common geometric parameters of both systems have been found for 2a.

Increased inspiratory esophagogastric junction pressure in systemic sclerosis: an add-on to antireflux barrier.

AIM: To investigate crural diaphragm (CD) function in systemic sclerosis (SSc) using high-resolution manometry and standardized inspiratory maneuvers. METHODS: Eight SSc volunteers (average age, 40.1 years; one male) and 13 controls (average age, 32.2 years; six males) participated in the study. A high-resolution manometry/impedance system measured the esophagus and esophagogastric junction (EGJ) pressure profile during swallows and two respiratory maneuvers: sinus arrhythmia maneuver (SAM; the average of six EGJ peak pressures during 5-s deep inhalations) and threshold maneuver (TM; the EGJ peak pressures during forced inhalation under 12 and 24 cmH2O loads). Inspiratory diaphragm lowering (IDL) was taken as the displacement of the EGJ high-pressure zone during the SAM. RESULTS: SSc patients had lower mean lower esophageal sphincter pressure than controls during normal breathing (19.7±2.8 mmHg vs 32.2±2.7 mmHg, P=0.007). Sinus arrhythmia maneuver pressure was higher in SSc patients than in controls (142.6±9.4 mmHg vs 104.6±13.8 mmHg, P=0.019). Sinus arrhythmia maneuver pressure normalized to IDL was also higher in SSc patients than in controls (83.8±13.4 mmHg vs 37.5±6.9 mmHg, P=0.005). Threshold maneuver pressures normalized to IDL were also greater in SSc patients than in controls (TM 12 cmH2O: 85.1±16.4 mmHg vs 43.9±6.3 mmHg, P=0.039; TM 24 cmH2O: 85.2±16.4 mmHg vs 46.2±6.6 mmHg, P=0.065). Inspiratory diaphragm lowering in SSc patients was less than in controls (2.1±0.3 cm vs 3±0.2 cm, P=0.011). CONCLUSION: SSc patients had increased inspiratory EGJ pressure. This is an add-on to EGJ pressure and indicates that the antireflux barrier can be trained.

The participation of the nitrergic pathway in increased rate of transitory relaxation of lower esophageal sphincter induced by rectal distension in dogs.

CONTEXT: The rectal distension in dogs increases the rate of transitory lower esophageal sphincter relaxation considered the main factor causing gastroesophageal reflux. OBJECTIVES: The aim of this study was evaluate the participation of the nitrergic pathway in the increased transitory lower esophageal sphincter relaxation rate induced by rectal distension in anesthetized dogs. METHODS: Male mongrel dogs (n = 21), weighing 10-15 kg, were fasted for 12 hours, with water ad libitum. Thereafter, they were anesthetized (ketamine 10 mg.Kg-1 + xylazine 20 mg.Kg-1), so as to carry out the esophageal motility evaluation protocol during 120 min. After a 30-minute basal period, the animals were randomly intravenous treated whith: saline solution 0.15M (1ml.Kg-1), L-NAME (3 mg.Kg-1), L-NAME (3 mg.Kg-1) + L-Arginine (200 mg.Kg-1), glibenclamide (1 mg.Kg-1) or methylene blue (3 mg.Kg-1). Forty-five min after these pre-treatments, the rectum was distended (rectal distension, 5 mL.Kg-1) or not (control) with a latex balloon, with changes in the esophageal motility recorded over 45 min. Data were analyzed using ANOVA followed by Student Newman-Keuls test. RESULTS: In comparison to the respective control group, rectal distension induces an increase in transitory lower esophageal sphincter relaxation. Pre-treatment with L-NAME or methylene blue prevents (P<0.05) this phenomenon, which is reversible by L-Arginine plus L-NAME. However, pretreating with glibenclamide failed to abolish this process. CONCLUSIONS: Therefore, these experiments suggested, that rectal distension increases transitory lower esophageal sphincter relaxation in dogs via through nitrergic pathways.

The participatinn of the nitrergic pathway in icreased rate of transitory relaaxation of lower esophageal sphincter induced by rectal distension in dogs / A participação da via nitrérgica no aumento da taxa de relaxamento transitório do esfíncter esofágico inferior induzida pela distensão retal em cães

Context The rectal distension in dogs increases the rate of transitory lower esophageal sphincter relaxation considered the main factor causing gastroesophageal reflux. Objectives The aim of this study was evaluate the participation of the nitrergic pathway in the increased transitory lower esophageal sphincter relaxation rate induced by rectal distension in anesthetized dogs. Methods Male mongrel dogs (n = 21), weighing 10-15 kg, were fasted for 12 hours, with water ad libitum. Thereafter, they were anesthetized (ketamine 10 mg.Kg-1 + xylazine 20 mg.Kg-1), so as to carry out the esophageal motility evaluation protocol during 120 min. After a 30-minute basal period, the animals were randomly intravenous treated whith: saline solution 0.15M (1ml.Kg-1), L-NAME (3 mg.Kg-1), L-NAME (3 mg.Kg-1) + L-Arginine (200 mg.Kg-1), glibenclamide (1 mg.Kg-1) or methylene blue (3 mg.Kg-1). Forty-five min after these pre-treatments, the rectum was distended (rectal distension, 5 mL.Kg-1) or not (control) with a latex balloon, with changes in the esophageal motility recorded over 45 min. Data were analyzed using ANOVA followed by Student Newman-Keuls test. Results In comparison to the respective control group, rectal distension induces an increase in transitory lower esophageal sphincter relaxation. Pre-treatment with L-NAME or methylene blue prevents (P<0.05) this phenomenon, which is reversible by L-Arginine plus L-NAME. However, pretreating with glibenclamide failed to abolish this process. Conclusions Therefore, these experiments suggested, that rectal distension increases transitory lower esophageal sphincter relaxation in dogs via through nitrergic pathways. .

