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1.
Am J Physiol Gastrointest Liver Physiol ; 321(5): G461-G476, 2021 11 01.
Article En | MEDLINE | ID: mdl-34431405

Multiple theories have been proposed describing the pathogenic mechanisms of Helicobacter pylori (H. pylori)-associated gastric motility disorders. We assessed ex vivo pyloric activity in H. pylori-infected rats, and tried to explore the associated ghrelin hormone alteration and pyloric fibrogenesis. In addition, miR-1 was assessed in pyloric tissue samples, being recently accused of having a role in smooth muscle dysfunction. Ninety adult male Wistar albino rats were assigned into nine groups: 1) control group, 2) sterile broth (vehicle group), 3) amoxicillin control, 4) omeperazole control, 5) clarithromycin control, 6) triple therapy control, 7) H. pylori- group, 8) H. pylori-clarithromycin group, and 9) H. pylori-triple therapy group. Urease enzyme activity was applied as an indicator of H. pylori infection. Ex vivo pyloric contractility was evaluated. Serum ghrelin was assessed, and histological tissue evaluation was performed. Besides, pyloric muscle miR-1 expression was measured. The immunological epithelial to mesenchymal transition (EMT) markers; transforming growth factor ß (TGFß), α-smooth muscle actin (α-SMA), and E-cadherin-3 were also evaluated. By H. pylori infection, a significant (P < 0.001) reduced pyloric contractility index was recorded. The miR-1 expression was decreased (P < 0.001) in the H. pylori-infected group, associated with reduced serum ghrelin, elevated TGFß, and α-SMA levels and reduced E-cadherin levels. Decreased miR-1 and disturbed molecular pattern were improved by treatment. In conclusion, H. pylori infection was associated with reduced miR-1, epithelial to mesenchymal transition, and pyloric hypomotility. The miR-1 may be a target for further studies to assess its possible involvement in H. pylori-associated pyloric dysfunction, which might help in the management of human H. pylori manifestations and complications.NEW & NOTEWORTHY This work is investigating functional, histopathological, and molecular changes underlying Helicobacter pylori hypomotility and is correlating these with miR-1, whose disturbance is supposed to be involved in smooth muscle dysfunction and cell proliferation according to literature. Epithelial to mesenchymal transition and reduced ghrelin hormone may contribute to H. pylori infection-associated hypomotility. H. pylori infection was associated with reduced pyloric miR-1 expression. Targeting miR-1 could be valuable in the clinical management of pyloric hypofunction.


Epithelial-Mesenchymal Transition , Gastrointestinal Motility , Helicobacter Infections/microbiology , Helicobacter pylori/pathogenicity , Muscle, Smooth/microbiology , Pylorus/microbiology , Stomach Diseases/microbiology , Actins/metabolism , Animals , Anti-Bacterial Agents/pharmacology , Cadherins/metabolism , Disease Models, Animal , Drug Therapy, Combination , Epithelial-Mesenchymal Transition/drug effects , Gastrointestinal Motility/drug effects , Ghrelin/blood , Helicobacter Infections/drug therapy , Helicobacter Infections/metabolism , Helicobacter Infections/physiopathology , Male , MicroRNAs/genetics , MicroRNAs/metabolism , Muscle, Smooth/drug effects , Muscle, Smooth/metabolism , Muscle, Smooth/physiopathology , Proton Pump Inhibitors/pharmacology , Pylorus/drug effects , Pylorus/metabolism , Pylorus/physiopathology , Rats, Wistar , Stomach Diseases/drug therapy , Stomach Diseases/metabolism , Stomach Diseases/physiopathology , Transforming Growth Factor beta/metabolism
2.
Am J Physiol Gastrointest Liver Physiol ; 321(2): G133-G138, 2021 08 01.
Article En | MEDLINE | ID: mdl-34160292

Until recently, gastric motility measurements in humans were mostly limited to accommodation (using barostat or 3-dimensional imaging studies of gastric volume) and gastric emptying tests, the latter being the only one performed in routine clinical care. Accurate and easy to use techniques were lacking to assess pyloric function in health and disease. Recently, pyloric distensibility has been developed and validated to assess pyloric opening. Several studies confirmed that pyloric distensibility was decreased in gastroparesis and correlated with gastric emptying as well as gastroparesis symptoms. In addition, pyloric distensibility may predict outcome of endoscopic techniques targeting the pylorus, namely intrapyloric botulinum toxin injection and gastric per-oral pyloromyotomy. Pyloric distensibility appears therefore to be a promising and useful new tool in the workup of gastroparesis patients.


