Update on Endoscopic Treatments for Obesity.

PURPOSE OF REVIEW: Increased morbidity seen with rising obesity rates continues to place an unheralded burden on our health system. Lack of higher bariatric surgery utilization and limitations with lifestyle modification and pharmacotherapy highlights the need for additional therapies for obesity. Endoscopic bariatric and metabolic therapies (EBMT) are effective, safe treatments for obesity. Current FDA-approved EBMT are confined to gastric modalities while small bowel directed therapies are still considered investigational. This review highlights current modalities of EBMT. RECENT FINDINGS: Many randomized controlled trials have been performed, including both open label and sham-controlled, which have demonstrated safety and efficacy of EBMT over lifestyle therapy alone. In addition, emerging evidence from clinical experience further supports EBMT for treatment of obesity. Current evidence supports the safety and efficacy of EBMT for obesity treatment in conjunction with lifestyle therapy. They can also be used concurrently with weight loss medications to increase total weight loss.

Role of short interval FLIP panometry in predicting long-term outcomes after per-oral endoscopic myotomy.

BACKGROUND: The Eckardt score (ES) is used to assess symptom response to Per-Oral Endoscopic Myotomy (POEM), but reliable methods to assess physiologic success are needed. Functional lumen imaging probe (FLIP) panometry has a potential role in post-POEM follow-up to predict long-term outcomes. The aim of this study was to assess the correlation between clinical success and FLIP parameters following POEM to determine if short interval FLIP could predict long-term outcomes. METHODS: This was a prospective study of adult patients who underwent POEM with short interval follow-up FLIP between 11/2017 and 3/2020. Clinical success was defined as post-procedure ES ≤ 3. Physiologic success was based on an esophago-gastric junction distensibility index (EGJ-DI) > 2.8 mm2/mmHg on FLIP. RESULTS: 47 patients (55% female, mean age 55 years) were included in the study. Clinical success after POEM was seen in 45 (96%) patients (mean ES 6.5 ± 2.2 pre and 0.83 ± 1.0 post-POEM, p < 0.001). Physiologic success was noted in 43 (91.5%) patients (mean EGJ-DI 6.1 mm2/mmHg ± 2.5). Among 4 patients not meeting criteria for physiologic success, EGJ-DI was 2.5-2.6. There was no correlation between post-POEM EGJ-DI and ES in the short term or long term. Significant reflux esophagitis was seen in 6 (12.8%) patients with no difference in mean EGJ-DI with vs without esophagitis (5.9 vs 6.1, p = 0.44). CONCLUSION: Post-POEM endoscopy with FLIP is useful to both assess EGJ physiology and to examine for reflux esophagitis. Short interval FLIP has limited utility to predict long-term patient outcomes or risk of acid reflux.

Validation of classic and expanded criteria for endoscopic submucosal dissection of early gastric cancer: 7 years of experience in a Western tertiary cancer center.

OBJECTIVE: Our aim was to evaluate the Japan Gastroenterological Endoscopy Society criteria for endoscopic submucosal resection of early gastric cancer (EGC) based on the experience in a Brazilian cancer center. METHODS: We included all patients who underwent endoscopic submucosal resection for gastric lesions between February 2009 and October 2016. Demographic data and information regarding the endoscopic resection, pathological report and follow-up were obtained. Statistical calculations were performed with Fisher's exact test and chi-square tests, with 95% confidence intervals. RESULTS: In total, 76% of the 51 lesions were adenocarcinomas, 16% were adenomas, and 8% had other diagnoses. The average size was 19.9 mm (±11.7). The average procedure length was 113.9 minutes (±71.4). The complication rate was 21.3%, with only one patient who needed surgical treatment (transmural perforation). Among the adenocarcinomas, 39.5% met the classic criteria for curability, 31.6% met the expanded criteria and 28.9% met the criteria for noncurative resection. Analysis of the indication criteria and curability revealed differences among cases with "only-by-size" expanded criteria (64.28%), other expanded criteria (40%) and classic criteria (89.47%), with a p-value of 0.049. During follow-up (15.8 months; ±14.3), 86.1% of the EGC patients had no recurrence. When well-differentiated and poorly differentiated lesions or lesions included in the classic and expanded criteria were compared, there were no differences in recurrence. The noncurative group presented a higher recurrence rate than the classic group (p=0.014). CONCLUSION: These results suggest that the Japanese endoscopic submucosal resection criteria might be useful for endoscopic treatment of EGC in Western countries.

