RESUMO
OBJECTIVE: To evaluate the impact of MSA on lower esophageal sphincter (LES) and esophageal body using high resolution impedance manometry. BACKGROUND: MSA is an effective treatment in patients with gastroesophageal reflux disease, but there is limited data on its impact on esophageal functional physiology. METHODS: Patients who underwent MSA were approached 1-year after surgery for objective foregut testing consists of upper endoscopy, esophagram, high resolution impedance manometry, and esophageal pH-monitoring. Postoperative data were then compared to the preoperative measurements. RESULTS: A total of 100 patients were included in this study. At a mean follow up of 14.9(10.1) months, 72% had normalization of esophageal acid exposure. MSA resulted in an increase in mean LES resting pressure [29.3(12.9) vs 25(12.3), P < 0.001]. This was also true for LES overall length [2.9(0.6) vs 2.6(0.6), P = 0.02] and intra-abdominal length [1.2(0.7) vs 0.8(0.8), P < 0.001]. Outflow resistance at the EGJ increased after MSA as demonstrated by elevation in intrabolus pressure (19.6 vs 13.5 mmHg, P < 0.001) and integrated relaxation pressure (13.5 vs 7.2, P < 0.001). MSA was also associated with an increase in distal esophageal body contraction amplitude [103.8(45.4) vs 94.1(39.1), P = 0.015] and distal contractile integral [2647.1(2064.4) vs 2099.7(1656.1), P < 0.001]. The percent peristalsis and incomplete bolus clearance remained unchanged ( P = 0.47 and 0.08, respectively). CONCLUSIONS: MSA results in improvement in the LES manometric characteristics. Although the device results in an increased outflow resistance at the EGJ, the compensatory increase in the force of esophageal contraction will result in unaltered esophageal peristaltic progression and bolus clearance.
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Líquidos Corporais , Refluxo Gastroesofágico , Humanos , Junção Esofagogástrica/cirurgia , Refluxo Gastroesofágico/cirurgia , Impedância Elétrica , Monitoramento do pH EsofágicoRESUMO
BACKGROUND: Magnetic sphincter augmentation (MSA) erosion, disruption or displacement clearly requires device removal. However, up to 5.5% of patients without anatomical failure require removal for dysphagia or recurrent GERD symptoms. Studies characterizing these patients or their management are limited. We aimed to characterize these patients, compare their outcomes, and determine the necessity for further reflux surgery. METHODS: This is a retrospective review of 777 patients who underwent MSA at our institution between 2013 and 2021. Patients who underwent device removal for persistent dysphagia or recurrent GERD symptoms were included. Demographic, clinical, objective testing, and quality of life data obtained preoperatively, after implantation and following removal were compared between removal for dysphagia and GERD groups. Sub-analyses were performed comparing outcomes with and without an anti-reflux surgery (ARS) at the time of removal. RESULTS: A total of 40 (5.1%) patients underwent device removal, 31 (77.5%) for dysphagia and 9 (22.5%) for GERD. After implantation, dysphagia patients had less heartburn (12.9-vs-77.7%, p = 0.0005) less regurgitation (16.1-vs-55.5%, p = 0.0286), and more pH-normalization (91.7-vs-33.3%, p = 0.0158). Removal without ARS was performed in 5 (55.6%) GERD and 22 (71.0%) dysphagia patients. Removal for dysphagia patients had more complete symptom resolution (63.6-vs-0.0%, p = 0.0159), freedom from PPIs (81.8-vs-0.0%, p = 0.0016) and pH-normalization (77.8-vs-0.0%, p = 0.0455). Patients who underwent removal for dysphagia had comparable symptom resolution (p = 0.6770, freedom from PPI (p = 0.3841) and pH-normalization (p = 0.2534) with or without ARS. Those who refused ARS with removal for GERD had more heartburn (100.0%-vs-25.0%, p = 0.0476), regurgitation (80.0%-vs-0.0%, p = 0.0476) and PPI use (75.0%-vs-0.0%, p = 0.0476). CONCLUSIONS: MSA removal outcomes are dependent on the indication for removal. Removal for dysphagia yields excellent outcomes regardless of anti-reflux surgery. Patients with persistent GERD had worse outcomes on all measures without ARS. We propose a tailored approach to MSA removal-based indication for removal.