Gastroparesis/physiopathology , Pylorus/physiology , Animals , Gastric Emptying , Gastroparesis/diagnostic imaging , Gastroparesis/surgery , Humans , Pyloromyotomy/methods , Pylorus/physiopathology
3.
Neurogastroenterol Motil ; 33(8): e14064, 2021 08.
Article En | MEDLINE | ID: mdl-33314491

BACKGROUND: Recent studies have shown that pyloric distensibility is altered in 30-50% of gastroparetic patients but the number of diabetic patients included in prior reports has been small. The aim of the present study was to assess pyloric sphincter measurements in diabetic patients with gastroparesis and to determine whether diabetes characteristics were correlated to pyloric disfunction. METHODS: Pyloric distensibility and pressure were measured using EndoFLIP® system in 46 patients with diabetic gastroparesis (DGP) and compared with 21 healthy volunteers (HV), and 33 patients with idiopathic gastroparesis (IGP). Altered pyloric distensibility was defined as the measurement below 10 mm2 /mmHg at 40 ml of inflation. In diabetic patients, blood glucose, glycated hemoglobin, duration, complications, and treatments were collected. KEY RESULTS: Mean pyloric distensibility at 40 ml of inflation was lower in DGP and IGP groups with, respectively, 10.8 ± 0.9 mm2 /mmHg and 14.8 ± 2.2 mm2 /mmHg in comparison with the HV group (25.2 ± 2.3 mm2 /mmHg; p < 0.005). 56.5% of patients had a decreased pyloric distensibility in the DGP group, 51.5% of patients in the IGP group, and 10% of patients in the HV group. No correlation was found between pyloric sphincter measurements and diabetes characteristics, including blood glucose, glycated hemoglobin, diabetes mellitus type, neuropathy, or GLP1 agonists intake. CONCLUSION AND INTERFERENCES: Pyloric sphincter distensibility and pressure were altered both in diabetic and idiopathic gastroparesis. Pyloric sphincter distensibility was not correlated to diabetes parameters.


Diabetes Complications/physiopathology , Gastroparesis/physiopathology , Pylorus/physiopathology , Adult , Blood Glucose/metabolism , Diabetes Complications/blood , Female , Gastric Emptying , Gastroparesis/blood , Gastroparesis/etiology , Glycated Hemoglobin/metabolism , Humans , Male , Middle Aged , Retrospective Studies
4.
Surg Clin North Am ; 100(6): 1193-1200, 2020 Dec.
Article En | MEDLINE | ID: mdl-33128888

Peroral pyloromyotomy, an innovative intramural endoscopic surgery procedure, is a successful management option for appropriately selected patients who suffer from medically refractory gastroparesis. Gastroparesis is a debilitating disorder of the gastrointestinal tract, which significantly decreases quality of life and overall survival. This article describes the history and background, the indications for, the diagnosis of, and the preparation, technique, and short-term outcomes of peroral pyloromyotomy.


Gastroparesis/surgery , Pyloromyotomy , Combined Modality Therapy , Gastroparesis/diagnosis , Gastroparesis/therapy , Humans , Patient Care Team , Perioperative Care , Pyloromyotomy/methods , Pyloromyotomy/standards , Pylorus/anatomy & histology , Pylorus/physiology , Pylorus/physiopathology
5.
Ann R Coll Surg Engl ; 102(9): 693-696, 2020 Nov.
Article En | MEDLINE | ID: mdl-32538118

INTRODUCTION: The incidence of delayed gastric emptying (DGE) following oesophagogastrectomy with gastric conduit reconstruction is reported to be between 1.7% and 50%. This variation is due to differing practices of intraoperative pylorus drainage procedures, which increase the risk of postoperative biliary reflux and dumping syndrome, resulting in significant morbidity. The aim of our study was to establish rates of DGE in people undergoing oesophagogastrectomy without routine intraoperative drainage procedures, and to evaluate outcomes of postoperative endoscopically administered Botulinum toxin into the pylorus (EBP) for people with DGE resistant to systemic pharmacological treatment. METHODS: All patients undergoing oesophagogastrectomy between 1 January 2016 and 31 March 2018 at our unit were included. No intraoperative pyloric drainage procedures were performed, and DGE resistant to systemic pharmacotherapy was managed with EBP. RESULTS: Ninety-seven patients were included. Postoperatively, 29 patients (30%) were diagnosed with DGE resistant to pharmacotherapy. Of these, 16 (16.5%) were diagnosed within 30 days of surgery. The median pre-procedure nasogastric tube aspirate was 780ml; following EBP, this fell to 125ml (p<0.001). Median delay from surgery to EBP in this cohort was 13 days (IQR 7-16 days). Six patients required a second course of EBP, with 100% successful resolution of DGE before discharge. There were no procedural complications. CONCLUSIONS: This is the largest series of patients without routine intraoperative drainage procedures. Only 30% of patients developed DGE resistant to pharmacotherapy, which was managed safely with EBP in the postoperative period, thus minimising the risk of biliary reflux in people who would otherwise be at risk following prophylactic pylorus drainage procedures.


