Long-term Outcome of Gastric Per-Oral Endoscopic Pyloromyotomy in Treatment of Gastroparesis.

BACKGROUND & AIMS: Gastric per oral endoscopic pyloromyotomy (GPOEM) is a promising treatment for gastroparesis. There are few data on the long-term outcomes of this procedure. We investigated long-term outcomes of GPOEM treatment of patients with refractory gastroparesis. METHODS: We conducted a retrospective case-series study of all patients who underwent GPOEM for refractory gastroparesis at a single center (n = 97), from June 2015 through March 2019; 90 patients had more than 3 months follow-up data and were included in our final analysis. We collected data on gastroparesis cardinal symptom index (GCSI) scores (measurements of postprandial fullness or early satiety, nausea and vomiting, and bloating) and SF-36 questionnaire scores (measures quality of life). The primary outcome was clinical response to GPOEM, defined as a decrease of at least 1 point in the average total GCSI score with more than a 25% decrease in at least 2 subscales of cardinal symptoms. Recurrence was defined as a return to baseline GCSI or GCSI scores of 3 or more for at least 2 months after an initial complete response. The secondary outcome was the factors that predict GPOEM failure (no response or gastroparesis recurrence within 6 months). RESULTS: At initial follow-up (3 to 6 months after GPOEM), 73 patients (81.1%) had a clinical response and significant increases in SF-36 questionnaire scores (indicating increased quality of life) whereas 17 patients (18.9%) had no response. Six months after GPOEM, 7.1% had recurrence. At 12 months, 8.3% of patients remaining in the study had recurrence. At 24 months, 4.8% of patients remaining in the study had a recurrence. At 36 months, 14.3% of patients remaining in the study had recurrence. For patients who experienced an initial clinical response, the rate of loss of that response per year was 12.9%. In the univariate and multivariate regression analysis, a longer duration of gastroparesis reduced the odds of response to GPOEM (odds ratio [OR], 0.092; 95% CI, 1.04-1.3; P = .001). On multivariate logistic regression, patients with high BMIs had increased odds of GPOEM failure (OR, 1.097; 95% CI, 1.022-1.176; P = .010) and patients receiving psychiatric medications had a higher risk of GPOEM failure (OR, 1.33; 95% CI, 0.110-1.008; P = .052). CONCLUSIONS: In retrospective analysis of 90 patients who underwent GPOEM for refractory gastroparesis, 81.1% had a clinical response at initial follow-up of their procedure. 1 year after GPOEM, 69.1% of all patients had a clinical response and 85.2% of initial responders maintained a clinical response. Patients maintained a clinical response and improved quality of life for as long as 3 years after the procedure. High BMI and long duration gastroparesis were associated with failure of GPOEM.

Short-term outcomes of double versus single pyloromyotomy at peroral endoscopic pyloromyotomy in the treatment of gastroparesis (with video).

BACKGROUND AND AIMS: The prevalence of gastroparesis (Gp), a chronic debilitating disorder, and resulting hospitalizations are increasing. Gastric peroral endoscopic pyloromyotomy (POP or GPOEM) is a novel technique in the treatment of refractory Gp. Despite the initial promising results of GPOEM, one-third of patients do not exhibit any clinical response. Furthermore, loss of clinical response was reported in several studies. No response or loss of response after GPOEM may be related to inadequate myotomy. The aim of our study is to examine whether double pyloromyotomy at GPOEM is superior to single pyloromyotomy. METHOD: A retrospective case-controlled study of patients who underwent GPOEM for refractory Gp at our tertiary care institution between June 2015 and March 2018 was performed. Because the follow-up time for the single myotomy group was much longer than that of the double myotomy group, we matched the length of follow-up for the single myotomy group to that of the double myotomy group. The outcomes were measured by the changes in the Gastroparesis Cardinal Symptom Index (GCSI) before and 3 to 6 months after the procedure. Adverse events and other procedural and clinical parameters were also compared. RESULTS: Ninety patients underwent GPOEM (55 single and 35 double pyloromyotomy). The mean age was 47 ± 14 years, and the mean duration of symptoms was 5.3 ± 4.4 years. The average GCSI score was 3.8 before the GPOEM, and the average GCSI score 6 months after procedure was 1.8. Thirty-seven of 55 (67%) patients who underwent single pyloromyotomy achieved clinical response compared with 30 of 35 (86%) patients who underwent double pyloromyotomy. There were no significant differences for procedure time, postoperative pain, or length of hospital stay between the 2 groups. There was no difference in adverse events in the 2 pyloromyotomy groups. CONCLUSION: Double pyloromyotomy is a safe and feasible technique during GPOEM. Clinical success was higher in patients undergoing double pyloromyotomy compared with single pyloromyotomy in this nonrandomized, short-term follow-up study. Long-term studies are needed to further confirm our results.