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Transtornos de Deglutição , Refluxo Gastroesofágico , Laparoscopia , Humanos , Esfíncter Esofágico Inferior/cirurgia , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/cirurgia , Azia/cirurgia , Qualidade de Vida , Refluxo Gastroesofágico/complicações , Refluxo Gastroesofágico/cirurgia , Estudos Retrospectivos , Fenômenos Magnéticos , Resultado do TratamentoRESUMO
INTRODUCTION: Pyloroplasty and gastric peroral endoscopic myotomy (G-POEM) are effective surgeries for gastroparesis. The primary aim of this study was to evaluate outcomes of pyloroplasty and G-POEM in patients with gastroparesis and determine factors associated with favorable outcome. The secondary aim was to assess the utility of clinical response to preoperative pyloric dilation or botulinum toxin injection (Botox) on surgical outcome, a factor conventionally used as a favorable marker. METHODS: There were 204 patients who underwent pyloroplasty (n = 177) or G-POEM (n = 27) for gastroparesis at our institution from 2014 to 2021. Demographic and clinical parameters were analyzed to assess their impact on surgical outcome. A subgroup of patients who had pyloric dilation or Botox injection were assessed separately. Favorable outcome was defined as patient reported complete resolution of the predominant gastroparesis symptom. RESULTS: Favorable outcome was achieved in 78.4% of patients (pyloroplasty: 79.7% and G-POEM: 70.4%, p = 0.274). Among 61 patients where pre- and postoperative gastric emptying studies (GES) were available, mean 4-hour retention significantly improved from 33.5 to 15.0% (p < 0.001) and 77.0% of patients achieved normalization. Favorable outcome was not significantly impacted by etiology of gastroparesis (p = 0.120), GERD (p = 0.518), or primary gastroparesis symptom (p = 0.244). Age ≥ 40 was a significant predictor of favorable surgical outcome on multivariate analysis [OR: 2.476 (1.224-5.008), p = 0.012]. Among the patients who had preoperative dilation (n = 82) or Botox injection (n = 46), response to these interventions was not a predictor of favorable surgical outcome (p = 0.192 and 0.979, respectively). However, preoperative Botox injection, regardless of response to injection, was associated with favorable surgical outcome [OR: 3.205 (CI 1.105-9.299), p = 0.032]. CONCLUSION: Symptomatic improvement after pyloroplasty or G-POEM is independent of etiology of gastroparesis, GERD, and primary symptom. Response to dilation or Botox are not markers of response to surgery. However, patients who receive Botox are 3.2 times more likely to improve postoperatively.
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Toxinas Botulínicas Tipo A , Acalasia Esofágica , Refluxo Gastroesofágico , Gastroparesia , Humanos , Gastroparesia/etiologia , Gastroparesia/cirurgia , Dilatação/efeitos adversos , Acalasia Esofágica/complicações , Resultado do Tratamento , Esfíncter Esofágico Inferior , Piloro/cirurgia , Refluxo Gastroesofágico/complicações , Esvaziamento GástricoRESUMO
BACKGROUND: Dysphagia is the most common complaint after magnetic sphincter augmentation (MSA), with nearly one-third of patients requiring at least one dilation following MSA. A subset of patients require frequent dilations, but there is a paucity of data on the characteristics of this population. This study aimed to identify predictors of the need for frequent dilations within the first year after implant and to assess these patients' outcomes. METHODS: This is a retrospective review of prospectively collected data of patients who underwent MSA over an 8-year period. Frequent dilations were defined as 2 or more dilations within 1 year of surgery. Patients completed baseline and 1-year postoperative GERD-HRQL questionnaires and objective physiology testing. Baseline demographic, clinical characteristics, and objective testing data were compared between patients who did and did not require frequent dilations. RESULTS: A total of 697 (62.7% female) patients underwent MSA, with 62 (8.9%) patients requiring frequent dilation. At a mean (SD) of 12.3 (3.4) months follow-up, the frequent dilation group had higher median GERD-HRQL total scores (21.0 vs. 5.0, p < 0.001), PPI use (20.8% vs.10.1%, p = 0.023), dissatisfaction (46.7% vs. 11.6%, p < 0.001), and device removal (25.8% vs. 2.2%, p < 0.001) rates. Acid normalization was comparable (p = 0.997). Independent predictors of frequent dilation included preoperative odynophagia (OR 2.85; p = 0.001), IRP > 15 mmHg (OR 2.88; p = 0.006), and > 30% incomplete bolus clearance (OR 1.94; p = 0.004). At a mean (SD) of 15.7 (10.7) months, 28 (45.1%) patients underwent device removal after frequent dilation. Independent predictors of device removal after frequent dilation within 5 years of surgery were preoperative odynophagia (OR 7.18; p = 0.042), LES resting pressure > 45 mmHg (OR 28.5; p = 0.005), and ≥ 10% failed swallows (OR 23.5; p < 0.001). CONCLUSIONS: The need for frequent dilations after MSA is a marker for poor symptom control, dissatisfaction, and device removal. Patients with preoperative odynophagia, high LES pressures, and poor esophageal motility should be counseled of their risk for these poor outcomes.
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Transtornos de Deglutição , Refluxo Gastroesofágico , Laparoscopia , Humanos , Feminino , Masculino , Refluxo Gastroesofágico/etiologia , Refluxo Gastroesofágico/cirurgia , Esfíncter Esofágico Inferior/cirurgia , Dilatação , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/cirurgia , Estudos Retrospectivos , Qualidade de Vida , Fenômenos Magnéticos , Resultado do TratamentoRESUMO
INTRODUCTION: Magnetic sphincter augmentation (MSA) is an effective treatment for patients with gastroesophageal reflux disease. In early studies, patients with a hiatal hernia (HH) ≥ 3 cm were excluded from consideration for implantation and initially the FDA considered its use as "precautionary" in this context. This early approach has led to an attitude of hesitance among some surgeons to offer this therapy to patients with HH. This study was designed to evaluate the impact of HH status on the outcome of MSA and to report the rate of HH recurrence after MSA. METHODS AND PROCEDURES: This is a retrospective review of prospectively collected data of patients who underwent MSA between June 2013 and August 2017. Baseline clinical and objective data were collected. Patients were divided into four groups based on HH status: no HH, small HH (< 3 cm), large HH (≥ 3 cm), and paraesophageal hernia (PEH). Patient satisfaction, GERD-HRQL and RSI data, freedom from PPI, need for postoperative dilation, length of hospitalization, 90-day readmission rate, need for device removal, and HH recurrence was compared between groups. RESULTS: There were 350 patients [60% female, mean (SD) age: 53.5 (13.8)] who underwent MSA. There were 65 (18.6%) with no HH, 205 (58.6%) with small HH (< 3 cm), 58 (16.6%) with large HH (≥ 3 cm) and 22 (6.2%) with PEH. At a mean follow-up of 13.6 (10.4) months, the rate of outcome satisfaction was similar between the groups (86%, 87.9%, 92.2% and 93.8%, p = 0.72). This was also true for GERD-HRQL total score clinical improvement (79.1%, 77.8%, 82% and 87.5%, p = 0.77). The rate of postoperative dysphagia (p = 0.33) and freedom from PPIs (p = 0.96) were similar among the four groups. Duration of hospitalization was higher among those with a large HH or PEH, and only PEH patients had a higher 90-day readmission rate (p = 0.0004). There was no difference between the need for dilation among groups (p = 0.13). The need for device removal (5% overall) was similar between the four groups (p = 0.28). HH recurrence was 10% in all groups combined, and only 7 of 240 (2.9%) patients required reoperation; the majority of these patients underwent a minimal dissection approach (no hernia repair) at the index operation. The incidence of recurrent HH increased in direct correlation with the preoperative HH size (0%, 10.1%, 16.6 and 20%, p = 0.032). CONCLUSION: In the largest series of MSA implantation, we demonstrate that the excellent outcomes and high degree of satisfaction after MSA are independent of the presence or size of HH. Despite higher rates of hernia recurrence in large HH and PEH patients, the rates of postoperative endoscopic intervention, and device removal is similar to those with no or small HH. The minimal dissection approach to MSA should be abandoned.