Botulinum Toxins, Type A/therapeutic use , Esophagectomy/adverse effects , Gastrectomy/adverse effects , Gastroparesis/drug therapy , Gastroscopy , Pylorus/drug effects , Botulinum Toxins, Type A/administration & dosage , Esophageal Neoplasms/surgery , Esophagectomy/methods , Female , Gastrectomy/methods , Gastroparesis/etiology , Gastroscopy/methods , Humans , Male , Pylorus/physiopathology , Stomach Neoplasms/surgery
6.
Neurogastroenterol Motil ; 32(11): e13892, 2020 11.
Article En | MEDLINE | ID: mdl-32542920

BACKGROUND: Functional Lumen Imaging Probe (EndoFLIP) tests typically measure static pyloric parameters, but the pylorus exhibits phasic variations on manometry. Dynamic changes in pyloric function have not been quantified using EndoFLIP, and the impact of Gastric Per-Oral Endoscopic Myotomy (G-POEM) on static and dynamic pyloric activity in gastroparesis is unknown. METHODS: EndoFLIP balloon inflation to 30, 40, and 50 mL was performed to measure mean, maximum, and minimum values and variability in pyloric diameter and distensibility before and after G-POEM in 20 patients with refractory gastroparesis. The impact of phasic contractions on these pyloric measures was compared. KEY RESULTS: G-POEM increased mean (P < .0001) and maximum (P = .0002) pyloric diameters and mean (P = .02) and maximum (P = .02) pyloric distensibility on 50 mL EndoFLIP inflation but not intraballoon pressures or minimum diameters or distensibility. Temporal variability of pyloric diameter (P = .02) and distensibility (P = .02) also increased after G-POEM. Phasic coupled contractions propagating from the antrum through the pylorus were observed in 37.5% of recordings; other phasic activity including isolated pyloric contractions were seen in 23.3%. Variability of pyloric diameter and distensibility tended to be higher during recordings with phasic activity. Some pyloric responses to G-POEM were influenced by age, gastroparesis etiology, gastric emptying, and prior botulinum toxin injection. CONCLUSIONS & INFERENCES: Pyloric activity exhibits dynamic changes on EndoFLIP testing in gastroparesis. G-POEM increases maximal but not minimal diameter and distensibility with increased variations, suggesting this therapy enhances pyloric opening but may not impair pyloric closure. Phasic pyloric contractions contribute to variations in pyloric activity.


Gastroparesis/surgery , Pyloromyotomy/methods , Pylorus/physiopathology , Adult , Female , Gastroparesis/physiopathology , Humans , Male , Middle Aged , Treatment Outcome
8.
Neurogastroenterol Motil ; 32(5): e13790, 2020 05.
Article En | MEDLINE | ID: mdl-31916346

BACKGROUND AND STUDY AIMS: History of gastric surgery is found in 10% of patients with gastroparesis, and vagal lesion is often suspected to be the cause of pylorospasm. Recently, pyloric distensibility measurement using the EndoFLIP® system showed that pylorospasm was present in 30%-50% of gastroparetic patients. Our objective was to assess whether pylorospasm, diagnosed using EndoFLIP® system was observed in three different types of gastric surgeries: antireflux surgery, sleeve gastrectomy, and esophagectomy. PATIENTS AND METHODS: Pyloric distensibility and pressure were measured using the EndoFLIP® system in 43 patients from two centers (18 antireflux surgery, 16 sleeve gastrectomy, and nine esophagectomy) with dyspeptic symptoms after gastric surgery, and in 21 healthy volunteers. Altered pyloric distensibility was defined as distensibility below 10 mm2 /mm Hg as previously reported. RESULTS: Compared to healthy volunteers (distensibility: 25.2 ± 2.4 mm2 /mm Hg; pressure: 9.7 ± 4.4 mm Hg), pyloric distensibility was decreased in 61.1% of patients in the antireflux surgery group (14.5 ± 3.4 mm2 /mm Hg; P < .01) and 75.0% of patients in the esophagectomy group (10.8 ± 2.1 mm2 /mm Hg; P < .05), while pyloric pressure was only increased in the antireflux surgery group (18.9 ± 2.2 mm Hg; P < .01). Pyloric distensibility and pressure were similar in healthy volunteers and in sleeve gastrectomy (distensibility: 20.3 ± 3.8 mm2 /mm Hg; pressure: 15.8 ± 1.6 mm Hg) groups, with decreased pyloric distensibility affecting 18.7% of sleeve gastrectomy patients. CONCLUSION: Antireflux surgery and esophagectomy were associated with pylorospasm although pylorospasm was not found in all patients. Sleeve gastrectomy was not associated with altered pyloric distensibility nor altered pyloric pressure.


