Endoscopic Ultrasound-guided Radiofrequency Ablation Versus Surgical Resection for Treatment of Pancreatic Insulinoma.

BACKGROUND & AIMS: Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) is emerging as a safe and effective treatment for pancreatic neuroendocrine tumors. We aimed to compare EUS-RFA and surgical resection for the treatment of pancreatic insulinoma (PI). METHODS: Patients with sporadic PI who underwent EUS-RFA at 23 centers or surgical resection at 8 high-volume pancreatic surgery institutions between 2014 and 2022 were retrospectively identified and outcomes compared using a propensity-matching analysis. Primary outcome was safety. Secondary outcomes were clinical efficacy, hospital stay, and recurrence rate after EUS-RFA. RESULTS: Using propensity score matching, 89 patients were allocated in each group (1:1), and were evenly distributed in terms of age, sex, Charlson comorbidity index, American Society of Anesthesiologists score, body mass index, distance between lesion and main pancreatic duct, lesion site, size, and grade. Adverse event (AE) rate was 18.0% and 61.8% after EUS-RFA and surgery, respectively (P < .001). No severe AEs were observed in the EUS-RFA group compared with 15.7% after surgery (P < .0001). Clinical efficacy was 100% after surgery and 95.5% after EUS-RFA (P = .160). However, the mean duration of follow-up time was shorter in the EUS-RFA group (median, 23 months; interquartile range, 14-31 months vs 37 months; interquartile range, 17.5-67 months in the surgical group; P < .0001). Hospital stay was significantly longer in the surgical group (11.1 ± 9.7 vs 3.0 ± 2.5 days in the EUS-RFA group; P < .0001). Fifteen lesions (16.9%) recurred after EUS-RFA and underwent a successful repeat EUS-RFA (11 patients) or surgical resection (4 patients). CONCLUSION: EUS-RFA is safer than surgery and highly effective for the treatment of PI. If confirmed in a randomized study, EUS-RFA treatment can become first-line therapy for sporadic PI.

The POEM bottom-up technique for achalasia.

BACKGROUND: POEM (Per Oral Endoscopic Myotomy) is rapidly becoming a valid option for surgical myotomy in achalasia patients. Several techniques to perform POEM are described, but all concentrate on the division of the circular muscle fibers in a proximal-to-distal fashion. Our aim is to present the distal-to-proximal, or the bottom-up technique using the Flush/Dual knife, which overcomes the disadvantages of the standard technique. METHODS: A retrospective study on a prospectively maintained database was performed on all patients treated by POEM in our institution. Clinical presentation, operating time, adverse events, and outcomes were studied. RESULTS: POEM was performed on 105 achalasia patients. The first 15 cases were performed using the standard technique and were compared to the next 90 cases performed using the bottom-up technique. The average preop Eckardt scores in the standard and bottom-up groups were 9.5 and 8.8, respectively, declining to 1.4 and 0.5, 3 months post myotomy (p < 0.001). The average procedure time was 111.2 min for the standard technique and 74.3 for the bottom-up technique. (p = 0.002). Perioperative adverse events included 14 instances of pneumoperitoneum, 3 tunnel leaks, and 4 patients with fever on postoperative day one. Pneumoperitoneum needing decompression and postoperative fever were more prevalent in the standard technique group. CONCLUSIONS: As POEM is becoming more common for the treatment of achalasia, refinements of the technique and instruments used are valuable. We compared our experience of the standard technique to our bottom-up technique and found the latter to be equally effective as well as safer, faster, and easier. We, therefore, suggest considering performing POEM in this technique.

G-EYE colonoscopy is superior to standard colonoscopy for increasing adenoma detection rate: an international randomized controlled trial (with videos).

