Prognostic Value of Pre-Operative Intragastric Meal Distribution in Gastric Emptying Scintigraphy for Long-Term Success of Gastric Peroral Endoscopic Myotomy in Gastroparesis.

BACKGROUND AND AIMS: Gastric emptying scintigraphy (GES) is the gold standard for the diagnosis of gastroparesis. However, data are lacking regarding the prognostic value of pre-operative intragastric meal distribution during GES, in patients undergoing gastric peroral endoscopic myotomy (GPOEM) for gastroparesis. This study investigated the association of GES morphologic parameters and the long-term clinical success of G-POEM. METHODS: This retrospective study included patients who underwent G-POEM for refractory gastroparesis in a tertiary center with preoperative GES data. Intragastric meal distribution was measured using the proximal to distal count ratio (PDCR) at 0, 1, 2 and 4 hours (h), and the retention index (RI) was calculated. Clinical success was defined as a decrease of at least 50% in the post-G-POEM Gastroparesis Cardinal Symptom Index (GCSI) total score. RESULTS: In total, 77 patients were included with a mean follow-up of 40.14 months. Clinical success was observed in 54.55% of patients. The RI was not associated with clinical success. Only PDCR at 0h (PDCR0) was associated with clinical success. In univariate analysis, the median PDCR0 was 6.0 (IQR 5.59) in patients with clinical success and 4.29 (IQR 4.51) in patients with clinical failure (p=0.019). In multivariate analysis, PDCR0 > 5.25 was associated with clinical success (HR = 4.36 [1.55;12.26], p=0.00524). CONCLUSIONS: This study suggests that in patients with gastroparesis, High PDCR0 value (suggestive for a preferential fundic meal distribution) during preoperative GES is associated with long-term clinical response to G-POEM.

Gastric peroral endoscopic myotomy versus botulinum toxin injection for the treatment of refractory gastroparesis: results of a double-blind randomized controlled study.

INTRODUCTION: Gastric peroral endoscopic myotomy (G-POEM) is a promising technique for treating refractory gastroparesis. We present the first double-blind randomized study comparing the clinical efficacy of G-POEM versus pyloric botulinum toxin injection (BTI). METHODS: This randomized study, conducted in two expert centers, enrolled patients with refractory gastroparesis, medically managed for >6 months and confirmed by gastric emptying scintigraphy (GES), into two groups, G-POEM versus BTI, with follow-up of 1 year. The primary end point was the 3-month clinical efficacy, defined as a >1-point decrease in the mean Gastroparesis Cardinal Symptom Index (GCSI) score. Secondary end points were: 1-year efficacy, GES evolution, adverse events, and quality of life. RESULTS: 40 patients (22 women; mean age 48.1 [SD 17.4]), with mean symptom duration of 5.8 (SD 5.7) years, were randomized. Etiologies included idiopathic (n=18), diabetes (n=11), postoperative (n=6), and mixed (n=4). G-POEM showed a higher 3-month clinical success than BTI (65% vs. 40%, respectively; P=0.10), along with non-significantly higher 1-year clinical success (60% vs. 40%, respectively) on intention-to-treat analysis. The GCSI decreased in both groups at 3 months and 1 year. Only three minor adverse events occurred in the G-POEM group. The GES improvement rate was 72% in the G-POEM group versus 50% in the BTI group (non-significant). CONCLUSION: G-POEM seems to have a higher clinically relevant success rate than BTI, but this was not statistically demonstrated. This study confirms the interest in treatments targeting the pylorus, either mechanically or chemically, for managing refractory gastroparesis.

Gastric volumetry for the assessment of fundic compliance and visceral hypersensitivity in patients with gastroparesis: a retrospective comparative study.