Digestive System Surgical Procedures/adverse effects , Gastroparesis/etiology , Pylorus/physiopathology , Adult , Aged , Endoscopy, Digestive System/methods , Esophagectomy/adverse effects , Female , Gastrectomy/adverse effects , Gastroparesis/diagnosis , Humans , Male , Middle Aged
9.
Am J Gastroenterol ; 114(11): 1716-1725, 2019 11.
Article En | MEDLINE | ID: mdl-31464739

The impact of opioid use on the lower gastrointestinal tract is well described, but recent opioid crisis has caused increased awareness of the detrimental effects of these drugs on esophageal and gastroduodenal motility. Opioid use has been associated with increased incidence of spastic esophageal motility disorders and gastroduodenal dysfunction. Opioid receptors are present with high abundance in the myenteric and submucosal plexus of the enteric nervous system. Activation of these receptors leads to suppressed excitability of the inhibitory musculomotor neurons and unchecked tonic contraction of the autogenic musculature (such as the lower esophageal sphincter and the pylorus).


Analgesics, Opioid/pharmacology , Enteric Nervous System/drug effects , Gastrointestinal Diseases , Opioid-Related Disorders , Esophageal Sphincter, Lower/innervation , Esophageal Sphincter, Lower/physiopathology , Gastrointestinal Diseases/chemically induced , Gastrointestinal Diseases/physiopathology , Gastrointestinal Diseases/therapy , Humans , Opioid-Related Disorders/physiopathology , Opioid-Related Disorders/therapy , Pylorus/innervation , Pylorus/physiopathology
10.
World J Gastroenterol ; 25(21): 2581-2590, 2019 Jun 07.
Article En | MEDLINE | ID: mdl-31210711

Gastroparesis, or symptomatic delayed gastric emptying in the absence of mechanical obstruction, is a challenging and increasingly identified syndrome. Medical options are limited and the only medication approved by the Food and Drug Administration for treatment of gastroparesis is metoclopramide, although other agents are frequently used off label. With this caveat, first-line treatments for gastroparesis include dietary modifications, antiemetics and promotility agents, although these therapies are limited by suboptimal efficacy and significant medication side effects. Treatment of patients that fail first-line treatments represents a significant therapeutic challenge. Recent advances in endoscopic techniques have led to the development of a promising novel endoscopic therapy for gastroparesis via endoscopic pyloromyotomy, also referred to as gastric per-oral endoscopic myotomy or per-oral endoscopic pyloromyotomy. The aim of this article is to review the technical aspects of the per-oral endoscopic myotomy procedure for the treatment of gastroparesis, provide an overview of the currently published literature, and outline potential next directions for the field.


Gastroparesis/surgery , Gastroscopy/methods , Natural Orifice Endoscopic Surgery/methods , Pyloromyotomy/methods , Gastroparesis/physiopathology , Gastroscopy/trends , Humans , Natural Orifice Endoscopic Surgery/trends , Pyloromyotomy/trends , Pylorus/physiopathology , Pylorus/surgery , Treatment Outcome
11.
Gastrointest Endosc ; 90(5): 754-760.e1, 2019 11.
Article En | MEDLINE | ID: mdl-31028783

BACKGROUND AND AIMS: Recent studies have reported that pyloric distensibility was altered in 30% to 50% of patients with gastroparesis, and this was correlated with gastric emptying and symptom severity. The aim of this study was to assess whether pyloric distensibility measurement was predictive of symptomatic response after intrapyloric botulinum toxin (BT) injection. METHODS: Pyloric distensibility was measured using the EndoFLIP system (Crospon, Galway, Ireland) before intrapyloric BT injection. Altered pyloric distensibility was defined as distensibility below 10 mm2/mm Hg. Total symptomatic score (TSS), dyspeptic symptoms, Gastrointestinal Quality of Life Index (GIQLI), and gastric emptying were investigated prospectively before and 3 months after BT injection. RESULTS: Nineteen of 35 patients had altered pyloric distensibility. In those patients, TSS decreased at 3 months from 13.5 to 10.5 (P < .01), whereas it remained unchanged in patients with normal pyloric distensibility (P = .7). Gastric fullness (from 3.5 to 2.5; P = .03) and bloating (from 3.0 to 2.0; P = .01) were the only symptoms that improved in patients with altered pyloric distensibility, whereas none of them was improved in patients with normal pyloric distensibility. GIQLI score increased from 59.5 to 76.5 in patients with altered pyloric distensibility (P = .02), whereas there was no statistical difference (P = .43) in patients with normal pyloric distensibility. In patients with altered pyloric distensibility, gastric emptying half time was 223 minutes before and 190 minutes 3 months after injection (P = .02), whereas it remained unchanged in patients with normal pyloric distensibility (P = .6). CONCLUSIONS: Pyloric distensibility measurement before intrapyloric BT injection predicted symptomatic and quality of life response 3 months after injection in patients with gastroparesis.


