Introduction

Although endoscopic submucosal dissection (ESD) is established as first-choice treatment for early esophageal squamous cell carcinoma (ESCC) worldwide, most data on outcomes are derived from Asian studies. Therefore, we aimed to evaluate the short- and long-term outcomes of ESD for patients with early ESCC in a Western cohort.

Aims & Methods

In this retrospective cohort study, patients with early ESCC amendable for ESD were included in four tertiary referral hospitals in the Netherlands between 2012 and 2017. All procedures were performed by experienced endoscopists who were specifically trained in ESD. The decision for and choice of additional treatment following ESD was made on a per-patient basis. For this study, dedicated research fellows collected all relevant data by reviewing the electronic patients files. Data concerning long-term outcomes were checked with general practitioners or referral hospitals, when applicable. Outcomes included technical success, R0 resection (i.e. tumor-free lateral and vertical margins), curative resection (i.e. en-bloc radical resection with histology no more advanced than T1sm1, good differentiation and absence of lymphovascular invasion) and recurrence rates, as well as ESCC-specific and overall survival.

Results

We included 68 patients (34 males; mean age 69) with a median tumor size of 3cm (range 1-12) and circumferential extent of 50% (range 10-100), in whom ESD was technically successful in 66/68 patients (97%). While en-bloc resection was achieved in 64/66 technically successful ESDs (97%), R0 resection was accomplished in 54/66 patients (82%). Overall, a curative resection was achieved in only 34/66 patients (52%). Among the patients with a non-curative resection, 16/32 (50%) underwent additional treatment receiving either argon plasma coagulation for tumor-positive resection margins (n=1), selective lymph node dissection (n=1), definite chemoradiation therapy (n=4) or esophagectomy ± neoadjuvant chemoradiation therapy (n=10). Endoscopic surveillance was preferred in the other half of patients with a non-curative resection (16/32; 50%) based on significant comorbidities or patient choice. During a median follow-up of 66 months (p25-p75 43-88), 12/66 patients (18%) developed a local recurrence which could be treated endoscopically in most cases (10/12; 83%). Locoregional lymph node metastasis and distant metastasis were observed in 6 (6/66; 9%) and 3 (3/66; 5%) patients, respectively. A total of 30 patients (30/66; 45%) died during follow-up, of which the minority (7/30; 23%) was ESCC-related deaths. The 5-year overall and ESCC-specific survival probability were 64% (95% CI 53-76%) and 88% (95% CI 79-97%), respectively. More importantly, overall survival did not significantly differ between patients with and without curative resections (p = 0.69). In addition, no significant difference was seen for ESCC-specific survival between patients with or without additional treatment after a non-curative resection (p = 0.07).

Conclusion

In this Western cohort with long-term follow-up, the efficacy and safety of ESD for early ESCC was confirmed although the rate of non-curative resections was substantial. Irrespective of non-curative or curative resection, the long-term prognosis of these patients was limited mainly due to competing mortality. Considering additional treatment after a non-curative resection did not influence survival, the potential benefit of adjuvant therapy should be carefully balanced against the risk of dying from another cause than esophageal cancer on an individual basis.

Disclosure

C.N. Frederiks has received speaker's fee from Pentax Medical.
R.E. Pouw is a consultant for MicroTech, and has received speaker’s fee from Medtronic.
J.J.G.H.M. Bergman is a consultant for Medtronic, Cook Medical, and Boston Scientific, and has received research funding from Pentax Medical, C2 Therapeutics, Medtronic, Aqua Medical, Olympus Endoscopy, and Fuji-film.
B.L.A.M. Weusten has received research funding from Pentax Medical, C2 Therapeutics, and Aqua Medical. The remaining authors declare to have no disclosures relevant to this manuscript.

Introduction

Dietary and lifestyle recommendations are the cornerstones of the treatment of GERD. However, the evidence of the efficacy of those recommendations is lacking. We performed a retrospective analysis of the GISTAR study¹ participants evaluating the symptoms of GERD and dietary and lifestyle parameters developing a tool for predicting GERD symptoms based on the aforementioned criteria.

Aims & Methods

The aim of the study was to analyse the factors pointing to GERD symptoms through the use of data mining and decision tree classifier.
Methods: GERD diagnosis was evaluated using a self-assessment questionnaire ². Dietary, demographic and lifestyle data were collected within the GISTAR study protocol¹. 3340 40-64 year old participants from the GISTAR study were included in the analysis. 1670 of them did not have GERD symptoms. 41 attributes describing demographic, lifestyle, and dietary habits were used for these respondents to induce a decision tree classification model using Orange Data Mining software³.

Results

Fried potatoes including French fries were the most predictive factor of GERD symptoms (65.3% with symptoms; 1516 from 2321), especially for females (82.6%; 1048/1228). This was more pronounced in the group who consumed sweets once per week (87.2%, 950/1090). In males, who consumed fried potatoes, the next most important factor was the consumption of sweets (46.3%, 431/930).
For participants who didn’t consume fried potatoes (14.6%; 147/1008), 1-3 cups of green tea (37.9%; 66/174) and male gender (71.4 % 20/28) were predictors of GERD symptoms.
The accuracy of the decision tree model was: sensitivity (74.8%), precision (75.6%), specificity (75.9%) and AUC (0.841%).

Conclusion

Fried potatoes, female gender and consumption of sweets are the risk factors predicting the diagnosis of GERD. None of the lifestyle factors were displayed as significant.