BACKGROUND AND AIMS: Colorectal cancer (CRC) is largely preventable with routine screening and surveillance colonoscopy; however, interval cancers arising from precancerous lesions missed by standard colonoscopy still occur. An increased adenoma detection rate (ADR) has been found to be inversely associated with interval cancers. The G-EYE device includes a reusable balloon integrated at the distal tip of a standard colonoscope, which flattens haustral folds, centralizes the colonoscope's optics, and reduces bowel slippage. The insufflated balloon also aims to enhance visualization of the colon during withdrawal, thereby increasing the ADR. METHODS: In this randomized, controlled, international, multicenter study (11 centers), patients (aged ≥50 years) referred to colonoscopy for screening, surveillance, or changes in bowel habits were randomized to undergo either balloon-assisted colonoscopy by using an insufflated balloon during withdrawal or standard high-definition colonoscopy. The primary endpoint was the ADR. RESULTS: One thousand patients were enrolled between May 2014 and September 2016 to undergo colonoscopy by experienced endoscopists; 803 were finally analyzed (standard colonoscopy n = 396; balloon-assisted colonoscopy n = 407). Baseline parameters were similar in both groups. Balloon-assisted colonoscopy provided a 48.0% ADR compared with 37.5% in the standard colonoscopy group (28% increase; P = .0027). Additionally, balloon-assisted colonoscopy provided for a significant increase in detection of advanced (P = .0033) flat adenomas (P < .0001) and sessile serrated adenomas/polyps (P = .0026). CONCLUSION: Balloon-assisted colonoscopy yielded a higher ADR and increased the detection of advanced, flat, and sessile serrated adenomas/polyps when compared with standard colonoscopy. Improved detection by the G-EYE device could impact the quality of CRC screening by reducing miss rates and consequently reducing interval cancer incidence. (Clinical trial registration number: NCT01917513.).

[PER-ORAL ENDOSCOPIC MYOTOMY - SUMMARY OF FIVE YEARS EXPERIENCE].

INTRODUCTION: Esophageal achalasia is a rare condition, characterised by progressive dysphagia due to innervation of the esophageal muscles and non-relaxation of the lower esophageal sphincter. The standard of care of surgical treatment is laparoscopic Heller myotomy. POEM-Peroral endoscopic myotomy is a new approach offering incision-less and selective myotomy. AIMS: This study aims to describe our experience and outcomes using this new surgical technique. METHODS: We performed a retrospective study using prospectively maintained data of all achalasia patients treated by POEM in our department. Data collected included patient demographics, gender, age, BMI, data related to the disease course in addition to data related to the surgery itself as well as both short and long term post-operative follow-up. RESULTS: Over the course of five years we performed 86 POEM operations, demonstrating a decrease in the Eckardt score from a mean of 8.87 to a mean of 0.7 in the immediate postoperative. Mean operative time was 86 minutes, with mean hospitalization time of 4 days. Intraoperative complications included 2 mucosal injuries while post-operative complications included 4 incomplete mucosal closures, 5 recurrent dysphagia and 5 patients with reflux requiring medical therapy. CONCLUSIONS: In the last decade, POEM procedure is being performed worldwide and has been performed in our department for the past five years. Our results show a success rate of 94.2% with minor complications. In our institution, as in many institutions globally, POEM is the preferred method for treating achalasia.

Endoscopic submucosal dissection of cecal lesions in proximity to the appendiceal orifice.

BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) is performed for treatment of various gastrointestinal lesions; however, the cecum in proximity to the appendiceal orifice remains a challenging area. We reviewed our experience with cecal ESD near the appendiceal orifice in order to clarify whether this procedure is a safe and effective therapeutic option. PATIENTS AND METHODS: We retrospectively reviewed ESD for lesions within approximately 12 mm of the appendiceal orifice at Kobe University Hospital and an affiliated hospital between January 2003 and December 2014. Lesions were classified as: Type 0, proximity to the appendiceal orifice but does not reach it; Type 1, reaches border of the appendix, but does not enter orifice; Type 2, enters orifice, and transition to normal appendiceal mucosa is discernible on inspection of the appendiceal lumen; and Type 3, enters orifice deeply and tumor edge cannot be observed. ESD was not performed for Type 3 lesions unless appendectomy was performed prior to ESD. RESULTS: A total of 76 lesions satisfied the inclusion criteria (47 Type 0 lesions, 20 Type 1, 6 Type 2, and 3 Type 3). En bloc resection was achieved in 72 lesions (94.7 %). Median specimen size was 49 mm (range 15 - 114 mm), and median tumor size was 35.5 mm (10 - 110 mm). One patient experienced postoperative bleeding, which was treated by endoscopic hemostasis. Another patient who experienced intraoperative perforation and was treated by clip closure later developed appendicitis; he underwent emergency ileocecal surgical resection. Another patient experienced postoperative appendicitis and recovered with antibiotic treatment. CONCLUSIONS: ESD in close proximity to the appendiceal orifice seems safe and effective.

