Introduction

The latest ESGE technical review guideline advocates real-time monitoring in the first hour of small bowel capsule endoscopy (SBCE) to ensure entire small bowel visualization. However, a survey demonstrated poor adherence to this statement in clinical practice, and supporting data are scarce.

Aims & Methods

We aimed to evaluate predictive factors of incomplete SBCE and to ascertain the importance and cost-effectiveness of real-time monitoring.
We retrospectively included consecutive patients who ingested SBCE (PillCam SB3) at our tertiary referral center from 2013 to 2020. Clinical and endoscopic characteristics were analyzed. Real-time monitoring was not applied according to local protocol. Prolonged gastric transit time (GTT) was defined when the capsule crossed the pylorus > 2 hours from ingestion, and prolonged small bowel transit time (SBTT) when cecum was reached > 6 hours from pylorus crossing. A logistic regression analysis was done to find significative risk factors associated with incomplete SBCE. Exclusion criteria included: capsule retention, endoscopic delivery of capsule, and major technical issues (i.e., eating within a standard gastric transit time of the capsule or major recording issues).

Results

A total of 859 SBCE were analyzed, with a completion rate of 94.5%. A prolonged GTT and a prolonged SBTT were found in respectively 46 (5.4%) and 152 (17.6%) procedures. At multivariate analysis, one modifiable (prolonged GTT[p=0.02]) and two unmodifiable risk factors (inpatient status [p<0.01] and history of incomplete SBCE [p=0.02]) were associated with a higher rate of incomplete SBCE, with increased odds ratio of 3.0 (CI95%= 1.2-7.4), 2.3 (CI95%= 1.2–4.2), and 3.7 (CI95%= 1.2-11.9), respectively. Pretest probability of SBCE completion rate was 90.5% and 95.7% in patients with and without unmodifiable risk factors (p=0.01).
Considering the rates of prolonged GTT, the number of patients to be monitored with real-time viewer to identify and treat one patient with prolonged GTT is 14.5 in patients with unmodifiable risk factors for incomplete SBCE and 20.3 in patients without risk factors for incomplete SBCE (p=0.27).
Direct cost for 1-hour real-time monitoring and intervention in case of prolonged GTT (i.e., dedicated room, nurse, +/- metoclopramide and IV access) are equal to circa 35 €. If all patients of our cohort would undergo real-time monitoring, the expense would be equal to 30065 €. Given that in our cohort 6 patients had an incomplete SBCE, the cost of RTM to prevent one incomplete SBCE would be equal to 5010 €. If RTM would be limited to patients with unmodifiable risk factors for incomplete SBCE, the total cost would be equal to 6615 €. In this sub-group only 2 patients had an incomplete SBCE, therefore, to prevent one incomplete SBCE, the total expense would be 3307 €.

Conclusion

The inpatient status, a prolonged GTT and a previous incomplete SBCE are risk factors for incomplete SBCE. According to our direct costs analysis, the number needed to treat one prolonged GTT to decrease the rate of incomplete SBCE appears to be cost-effective in patients with unmodifiable risk factors (i.e., inpatient status and history of incomplete SBCE).

Introduction

Per-oral endoscopic myotomy (POEM) has revolutionised achalasia treatment, nevertheless there is still a lack of technical standardization. No clear definition of “long”, “standard” or “short” POEM exists to date. With the exception of type III achalasia, there is evidence that myotomy limited to the lower esophageal sphincter (<6 cm) may be highly effective, time-saving and associated with less post-postoperative gastroesophageal reflux, yet it is common practice to use long myotomy in these patients.

Aims & Methods

We conducted a systematic review with meta-analysis to define current myotomy length standards during POEM. A literature search was performed on MEDLINE-Pubmed, Embase, Scopus, and Cochrane Library (from inception to December 2022). We included prospective, retrospective clinical studies and randomized controlled trials reporting technical details of POEM, in which no definite or comparative myotomy length was intentionally adopted thus representing a “standard” myotomy for the operator. The primary outcome was the pooled mean total myotomy length. Secondary outcomes included clinical success and reflux symptoms. Main exclusion criteria were: patient age < 18 years; studies providing achalasia diagnosis without high-resolution manometry, studies including patients with non-achalasia esophageal motility disorders, studies comparing different myotomy lengths or adopting pre-specified myotomy lengths, studies including type III achalasia patients only. Sub-group analyses were performed to explore heterogeneity across studies and to assess the impact of different subtypes, geography and time trends on the primary outcome.