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Esfíncter Esofágico Inferior/cirurgia , Hérnia Hiatal/cirurgia , Adulto , Idoso , Feminino , Humanos , Magnetismo , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Inibidores da Bomba de Prótons/uso terapêutico , Qualidade de Vida , Recidiva , Estudos RetrospectivosRESUMO
INTRODUCTION: Magnetic sphincter augmentation (MSA) is a promising antireflux surgical treatment. The cost associated with the device may be perceived as a drawback by payers, which may limit the adoption of this technique. There are limited data regarding the cost of MSA in the management of reflux disease. The aims of the study were to report the clinical outcome and quality of life measures in patients after MSA and to compare the pharmaceutical and procedure payer costs and the disease-related and overall expense of MSA compared to laparoscopic Nissen fundoplication (LNF) from a payer perspective. METHODS AND PROCEDURES: This prospective observational study was performed in conjunction with the region's largest health insurance company. Data were collected on patients who underwent MSA over a 2-year period beginning in September 2015 at the study network hospitals. The LNF comparison group was procured from members' claims data of the payer. Inclusion was predicated by patients having continuous coverage during study period. The total procedural reimbursement and the disease-related and overall medical claims submitted up to 12 months prior to surgery and up to 12 months following surgery were obtained. The payer reimbursement data are presented as allowed cost per member per month (PMPM). These values were then compared between groups. RESULTS: There were 195 patients who underwent MSA and 1131 that had LNF. MSA results in comparable symptom control, PPI elimination rate, and quality of life measures compared to values reported for LNF in the literature. The median (IQR) reimbursement of surgery was $13,522 (13,195-14,439) for those who underwent MSA and $13,388 (9951-16,261) for patients with LNF, p = 0.02. In patients who underwent MSA, the median reimbursement related to the upper gastrointestinal disease was $ 305 PMPM, at 12 months prior to surgery and $ 104 at 12 months after surgery, representing 66% decrease in cost. These values were $ 233 PMPM and $126 PMPM for patients who underwent LNF, representing a 46% decrease (p = 0.0001). At 12 months following surgery, the reimbursement for overall medical expenses had decreased by 10.7% in the MSA group and 1.4% in the LNF group when compared to the preoperative baseline reimbursement. The reimbursement for PPI use after surgery showed a 95% decrease in the MSA group and 90% among LNF group when compared to the preoperative baseline (p = 0.10). CONCLUSION: When compared with LNF, MSA results in a reduction of disease-related expenses for the payer in the year following surgery. While MSA is associated with a higher procedural payer cost compared to LNF, payer costs may offset due to reduction in the expenses after surgery.
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Esofagoplastia/métodos , Fundoplicatura/economia , Fundoplicatura/métodos , Refluxo Gastroesofágico/cirurgia , Laparoscopia/economia , Laparoscopia/métodos , Transtornos de Deglutição/etiologia , Atenção à Saúde , Esofagoplastia/economia , Esofagoplastia/instrumentação , Feminino , Custos de Cuidados de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Ohio , Pennsylvania , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Qualidade de Vida , Resultado do TratamentoRESUMO
BACKGROUND: Salivary pepsin measurement has been reported to be useful for diagnosing gastroesophageal reflux disease (GERD). This study aimed to clarify the usefulness of salivary pepsin measurement in patients with proton pump inhibitor (PPI)-refractory GERD symptoms without erosive esophagitis. METHODS: One hundred and two patients were included. Over seven days after terminating PPI treatment, all patients underwent a 24-h pH-impedance test and salivary pepsin measurement. In patients whose main symptoms included laryngopharyngeal symptoms, a hypopharyngeal multichannel intraluminal impedance (HMII) test was performed, whereas in other patients, a conventional combined multichannel intraluminal impedance-pH (MII-pH) test was performed. In the HMII tests, patients were divided into abnormal proximal exposure (APE) and non-APE groups. Salivary pepsin concentrations were compared according to acid exposure time (AET) values and were also compared between the APE and non-APE groups. RESULTS: The median salivary pepsin concentration in patients with AET > 6% was significantly higher than that in patients with AET ≤ 6% (345.0 [170.0-469.3] ng/mL vs. 120.0 [97.0-290.1] ng/mL, p < 0.01). The sensitivity, specificity, positive predictive value, and negative predictive value of a positive test (> 109 ng/mL) to diagnose patients with AET > 6% were 75.0%, 51.3%, 32.1%, and 86.9%, respectively. There was no significant difference between concentrations in the APE group and concentrations in the non-APE group. CONCLUSIONS: In patients with PPI-refractory nonerosive reflux disease, salivary pepsin measurement may help diagnose patients who have conclusive evidence of reflux, whereas it is not adequate for identifying patients with APE.