BACKGROUND/AIMS: The evaluation of visceral hypersensitivity and gastric accommodation in patients with gastroparesis (GP) is difficult. CT-scan gastric volumetry allows to test the distension of different regions of the stomach. We aimed to study gastric volumes and patient's sensitivity to gastric distension between in patients with GP compared to patients with GERD. METHOD: Retrospective study including patients who had CT-scan volumetry for GP or GERD. Two CT-scan series were made after gastric distension: left lateral decubitus 30° (LLD30) for antrum and right lateral decubitus (RLD) for body. Pain and discomfort were assessed using visual analogue scale (VAS). Gastric volumes were measured for LLD30 and RLD. RESULTS: 13 patients (7 GP and 6 GERD) were included. Mean age was 35.6+/-7.3 years. Median gastric volume in the RLD was lower in GP vs GERD (927+/-208 ml vs. 1115+/-163 ml; p = 0.046) while it was similar for LLD30 (1053+/-228 ml vs. 1054+/-193 ml; p = 0.603). GP patients had significantly more pain and discomfort during the procedure: pain VAS for GP was 6[0-9] versus 0[0-2] for GERD, p = 0.004, discomfort VAS for GP was 7[4-10] versus 4[0-5] for GERD, p = 0.007. 66.7% of GERD patients felt no pain vs. 14.3% in GP, p = 0.053. CONCLUSION: This pilot study suggests that GP could be associated with a reduced gastric volume compared to GERD in RLD after gaseous distension. In contrast, patient self-assessment of pain related to gastric distension was greater int GP patients. A lack of fundus accommodation and visceral hypersensitivity could explain some mechanisms in the genesis of GP symptoms.

Gastroparesis is associated with lower volumes in right lateral decubitus suggesting a lower distensibility of the fundus.Gastric volumetry is more painful in patients with gastroparesis than GERD controls, suggesting visceral hypersensitivity to mechanical distension.

Effectiveness of endoscopic ultrasound (EUS)-guided choledochoduodenostomy vs. EUS-guided gallbladder drainage for jaundice in patients with malignant distal biliary obstruction after failed endoscopic retrograde cholangiopancreatography: Retrospective, multicenter study (GALLBLADEUS Study).

OBJECTIVES: The aim of this study was to compare endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) vs. EUS-gallbladder drainage (EUS-GBD) in cases of failed endoscopic retrograde cholangiopancreatography (ERCP) for jaundice resulting from malignant distal biliary obstruction (MDBO). METHODS: This multicenter retrospective study included patients with obstructive jaundice secondary to MDBO who underwent EUS-GBD or EUS-CDS with lumen-apposing metal stents after failed ERCP. The primary end-point was clinical success rate. Secondary end-points were technical success, periprocedural adverse events rate (<24 h), late adverse events rate (>24 h), overall survival, and time to recurrent biliary obstruction. RESULTS: A total of 78 patients were included: 41 underwent EUS-GBD and 37 underwent EUS-CDS. MDBO was mainly the result of pancreatic cancer (n = 63/78, 80.7%). Clinical success rate was similar for both procedures: 87.8% for EUS-GBD and 89.2% for EUS-CDS (P = 0.8). Technical success rate was 100% for EUS-GBD and 94.6% for EUS-CDS (P = 0.132). Periprocedural morbidity (<24 h) rates were similar between both groups: 4/41 (9.8%) for EUS-GBD and 5/37 (13.5%) for EUS-CDS (P = 0.368). There was a significantly higher rate of late morbidity (>24 h) among patients in the EUS-CDS group (8/37 [21.6%]) than in the EUS-GBD group (3/41 [7.3%]) (P = 0.042). The median follow-up duration was 4.7 months. Overall survival and time to recurrent biliary obstruction did not significantly differ between the groups. DISCUSSION: After failed ERCP for MDBO, EUS-GBD and EUS-CDS show comparable clinical success rates and technical success. EUS-GBD appears to be a promising alternative for MDBO, even as a second-line treatment after failed ERCP. Further studies are needed to validate these findings and compare the long-term outcomes of EUS-GBD and EUS-CDS.

Peroral endoscopic myotomy and valve section for treatment of persistent and disabling dysphagia after laparoscopic fundoplication (with video).

BACKGROUND AND AIMS: The use of laparoscopic fundoplication (LF) to treat refractory GERD may induce refractory dysphagia (5%-10%). The management is complex, and peroral endoscopic myotomy (POEM) including valve incision is a new therapeutic option. METHODS: This retrospective study involved patients with postfundoplication refractory dysphagia treated by POEM associated with complete wrap incision. Patients were evaluated with Eckardt and dysphagia scores. Study objectives were to evaluate clinical and technical outcomes, adverse events, and GERD recurrence. RESULTS: Twenty-six patients, with a mean age of 57.3 ± 15.6 years, were included. Mean follow-up was 25.3 ± 17.6 months. The technical and clinical success rates were 96% and 84.6%, respectively. Among failures, 1 patient underwent Lewis-Santy, 2 required dilations, and 1 was lost to follow-up. Three late recurrences occurred and were endoscopically managed. Five patients (19%) had GERD recurrence that was mainly improved by proton pump inhibitors. CONCLUSIONS: POEM with fundoplication is a serious therapeutic option for managing persistent dysphagia after LF, with a low risk of GERD recurrence.