Gastric peroral endoscopic pyloromyotomy versus gastric electrical stimulation in the treatment of refractory gastroparesis: a propensity score-matched analysis of long term outcomes.

BACKGROUND : Gastric peroral endoscopic pyloromyotomy (G-POEM) and gastric electrical stimulation (GES) have been reported as treatment options for refractory gastroparesis. In this study, we compared the long term clinical outcomes of G-POEM versus GES in the treatment of such patients. METHODS : We retrospectively evaluated 111 consecutive patients with refractory gastroparesis between January 2009 and August 2018. To overcome selection bias, we used propensity score matching (1:1) between G-POEM and GES treatment. The primary outcome was the duration of clinical response. RESULTS : After propensity score matching, 23 patients were included in each group. After a median follow-up of 27.7 months, G-POEM had a significantly better and longer clinical response than GES (hazard ratio [HR] for clinical recurrence 0.39, 95 % confidence interval [CI] 0.16 - 0.95; P = 0.04). The median duration of response was 25.4 months (95 %CI 8.7 - 42.0) in the GES group and was not reached in the G-POEM group. The Kaplan - Meier estimate of 24-month clinical response rate was 76.6 % with G-POEM vs. 53.7 % with GES. GES appeared to have little effect on idiopathic gastroparesis (HR for recurrence with G-POEM vs. GES 0.35, 95 %CI 0.13 - 0.95; P = 0.05). The incidence of adverse events was higher in the GES group (26.1 % vs. 4.3 %; P = 0.10). CONCLUSION : Among patients with refractory gastroparesis, clinical response was better and lasted longer with G-POEM than with GES. The positive outcomes with G-POEM are likely to derive from the superior clinical response in patients with idiopathic gastroparesis. Further studies are needed to confirm these findings.

The incidence of lymph node metastasis in submucosal early gastric cancer according to the expanded criteria: a systematic review.

BACKGROUND: For successful endoscopic treatment of early gastric cancer (EGC), absolute criteria for a curative en bloc resection were initially established to include predominantly differentiated mucosal lesions ≤ 2 cm in diameter without ulceration. These indications were subsequently expanded to include larger, ulcerated, and predominantly undifferentiated mucosal lesions. In addition, differentiated type adenocarcinomas ≤ 3 cm with slight submucosal invasion of < 500 µm (pT1b1) are regarded as "curative" under the expanded criteria. However, data derived from studies of surgical specimens in patients with pT1b1 EGC have yielded varying rates of lymph node metastasis (LNM). METHOD: A systemic review was conducted using the pooled analysis to calculate the incidence of LNM in pT1b1 EGC, and to investigate whether using a cut-off value of < 300 µm would decrease the risk of LNM in patients with submucosal EGC. RESULTS: Nineteen articles were included. 1507 patients with pT1b1 EGC met the expanded indications. The incidence of LNM was 3% (45 out of 1507 patients). In a subgroup analysis of three studies, there was no significant difference in the LNM between pT1b EGC < 300 µm and < 500 µm [3/121(2.5%) vs. 5/180 (2.8%)] (OR 0.89, 95% CI 0.22-3.54). CONCLUSION: Overall, expanding the indications for endoscopic resection of EGC to include lesions ≤ 3 cm T1b1 is associated with a potential risk of LNM of 3%. In countries outside of Japan, we found a slightly higher risk of LNM (4.0%). These estimates of LNM should be incorporated into decisions regarding further management of patients with EGC ≤ 3 cm who are found to have slight submucosal invasion (< 500 µm) in an ESD specimen. Standardization of specimen handling and histological evaluation is essential if the Japanese results of endoscopic treatment for EGC are to be successfully applied in other parts of the world.