Risk assessment of lymph node metastases in early gastric adenocarcinoma fulfilling expanded endoscopic resection criteria.

BACKGROUND AND AIMS: Early gastric cancer (EGC) is known to present a low rate of lymph node metastases (LNMs). Gastrectomy with D2 lymphadenectomy is usually curative for EGC. Endoscopic submucosal dissection (ESD) is a well-accepted treatment modality for lesions that meet the classic criteria: those mucosal differentiated adenocarcinoma measuring 20 mm or less, without ulceration. Expanded criteria for ESD have been proposed based on a null LNM rate from large gastrectomy series from Japan. Patients with LNM have been reported in Western centers, heightening the need for validation of expanded criteria. Our aim was to assess the risk of LNM in gastrectomy specimens of patients with EGC who met the expanded criteria for ESD. METHODS: We conducted an evaluation of gastrectomy specimens including LNM staging of patients submitted to gastrectomy for EGC in a 39-year retrospective cohort. RESULTS: A total of 389 surgical specimens were included. From them, 135 fulfilled criteria for endoscopic resection. None of the 31 patients with classic criteria had LNM. From the 104 patients with expanded criteria, 3 had LNM (n = 104 [2.9%], 95% confidence interval, .7%-8.6%), all of them with undifferentiated tumors without ulceration, measuring less than 20 mm. CONCLUSIONS: There is a small risk of LNM in EGC when expanded criteria for ESD are met. Refinement of the expanded criteria for the risk of LNM may be desirable in a Brazilian cohort. Meanwhile, the decision to complement the endoscopic treatment with gastrectomy will have to take into consideration the individual risk of perioperative morbidity and mortality.

Validation of classic and expanded criteria for endoscopic submucosal dissection of early gastric cancer: 7 years of experience in a Western tertiary cancer center

OBJECTIVE: Our aim was to evaluate the Japan Gastroenterological Endoscopy Society criteria for endoscopic submucosal resection of early gastric cancer (EGC) based on the experience in a Brazilian cancer center. METHODS: We included all patients who underwent endoscopic submucosal resection for gastric lesions between February 2009 and October 2016. Demographic data and information regarding the endoscopic resection, pathological report and follow-up were obtained. Statistical calculations were performed with Fisher's exact test and chi-square tests, with 95% confidence intervals. RESULTS: In total, 76% of the 51 lesions were adenocarcinomas, 16% were adenomas, and 8% had other diagnoses. The average size was 19.9 mm (±11.7). The average procedure length was 113.9 minutes (±71.4). The complication rate was 21.3%, with only one patient who needed surgical treatment (transmural perforation). Among the adenocarcinomas, 39.5% met the classic criteria for curability, 31.6% met the expanded criteria and 28.9% met the criteria for noncurative resection. Analysis of the indication criteria and curability revealed differences among cases with "only-by-size" expanded criteria (64.28%), other expanded criteria (40%) and classic criteria (89.47%), with a p-value of 0.049. During follow-up (15.8 months; ±14.3), 86.1% of the EGC patients had no recurrence. When well-differentiated and poorly differentiated lesions or lesions included in the classic and expanded criteria were compared, there were no differences in recurrence. The noncurative group presented a higher recurrence rate than the classic group (p=0.014). CONCLUSION: These results suggest that the Japanese endoscopic submucosal resection criteria might be useful for endoscopic treatment of EGC in Western countries.

Caracterização dos fenótipos de mucina podem prever a recorrência do câncer gástrico precoce após a mucosectomia endoscópica / Characterization of the mucin phenotype can predict gastric cancer recurrence after endoscopic mucosal resection