References

1. Leja M, Park JY, Murillo R, et al. Multicentric randomised study of Helicobacter pylori eradication and pepsinogen testing for prevention of gastric cancer mortality: the GISTAR study. BMJ Open 2017;7:e016999. doi: 10.1136/bmjopen-2017-016999
2. Jones R, Junghard O, Dent J, Vakil N, Halling K, Wernersson B, Lind T. Development of the GerdQ, a tool for the diagnosis and management of gastro-oesophageal reflux disease in primary care. Aliment Pharmacol Ther. 2009 Nov 15;30(10):1030-8. doi: 10.1111/j.1365-2036.2009.04142.x. Epub 2009 Sep 8. PMID: 19737151.
3. Demsar J, Curk T, Erjavec A, Gorup C, Hocevar T, Milutinovic M, Mozina M, Polajnar M, Toplak M, Staric A, Stajdohar M, Umek L, Zagar L, Zbontar J, Zitnik M, Zupan B (2013) Orange: Data Mining Toolbox in Python, Journal of Machine Learning Research 14(Aug): 2349−2353.

Introduction

Gastrointestinal involvement is universal among patients with systemic sclerosis (SSc). Small intestinal dysfunction manifests with non-specific gastrointestinal symptoms (abdominal pain, distension, nausea, or vomiting), along with objective signs such as malnutrition, small intestinal bacterial overgrowth, and, in severe cases, chronic intestinal pseudo-obstruction. The pathogenesis of small intestinal dysmotility in SSc has been proposed to follow a sequential progression, beginning with neuropathy, progressing to myopathic damage, and ultimately culminating in fibrosis. Currently, there are no diagnostic techniques available to differentiate between stages of small intestinal involvement.

Aims & Methods

Aim: To assess the discriminative potential of high-resolution jejunal manometry in categorizing small intestinal dysmotility among patients with SSc.

Prospective study evaluating small intestinal motility in consecutive patients with SSc and digestive symptoms between January 2018 and July 2023 and healthy volunteers as controls. A 35-channel high-resolution manometry catheter was trans-nasally inserted into the jejunum under fluoroscopic radiological guidance. Small intestinal motility was continuously recorded for 5 h; 3 h fasting and 2 hours during continuous nutrient perfusion at 2 kcal/min. Tracings were analyzed by conventional qualitative analysis (identifying neuropathic and myopathic motility patterns) and by quantitative analysis of high-resolution parameters (measuring a motility index (MI) that integrates contractile frequency and amplitude over time, and manually counting the number of propagated contractile fronts)

Results

Twenty patients (52 ± 10 years, 95% women) with SSc and 18 healthy subjects (HS) (27 ± 6 years, 78% women) were included. By conventional visual analysis, 6 (30%) patients exhibited abnormal small intestinal motility patterns indicative of neuropathic involvement (uncoordinated bursts n=3 and postprandial minute-rhythm n=3), and 7 (35%) patients showed diminished contractile activity during fasting and after nutrient infusion (mean amplitude <20mmHg), indicative of myopathic involvement. The remaining 7 (35%) patients had apparently normal small intestinal motility.
Quantitative analysis of high-resolution parameters detected additional abnormalities in patients with SSc compared to healthy controls (table 1). A significant decrease in fasting (phase II) propagated fronts was observed in all subgroups, including those with apparently normal motility by conventional analysis. The postprandial response to nutrient infusion was reduced in 15 of 20 patients with SSc. All patients with myopathic involvement had a null response to nutrient infusion. Patients with neuropathic patterns and those with apparently normal motility by conventional analysis also exhibited a poor postprandial response, which was similarly reduced in both groups.

Table 1: Results from quantitative analysis of high-resolution jejunal manometry

Conclusion

High-resolution jejunal manometry detects abnormalities in fasting and postprandial small intestinal motility in patients with systemic sclerosis, even at early stages of intestinal involvement, when neuropathic and myopathic patterns are not evident.

References

Alcala-Gonzalez LG, Malagelada C, Galan C, Nieto A, Accarino A, Azpiroz F. Propagation patterns of jejunal motor activity measured by high-resolution water-perfused manometry. Neurogastroenterol Motil. 2021 Dec;33(12):e14240. doi: 10.1111/nmo.14240. Epub 2021 Aug 11. PMID: 34378830.

Disclosure

Nothing to declare

Clinical Case Summary

A 28-year-old patient presented with recurrent episodes of overt gastrointestinal bleeding, requiring multiple blood transfusions over the past two months (5 units of packed red blood cells). Despite undergoing UGI endoscopy and colonoscopy twice at other medical centers, no abnormalities were detected. CT enterography with CT angiography yielded normal results. To further investigate, the patient underwent antegrade and retrograde power spiral enteroscopy, revealing gross active bleeding from a site of hookworm bite in the jejunum. Following the procedure, the patient was discharged with antihelminthic therapy. However, a week later, he experienced abdominal pain, difficulty passing stools, intermittent rectal bleeding again, and low-grade fever. A relook sigmoidoscopy revealed a large hematoma with intraluminal compression in the sigmoid colon. CT scan confirmed a localized sealed-off perforation along with the hematoma. Management included percutaneous aspiration of the hematoma, intravenous antibiotics, and repeat blood transfusion. Anti-helminthic therapy continued, and the patient recovered completely after approximately four weeks which was confirmed by sigmoidoscopy. The mechanism of this sigmoid colon hematoma involves potential mechanical injury by the overtube's spiral tip during insertion or manipulation. Although the localized perforation was sealed off in this case, the preceding bleeding and drop in hemoglobin complicated the initial treatment plan. Considering such technical challenges, the equipment and technology have now been withdrawn globally by the manufacturer. Close monitoring of patient symptoms, and vital signs, and prompt discontinuation of the procedure in case of discomfort or pain are crucial in preventing such complications. As advanced endoscopic techniques become more prevalent, maintaining a cautious approach towards technology and addressing complications promptly is essential for ensuring patient safety and effective care