Endoscopic submucosal dissection for early neoplastic lesions in the surgically altered stomach: a systematic review and meta-analysis.

INTRODUCTION AND AIM: Endoscopic submucosal dissection (ESD) for early gastric cancer is highly effective and well established. Performing ESD in the surgically altered stomach (SAS) is challenging. The aim of this meta-analysis is to assess the safety and efficacy of ESD for patients with early neoplastic lesions occurring in the SAS with a subgroup analysis of lesions occurring on the suture line compared to non-suture line lesions and outcomes in the remnant stomach compared to the gastric tube. METHODS: We performed a literature search of the PubMed, Embase, and CINAHL electronic databases from January 2000 to November 2017 for articles reporting the safety and efficacy of ESD in the surgically altered stomach. SAS was defined as the remnant stomach following gastrectomy and gastric tube following esophagectomy. Meta-analysis was performed using Review Manager version 5.3 software. RESULTS: A total of 21 articles, with 903 lesions occurring in the remnant stomach or gastric tube, were included in this study. There was no significant difference between en bloc (RR 0.99, 95% CI 0.91-1.08), curative resection (RR 1.03, 95% CI 0.84-1.26), or bleeding rates (RR 1.40, 95% CI 0.18-10.72) between lesions in the remnant stomach and gastric tube. However, perforation was significantly higher in the gastric tube (RR 5.19, 95% 1.27-21.25). Suture line lesions had a significantly higher risk of perforation (RR 4.55, 95% CI 2.13-9.74). CONCLUSION: ESD for early neoplastic lesions occurring in the SAS is a safe and efficacious with similar en bloc and curative resection rates compared to the anatomically normal stomach. ESD for lesions on the suture line or in the gastric tube is associated with an increased risk of perforation which can be managed endoscopically.

Cohort study comparing the diagnostic yields of 2 different EUS fine-needle biopsy needles.

BACKGROUND AND AIMS: Two second-generation, flexible EUS fine-needle biopsy (FNB) needles have been marketed recently in the United States. Thus far, there have been no comparative studies of the diagnostic yield of these needles. The aim of this study was to compare the diagnostic yield achieved with FNB by using 1 needle during 1 time period and the other needle during a second time period. METHODS: Consecutive patients with solid lesions undergoing EUS-FNB by using 1 of two 22-gauge FNB needles (Franseen needle or fork-tip) at 2 different time intervals were included. The final diagnosis was based on positive pathology results. In cases of a negative pathology result, the final diagnosis was based on clinical and imaging follow-up. RESULTS: A total of 194 lesions (97 in each group) were sampled in 179 patients. Rapid on-site evaluation (ROSE) was used in 12% of cases. The overall diagnostic yield was lower in the Franseen needle group compared with the fork-tip needle group (61/97 [63%] vs 75/97 [77%], odds ratio (OR) 2.01, 1.07-3.8; P = .027). Similarly, subanalysis of the yield for solid pancreatic masses demonstrated a lower yield with the Franseen needle (34/53 [64%] vs 40/47 [85%], OR 3.4, 9.1-8.9; P = .017). Multivariate analysis controlling for the number of passes, site, and lesion size did not have any effect on diagnostic yield. There were no adverse events in either group. CONCLUSION: In this first, large, single-center comparative cohort study of 2 new, second-generation EUS-FNB needles of different design, the diagnostic yield when used primarily without ROSE was high in both groups but was significantly higher when a fork-tip needle was used.

The incidence of lymph node metastasis in early gastric cancer according to the expanded criteria in comparison with the absolute criteria of the Japanese Gastric Cancer Association: a systematic review of the literature and meta-analysis.