Results

From initial 7,172 records, after exclusion criteria were applied, a total of 25 articles were included. Of those, 6 provided results on the primary outcome in separate subgroups and were therefore included as separate studies. Overall, 31 studies with a total 3023 patients were evaluated. The pooled mean of total myotomy length was 10.39 cm (95% CI 10.06-10.71; I² 99.3%). The pooled mean of esophageal and gastric myotomy length, provided by 17 studies, was 7.11 cm (95% CI 6.51-7.71; I² 99.8%) and 2.81 cm (95% CI 2.41-3-22; I² 99.8%) respectively. At the subgroup analysis for achalasia subtypes, pooled mean length in non-spastic achalasia (type I and II) was 10.17 cm (95% CI 9.91-10.43; I² 94.2%), while in type III attested at 14.02 cm (95% CI 10.59-17.44; I² 98.9%). Pooled mean myotomy length for studies conducted between 2014-2018 was 10.56 cm (95% CI 9.51-11.61; I² 99.0%) while studies between 2019-2022 showed a mean length of 10.3 cm (95% CI 9.99-10.61; I² 99.6%). No geographical difference was observed: in eastern countries mean length was 10.2 cm (95% CI 9.12-10.92; I² 98.9%), while in western countries was 10.95 cm (95% CI 9.83-12.07; I² 99.5%). At a median follow-up of 29 months, the pooled clinical success rate was 91% (95% CI 88.9%-93.2%; I² 67.2%), while the pooled rate of post-POEM clinical reflux was 26% (95% CI 21.0%-31.3%; I² 89.5%).

Conclusion

Our meta-analysis found that the pooled mean myotomy length during a "standard” POEM is 10.4 cm, remaining over 10 cm in non-spastic (type I and II) achalasia. The high heterogeneity across studies confirms that POEM technique needs further standardization. We found no time trend towards adopting short POEM, despite recent evidence supporting efficacy and safety of this approach.

Introduction

Nowadays one of the biggest healthcare burdens is the diseases of the gastrointestinal tract (GIT). Taking into consideration, that the human gut harbors more than 10¹⁴ CFU of bacteria, through the years scientists have linked those diseases to bacteria species like: Bacteroides fragilis, Fusobacterium nucleatum, Escherichia coli, and Helicobacter pylori. Nevertheless, according to World Health Organisation (WHO), Klebsiella pneumoniae is the priority pathogen with the main bacterial pool in the gastrointestinal tract and is easily transmitted between patients, leading to nosocomial outbreaks. Therefore, scientific research with dependable murine models of Klebsiella pneumoniae infection in GIT is highly required.

Aims & Methods

Within the frames of this study, we aimed to develop a dependable mice model for gastrointestinal tract infection of K. pneumoniae as a method for testing novel antimicrobial therapies. Three different study design settings, overall, six experimental groups, and two bacterial strains (ATCC12657, ATCC43816) were used to test the most effective approach for Klebsiella pneumoniae infection: Control groups (10⁸ CFU: G1 - K. pneumoniae ATCC12657; G4 - K. pneumoniae ATCC43816); antibiotics (penicillin 2000 U/ml, streptomycin 2 mg/ml) pre-treated groups with ampicillin therapy (125 mg/l) (10⁸ CFU: G2 - K. pneumoniae ATCC12657; G3, G5, G6 - K. pneumoniae ATCC43816). Real-time PCR for khe (specific K. pneumoniae gene) and 16S rRNA gene sequencing was performed on DNA extracted from faecal samples of the study animals.

Results

The gastrointestinal K. pneumoniae colonization was detected in the antibiotic pre-treated mice group followed by the introduction of K. pneumoniae in all study groups. The control groups of just K. pneumoniae inoculation for three continuous days resulted in (G1) 2,1 x 10⁸ CFU/50mg and (G4) 6.39 x 10⁸ CFU/50mg (p=0,008). To disrupt the host microbiota, the antibiotic pre-treatment in drinking water (streptomycin and penicillin) for three continuous days and low dose ampicillin afterward, were used in two study groups (G2) 6,67 x 10⁸ CFU/50 mg; (G3) 8,24 x 10⁸ CFU/50 mg (p=0,03). Because of sufficient colonization results using three days of antibiotic pre-treatment, one study group was tested with a singular dose of streptomycin and penicillin before bacterial inoculation ((G5) 6,24 x 10⁸ CFU/50 mg) and another one with additional ampicillin therapy ((G6) 9,01 x 10⁸CFU/50 mg) (p=0,31). Analysis of the gastrointestinal tract colonization with K. pneumoniae proved effective with or without antibiotic pre-treatment. The effectiveness and differences in microbiota using two bacterial species were also confirmed by 16S rRNA gene sequencing. All above-mentioned results are statistically significant considering p<0.05 with ±95% confidence intervals.