Training in esophageal peroral endoscopic myotomy (POEM) on an ex vivo porcine model: learning curve study and training strategy.

BACKGROUND: Peroral endoscopic myotomy (POEM) is a very effective treatment for achalasia. However, training remains non-standardized. We evaluated a training curriculum, including ex vivo cases, followed by patients' cases under expert supervision. The objective was to establish a learning curve of POEM. MATERIALS AND METHODS: Four operators having completed advanced endoscopy fellowship were involved. They had already observed > 30 cases performed by experts. They performed 30 POEMs standardized (tunnel and myotomy lengths) procedures on ex vivo porcine model. Procedural times, number/volume of injections, mucosal and serous perforations, and myotomy length were collected. The learning curve was assessed using dissection speed (DS) and a dedicated performance score (PS), including learning rate (LR) and learning plateau (LP). RESULTS: The operators completed all cases within 4 months (median of 3.5 cases/week). The mean procedural time was 43.3 min ± 14.4. Mean myotomy length was 70.0 mm ± 15.6 mm. Dissection speed averaged 1.78 mm/min ± 0.78. Using DS and PS as parameter, the LR was reached after 12.2 cases (DS = 2.0 mm/min) and 10.4 cases, respectively. When comparing the LP and the plateau phase, the DS was slower (1.3 ± 0.5 mm/min versus 2.1 ± 0.54 mm/min, p < 0.005) and perforations were decreased: 0.35 ± 0.82 in LP vs. 0.16 ± 0.44 in PP. Following this training, all operators performed 10 supervised cases and are competent in POEM. CONCLUSION: The association of observed cases and supervised ex vivo model training is effective for starting POEM on patients. The learning curve is 12 cases to reach a plateau.

Gastric peroral endoscopic myotomy in refractory gastroparesis: long-term outcomes and predictive score to improve patient selection.

BACKGROUND AND AIMS: Limited data exist concerning the long-term efficiency of gastric peroral endoscopic myotomy (G-POEM) as a treatment of refractory gastroparesis. This study evaluated the 3-year results of G-POEM in patients with refractory gastroparesis. METHODS: This was a prospective multicenter study of all G-POEM operations performed in 2 expert French centers for 46 patients with refractory gastroparesis with at least 3 years of follow-up. RESULTS: Clinical success was 65.2% at 36 months. There was significant improvement in symptom severity. Median Gastroparesis Cardinal Symptom Index decreased from 3.33 to 1.80 (P < .0001), with improvement in all subscales. We created a predictive score concerning G-POEM success (G-POEM predictive score) to which points were assigned as follows: nausea subscale <2: predictive of success, 1 point; satiety subscale >4: predictive of success, 1 point; bloating subscale >3.5: predictive of success, 1 point; percentage of gastric retention at 4 hours on scintigraphy >50%: 1 point. A threshold of 2 was identified by receiver operating characteristic curve analysis with an area under the curve of .825 that predicted clinical success with a sensitivity of 93.3% (95% confidence interval [CI], .77-.99), specificity of 56.3% (95% CI, .33-.77), positive predictive value of 80% (95% CI, .67-.93), negative predictive value of 81.8% (95% CI, .59-1.00), and accuracy of 80.4% (95% CI, .69-.92). Patients with a score ≥2 were significantly more likely to be responders at 3 years than were patients with a score <2 (80% and 18%, respectively; P = .0004). CONCLUSIONS: The clinical success of G-POEM for refractory gastroparesis was 65.2% at 36 months. Our predictive score offers an easy tool that needs to be confirmed in other studies.

Detection of soluble biomarkers of pancreatic cancer in endoscopic ultrasound-guided fine-needle aspiration samples.