ABSTRACT BACKGROUND: Endoscopic mucosal resection is still considered an accepted treatment for early gastric cancer for selected cases. Histopathologic criteria for curative endoscopic resection are intramucosal well-differentiated adenocarcinoma, lateral and deep margins free of tumor, no histological ulceration, and no venous or lymphatic embolism. A 5% local recurrence rate has been described even when all the above-mentioned criteria are met. On the other hand, antigen expression by tumoral cells has been related to the biological behavior of several tumors. OBJECTIVE: To evaluate whether early gastric cancer mucin immunoexpression, p53 and Ki-67, can predict recurrence after endoscopic mucosal resection, even when standard histopathologic criteria for curative measures have been attempted. METHODS: Twenty-two patients with early gastric cancer were considered to have been completely resected by endoscopic mucosal resection. Local recurrence occurred in 5/22 (22.7%). Immunohistochemical study was possible in 18 (81.8%) resected specimens. Patients were divided in two groups: those with and those without local recurrence. They were compared across demographic, endoscopic, histologic data, and immunohistochemical factors for MUC2, MUC5a, CD10, p53, and Ki-67. RESULTS: Mucin immunoexpression allowed a reclassification of gastric adenocarcinoma in intestinal (10), gastric (2), mixed (4), and null phenotypes (2). Mixed phenotype (positive for both MUC2 and MUC5a) was found in 80% of cases in the local recurrence group, while the intestinal type (positive MUC2 and negative MUC5a) was found in 76.9% of cases without local recurrence (P=0.004). Other observed features did not correlate with neoplastic recurrence. CONCLUSION: The mixed phenotype of early gastric adenocarcinoma is associated with a higher probability of local recurrence after endoscopic mucosal resection.

RESUMO CONTEXTO: A ressecção endoscópica da mucosa é tratamento aceito para o tratamento do câncer gástrico precoce em casos selecionados. Os critérios histopatológicos favoráveis à ressecção endoscópica curativa são adenocarcinomas intramucosos, bem diferenciados, com margens lateral e profunda livres, ausência de ulceração ou de embolização angiolinfática. Taxas de recorrência local próximas a 5% têm sido descritas mesmo quando se cumprem tais critérios. Por outro lado, a expressão antigênica por células tumorais tem sido relacionada com o comportamento biológico de diversos tumores. OBJETIVO: Avaliar se a imunoexpressão de mucinas, p53 e Ki-67 podem predizer a recorrência tumoral após mucosectomia endoscópica no câncer gástrico precoce, mesmo se critérios de cura histopatológicos forem atingidos. MÉTODOS: Vinte e dois pacientes com critérios de cura para ressecção endoscópica e sumetidos a mucosectomia foram selecionados. A recorrência local ocorreu em 5/22 (22,7%). O estudo imunohistoquímico foi realizado em 18 (81,8%) espécimens. Os pacientes foram divididos em grupos com e sem recorrência local. Foram comparados quanto a dados demográficos, endoscópicos, histológicos e fatores imunohistoquímicos para MUC2, MUC5A, CD10, p53, e Ki-67. RESULTADOS: A imunoexpressão de mucinas permitiu a reclassificação dos adenocarcinomas gástricos em intestinal (10), gástrico (2), e de fenótipo misto (4) e nulo (2). Os fenótipos mistos (positivos tanto para MUC2 quanto para MUC5A) foram encontrados em 80% dos casos no grupo de recorrência local, enquanto tipos intestinais (MUC2 positivo e MUC5A negativo) foram identificados em 76,9% dos casos sem recorrência (P=0,004). Os outros fatores observados não se relacionaram com a recorrência tumoral. CONCLUSÃO: O fenótipo misto do câncer gástrico precoce está associado a maior probabilidade de recorrência local após a mucosectomia.

CHARACTERIZATION OF THE MUCIN PHENOTYPE CAN PREDICT GASTRIC CANCER RECURRENCE AFTER ENDOSCOPIC MUCOSAL RESECTION.

BACKGROUND: Endoscopic mucosal resection is still considered an accepted treatment for early gastric cancer for selected cases. Histopathologic criteria for curative endoscopic resection are intramucosal well-differentiated adenocarcinoma, lateral and deep margins free of tumor, no histological ulceration, and no venous or lymphatic embolism. A 5% local recurrence rate has been described even when all the above-mentioned criteria are met. On the other hand, antigen expression by tumoral cells has been related to the biological behavior of several tumors. OBJECTIVE: To evaluate whether early gastric cancer mucin immunoexpression, p53 and Ki-67, can predict recurrence after endoscopic mucosal resection, even when standard histopathologic criteria for curative measures have been attempted. METHODS: Twenty-two patients with early gastric cancer were considered to have been completely resected by endoscopic mucosal resection. Local recurrence occurred in 5/22 (22.7%). Immunohistochemical study was possible in 18 (81.8%) resected specimens. Patients were divided in two groups: those with and those without local recurrence. They were compared across demographic, endoscopic, histologic data, and immunohistochemical factors for MUC2, MUC5a, CD10, p53, and Ki-67. RESULTS: Mucin immunoexpression allowed a reclassification of gastric adenocarcinoma in intestinal (10), gastric (2), mixed (4), and null phenotypes (2). Mixed phenotype (positive for both MUC2 and MUC5a) was found in 80% of cases in the local recurrence group, while the intestinal type (positive MUC2 and negative MUC5a) was found in 76.9% of cases without local recurrence (P=0.004). Other observed features did not correlate with neoplastic recurrence. CONCLUSION: The mixed phenotype of early gastric adenocarcinoma is associated with a higher probability of local recurrence after endoscopic mucosal resection.