A computer-aided polyp detection system in screening and surveillance colonoscopy: an international, multicentre, randomised, tandem trial.

BACKGROUND: Studies on the effect of computer-aided detection (CAD) in a daily clinical screening and surveillance colonoscopy population practice are scarce. The aim of this study was to evaluate a novel CAD system in a screening and surveillance colonoscopy population. METHODS: This multicentre, randomised, controlled trial was done in ten hospitals in Europe, the USA, and Israel by 31 endoscopists. Patients referred for non-immunochemical faecal occult blood test (iFOBT) screening or surveillance colonoscopy were included. Patients were randomomly assigned to CAD-assisted colonoscopy or conventional colonoscopy; a subset was further randomly assigned to undergo tandem colonoscopy: CAD followed by conventional colonoscopy or conventional colonoscopy followed by CAD. Primary objectives included adenoma per colonoscopy (APC) and adenoma per extraction (APE). Secondary objectives included adenoma miss rate (AMR) in the tandem colonoscopies. The study was registered at ClinicalTrials.gov, NCT04640792. FINDINGS: A total of 916 patients were included in the modified intention-to-treat analysis: 449 in the CAD group and 467 in the conventional colonoscopy group. APC was higher with CAD compared with conventional colonoscopy (0·70 vs 0·51, p=0·015; 314 adenomas per 449 colonoscopies vs 238 adenomas per 467 colonoscopies; poisson effect ratio 1·372 [95% CI 1·068-1·769]), while showing non-inferiority of APE compared with conventional colonoscopy (0·59 vs 0·66; p<0·001 for non-inferiority; 314 of 536 extractions vs 238 of 360 extractions). AMR in the 127 (61 with CAD first, 66 with conventional colonoscopy first) patients completing tandem colonoscopy was 19% (11 of 59 detected during the second pass) in the CAD first group and 36% (16 of 45 detected during the second pass) in the conventional colonoscopy first group (p=0·024). INTERPRETATION: CAD increased adenoma detection in non-iFOBT screening and surveillance colonoscopies and reduced adenoma miss rates compared with conventional colonoscopy, without an increase in the resection of non-adenomatous lesions. FUNDING: Magentiq Eye.

Post-POEM Contrast-Enhanced Swallow Study: Is It Always Necessary?

BACKGROUND: Peroral endoscopic myotomy (POEM) is rapidly becoming the procedure of choice for treating esophageal achalasia. In most centers, contrast-enhanced swallow studies (CESS) are routinely performed postoperatively to confirm mucosal integrity. The aim of this study was to determine the necessity of performing these studies routinely after POEM. METHODS: A retrospective review of a prospectively maintained database of patients who underwent POEM between December 2012 and November 2020 was performed. All patients underwent a CESS on the first postoperative day. Medical records including vital signs, complete blood count, and POD-1 CESS were evaluated. RESULTS: One hundred thirty-four consecutive patients were included in the study. Sixty-nine (51.49%) CESS showed abnormal findings; while most findings did not change the postoperative course, five (7.2%) demonstrated tunnel leaks, which did alter the overall management. Screening patients for fever, tachycardia, or leukocytosis on POD-1 had a 100% sensitivity and a 62% specificity for finding a clinically significant complication on CESS. CONCLUSIONS: The study findings suggest that performing routine contrast-enhanced swallow studies on all patients is not necessary following POEM, as leaks can be screened for by clinical or laboratory abnormalities. Herein, we propose an algorithm based on objective measurable findings for the selection of patients who should undergo CESS.