Contexto A distensão retal aumenta a taxa de relaxamento transitório do esfíncter esofágico inferior em cães, sendo o relaxamento transitório do esfíncter esofágico inferior considerado o principal fator responsável pelo refluxo gastroesofágico. Objetivos Avaliar a participação da via nitrérgica no aumento da taxa relaxamento transitório do esfíncter esofágico inferior induzida por distensão retal em cães anestesiados. Métodos Cães sem raça definida, machos (n = 21), pesando entre 10-15 kg, foram mantidos em jejum durante 12 horas, no entanto, com água ad libitum. Depois disso, eles foram anestesiados (cetamina 10 mg.Kg-1 + xilazina 20 mg.Kg-1), para a realização do protocolo de avaliação da motilidade esofágica durante 120 minutos. Após um período basal de 30 minutos, os animais foram aleatoriamente tratados intravenosa com: solução salina 0,15 (1 ml.Kg-1), L-NAME (3 mg.Kg-1), L-NAME (3 mg.Kg-1) + L-arginina (200 mg.Kg-1), glibenclamida (1 mg.Kg-1) e azul de metileno (3 mg.Kg-1). Quarenta e cinco minutos após os pré-tratamentos, o reto foi distendido com um balão de látex (DR, 5 mg.Kg-1) ou não (grupo controle), e as variações da motilidade esofágica foram registradas e gravadas ao longo dos 45 minutos seguintes. Os dados foram analisados utilizando-se ANOVA seguido pelo teste de Student Newman-Keuls. Resultados Em comparação com o respectivo grupo controle, a distensão retal demonstrou induzir um aumento na taxa de relaxamento transitório do esfíncter esofágico inferior. O pré-tratamento com L -NAME ou azul de metileno impediu (P<0,05) este fenômeno, que foi reversível após a administração de L-Arginina + L-NAME. No entanto, o pré-tratamento com a glibenclamida não ...

Inspiratory muscle training improves antireflux barrier in GERD patients.

The crural diaphragm (CD) is an essential component of the esophagogastric junction (EGJ), and inspiratory exercises may modify its function. This study's goal is to verify if inspiratory muscle training (IMT) improves EGJ motility and gastroesophageal reflux (GER). Twelve GER disease [GERD; 7 males, 20-47 yr, 9 esophagitis, and 3 nonerosive reflex disease (NERD)] and 7 healthy volunteers (3 males, 20-41 yr) performed esophageal pH monitoring, manometry, and heart rate variability (HRV) studies. A 6-cm sleeve catheter measured average EGJ pressure during resting, peak inspiratory EGJ pressures during sinus arrhythmia maneuver (SAM) and inhalations under 17-, 35-, and 70-cmH2O loads (TH maneuvers), and along 1 h after a meal. GERD patients entered a 5-days-a-week IMT program. One author scored heartburn and regurgitation before and after IMT. IMT increased average EGJ pressure (19.7 ± 2.4 vs. 29.5 ± 2.1 mmHg; P < 0.001) and inspiratory EGJ pressure during SAM (89.6 ± 7.6 vs. 125.6 ± 13.3 mmHg; P = 0.001) and during TH maneuvers. The EGJ-pressure gain across 35- and 70-cmH2O loads was lower for GERD volunteers. The number and cumulative duration of the transient lower esophageal sphincter relaxations decreased after IMT. Proximal progression of GER decreased after IMT but not the distal acid exposure. Low-frequency power increased after IMT and the higher its increment the lower the increment of supine acid exposure. IMT decreased heartburn and regurgitation scores. In conclusion, IMT improved EGJ pressure, reduced GER proximal progression, and reduced GERD symptoms. Some GERD patients have a CD failure, and IMT may prove beneficial as a GERD add-on treatment.

Dyspeptic symptoms and delayed gastric emptying of solids in patients with inactive Crohn's disease.

BACKGROUND: Patients with Crohn's disease (CD) have been shown to present dyspeptic symptoms more frequently than the general population. Some of these symptoms could be related to motility disorders to some degree. Then, we propose to investigate whether gastric emptying of solids in patients with inactive CD is delayed and to determine the relationships between gastric emptying and dyspeptic symptoms in inactive CD. METHODS: Twenty-six patients with inactive Crohn's disease, as defined by a Crohn's Disease Activity Index (CDAI) < 150, underwent a gastric emptying test by breath test using 13C octanoic acid coupled to a solid meal and answered a validated questionnaire (The Porto Alegre Dyspeptic Symptoms Questionnaire) to assess dyspeptic symptoms. Patients with scores ≥ 6 were considered to have dyspepsia. The control group was composed by 19 age- and sex-matched healthy volunteers. RESULTS: Patients with CD had a significantly longer t 1/2 and t lag (p<0.05) than the controls. CD patients with dyspepsia had significantly (p<0.05) prolonged gastric emptying when compared to patients without dyspeptic symptoms. When the individual symptom patterns were analyzed, only vomiting was significantly associated with delayed gastric emptying (p<0.05). There was no difference between the subgroups of patients with respect to gender, CDAI scores, disease location, clinical behavior (obstructive/obstructive) or previous gastrointestinal surgery. CONCLUSION: Delayed gastric emptying in inactive Crohn's disease patients seems to be associated with dyspeptic symptoms, particularly vomiting, even without any evidence of gastrointestinal obstruction.