BACKGROUND: Biomarkers are urgently needed for pancreatic ductal adenocarcinoma (PDAC). Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is the cornerstone for diagnosing PDAC. We developed a method for discovery of PDAC biomarkers using the discarded EUS-FNA liquid. METHODS: This retrospective study included 58 patients with suspected pancreatic lesions who underwent EUS-FNA. Protein extracts from EUS-FNA liquid were analyzed by mass spectrometry. Proteomic and clinical data were modeled by supervised statistical learning to identify protein markers and clinical variables that distinguish PDAC. RESULTS: Statistical modeling revealed a protein signature for PDAC screening that achieved high sensitivity and specificity (0.92, 95 % confidence interval [CI] 0.79-0.98, and 0.85, 95 %CI 0.67-0.93, respectively). We also developed a protein signature score (PSS) to guide PDAC diagnosis. In combination with patient age, the PSS achieved 100 % certainty in correctly identifying PDAC patients > 54 years. In addition, 3 /4 inconclusive EUS-FNA biopsies were correctly identified using PSS. CONCLUSIONS: EUS-FNA-derived fluid is a rich source of PDAC proteins with biomarker potential. The PSS requires further validation and verification of the feasibility of measuring these proteins in patient sera.

Mycophenolate mofetil decreases humoral responses to three doses of SARS-CoV-2 vaccine in liver transplant recipients.

BACKGROUND AND AIMS: After 2 doses, the efficacy of anti-SARS-CoV-2 vaccination seems to be lower in solid organ transplant recipients than in the immunocompetent population. The objective of this study was to determine the humoral response rate after vaccination, including with a booster dose, and to identify risk factors for non-responsiveness in liver transplant recipients. METHODS: We included all patients seen in consultation in two French liver transplant centres between January 1, 2021, and March 15, 2021. RESULTS: 598 liver transplant recipients were enrolled and 327 were included for analysis. Sixteen patients received one dose, 63 patients two doses and 248 patients three doses. Anti-SARS-Cov-2 antibodies were detected in 242 out of 327 (74.0%) liver transplant patients after vaccination. Considering an optimal serologic response defined as an antibody titre >260 BAU/ml, 172 patients (52.6%) were responders. Mycophenolate mofetil (MMF) treatment was an independent risk factor for a failure to develop anti-SARS-CoV-2 antibodies after vaccination (OR 0.458; 95%CI 0.258-0.813; p = .008). Conversely, male gender (OR 2.247, 95%CI 1.194-4.227; p = .012) and receiving an mRNA vaccine (vs a non-mRNA vaccine) (OR 4.107, 95%CI 1.145-14.731; p = .030) were independent predictive factors for developing an optimal humoral response after vaccination. None of the patients who received the vaccine experienced any serious adverse events. CONCLUSIONS: Even after a third booster dose, response rate to vaccination is decreased in liver transplant recipients. MMF appears to be a major determinant of seroconversion and optimal response to vaccination in these patients.

Assessment of long-term results of repeated dilations and impact of a scheduled program of dilations for refractory esophageal strictures: a retrospective case-control study.

INTRODUCTION: In patients with benign and refractory esophageal strictures (BES), repeating initial dilations in short intervals could be recommended, but little data are available to validate this strategy. Our aim was to evaluate long-term results of a scheduled program of repeated and sustained esophageal dilations in patients with refractory strictures. METHODS: Patients with BES requiring five or more dilations were retrospectively included and divided in two groups for analysis: a SCHEDULED group (SDG) where patients were systematically rescheduled for the 5 first dilations; ON-DEMAND group (ODG) where patients were dilated only in case of recurrence of the dysphagia. Comparison between SDG and ODG was done with a 1:1 matching analysis and etiology of stricture. Clinical success was defined as the absence of dysphagia for more than a year. RESULTS: 39 patients with refractory BES were included with post-operative stenosis in 51.2% and post-caustic injury 28.2%; 10 were in SDG and 29 in ODG. In overall analysis (39 patients), the follow-up was 64.4 ± 32 months, success rate was 79.5% and duration of treatment was 27.3 ± 20 months, and mean number of dilations was 11.7 per patient. The need for dilations decreased significantly after 18 months of treatment with an average of 0.56 dilations per semester. Self-expandable metallic stent insertion was associated with an increased rate of complications (5.9% vs 59.1% p = 0.001). In matched analysis (10 ODG vs 10 SDG patients), the duration of treatment was lower in SDG (18.8 vs 41.4 months, p = 0,032) with a higher probability of remission (survival analysis, Log-rank: p = 0,019) and the success rate did not differ between ODG and SDG patients (80% vs 90%; NS). CONCLUSION: Overall, long-term esophageal dilations resulted in a 79.5% success rate and the need for further dilatations decreased significantly in both groups after 18-month follow-up. A scheduled dilation program was associated with a higher probability of final success and lower treatment duration.