BACKGROUND AND AIMS: Japanese criteria for curative endoscopic resection of early gastric cancer initially included nonulcerated, well-differentiated mucosal lesions ≤2 cm in diameter, known as the absolute criteria. Subsequently, these indications were expanded to include larger, ulcerated, and undifferentiated mucosal lesions as well as differentiated lesions with slight submucosal invasion. Whether patients meeting the expanded criteria can be managed safely without gastrectomy and lymph node dissection has been controversial. The risk of lymph node metastasis (LNM) in patients who met the expanded criteria is a critical factor in determining the best course of management for these patients. METHODS: We comprehensively searched main reference databases for studies that included patients who underwent gastrectomy and lymph node dissection for early gastric cancer. A meta-analysis was conducted by using the random effects model. Relative risk reduction was used to compare the incidence of LNM in patients meeting the absolute criteria as compared with those meeting the expanded criteria. RESULTS: Twelve studies met the inclusion criteria, providing a total of 9798 patients. The incidence of LNM was 0.2% for patients who met the absolute criteria as compared with 0.7% for patients who met the expanded criteria. Analysis of the various components of the expanded criteria was conducted, revealing that the incidence of LNM for differentiated mucosal lesions ≤3 cm with ulceration and for differentiated mucosal lesions without ulceration, irrespective of size, was 16 of 2814 (0.57%), reference range (RR) 3.01; P = .02 and 8 of 3004 (0.27%), RR 1.69; P = .37, respectively, only marginally higher than the risk of LNM associated with the absolute criteria. In contrast, undifferentiated mucosal lesions ≤2 cm and differentiated lesions <3 cm with slight submucosal invasion had a significantly higher incidence of LNM in comparison with the absolute criteria (25/972 [2.6%], RR 6.79; P = .0004 and 8/315 [2.5%], RR 6.30; P = .004, respectively). CONCLUSION: Overall, expanding the indication for endoscopic resection to include mucosal nonulcerated differentiated lesions irrespective of size and differentiated mucosal ulcerated lesions <3 cm is justified with minimal increased risk in comparison to the absolute criteria. However, expanding the indication for undifferentiated lesions ≤2 cm and differentiated lesions with slight submucosal invasion (T1b) should be balanced with the risks of surgery, given the increased risk of LNM in these patients.

Correlation between adenoma detection rate and novel quality indicators for screening colonoscopy. A proposal for quality measures tool kit.

BACKGROUND AND AIMS: Adenoma detection rate (ADR) is the most validated quality indicator for colonoscopy. Calculating ADR may not yield information in regards to advanced adenoma detection rate (advanced ADR). In addition, calculating ADR for individual endoscopists cannot distinguish between those who find only one versus more than one adenoma per colonoscopy. Several novel quality indictors were recently proposed to ensure adequate assessment of quality during colonoscopy. Our study aims to determine the correlation between ADR and novel quality indicators. METHODS: A retrospective cohort study of patients undergoing screening colonoscopy in a university hospital setting. Patient characteristics and colonoscopy findings were combined and analyzed to calculate the correlation of ADR with novel quality indicators using Spearman's rank-order correlation were used. RESULTS: A total of 1433 patients out of 2116 patients met the inclusion criteria. There was a significant positive correlation between ADR correlated with [advanced-ADR-2, nonadvanced-ADR, adenoma per colonoscopy, Multiplicity detection rate and ADR-Plus] r = (0.82, 0.99, 0.99, 0.07 and 0.85), respectively. However, ADR did not correlate with advanced-ADR and adenomas per positive participant. CONCLUSION: Adding advanced-ADR and adenomas per positive participant to ADR may create a more comprehensive quality indicators tool kit, which is sensitive and difficult to game. Future studies are needed to investigate the impact of the tool kit on the interval cancers and adenoma missing rate.

Lack of functionally active sweet taste receptors in the jejunum in vivo in the rat.