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Refluxo Gastroesofágico/metabolismo , Pepsina A/análise , Inibidores da Bomba de Prótons/uso terapêutico , Saliva/metabolismo , Adulto , Idoso , Resistência a Medicamentos , Impedância Elétrica , Monitoramento do pH Esofágico/métodos , Feminino , Refluxo Gastroesofágico/diagnóstico , Refluxo Gastroesofágico/tratamento farmacológico , Humanos , Hipofaringe/patologia , Refluxo Laringofaríngeo/diagnóstico , Refluxo Laringofaríngeo/epidemiologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Clinical characteristics of laryngopharyngeal reflux (LPR) in Japanese population remain unclear, and its treatment outcome is suboptimal. The objectives of this study were to evaluate Japanese patients with LPR symptoms using hypopharyngeal multichannel intraluminal impedance (HMII) and to assess the outcome of antireflux surgery (ARS). METHODS: Subjects included patients who had LPR symptoms for > 12 weeks or laryngoscopic findings suggestive of LPR and underwent laryngoscopy and esophageal testing including HMII. Abnormal proximal exposure (APE) was defined as LPR ≥ 1/day and/or full column reflux (FCR) (reflux 2 cm distal to the upper esophageal sphincter) ≥ 5/day on HMII. Patients with APE were offered ARS and the outcome of ARS was objectively assessed using Reflux Symptom Index (RSI). RESULTS: From July 2015 to September 2016, 52 patients with LPR symptoms (28 men, 24 women, median BMI 22.3) underwent HMII, and 38 patients (73%) had APE. Of them, 29 (76%) patients were not obese (BMI < 25) and 19 (50%) patients had a negative DeMeester score. Approximately one-third of LPR and FCR events were non-acid in the distal esophagus. A positive symptom-association probability was seen only in 18 patients (35%). Mild esophagitis and hiatal hernia were found in 5 (10%) and 23 (48%) patients, respectively. All 12 patients (100%) who had undergone ARS were able to discontinue PPI and had a significant improvement in the RSI scores postoperatively (22.9 ± 10.0 vs. 6.8 ± 6.8, p < .001). CONCLUSIONS: APE was frequently observed in Japanese patients with LPR symptoms. Obesity and esophagitis were uncommon in this population. Since a large number of patients with APE had negative DeMeester score and proximal reflux events were often non-acid, a conventional pH monitoring is insufficient. HMII is crucial to evaluate patients with LPR symptoms as the documentation of APE is a key for successful outcome of ARS.
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Impedância Elétrica , Fundoplicatura , Hipofaringe/fisiologia , Refluxo Laringofaríngeo/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Esofagite/epidemiologia , Feminino , Humanos , Refluxo Laringofaríngeo/diagnóstico , Laringoscopia , Masculino , Manometria , Pessoa de Meia-Idade , Obesidade/epidemiologia , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: Improved methods of diagnosis of laryngopharyngeal reflux (LPR) would enable surgeons to better identify patients who may benefit from antireflux surgery (ARS). The objective of the present study was to assess if hypopharyngeal Pepsin and Sep70 expression combined with hypopharyngeal multichannel intraluminal impedance (HMII) has the potential to increase diagnostic sensitivity of LPR. METHODS: This study was performed on patients who underwent unsedated transnasal endoscopy with hypopharyngeal biopsy and 24-h HMII to determine abnormal proximal exposure (APE) and DeMeester score (DMS) from 2013 to 2016. Pepsin and Sep70 protein expression was assessed by Western blots of biopsy specimens. The outcomes of ARS were assessed using reflux symptom index (RSI). HMII APE classification, Sep 70, and Pepsin protein levels were compared in normative and symptomatic LPR patients and further analyzed alongside quality of life changes following ARS. RESULTS: Of 30 subjects enrolled, 23 were excluded for abnormal HMII results or endoscopic evidence of esophagitis. Seven subjects and 105 patients were included in the normative and symptomatic groups, respectively. Compared to the normative group, only Pepsin expression was significantly higher in the symptomatic group [APE+/LPR+ (p = 0.000), APE+/LPR- (p = 0.001), and APE- (p = 0.047)]. Further, the ratio of Sep70/Pepsin was significantly lower in the symptomatic group [APE+/LPR+ (p = 0.008), APE+/LPR- (p = 0.000), and APE- (p = 0.050)], and a cutoff ratio for a diagnosis of LPR was established as < 158. Of 105 symptomatic patients, 48 patients underwent ARS. Of these, 17 patients had complete pre- and post-RSI questionnaires. LPR symptoms improved in 15 (88%), of whom 2 were APE- but met criteria for a diagnosis of LPR based on the Sep70/Pepsin cutoff. CONCLUSIONS: The identified Sep70/Pepsin ratio may serve as a reliable biomarker for the diagnosis of LPR. As a result, this may help identify additional patients who have a false-negative HMII result due to the 24-h testing window.