Conclusion

Our study demonstrates that colonization of mice intestinal tract by K. pneumoniae can be achieved with or without eradicating resident gut microbiota. Nevertheless, any of the six murine models can be used in further studies of GIT diseases.

References

1. Kaur, Christina Parvinder, et al. “Impact of Klebsiella Pneumoniaein Lower Gastrointestinal Tract Diseases.” Journal of Digestive Diseases, vol. 19, no. 5, 2018, pp.262–271., https://doi.org/10.1111/1751-2980.12595.
2. Zhou, Bolun, et al. “Intestinal Flora and Disease Mutually Shape the Regional Immune System in the Intestinal Tract.” Frontiers in Immunology, vol. 11, 2020, https://doi.org/10.3389/fimmu.2020.00575.

Introduction

Anastomotic leak remains one of the most critical complication after Ivor-Lewis esophagectomy [1][2]. While intra-cavitary approach for Endoscopic Vacuum Therapy (EVT) has been proved effective for the treatment of large dehiscences [3], no data exist comparing intraluminal EVT and Self-expanding Metal Stent (SEMS) in the management of non-large (<3 cm) anastomotic dehiscences.

Aims & Methods

In this matched-at-enrollment case-control study (1:1), we included patients who received EVT and SEMS for non-large (<3 cm) anastomotic dehiscences after oncologic Ivor-Lewis esophagectomy between May 2014 and July 2022. The primary outcome was successful closure of the leak. Exclusion criteria were: anastomotic dehiscences > 3 cm, early (≤ 2 days) and late (4 weeks) diagnosis after surgery, severe gastric conduit necrosis, sepsis/septic shock at diagnosis.

Results

Overall, 22 patients treated with EVT and 22 treated with SEMS, were matched by age (p=0.070), sex (p=0.262), BMI (0,247), American Society of Anesthesiologists (ASA) score (p=0.386), neoadiuvant radio/chemotherapy (p=0.15), dehiscence diagnosis modality (0.761), defect type (leak or fistula) (p=1.00), PCR values (p=0.103) surgical re-intervention before endoscopic treatment (p=0.472) and leak size (p=0.931). EVT and SEMS revealed no difference in leak resolution (90.9% vs 72.7%, respectively; p=0.21), whereas EVT group was associated with higher number of procedures (4.41 vs 2.18, p= 0.05, respectively). Concerning adverse events (AE’s), both EVT and SEMS showed no statistical difference in AE’s rates (p=0.61). Overall outcomes of endoscopic procedures are shown in Table 1.

Conclusion

EVT and SEMS has shown similar efficacy outcomes in the treatment of non-large (< 3 cm) anastomotic defects after Ivor-Lewis esophagectomy. Prospective comparison data are needed to validated these findings.

References

1. Seesing MFJ, Gisbertz SS, Goense L, van Hillegersberg R, Kroon HM, Lagarde SM, Ruurda JP, Slaman AE, van Berge Henegouwen MI, Wijnhoven BPL (2017) A Propensity Score Matched Analysis of Open Versus Minimally Invasive Transthoracic Esophagectomy in the Netherlands. Ann Surg 266: 839–846
2. Kassis ES, Kosinski AS, Ross P Jr, Koppes KE, Donahue JM, Daniel VC (2013) Predictors of anastomotic leak after esophagectomy: an analysis of the society of thoracic surgeons general thoracic database. Ann Thorac Surg 96: 1919–1926
3. Zhang CC, Liesenfeld L, Klotz R, Koschny R, Rupp C, Schmidt T, Diener MK, Müller-Stich BP, Hackert T, Sauer P, Büchler MW, Schaible A (2021) Feasibility, effectiveness, and safety of endoscopic vacuum therapy for intrathoracic anastomotic leakage following transthoracic esophageal resection. BMC Gastroenterol 21:72

Disclosure

Prof. Silvio Danese has served as a speaker, consultant, and advisory board member for Schering-Plough, AbbVie, Actelion, Alphawasserman, AstraZeneca, Cellerix, Cosmo Pharmaceuticals, Ferring, Genentech, Grunenthal, Johnson and Johnson, Millenium Takeda, MSD, Nikkiso Europe GmbH, Novo Nordisk, Nycomed, Pfizer, Pharmacosmos, UCB Pharma and Vifor. The other authors declare no conflict of interests. Dr Francesco Vito Mandarino, Dr Alberto Barchi, Dr Lorenzo Leone, Dr Lorella Fanti, Dr Francesco Azzolini, Dr Edi Viale, Dr Dario Esposito, Dr Noemi Salmeri, Dr Francesco Puccetti, Dr Lavinia Barbieri, Dr Andrea Cossu, Dr Elio Treppiedi, Dr Ugo Elmore and Prof Riccardo Rosati have no conflict of interest to disclose.