Botulinum Toxins/therapeutic use , Gastroparesis/drug therapy , Gastroparesis/physiopathology , Neurotoxins/therapeutic use , Pylorus/drug effects , Pylorus/physiopathology , Botulinum Toxins/administration & dosage , Breath Tests , Female , Gastric Emptying , Humans , Injections , Male , Middle Aged , Neurotoxins/administration & dosage , Quality of Life , Severity of Illness Index , Symptom Assessment
12.
Rev. medica electron ; 41(1): 189-195, ene.-feb. 2019. graf
Article Es | CUMED | ID: cum-75876

RESUMEN El doble píloro es una comunicación anormal entre el antro gástrico y el bulbo duodenal y representa un raro hallazgo endoscópico. Se presentó un paciente de 80 años de edad, con antecedentes de hipertensión arterial, fumador inveterado, tomador de aspirina, que presentó melena aproximadamente 15 días antes del ingreso. La videoendoscopia reveló la existencia de dos orificios similares en el antro, que se comunicaban con el bulbo duodenal de manera independiente que fueron catalogados como píloros. La comunicación se constató con el paso del endoscopio a su través. Se impuso tratamiento médico con inhibidores de la bomba de protones y la evolución fue favorable. Es el cuarto caso reportado en la literatura en nuestro país y el primero en la provincia de Matanzas (AU).


ABSTRACT Double pylorus is an abnormal communication between the gastric antrum and the duodenal bulb and represents a rare endoscopic finding. It is presented the case of a patient aged 80 years, with a background of arterial hypertension, inveterate smoker, taking aspirin, who presented melena about 15 days before the admission. The video-endoscopy revealed the existence of two similar orifices in the antrum that were independently communicating with the duodenal bulb and they went catalogued like pylori. The communication was proved by passing the endoscope through it. He was treated with IBP (the Spanish acronym for proton bomb inhibitors) and the evolution was favorable. It is the fourth case reported in the literature in Cuba and the first one in Matanzas (AU).


Humans , Male , Aged, 80 and over , Pylorus/abnormalities , Pylorus/physiopathology , Pylorus/diagnostic imaging , Endoscopy, Gastrointestinal/methods , Diverticulum, Colon/diagnostic imaging , Duodenal Ulcer/diagnostic imaging , Proton Pump Inhibitors/therapeutic use , Aspirin/therapeutic use , Melena/diagnosis , Barium Enema/methods , Smokers , Hypertension/diagnosis
13.
Rev. medica electron ; 41(1): 189-195, ene.-feb. 2019. graf
Article Es | LILACS, CUMED | ID: biblio-991337

RESUMEN El doble píloro es una comunicación anormal entre el antro gástrico y el bulbo duodenal y representa un raro hallazgo endoscópico. Se presentó un paciente de 80 años de edad, con antecedentes de hipertensión arterial, fumador inveterado, tomador de aspirina, que presentó melena aproximadamente 15 días antes del ingreso. La videoendoscopia reveló la existencia de dos orificios similares en el antro, que se comunicaban con el bulbo duodenal de manera independiente que fueron catalogados como píloros. La comunicación se constató con el paso del endoscopio a su través. Se impuso tratamiento médico con inhibidores de la bomba de protones y la evolución fue favorable. Es el cuarto caso reportado en la literatura en nuestro país y el primero en la provincia de Matanzas.


ABSTRACT Double pylorus is an abnormal communication between the gastric antrum and the duodenal bulb and represents a rare endoscopic finding. It is presented the case of a patient aged 80 years, with a background of arterial hypertension, inveterate smoker, taking aspirin, who presented melena about 15 days before the admission. The video-endoscopy revealed the existence of two similar orifices in the antrum that were independently communicating with the duodenal bulb and they went catalogued like pylori. The communication was proved by passing the endoscope through it. He was treated with IBP (the Spanish acronym for proton bomb inhibitors) and the evolution was favorable. It is the fourth case reported in the literature in Cuba and the first one in Matanzas.


Humans , Male , Aged, 80 and over , Pylorus/abnormalities , Pylorus/physiopathology , Pylorus/diagnostic imaging , Endoscopy, Gastrointestinal/methods , Diverticulum, Colon/diagnostic imaging , Duodenal Ulcer/diagnostic imaging , Proton Pump Inhibitors/therapeutic use , Aspirin/therapeutic use , Melena/diagnosis , Barium Enema/methods , Smokers , Hypertension/diagnosis
14.
Endoscopy ; 51(1): 40-49, 2019 01.
Article En | MEDLINE | ID: mdl-29895073