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Impedância Elétrica , Proteínas de Choque Térmico HSP70/metabolismo , Hipofaringe/metabolismo , Hipofaringe/fisiopatologia , Refluxo Laringofaríngeo/diagnóstico , Pepsina A/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: Peroral endoscopic myotomy (POEM) has been performed as a novel endoscopic procedure to treat achalasia with favorable outcome. The objective of this study was to assess the outcome of POEM in our initial series and to assess the safety and efficacy of POEM in a variety of esophageal motility-related clinical problems. METHODS: This is a retrospective cross-sectional study involving all patients with esophageal motility disorders defined by the Chicago classification, who had undergone consideration for POEM at our institution. Validated questionnaires such as gastroesophageal reflux disease health-related quality of life (GERD-HRQL), reflux symptom index (RSI) and achalasia disease-specific health-related quality of life were obtained pre- and postoperatively. RESULTS: From January 2013 to October 2014, a total of 35 POEMs (achalasia n = 25, non-achalasia n = 10) were performed on 33 patients (female n = 20, male n = 13, mean age 56.9 years). There was no mortality. The rate of inadvertent mucosotomy was 17.1%. The rate of complications requiring interventions was 5.7%. During a mean follow-up period of 7 months (range 0.5-17), 92% of patients with achalasia and 75% of those with non-achalasia motility disorders had a symptomatic improvement in dysphagia. Chest pain was completely resolved in all patients with achalasia (8/8) and 80% of patients with non-achalasia (4/5). The GERD-HRQL, RSI and dysphagia scores significantly improved after POEM in patients with achalasia. There was a significant improvement in GERD-HRQL and RSI scores, and a trend toward lower dysphagia score in patients with non-achalasia. CONCLUSIONS: The outcome of POEM to treat achalasia and non-achalasia motility disorders is consistent with previous studies. Potential benefit of POEM includes not only its flexibility to adjust the length and location of myotomy but also the ability to extend myotomy proximally without thoracoscopy or thoracotomy. POEM can be combined with laparoscopic procedures and used as "salvage" for localized esophageal dysmotility.
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Acalasia Esofágica/cirurgia , Esofagoscopia , Mucosa/cirurgia , Cirurgia Endoscópica por Orifício Natural , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
INTRODUCTION: Postoperative reflux remains to be a challenge for patients with achalasia undergoing Heller myotomy. Similarly, per-oral endoscopic myotomy (POEM) is gaining rapid acceptance but the impossibility of adding a fundoplication is questioned as the main pitfall to control reflux. Electrical stimulation of the lower esophageal sphincter (LES) has emerged as a new alternative for the treatment of reflux disease. The objective of this study was to evaluate the potential benefits of combining electrical stimulation with endoscopic esophageal myotomy to prevent post procedural reflux. METHODS: Five pigs were subjected to POEM. After myotomy was completed, two electrical leads were implanted at the LES level and electrical stimulation was applied with the Endostim system with a regimen of 215 µs (5 mA amplitude), at 20 Hz for 25 min. LES pressures were recorded with manometry at pre and post-myotomy and after LES stimulation. RESULTS: Myotomy was completed successfully in all cases. Mean pre-myotomy LES pressure was 35.99 ± 8.08 mmHg. After myotomy, the LES pressure significantly dropped to 10.60 ± 3.24 mmHg (p = 0.03). Subsequent to LES-EST, LES pressure significantly increased to 21.74 ± 4.65 mmHg (p = 0.01). CONCLUSIONS: The findings of this study show that LES-EST in healthy animals increases LES pressure after POEM procedure, and could be useful tool to minimize gastroesophageal reflux.
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Terapia por Estimulação Elétrica , Acalasia Esofágica/cirurgia , Esfíncter Esofágico Inferior , Refluxo Gastroesofágico/prevenção & controle , Cirurgia Endoscópica por Orifício Natural , Complicações Pós-Operatórias/prevenção & controle , Animais , Feminino , Fundoplicatura/métodos , Refluxo Gastroesofágico/etiologia , Manometria , Sus scrofa , Resultado do TratamentoRESUMO
INTRODUCTION: The management of laryngopharyngeal reflux (LPR) has been challenging. Hypopharyngeal multichannel intraluminal impedance (HMII) has shown to increase the sensitivity in diagnosing LPR. The objective of this study is to investigate the potential use of pepsin and Sep70 as diagnostic tools for detection of LPR in combination with HMII. MATERIALS AND METHODS: Tissue samples of hypopharynx, distal esophagus, and gastric cardia were collected from patients with LPR symptoms regardless of gastroesophageal reflux (GERD) diagnosis and underwent HMII to detect LPR and high esophageal reflux (HER: reflux 2 cm distal to upper esophageal sphincter) events. Patients were classified into two groups based on the presence of abnormal proximal exposure (APE), which was defined as LPR ≥1/day and/or HER ≥5/day: (1) positive-APE and (2) negative-APE. Patients with typical GERD symptoms without LPR symptoms who did not undergo HMII were used as a "control" GERD group. Protein was isolated from tissue samples and Western blot analysis of pepsin and Sep70 was performed. Pepsinogen was used as a control to differentiate pepsin from pepsinogen. Relative quantitation was performed using Image Studio Lite Software with normalization against the internal actin of each blot. RESULTS: From October 2012 to September 2013, 55 patients underwent HMII. Of 55, 20 patients underwent biopsies from hypopharynx (17 positive-APE and 3 negative-APE). Ten patients with typical GERD symptoms were identified from tissue bank as a "control" GERD group. Pepsin was detected in distal esophagus and hypopharynx in all groups without significant difference among groups. However, Sep70 in distal esophagus and hypopharynx was significantly depleted in the positive-APE group compared to the other groups (p = 0.032 and 0.002, respectively). CONCLUSION: Depletion of Sep70 with the presence of pepsin in the hypopharynx may indicate cellular injury in laryngopharynx due to constant proximal reflux. However, the normative data for these markers have to be validated.