Reproductive Outcomes Among Women of Childbearing Age with Achalasia After Peroral Endoscopic Myotomy: A Single-Center Experience.

Background: Achalasia may occasionally occur among women of childbearing age. Pregnancy may lead to deterioration of the disease and negatively affect maternal and perinatal outcomes. However, the impact of peroral endoscopic myotomy (POEM) on reproductive outcomes has been understudied. Methods: A retrospective study on prospectively maintained database, including women aged 18-45 who underwent POEM during 2012-2017 at a university hospital. Results: During the study period, POEM was performed in 86 patients. Of them, 23 were women of childbearing age (median age 31.9 [26.0-40.7] years). Follow-up data were available for a median of 24 [16-41] months. Treatment success (Eckardt score <3) was achieved in 22 (95.7%) women. Six (26.1%) women reported attempting to conceive after POEM. Overall, 7 post-POEM pregnancies among 5 women were encountered. All 7 pregnancies were naturally conceived with a median surgery-to-conception interval of 16 [10-21] months. The median gestational weight gain was 10 kg, and was insufficient in all pregnancies. None of the women was hospitalized during the index gestation. All pregnancies resulted in term live-birth vaginal delivery. The median neonatal birthweight was 2940 g, with only one case of a small-for-gestational age infant. Achalasia-related symptoms recurred during 2 pregnancies, with resolution following delivery. Conclusions: Pregnancy after POEM for the treatment of achalasia was associated with favorable maternal and perinatal outcomes. This data should reassure women who wish to conceive following peroral myotomy.

Staple Line Leaks Following Laparoscopic Sleeve Gastrectomy: Low Efficacy of the Over-the-Scope Clip.

PURPOSE: The over-the-scope clip (OTSC) enables non-surgical management of gastrointestinal defects. The aim of this study was to report our experience with OTSC for patients with staple line leaks following laparoscopic sleeve gastrectomy (LSG). MATERIALS AND METHODS: A prospectively maintained IRB-approved institutional database was queried for all patients treated with OTSC for staple line leaks following LSG from 2010 to 2018. Primary outcome was complete resolution of leak following OTSC. Secondary outcome was the number of additional procedures needed following OTSC. RESULTS: Twenty-six patients (13 males, 13 females) were treated with OTSC for staple line leaks following LSG. The median age was 35 years (range 18-62), and mean body mass index was 44 kg/m2. The median time from index operation to leak diagnosis and from leak diagnosis to OTSC was 18 days (range 2-118), and 6 days (range 1-120), respectively. The initial endoscopic treatment was OTSC (n = 19), stent (n = 5), clip (n = 1), and clip and biologic glue (n = 1). OTSC alone led to final resolution of leak in 8 patients (31%) within 43 days of clip deployment (range 5-87). Five leaks resolved after a combination of OTSC and stent (19%) and one leak (4%) resolved after endoscopic suturing following a failed OTSC. Eleven patients (42%) failed endoscopic management and underwent total gastrectomy and esophagojejunostomy. One mortality (4%) was noted. The number of additional endoscopic sessions ranged from 1 to 10 (median 2). CONCLUSIONS: OTSC carries a low success rate for controlling staple line leaks following LSG.

Long-term outcomes in MEN-1 patients with pancreatic neuroendocrine neoplasms: an Israeli specialist center experience.