BACKGROUND: Gastroparesis is a functional disorder with a variety of symptoms that is characterized by delayed gastric emptying in the absence of mechanical obstruction. A recent series of retrospective studies has demonstrated that peroral endoscopic pyloromyotomy (G-POEM) is a promising endoscopic procedure for treating patients with refractory gastroparesis. The aim of this prospective study was to evaluate the feasibility, safety, and efficacy of G-POEM. METHODS: 20 patients with refractory gastroparesis (10 diabetic and 10 nondiabetic) were prospectively included in the trial. Patients were treated by G-POEM after evaluation of pyloric function using an endoscopic functional luminal imaging probe. Clinical responses were evaluated using the Gastroparesis Cardinal Symptom Index (GCSI), and quality of life was assessed using the Patient Assessment of Upper Gastrointestinal Disorders - Quality of Life scale and the Gastrointestinal Quality of Life Index scores. Gastric emptying was measured using 4-hour scintigraphy before G-POEM and at 3 months. RESULTS: Feasibility of the procedure was 100 %. Compared with baseline values, G-POEM significantly improved symptoms (GCSI: 1.3 vs. 3.5; P < 0.001), quality of life, and gastric emptying (T½: 100 vs. 345 minutes, P < 0.001; %H2: 56.0 % vs. 81.5 %, P < 0.001; %H4: 15.0 % vs. 57.5 %, P = 0.003) at 3 months. The clinical success of G-POEM using the functional imaging probe inflated to 50 mL had specificity of 100 % and sensitivity of 72.2 % (P = 0.04; 95 % confidence interval 0.51 - 0.94; area under the curve 0.72) at a distensibility threshold of 9.2 mm2/mmHg. CONCLUSION: G-POEM was efficacious and safe for treating refractory gastroparesis, especially in patients with low pyloric distensibility.


Gastric Emptying , Gastroparesis , Pyloromyotomy , Pylorus , Quality of Life , Feasibility Studies , Female , France , Gastroparesis/diagnosis , Gastroparesis/etiology , Gastroparesis/psychology , Gastroparesis/surgery , Humans , Male , Middle Aged , Pilot Projects , Prospective Studies , Pyloromyotomy/adverse effects , Pyloromyotomy/methods , Pylorus/diagnostic imaging , Pylorus/physiopathology , Pylorus/surgery , Radionuclide Imaging/methods , Recovery of Function , Sensitivity and Specificity , Treatment Outcome
15.
Dis Esophagus ; 32(6)2019 Jun 01.
Article En | MEDLINE | ID: mdl-30508077

Delayed gastric emptying (DGE) after Ivor-Lewis esophagectomy occurs postoperatively in up to 50% of the patients. This pyloric dysfunction can lead to severe secondary complications postoperatively such as early aspiration, pneumonia or may even have an impact on anastomotic healing and therefore leakage. Early detection of DGE is essential to prevent further complications. The common treatment postoperatively is endoscopic pyloric balloon dilatation (EPBD) after symptoms already occurred. In our work, we analyzed patients who received a preoperative EPBD during the routine restaging endoscopy and compared those patients to a control group to analyze if preoperative EPBD may prevent postoperative DGE and secondary additional complications. We performed a single-center retrospective analysis of 115 patients who received an Ivor-Lewis esophagectomy by the same surgeon between June 2015 and October 2017. Out of these 115 patients, 91 (79.1%) patients received EPBD preoperatively during the staging/restaging endoscopy (PDG, pyloric dilatation group). In 24 (20.9%) patients, preoperative EPBD was not performed due to stenotic esophageal tumors or logistic reasons (NDG, non-pyloric dilatation group). Data of the PDG and NDG group were compared regarding the rate of postoperative DGE as well as DGE and EPBD related complications. In total, 21 (18.3%) patients developed pyloric dysfunction requiring a total of 27 EPBD during follow-up. There were 12 (13.2%) patients in the PDG and 9 (37.5%) patients in the NDG (p = 0.014), respectively. DGE-related complications such as anastomotic leaks (p = 0.466), pulmonary complications (p = 0.466) and longer median hospital stay (p = 0.685) were more frequent in the NDG group; however this difference did not reach statistical significance. The success rate for postoperative EPBD with 20-mm balloons was lower (58.5%) compared to the usage of 30-mm balloons (93.3%). All pre- and postoperative EPBD were performed without any complications. Preoperative EPBD is feasible, safe and can be combined with restating endoscopy. It seems that preoperative EPBD reduces the incidence of DGE and can prevent the need for early postoperative endoscopic interventions. Our recommendation is therefore to perform an EPBD preoperatively when possible to reduce postoperative complications to a minimum. For postoperative EPBD, we recommend the use of the 30-mm balloon due to lower redilatation rates.