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Proteínas de Choque Térmico HSP70/metabolismo , Hipofaringe/metabolismo , Refluxo Laringofaríngeo/diagnóstico , Pepsina A/metabolismo , Adulto , Idoso , Biomarcadores/metabolismo , Western Blotting , Impedância Elétrica , Feminino , Humanos , Concentração de Íons de Hidrogênio , Refluxo Laringofaríngeo/metabolismo , Laringoscopia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
INTRODUCTION: Electrical stimulation of the lower esophageal sphincter (LES) in gastroesophageal reflux disease (GERD) patients, using EndoStim(®) LES stimulation system (EndoStim BV, the Hague, Netherlands), enhances LES pressure, decrease distal esophageal acid exposure, improves symptoms, and eliminates the need in many patients for daily GERD medications. AIM: To evaluate, in a post hoc analysis, the effect of LES stimulation on proximal esophageal acid exposure in a subgroup of patients with abnormal proximal esophageal acid exposure. METHODS: Nineteen patients (median age 54 years; IQR 47-64; men-10) with GERD partially responsive to proton pump inhibitors (PPI), hiatal hernia ≤ 3 cm, esophagitis ≤ LA grade C underwent laparoscopic implantation of the LES stimulator. LES stimulation at 20 Hz, 215 µs, 5-8 m Amp sessions was delivered in 6-12, 30 min sessions each day. Esophageal pH at baseline and after 12-months of LES stimulation was measured 5 and 23 cm above the manometric upper border of LES. RESULTS: Total, upright and supine values of median (IQR) proximal esophageal pH at baseline were 0.4 (0.1-1.4), 0.6 (0.2-2.3), and 0 (0.0-0.2) %, respectively, and at 12 months on LES-EST were 0 (0-0) % (p = 0.001 total and upright; p = 0.043 supine comparisons). 24-hour distal esophageal acid exposure improved from 10.2 (7.6-11.7) to 3.4 (1.6-7.0) % (p = 0.001). Seven (37%) patients had abnormal (>1.1%) 24-hour proximal acid exposure at baseline; all normalized at 12 months (p = 0.008). In these 7 patients, total, upright, and supine median proximal acid exposure values at baseline were 1.7 (1.3-4.1), 2.9 (1.9-3.7), and 0.3 (0-4.9) %, respectively, and after 12 months of LES-EST were 0 (0-0.0), 0 (0-0.1), and 0 (0-0) % (p = 0.018 total and upright; p = 0.043 supine comparisons). Distal esophageal pH for this group improved from 9.3 (7.8-17.2) at baseline to 3.2 (1.1-3.7) % at 12-months (p = 0.043). There were no GI side effects such as dysphagia, gas-bloat or diarrhea or device or procedure related serious adverse events with LES-EST. There was also a significant improvement in their GERD-HRQL scores. CONCLUSION: LES-EST is associated with normalization of proximal esophageal pH in patients with GERD and may be useful in treating those with proximal GERD. The LES-EST is safe without typical side effects associated with traditional antireflux surgery.
Assuntos
Terapia por Estimulação Elétrica , Esfíncter Esofágico Inferior , Refluxo Gastroesofágico/terapia , Adulto , Idoso , Terapia por Estimulação Elétrica/instrumentação , Terapia por Estimulação Elétrica/métodos , Monitoramento do pH Esofágico , Feminino , Seguimentos , Refluxo Gastroesofágico/diagnóstico , Humanos , Laparoscopia , Masculino , Manometria , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Treatment of esophageal adenocarcinoma often involves surgical resection. Newer technologies in interventional endoscopy have led to a substantial paradigm shift in the management of early-stage neoplasia in Barrett's esophagus comprising high-grade dysplasia (HGD), intramucosal carcinoma, and, in some cases, submucosal carcinoma. However, there has been no consensus regarding the indications for esophageal preservation in these cases. In this work, consensus guidelines were established for the management of early-stage esophageal neoplasia considering clinically relevant aspects (age, comorbidities, and social environment) in each scenario. METHODS: Seventeen experts were invited to participate based on their background and clinical expertise at high-volume centers. A questionnaire was created that included four clinical scenarios covering a wide range of situations within HGD and/or early esophageal neoplasia, particularly where controversies are likely to exist. Each of the clinical scenarios was open to discussion subdivided by patient age (20, 50, and 80 s). For each clinical scenario an expert was chosen to defend that position. Each defense triggered a subsequent discussion during a consensus meeting. Conclusions of that discussion together with an accompanying literature analysis allowed experts to confirm or change their original choices and served as the basis for the recommendations stated in this article. RESULTS: There was 100 % consensus supporting esophageal preservation in patients with HGD, independent of patient age or Barrett's length. In patients with T1a adenocarcinoma, consensus for preservation was not reached (65 %) for young and middle-aged individuals but was supported for elderly patients (100 %). For T1b adenocarcinoma, consensus was reached for surgical resection (90 %), leaving organ preservation for patients with very low risk of nodal invasion or poor surgical candidates. CONCLUSION: Advances in endoscopic imaging and therapy allow for organ preservation in most settings of early-stage neoplasia of the esophagus, provided that the patient understands the implications of this decision.