PURPOSE: The decreased life expectancy of MEN-1 patients is mainly related to pancreatic neuroendocrine tumors (pNETs). At best, limited data is available on the natural history of MEN-1-associated pNETs, as these tumors are rare and have a wide range of biologic behavior. Our study aims to explore the clinical course of patients with MEN-1-associated pNETs and the long-term outcomes. METHODS: This longitudinal study was conducted on the MEN-1 cohort treated at our referral center over a 22-year period (1996-2018). Relevant clinical data were retrospectively analysed. RESULTS: Among the 33 MEN-1 patients included in our study, pNETs were identified in 21 subjects with a penetrance of 48% by the age of 50. Non-functioning and functioning pNETs were diagnosed in sixteen (76%) and five (24%) patients, respectively. Two-thirds of the patients had multifocal tumors. The median number of pancreatic macroscopic lesions per individual was 4.0 ± 3.9 (range 1-8) with a mean size of 1.3 ± 2.1 cm (range 0.5-10). The metastatic rate according to the dominant pNET lesion reached 100%, 62% and 6% for tumors sized > 4 cm, 2.1-4 cm, and 1-2 cm, respectively. Over the study period, one or more therapeutic interventions for pNETs were required in 20 out of the 21 patients. pNET-related metastatic complication was the main cause of death within this MEN-1 cohort. The overall survival rate for the pNETs patients was 86% during a mean follow-up period of 8.0 ± 4.6 years. CONCLUSIONS: In our MEN-1 cohort, non-functioning pNETs were the most frequent type of pancreaticoduodenal tumor, and the tumor size correlated with the risks of metastasis and death. Increased awareness, early diagnosis, and a multidisciplinary approach may improve the associated morbidity and mortality in these patients.

Endoscopic Ultrasound-Guided Angiotherapy for Gastric Varices: A Single Center Experience.

There are limited efficacious therapeutic options for management of gastric variceal bleeding. Treatment modalities include transjugular intrahepatic portosystemic shunt, surgical shunts, and endoscopic interventions, including the recent advancement of endoscopic ultrasound (EUS)-guided coiling. We present a case series of 10 patients with portal hypertension (7 with liver cirrhosis and 3 without cirrhosis), complicated by gastric varices (GV) with bleeding. All cases were treated successfully with EUS-guided coiling leading to variceal eradication. There were 10 occurrences of minimal self-limited bleeding at the puncture site during the procedure, and only one occurrence of major bleeding that necessitated cyanoacrylate glue injection for homeostasis. There were no other adverse events within a mean follow-up time of 9.7 months (range, 1-28 months). Conclusion: In our series, EUS-guided angiotherapy was effective for GV eradication with a high safety profile.

Endoscopic Ultrasound-Guided Radiofrequency Ablation: A New Therapeutic Approach for Pancreatic Neuroendocrine Tumors.

CONTEXT: Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) is rapidly emerging as feasible therapy for patients with pancreatic neuroendocrine tumors (pNETs) in selected cases, as a result of its favorable safety profile. OBJECTIVE: To assess the feasibility, safety, and efficacy of EUS-RFA in a cohort of patients with functional and nonfunctional pNETs (NF-pNETs). DESIGN: Data on pNET patients treated with EUS-RFA between March 2017 and October 2018 at two tertiary centers was retrospectively analyzed. RESULTS: The cohort included 18 adults (eight women, 10 men), aged 60.4 ± 14.4 years (mean ± SD), seven insulinoma patients, and 11 patients with NF-pNETs. Twenty-seven lesions with a mean diameter of 14.3 ± 7.3 mm (range 4.5 to 30) were treated. Technical success defined as typical postablative changes on a surveillance imaging was achieved in 26 out of 27 lesions. Clinical response with normalization of glucose levels was observed in all (seven of seven) insulinoma cases within 24 hours of treatment. Overall, there were no major complications 48 hours postprocedure. No clinically significant recurrences were observed during mean follow-up of 8.7 ± 4.6 months (range 2 to 21 months). CONCLUSIONS: EUS-guided RFA of pNETs is a minimally invasive, safe, and technically feasible procedure for selected patients.

Variable Features of Juvenile Polyposis Syndrome With Gastric Involvement Among Patients With a Large Genomic Deletion of BMPR1A.