Adenocarcinoma/surgery , Carcinoma, Squamous Cell/surgery , Dilatation , Esophageal Neoplasms/surgery , Esophagectomy/adverse effects , Gastric Emptying , Gastroparesis/prevention & control , Pylorus/physiopathology , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/pathology , Dilatation/methods , Esophageal Neoplasms/pathology , Esophagectomy/methods , Female , Gastroparesis/etiology , Gastroparesis/physiopathology , Humans , Male , Middle Aged , Neoplasm Staging , Postoperative Complications/etiology , Postoperative Complications/physiopathology , Postoperative Complications/prevention & control , Preoperative Care , Retrospective Studies
16.
Am J Physiol Gastrointest Liver Physiol ; 315(6): G980-G990, 2018 12 01.
Article En | MEDLINE | ID: mdl-30285465

An impaired nitrergic system and altered redox signaling contribute to gastric dysmotility in diabetics. Our earlier studies show that NF-E2-related factor 2 (NRF2) and phase II antioxidant enzymes play a vital role in gastric neuronal nitric oxide synthase (nNOS) function. This study aims to investigate whether supplementation of sepiapterin (SEP), a precursor for tetrahydrobiopterin (BH4) (a cofactor of NOS) via the salvage pathway, restores altered nitrergic systems and redox balance in spontaneous diabetic (DB) female rats. Twelve-week spontaneous DB and age-matched, non-DB rats, with and without dietary SEP (daily 20 mg/kg body wt for 10 days) treatment, were used in this study. Gastric antrum muscular tissues were excised to investigate the effects of SEP in nitrergic relaxation and the nNOS-nitric oxide (NO)-NRF2 pathway(s). Dietary SEP supplementation significantly ( P < 0.05) reverted diabetes-induced changes in nNOS dimerization and function; nitric oxide (NO) downstream signaling molecules; HSP-90, a key regulator of nNOSα activity and dimerization; miRNA-28 that targets NRF2 messenger RNA (mRNA), and levels of microRNA (miRNA) biogenesis pathway components, such as DGCR8 (DiGeorge Syndrome Critical Region Gene 8) and TRBP (HIV1-1 transactivating response RNA-binding protein). These findings emphasize the importance of the BH4 pathway in regulating gastric motility functions in DB animals by modulating nNOSα dimerization in association with changes in enteric NRF2 and NO downstream signaling. Our results also identify a new pathway, wherein SEP regulates NRF2 mRNA turnover by suppressing elevated miRNA-28, which could be related to alterations in miRNA biogenesis pathway components. NEW & NOTEWORTHY This study is the first to show a causal link between NF-E2-related factor 2 (NRF2) and neuronal nitric oxide synthase (nNOS) in gastric motility function. Our data demonstrate that critical regulators of the miRNA biosynthetic pathway are upregulated in the diabetic (DB) setting; these regulators were rescued by sepiapterin (SEP) treatment. Finally, we show that low dihydrofolate reductase expression may lead to impaired nNOS dimerization/function-reduced nitric oxide downstream signaling and elevate oxidative stress by suppressing the NRF2/phase II pathway through miRNA; SEP treatment restored all of the above in DB gastric muscular tissue. We suggest that tetrahydrobiopterin supplementation may be a useful therapy for patients with diabetes, as well as women with idiopathic gastroparesis.


Diabetes Mellitus/drug therapy , Gastrointestinal Motility , NF-E2-Related Factor 2/metabolism , Nitric Oxide Synthase Type I/metabolism , Pterins/therapeutic use , Pylorus/drug effects , Animals , Diabetes Mellitus/physiopathology , Female , HSP90 Heat-Shock Proteins/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Muscle Relaxation , NF-E2-Related Factor 2/genetics , Pterins/pharmacology , Pylorus/metabolism , Pylorus/physiopathology , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats , Rats, Wistar , Signal Transduction
18.
J Pediatr Surg ; 53(11): 2112-2116, 2018 Nov.
Article En | MEDLINE | ID: mdl-29754879

BACKGROUND: Congenital pyloric atresia (CPA) is a rare anomaly with an incidence of 1 in 100,000 live births. Depending on the type of anomaly patients can either present in the neonatal period or later in life with subtle nonspecific signs and symptoms. We present our institute's experience in handling these cases over the last decade and highlight lessons learnt. MATERIALS AND METHODS: We retrospectively reviewed records of patients diagnosed with CPA and managed at our centre between Jan 2006 to June 2016. We looked into the period of gestation, birth weight, gender, age at onset of symptoms, age at presentation to the hospital, symptoms, investigations, associated anomalies, management and outcomes and follow up periods. RESULTS: Nine patients were operated during the ten year period of study (6 males and 3 females). The median age at onset of symptoms was 06 months (01 day-36 months) and the median age of reporting to the hospital was 07 months (01 day-44 months) with a mean delay of 5 months between onset of symptoms and reporting to hospital. Six patients (67%) had associated anomalies including one with posterior urethral valve which has been reported for the first time in literature. Four out of five (80%) late presenters underwent an upper gastrointestinal endoscopy for diagnostic confirmation. All patients were operated upon and Type 1 CPA was seen in five patients (56%), Type 2 in two patients (33%) and Type 3 in one patient (11%). The overall survival was 89% as one patient with associated Epidermolysis Bullosa expired after 4 months due to fulminant sepsis. Three patients were lost to follow up and amongst the remaining five; the median follow up period is 36 months. CONCLUSION: CPA is a rare entity that may present late with subtle signs like failure to thrive and nonbilious vomit. A high index of suspicion is mandated in these cases and an Upper Gastrointestinal Endoscopy will help in early diagnosis and avoid further unnecessary investigations. A feeding jejunostomy may benefit malnourished sick children before definitive surgery. LEVEL OF EVIDENCE: Level 3, Type of study: Retrospective study.