Assuntos
Adenocarcinoma/cirurgia , Neoplasias Esofágicas/cirurgia , Algoritmos , Consenso , Esofagectomia , Humanos , Estadiamento de Neoplasias , Guias de Prática Clínica como AssuntoRESUMO
OBJECTIVE: The objective of this work was to gather an international consensus group to propose a global definition and diagnostic approach of laryngopharyngeal reflux (LPR) to guide primary care and specialist physicians in the management of LPR. METHODS: Forty-eight international experts (otolaryngologists, gastroenterologists, surgeons, and physiologists) were included in a modified Delphi process to revise 48 statements about definition, clinical presentation, and diagnostic approaches to LPR. Three voting rounds determined a consensus statement to be acceptable when 80% of experts agreed with a rating of at least 8/10. Votes were anonymous and the analyses of voting rounds were performed by an independent statistician. RESULTS: After the third round, 79.2% of statements (N = 38/48) were approved. LPR was defined as a disease of the upper aerodigestive tract resulting from the direct and/or indirect effects of gastroduodenal content reflux, inducing morphological and/or neurological changes in the upper aerodigestive tract. LPR is associated with recognized non-specific laryngeal and extra-laryngeal symptoms and signs that can be evaluated with validated patient-reported outcome questionnaires and clinical instruments. The hypopharyngeal-esophageal multichannel intraluminal impedance-pH testing can suggest the diagnosis of LPR when there is >1 acid, weakly acid or nonacid hypopharyngeal reflux event in 24 h. CONCLUSION: A global consensus definition for LPR is presented to improve detection and diagnosis of the disease for otolaryngologists, pulmonologists, gastroenterologists, surgeons, and primary care practitioners. The approved statements are offered to improve collaborative research by adopting common and validated diagnostic approaches to LPR. LEVEL OF EVIDENCE: 5 Laryngoscope, 134:1614-1624, 2024.
Assuntos
Refluxo Laringofaríngeo , Laringe , Humanos , Refluxo Laringofaríngeo/diagnóstico , Otorrinolaringologistas , Impedância Elétrica , Inquéritos e Questionários , Monitoramento do pH EsofágicoRESUMO
BACKGROUND: Activated hedgehog (Hh) pathway is associated with development of both Barrett esophagus (BE) and esophageal adenocarcinoma (EAC). We hypothesize that blockade of the Hh pathway with smoothened (Smo) inhibitor can prevent the development of BE/EAC in the Levrat model, in which induced gastroduodenoesophageal reflux (GDER) leads to esophageal carcinogenesis. METHODS: GDER was induced in 6- to 8-week-old male Sprague-Dawley rats. The Smo inhibitor (10 mg/kg/d) was given orally on postoperative weeks 10 to 16, 18 to 22, and 24 to 28, and rats were killed on week 28. The primary outcome measure was the incidence of BE and EAC. To examine potential therapeutic effects of Smo inhibition on tumor tissue, semiquantitative immunohistochemistry for Ki-67 and caspase 3 was performed. In treated animals that developed cancer, gene expression was analyzed. RESULTS: Thirty-eight of 48 controls and 32 of 46 treated animals survived to 28 weeks. messenger ribonucleic acid (mRNA) expression of Indian Hh, a ligand of transmembrane receptor patched 1, was 184× higher in BE and 99× higher in EAC compared with normal esophageal tissue (P = 0.0239 and P = 0.0004, respectively). Compared with controls, the incidence of BE and EAC was decreased in treated animals by 35.7% (relative risk reduction, 36%; P = 0.0015) and 36% (relative risk reduction, 62%; P = 0.0033), respectively. Compared with untreated EAC, Ki-67 was downregulated (P = 0.04) and cleaved caspase 3 was no different in treated EAC (P = 0.398). Of the 84 well-known genes involved in cancer drug resistance, 50 were dysregulated in treated EAC (P < 0.05 for each gene). CONCLUSIONS: Smo inhibitor prevents the development of BE and EAC in an in vivo model of GDER.
Assuntos
Adenocarcinoma/etiologia , Adenocarcinoma/prevenção & controle , Esôfago de Barrett/etiologia , Esôfago de Barrett/prevenção & controle , Neoplasias Esofágicas/etiologia , Neoplasias Esofágicas/prevenção & controle , Refluxo Gastroesofágico/complicações , Receptores Acoplados a Proteínas G/antagonistas & inibidores , Animais , Benzamidas/farmacologia , Caspase 3/metabolismo , Modelos Animais de Doenças , Expressão Gênica , Proteínas Hedgehog/metabolismo , Técnicas Imunoenzimáticas , Antígeno Ki-67/metabolismo , Masculino , Quinazolinas/farmacologia , RNA Mensageiro/análise , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Receptor SmoothenedRESUMO
The Hedgehog (Hh) pathway is known to be active in Barrett's carcinogenesis. Therefore, we evaluated the efficacy and underlying mechanisms of inhibition of cancer cell growth by the smoothened (Smo) antagonist BMS-833923 in esophageal adenocarcinoma (EAC) cell lines. Cell proliferation and apoptosis were evaluated by flow cytometry, Western blotting, immunofluorescence, and quantitative reverse transcription polymerase chain reactions. Results showed that the Smo antagonist led to reduced Hh pathway activity, resulting in decreased cell proliferation and induction of apoptosis via the intrinsic pathway in the esophageal cancer cells. In conclusion, the Smo antagonist may have application as an EAC chemotherapeutic agent.