OBJECTIVES: Loss-of-function mutations of BMPR1A cause juvenile polyposis syndrome (JPS), but large genomic deletions in BMPR1A are rare, reported in few families only, and data regarding the associated phenotype are limited. METHODS: We investigated clinical features and genomic data of 7 extended seemingly unrelated families with a genomic deletion of the entire coding region of BMPR1A. We defined mutation size, mutation prevalence, and tumor pathogenesis using whole-genome sequencing, targeted genotyping, and haplotype analysis. RESULTS: Patients with JPS from 7 families of Bukharin Jewish ancestry carried a deletion of 429 kb, encompassing the BMPR1A coding sequence and 8 downstream genes. Haplotype analysis and testing controls identified this as a common founder mutation occurring in 1/124 individuals of Bukharin origin. Tumor testing did not demonstrate loss of heterozygosity. Among carriers, JPS was almost fully penetrant, but clinical features varied widely, ranging from mild to very severe, including pan-enteric polyps, gastritis, and colorectal, esophageal, and testicular cancer, and carriers with phenotypes, which would not have raised suspicion of JPS. DISCUSSION: The phenotype in this large cohort was extremely variable, although all carriers shared the same variant and the same genetic background. New observations include a preponderance of adenomatous rather than juvenile polyps, possible association with testicular cancer, and unexpected upper gastrointestinal involvement.

New insights into the pathophysiology of gastrointestinal graft-versus-host disease using capsule endoscopy.

We investigated gastrointestinal graft-versus-host-disease using capsule endoscopy in patients with abdominal pain and/or diarrhea. We found severe pathology involving most of the gut including loss of villi, ulcerations, narrowing, bleeding and fistula formation. In 2 patients, capsule endoscopy alone established the diagnosis of graft-versus-host-disease. Some ulcerations were associated with cytomegalovirus infection.

Surface acoustic waves enhance neutrophil killing of bacteria.

Biofilms are structured communities of bacteria that play a major role in the pathogenicity of bacteria and are the leading cause of antibiotic resistant bacterial infections on indwelling catheters and medical prosthetic devices. Failure to resolve these biofilm infections may necessitate the surgical removal of the prosthetic device which can be debilitating and costly. Recent studies have shown that application of surface acoustic waves to catheter surfaces can reduce the incidence of infections by a mechanism that has not yet been clarified. We report here the effects of surface acoustic waves (SAW) on the capacity of human neutrophils to eradicate S. epidermidis bacteria in a planktonic state and within biofilms. Utilizing a novel fibrin gel system that mimics a tissue-like environment, we show that SAW, at an intensity of 0.3 mW/cm(2), significantly enhances human neutrophil killing of S. epidermidis in a planktonic state and within biofilms by enhancing human neutrophil chemotaxis in response to chemoattractants. In addition, we show that the integrin CD18 plays a significant role in the killing enhancement observed in applying SAW. We propose from out data that this integrin may serve as mechanoreceptor for surface acoustic waves enhancing neutrophil chemotaxis and killing of bacteria.

An endoscopic repair option for acquired esophagorespiratory fistulas.

Benign acquired esophagorespiratory fistulas (BERFs) represent a broad spectrum of anatomic pathology presenting in a wide variety of clinical settings. These fistulas can lead to severe respiratory compromise and rarely close spontaneously. Surgical fistula closure has been the traditional therapeutic approach, but is associated with significant morbidity and mortality. The recent advent of endoscopic technologies suggests that minimally invasive procedures may offer a safe alternative to surgery for the treatment of esophagorespiratory fistulas. In this article, we present our experience in treating complex benign esophagorespiratory fistulas of diverse etiologies utilizing a primarily minimal invasive, endoscopic, or combined surgical and endoscopic approaches. Our experience demonstrates that an endoscopic-based approach is safe and technically feasible and can, potentially, spare a subset of patients from open surgery. A multidisciplinary decision-making process, based on individualized parameters, is a prerequisite for a successful outcome.