IMPROVED EXPERIMENTAL MODEL TO EVALUATE SUBMUCOSAL INJECTION SOLUTIONS FOR ENDOSCOPIC SUBMUCOSAL DISSECTION / MODELO EXPERIMENTAL PARA AVALIAÇÃO DO TEMPO DE PERMANÊNCIA DAS SOLUÇÕES DE INJEÇÃO PARA DISSECÇÃO ENDOSCÓPICA DE SUBMUCOSA GÁSTRICA

Background: Endoscopic submucosal dissection carries an increased risk of bleeding and perforation. The creation of a long lasting submucosal cushion is essential for the safe and complete removal of the lesion. There is not a suitable experimental model for evaluation of the durability of the cushioning effect of different solutions. Aim: To describe an improved experimental model to evaluate submucosal injection solutions. Methods: A total of four domestic pigs were employed to evaluate two different submucosal fluid solutions in the gastric submucosa. After midline laparotomy, the anterior gastric wall was incised from the gastric body to the antrum and its mucosal surface was exposed by flipping inside out the incised gastric wall. Two different solutions (10% mannitol and normal saline) were injected in the submucosa of the anterior wall of the distal gastric body. All submucosal cushions were injected until they reach the same size, standardized as 1.0 cm in height and 2.0 cm in diameter. A caliper and a ruler were employed to guarantee accuracy of the measurements. Results: All four animal experiments were completed. All submucosal cushions had the exact same size measured with caliper and a ruler. By using the mannitol solution, the mean duration of the submucosal cushion was longer than the saline solution: 20 and 22 min (mean, 21 min) vs 5 and 6 min (mean, 5.5 min) Conclusions: This experimental model is simple and evaluate the duration, size, and effect of the submucosal cushion, making it more reliable than other models that employ resected porcine stomachs or endoscopic images in live porcine models.

Racional: Sabe-se que os maiores riscos na ressecção endoscópica da submucosa são o sangramento e a perfuração. A criação de um coxim submucoso duradouro é essencial para a remoção da lesão completa e com segurança. Atualmente não se conhece um modelo experimental adequado para avaliação da durabilidade do coxim submucoso com diferentes soluções. Objetivo : Descrever um modelo experimental melhorado para avaliar soluções de injeção de submucosa. Métodos: Foram utilizados quatro porcos domésticos para avaliar dois tipos diferentes de soluções para injeção na submucosa gástrica. Após laparotomia mediana, a parede gástrica anterior foi aberta no sentido corpo-antro e sua superfície mucosa foi exposta por eversão da abertura gástrica. Dois tipos diferentes de solução (manitol a 10% e solução salina normal) foram injetados na submucosa da parede gástrica anterior de corpo distal. Todos os coxins submucosos foram injetados até que alcançassem o mesmo tamanho, padronizado como 1,0 cm de altura por 2,0 cm de diâmetro. Foram aplicados régua e compasso para garantir a acurácia das medidas. Resultados: O experimento foi completo nos quatro animais. Todos os coxins submucosos tinham o mesmo tamanho, medido com régua e compasso. Com o uso da solução de manitol, a duração média do coxim submucoso foi maior que a da solução salina: 20 e 22 min (média 21 min) vs 5 e 6 min (média 5,5 min). Conclusões: Este modelo experimental é simples e permite analisar duração, tamanho e efeito do coxim submucoso, tornando-se mais confiável que outros modelos que empregam estômagos ressecados de porcos ou imagens endoscópicas de modelos porcinos vivos.

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

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

IMPROVED EXPERIMENTAL MODEL TO EVALUATE SUBMUCOSAL INJECTION SOLUTIONS FOR ENDOSCOPIC SUBMUCOSAL DISSECTION.