Endoscopic treatment of nonmalignant tracheoesophageal and bronchoesophageal fistula: results and prognostic factors for its success.

BACKGROUND: Nonmalignant esophago-respiratory fistulas (ERF) are frightening clinical situations, involving surgery with high morbi-mortality rate. We described the endoscopic management of benign ERF. The aim of the study was to describe outcomes of endoscopic treatment of nonmalignant ERF and to analyze factors associated with its success. METHODS: This is a retrospective study involving patients managed for benign ERF in our center between 2012 and 2016. The ERFs were classified into three groups of sizes: (I) punctiform, (II) medium, and (III) large. The primary aim was to document the endoscopic success (= fistula's healing after 6 months). The secondary objectives were characteristics of endoscopic treatment, the functional success and death, and identifying factors associated with success and death. RESULTS: 22 patients were included. The etiologies of ERF were surgery in 12 patients, esophageal dilatation in 3, invasive ventilation in 3, radiation therapy in 2, and tracheostomy in 2. Ninety-three procedures were performed (mean of number: 4.2 ± 4.5/patient). Twenty-one patients had stent placement, eight over-the-scope clips (OTSC), and seven a combined therapy. The endoscopic success rate was 45.5% (n = 10; 67% in punctiform, 50% in medium, and 14% in large ERF), and the functional success was 55% (n = 12). Serious adverse events occurred in 9 patients (40.9%). Six patients died (27%). The persistence of the orifice after 6 months of endoscopic treatment was associated with failure (OR 44; IC95: 3.38-573.4; p = 0.004 multivariate analysis). The orifice's size was associated with mortality [71% of death if large fistulas (p = 0.001) univariate analysis]. CONCLUSION: Endoscopic treatment of ERF leads to 45.5% of successful endoscopic closure and 55.5% of functional success, depending on fistula's orifice size. After 6 months without healing, the chances for success dramatically decrease.

Selective inner muscle layer myotomy is associated with lower pain and same clinical efficacy that full-thickness myotomy in patients treated by POEM for achalasia: a multicenter retrospective comparative analysis of 158 patients.

INTRODUCTION: The aim of this study was to compare the impact of the depth of myotomy (selective inner layer myotomy (SIM) vs. full-thickness myotomy (FTM)) on the outcome of patients treated with POEM for achalasia. METHODS: This was a retrospective, observational, conducted in two tertiary centers between October 2018 and September 2022. Patients were divided into two groups: SIM and FTM. The primary endpoint was clinical efficacy at 6 months, while secondary endpoints were postoperative criteria (such as pain, length of hospital stay, complications) and occurrence of gastroesophageal reflux disease (GERD) (esophagitis at 6 months, heartburn, and pH-metry). RESULTS: 158 patients were included in the study (33 in the FTM group and 125 in the SIM group). The success rates at 6 and 12 months were similar in both groups, with 84% and 70% in the SIM group versus 90% and 80% in the FTM group, respectively (p=0.57 and p=0.74). However, more opioid analgesics were consumed in the FTM group compared to the SIM group (41% vs 21%, p<0.01). The length of hospitalization was longer in the FTM group than in the SIM group (2.17 ± 2.62 vs 2.94 ± 2.33, p<0.001). The rate of esophagitis at 6 months was comparable (16% in the SIM group vs 12% in the FTM group, p=0.73). There was no significant difference in terms of heartburn at 6 or 12 months between the SIM and FTM groups (18.5% vs 3.8%, p=0.07 and 27% vs 12.5%, p=0.35, respectively). CONCLUSION: There was no significant difference in terms of clinical efficacy and GERD occurrence between FTM and SIM. However, full-thickness myotomy was associated with more postoperative pain and a longer length of hospital stay. Therefore, selective internal myotomy should be preferred over full-thickness myotomy.