Assuntos
Adenocarcinoma/metabolismo , Apoptose/fisiologia , Neoplasias Esofágicas/metabolismo , Receptores Acoplados a Proteínas G/antagonistas & inibidores , Adenocarcinoma/patologia , Western Blotting , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Esofágicas/patologia , Citometria de Fluxo , Imunofluorescência , Proteínas Hedgehog/metabolismo , Humanos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/fisiologia , Receptor SmoothenedRESUMO
Patient selection for endoscopic resection is based on meticulous endoscopic examination and histological assessment so as to avoid performing this procedure on patients with a high risk of lymph node involvement or metastatic disease. Currently, endoscopic mucosal resection (EMR) is used for tumors <2 cm, and endoscopic submucosal dissection (ESD) should be considered for tumors >2 cm. The advantage of ESD is that it achieves en-bloc resection of larger tumors, potentially reducing the risk of disease recurrence.
Assuntos
Dissecação/métodos , Endoscopia , Recidiva Local de Neoplasia/prevenção & controle , Neoplasias Gástricas/cirurgia , HumanosRESUMO
BACKGROUND: Populations at risk for esophageal adenocarcinoma remain poorly defined. Laryngeal symptoms can be secondary to laryngopharyngeal reflux (LPR) and can occur without associated gastroesophageal reflux symptoms such as heartburn and regurgitation. GOAL: We sought to determine the prevalence of Barrett esophagus (BE) in otolaryngology patients with laryngeal symptoms±typical gastroesophageal reflux disease (GERD) symptoms. STUDY: We performed a cross-sectional study of otolaryngology clinic patients who reported laryngeal symptoms. Symptoms, medications, and exposure histories were obtained. Unsedated transnasal endoscopy was performed. Suspected BE was biopsied and confirmed histologically. Risk factors and prevalence of BE were assessed. RESULTS: Two hundred ninety-five patients were enrolled [73% male, median age 60 y (interquartile range 51 to 68 y)]. The overall prevalence of BE was 11.8% (n=33). Antisecretory medication use was present in 56% (n=156) of patients at enrollment. Compared with patients without BE, patients with BE were more likely to be male (P=0.01) and to report occupational lung injury (P=0.001). Duration, but not severity of laryngeal symptoms, significantly increased the odds of BE (odds ratio, 5.64; 95% confidence interval, 1.28-24.83; for a duration of symptoms >5 y). Of patients with BE, 58% (n=19) had coexisting LPR and GERD symptoms and 30% (n=10) had only LPR symptoms. Presence and size of hiatal hernia and length of columnar-lined esophagus were significant risk factors for BE. CONCLUSIONS: Long-standing laryngeal symptoms are associated with the presence of BE in otolaryngology patients. Patients with chronic laryngeal symptoms and no identifiable ear, nose, or throat etiology for those symptoms may benefit from endoscopic screening regardless of whether typical GERD symptoms are present.
Assuntos
Esôfago de Barrett/epidemiologia , Endoscopia do Sistema Digestório/métodos , Refluxo Gastroesofágico/epidemiologia , Doenças da Laringe/etiologia , Idoso , Esôfago de Barrett/patologia , Biópsia , Estudos Transversais , Feminino , Refluxo Gastroesofágico/patologia , Hérnia Hiatal/epidemiologia , Hérnia Hiatal/patologia , Humanos , Doenças da Laringe/diagnóstico , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Fatores de TempoRESUMO
BACKGROUND: Peroral endoscopic myotomy (POEM) is an effective intervention for achalasia, but GERD is a major postoperative adverse event. This study aimed to characterize post-POEM GERD and identify preoperative or technical factors impacting development or severity of GERD. STUDY DESIGN: This is a retrospective review of patients who underwent POEM at our institution. Favorable outcome was defined as postoperative Eckardt score of 3 or less. Subjective GERD was defined as symptoms consistent with reflux. Objective GERD was based on a DeMeester score greater than 14.7 or Los Angeles grade C or D esophagitis. Severe GERD was defined as a DeMeester score greater than 50.0 or Los Angeles grade D esophagitis Preoperative clinical and objective data and technical surgical elements were compared between those with and without GERD. Multivariate logistic analysis was performed to identify factors associated with each GERD definition. RESULTS: A total of 183 patients underwent POEM. At a mean ± SD follow-up of 21.7 ± 20.7 months, 93.4% achieved favorable outcome. Subjective, objective, and severe objective GERD were found in 38.8%, 50.5%, and 19.2% of patients, respectively. Of those with objective GERD, 24.0% had no reflux symptoms. Women were more likely to report GERD symptoms (p = 0.007), but objective GERD rates were similar between sexes (p = 0.606). The independent predictors for objective GERD were normal preoperative diameter of esophagus (odds ratio [OR] 3.4; p = 0.008) and lower esophageal sphincter (LES) pressure less than 45 mmHg (OR 1.86; p = 0.027). The independent predictors for severe objective GERD were LES pressure less than 45 mmHg (OR 6.57; p = 0.007) and obesity (OR 5.03; p = 0.005). The length of esophageal or gastric myotomy or indication of procedure had no impact on the incidence or severity of GERD. CONCLUSION: The rate of pathologic GERD after POEM is higher than symptomatic GERD. A nonhypertensive preoperative LES is a predictor for post-POEM GERD. No modifiable factors impact GERD after POEM.