Digestive System Abnormalities , Infant, Newborn, Diseases , Pylorus , Birth Weight , Child, Preschool , Digestive System Abnormalities/physiopathology , Digestive System Abnormalities/surgery , Female , Humans , Infant , Infant, Newborn , Infant, Newborn, Diseases/physiopathology , Infant, Newborn, Diseases/surgery , Male , Pylorus/physiopathology , Pylorus/surgery , Retrospective Studies
19.
Nutr Diet ; 75(1): 30-34, 2018 02.
Article En | MEDLINE | ID: mdl-29411494

AIM: To determine whether the placement of a post-pyloric feeding tube (PPFT) can be taught safely and effectively to a critical care dietitian. METHODS: This is a prospective observational study conducted in an adult intensive care unit (ICU). The intervention consisted of 19 attempts at post-pyloric intubation by the dietitian. The 10 'learning' attempts were performed by the dietitian under the direction of an experienced (having completed in excess of 50 successful tube placements) user. A subsequent nine 'consolidation' attempts were performed under the responsibility of the intensive care consultant on duty. The primary outcome measures were success (i.e. tip of the PPFT being visible in or distal to the duodenum on X-ray) and time (minutes) to PPFT placement. Patients were observed for adverse events per standard clinical practice. RESULTS: A total of 19 post-pyloric tube placements were attempted in 18 patients (52 (23-70) years, ICU admission diagnoses: trauma n = 4; respiratory failure n = 3; and burns, pancreatitis and renal failure n = 2 each). No adverse events occurred. Most (75%) patients were sedated, and mechanically ventilated. Prokinetics were used to assist tube placement in 11% (2/19) of attempts, both of which were successful. Placement of PPFT was successful in 58% (11/19) of attempts. Whilst training, the success rate was 40% (4/10) compared with 78% (7/9) once training was consolidated (P = 0.17). In the successful attempts, the mean time to placement was 11.0 minutes (3.9-27.1 minutes). CONCLUSIONS: A dietitian can be trained to safely and successfully place PPFT in critically ill patients.


Critical Illness/therapy , Enteral Nutrition/methods , Intensive Care Units , Intubation, Gastrointestinal/instrumentation , Nutritionists , Pylorus/physiopathology , Adult , Aged , Australia/epidemiology , Critical Care , Enteral Nutrition/instrumentation , Female , Humans , Male , Middle Aged , Nutritionists/education , Practice Guidelines as Topic , Prospective Studies , Young Adult
20.
Ann Surg ; 267(6): 1021-1027, 2018 06.
Article En | MEDLINE | ID: mdl-28885510

OBJECTIVES: The aim of this study was to investigate the effect of pylorus resection on postoperative delayed gastric emptying (DGE) after partial pancreatoduodenectomy (PD). BACKGROUND: PD is the standard treatment for tumors of the pancreatic head. Preservation of the pylorus has been widely accepted as standard procedure. DGE is a common complication causing impaired oral intake, prolonged hospital stay, and postponed further treatment. Recently, pylorus resection has been shown to reduce DGE. METHODS: Patients undergoing PD for any indication at the University of Heidelberg were randomized to either PD with pylorus preservation (PP) or PD with pylorus resection and complete stomach preservation (PR). The primary endpoint was DGE within 30 days according to the International Study Group of Pancreatic Surgery definition. RESULTS: Ninety-five patients were randomized to PP and 93 patients to PR. There were no baseline imbalances between the groups. Overall, 53 of 188 patients (28.2%) developed a DGE (grade: A 15.5%; B 8.8%; C 3.3%). In the PP group 24 of 95 patients (25.3%) and in the PR group 29 of 93 patients (31.2%) developed DGE (odds ratio 1.534, 95% confidence interval 0.788 to 2.987; P = 0.208). Higher BMI, indigestion, and intraabdominal major complications were significant risk factors for DGE. CONCLUSIONS: In this randomized controlled trial, pylorus resection during PD did not reduce the incidence or severity of DGE. The development of DGE seems to be multifactorial rather than attributable to pyloric dysfunction alone. Pylorus preservation should therefore remain the standard of care in PD. TRIAL REGISTRATION: German Clinical Trials Register DRKS00004191.


Gastric Emptying , Pancreaticoduodenectomy/adverse effects , Pylorus/surgery , Body Mass Index , Double-Blind Method , Dyspepsia/complications , Humans , Pancreatic Neoplasms/surgery , Postoperative Complications/prevention & control , Pylorus/physiopathology , Risk Factors , Standard of Care
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