BACKGROUND: When studied in enterocyte-like cell lines (Caco-2 and RIE cells), agonists and antagonists of the sweet taste receptor (STR) augment and decrease glucose uptake, respectively. We hypothesize that exposure to STR agonists and antagonists in vivo will augment glucose absorption in the rat. MATERIALS AND METHODS: About 30-cm segments of jejunum in anesthetized rats were perfused with iso-osmolar solutions containing 10, 35, and 100 mM glucose solutions (n = 6 rats, each group) with and without the STR agonist 2 mM acesulfame potassium and the STR inhibitor 10 µM U-73122 (inhibitor of the phospholipase C pathway). Carrier-mediated absorption of glucose was calculated by using stereospecific and nonstereospecific (14)C-d-glucose and (3)H-l-glucose, respectively. RESULTS: Addition of the STR agonist acesulfame potassium to the 10, 35, and 100 mM glucose solutions had no substantive effects on glucose absorption from 2.1 ± 0.2 to 2.0 ± 0.3, 5.8 ± 0.2 to 4.8 ± 0.2, and 15.5 ± 2.3 to 15.7 ± 2.7 µmoL/min/30-cm intestinal segment (P > 0.05), respectively. Addition of the STR inhibitor (U-73122) also had no effect on absorption in the 10, 35, and 100 mM solutions from 2.3 ± 0.1 to 2.1 ± 0.2, 7.7 ± 0.5 to 7.2 ± 0.5, and 15.7 ± 0.9 to 15.2 ± 1.1 µmoL/min/30-cm intestinal segment, respectively. CONCLUSIONS: Provision of glucose directly into rat jejunum does not augment glucose absorption via STR-mediated mechanisms within the jejunum in the rat. Our experiments show either no major role of STRs in mediating postprandial augmentation of glucose absorption or that proximal gastrointestinal tract stimulation of STR or other luminal factors may be required for absorption of glucose to be augmented by STR.

Management of early gastric cancer meeting criteria for endoscopic resection: US population-based study.

Background and study aims The goal of this study was to assess surgical resection (SR) of early gastric cancer (EGC) fitting Japanese Gastric Cancer Association (JGCA) endoscopic resection (ER) criteria. Patients and methods We analyzed EGC data from the national Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015. Results A total of 2219 EGC cases were identified (1074 T1a and 1145 T1b). Of them, 409 met absolute criteria, 219 met expanded 1, 529 expanded 2, and 229 expanded 3. 259 lesions were treated endoscopically while 1007 were surgically resected (20.5 % vs 79.5 %, P  = 0.0001). Temporal analysis showed that the frequency of ER steadily increased while SR proportionally decreased during the study period. Cox proportion regression analysis adjusting for confound variables (including age, gender, and race) showed no significant difference in the risk of mortality following either surgery or endoscopy. Conclusions EGC can be safely treated with ER. However, EGC meeting JGCA ER criteria is largely treated with SR in the United States.

Long-term Outcome of Per-oral Endoscopic Myotomy Performed in the Endoscopy Unit With Trainees.

INTRODUCTION: Per-oral endoscopic myotomy (POEM) has been widely adopted for the treatment of achalasia as it provides a precise, tailored myotomy in a minimally invasive endoscopic procedure. Several short-term studies and a few long-term studies have confirmed that POEM is a safe and effective treatment for achalasia. However, the long-term outcome of POEM performed by trainees is unknown. MATERIALS AND METHODS: We conducted a retrospective study of all patients who underwent POEM for achalasia at our tertiary care center during December 2012 and January 2019. All procedures performed with trainees were included. The primary outcome was the clinical response to POEM, defined as an Eckardt score of <3 after POEM. Trainees were trained in performing mucosotomy and submucosal dissection, creating a submucosal tunnel, identifying gastroesophageal junction, and performing myotomy and closure of mucosal incision in a step-by-step fashion. Trainees' performance was evaluated by the mentor based on several key points in each step. RESULTS: A total of 153 consecutive patients with a median age of 57±18 years were analyzed in this study. Of the total patients, 69 (45%) were male. The median length of follow-up after POEM was 32 months (range: 7 to 77 mo). A clinically significant response to POEM was achieved in 95% of patients at year 1, 84% at year 2, 80% at year 3, 79% at year 4, 78% at year 5, and 78% at year 6 and above. All trainees obtained competence within 6 cases for each step and could perform the procedure alone after 20 supervised cases. CONCLUSIONS: Overall, 78% of patients maintained positive clinical response at 6 years following POEM procedure. The recurrence rate of symptoms following POEM was 22% at a 6-year follow-up. This long-term outcome of POEM performed with trainees was comparable to those without trainees in other studies. To our knowledge, this is the longest follow-up and the largest number of patients after the POEM procedure performed with trainees.

Proximal and Distal Gastric Retention Patterns in Gastroparesis and the Impact of Gastric Per-Oral Endoscopic Myotomy: A Retrospective Analysis Using Gastric Emptying Scintigraphy.