BACKGROUND: Endoscopic submucosal dissection carries an increased risk of bleeding and perforation. The creation of a long lasting submucosal cushion is essential for the safe and complete removal of the lesion. There is not a suitable experimental model for evaluation of the durability of the cushioning effect of different solutions. AIM: To describe an improved experimental model to evaluate submucosal injection solutions. METHODS: A total of four domestic pigs were employed to evaluate two different submucosal fluid solutions in the gastric submucosa. After midline laparotomy, the anterior gastric wall was incised from the gastric body to the antrum and its mucosal surface was exposed by flipping inside out the incised gastric wall. Two different solutions (10% mannitol and normal saline) were injected in the submucosa of the anterior wall of the distal gastric body. All submucosal cushions were injected until they reach the same size, standardized as 1.0 cm in height and 2.0 cm in diameter. A caliper and a ruler were employed to guarantee accuracy of the measurements. RESULTS: All four animal experiments were completed. All submucosal cushions had the exact same size measured with caliper and a ruler. By using the mannitol solution, the mean duration of the submucosal cushion was longer than the saline solution: 20 and 22 min (mean, 21 min) vs 5 and 6 min (mean, 5.5 min) CONCLUSIONS: This experimental model is simple and evaluate the duration, size, and effect of the submucosal cushion, making it more reliable than other models that employ resected porcine stomachs or endoscopic images in live porcine models.

A new technique for performing endoscopic pyloromyotomy by gastric submucosal tunnel dissection.

AIM: To investigate the feasibility of a new endoscopic pyloromyotomy technique. MATERIALS AND METHODS: Endoscopic pyloromyotomy through a gastric submucosal tunnel was performed in 6 pigs. At the greater curvature, 2 cm proximal to the pylorus, we incised the mucosa and dissected the submucosal tunnel up to the pyloric ring. The pyloric muscular ring was sectioned, and then the gastric mucosal incision was closed with metallic clips. The pigs were then euthanized and necropsies were performed. RESULTS: Section of the pyloric ring was successful in all 6 pigs. Small perforations occurred in 2 of the pigs, and there was limited bleeding in 1 pig. Necropsy and histologic evaluation confirmed the pyloric section. CONCLUSIONS: This technique is feasible, easy to perform, and maybe alternative to pyloroplasty in selected cases. Experimental comparative studies with other techniques still must be performed.

Deep sedation during gastrointestinal endoscopy: propofol-fentanyl and midazolam-fentanyl regimens.

AIM: To compare deep sedation with propofol-fentanyl and midazolam-fentanyl regimens during upper gastrointestinal endoscopy. METHODS: After obtaining approval of the research ethics committee and informed consent, 200 patients were evaluated and referred for upper gastrointestinal endoscopy. Patients were randomized to receive propofol-fentanyl or midazolam-fentanyl (n = 100/group). We assessed the level of sedation using the observer's assessment of alertness/sedation (OAA/S) score and bispectral index (BIS). We evaluated patient and physician satisfaction, as well as the recovery time and complication rates. The statistical analysis was performed using SPSS statistical software and included the Mann-Whitney test, χ² test, measurement of analysis of variance, and the κ statistic. RESULTS: The times to induction of sedation, recovery, and discharge were shorter in the propofol-fentanyl group than the midazolam-fentanyl group. According to the OAA/S score, deep sedation events occurred in 25% of the propofol-fentanyl group and 11% of the midazolam-fentanyl group (P = 0.014). Additionally, deep sedation events occurred in 19% of the propofol-fentanyl group and 7% of the midazolam-fentanyl group according to the BIS scale (P = 0.039). There was good concordance between the OAA/S score and BIS for both groups (κ = 0.71 and κ = 0.63, respectively). Oxygen supplementation was required in 42% of the propofol-fentanyl group and 26% of the midazolam-fentanyl group (P = 0.025). The mean time to recovery was 28.82 and 44.13 min in the propofol-fentanyl and midazolam-fentanyl groups, respectively (P < 0.001). There were no severe complications in either group. Although patients were equally satisfied with both drug combinations, physicians were more satisfied with the propofol-fentanyl combination. CONCLUSION: Deep sedation occurred with propofol-fentanyl and midazolam-fentanyl, but was more frequent in the former. Recovery was faster in the propofol-fentanyl group.