Gastroparesis is a debilitating disease of insufficient gastric emptying and visceral hypersensitivity characterized by nausea, vomiting, early satiety, and bloating. Gastric emptying scintigraphy (GES), in combination with typical symptoms and normal esophagogastroduodenoscopy findings, is used to diagnose the disease. Gastric per-oral endoscopic pyloromyotomy (G-POEM) has emerged as a novel technique for treating gastroparesis, with up to an 80% success rate. This procedure involves myotomy of the distal stomach. We hypothesize that responders to this therapy are characterized by more distal dysmotility than nonresponders, as defined by GES retention patterns. Methods: We used regional gastric emptying measurements from diagnostic GES to determine the proximal or distal predominance of disease for each patient. We then compared treatment response and symptoms in each patient to total gastric half-emptying time (T½), proximal gastric T½, and a ratio comparing the 2 values. Results: In total, 47 patients underwent G-POEM during the study period. A significant difference (P < 0.01) was found in proximal-to-total T½ ratio between responders and nonresponders. A significant difference between pre- and postprocedural proximal-to-total T½ ratios was identified for each patient. No correlations were identified between motility patterns and symptoms or in motility patterns among the different etiologies of the disease. Conclusion: Proximal-to-total T½ ratio may represent an important patient selection factor for G-POEM versus other treatment modalities going forward. Local retention patterns in GES may not inform the symptom profile in gastroparesis.

Morning versus afternoon adenoma detection rate: a systematic review and meta-analysis.

Adenoma detection rate (ADR) is a quality marker of colonoscopy and operator performance. Prior studies evaluating the effect of an extended workday on the ADR reported variable outcomes that remain controversial. Given the variable results of prior studies and the potential legal implications of reduced ADR in the afternoon, we aimed to further evaluate this parameter and its effect on ADR. We performed a systematic review of the PubMed, CINAHL and Scopus electronic databases. Studies were included if they reported ADR in patients undergoing colonoscopy in the morning session and the afternoon session. Afternoon sessions included both sessions following a morning shift and half-day block shifts. Subgroup analyses were performed for ADR comparing morning and afternoon colonoscopies in a continuous workday, advanced ADRs (AADRs) and polyp detection rates (PDRs) were also compared. Thirteen articles with 17 341 (61.2%) performed in the morning session and 10 994 (38.8%) performed in the afternoon session were included in this study. There was no statistical significance in the ADR or AADR between morning and afternoon sessions, respectively [relative risk (RR) 1.06, 95% confidence interval (CI) 0.99-1.14] and (RR 1.19, 95% CI 0.95-1.5). Afternoon procedures had a significantly higher PDR than morning procedures (RR 0.93, 95% CI 0.88-0.98). ADR was not significantly influenced in the afternoon session when operators continued to perform procedures throughout the day or on a half-day block schedule.

Rectal indomethacin reduces the risk of post-endoscopic retrograde cholangiopancreatography pancreatitis in low-risk patients.

BACKGROUND: Evidence shows that rectal indomethacin (RI) reduces the risk of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in high-risk patients. The prophylactic role of RI in low-risk patients has not yet been identified. The objective of our study was to evaluate the impact of RI in preventing PEP in low-risk patients. METHODS: A retrospective cohort study was conducted to evaluate the impact of RI in preventing PEP. RI was available starting November 2012. Patient characteristics and procedure details were collected. RESULTS: The study population included 2238 patients who underwent ERCP (1055 in the RI group and 1183 in the control group). PEP was diagnosed in 107 patients (4.8%). In a multivariate model of consecutive patients, RI reduced the incidence of PEP by 55% (odds ratio [OR] 0.45, 95% confidence interval [CI] 0.36-0.94; P=0.03). In a multivariate model that included 1874 (84%) low-risk patients, RI reduced the incidence of PEP by 62% (OR 0.38, 95%CI 0.19-0.74; P=0.004). Propensity-matched group analysis was performed for low-risk native papilla patients. RI reduced the incidence of PEP by 61% (OR 0.39, 95%CI 0.18-0.8; P=0.009). CONCLUSION: RI reduced PEP in consecutive as well as low-risk patients. RI should be administrated in consecutive patients unless contraindicated. Larger prospective studies are needed to confirm our results.