Introduction

The implementation of colorectal cancer screening programmes has been associated with an increase in the incidence of malignant polyps removed endoscopically. In those without endoscopic cure criteria, surgery can be performed to improve oncological outcomes.

Aims & Methods

Evaluate factors associated with the presence of residual malignant disease in the surgical specimen after endoscopic removal of a malignant polyp without endoscopic cure.
Retrospective, cohort study including patients with a malignant polyp endoscopically removed without endoscopic cure, who underwent surgery. The absence of endoscopic cure was defined as positive vertical resection margins (< 1 mm), poorly differentiated grade, depth of submucosal invasion > 1 mm, presence of lymphatic or vascular invasion, or presence of tumour budding. Patients with a synchronous neoplastic lesion and those with a malignant polyp without complete endoscopic removal were excluded.

Results

Included 74 consecutive patients submitted to surgery after the endoscopic removal of a malignant polyp without endoscopic cure. Most patients were male (62.2%), with a mean age of 64 ± 10 years. Regarding the endoscopic mucosal resection (EMR), 45 polyps were removed in one fragment (60.8%) and the other 29 were submitted to piecemeal EMR (39.2%). In 15 cases, snare tip spray coagulation (STSC) was performed at the margins of mucosal defects after EMR, 6 in normal-appearing margins (8.1%) and 9 in margins suspected of residual adenomatous tissue (12.2%). Considering the post-operative outcomes, 7 patients required surgical re-intervention (9.5%), 1 was admitted in the intensive care unit (1.4%), 1 patient died (1.4%), and 2 patients required re-hospitalization in the following 6 months (2.7%).
The presence of residual malignant disease in the surgical specimen occurred in 9 patients (12.2%), 7 had intramural disease (9.5%) and 2 had nodal metastasis (2.7%). Patients with polyps with a flat component were 5 times more likely to have residual disease in the surgical specimen (p=0.043). The polyp size and its location in the right colon were not associated with the presence of residual disease in the surgical specimen (p=0.140 and p=0.654, respectively). Patients with polyps submitted to piecemeal EMR were 7 times more likely to have residual disease in the surgical specimen (p=0.024), with 2 patients with residual disease after EMR in one fragment (4.4%) and 7 patients with residual disease from the piecemeal EMR group (24.1%). Those in which STSC was performed were also more likely to have residual disease in the surgical specimen (p<0.001). No statistically significant differences were found between the presence of positive margins, lymphatic or vascular invasion or well or moderately differentiated histologic grade, and the presence of residual disease in the surgical specimen (p=1.000, p=0.675 and p=0.686, respectively). Tumour budding was described in 3 patients, none of which had residual disease in the surgical specimen.

Conclusion

A minority of patients had residual malignant disease in the surgical specimen, with a higher risk for those with polyps with a flat component or that were submitted to piecemeal EMR. In fact, with piecemeal EMR almost one quarter of patients had residual disease e less than 5% of those with EMR in one fragment had residual disease in the surgical specimen, highlighting the need for a careful evaluation of the polyp before endoscopic removal and the importance of removal in one fragment, in case of suspected submucosal invasion.

Introduction

The ergonomics has been considered important in practicing surgical laparoscopy, and prior studies have shown significance of relevant factors e.g. operating room setup and design of surgical devices. However, little has been known in flexible endoscopy; How do endoscopists control flexible endoscopes? Which muscles are loaded during endoscopy? The deeper understanding of ergonomic aspects in flexible endoscopy is indispensable, since the number of endoscopies performed and its complexity are rapidly increasing.

Aims & Methods

We aimed to identify the differences of ergonomics between diagnostic endoscopy (EGD) and therapeutic endoscopy (ESD), by 1) multiple motion capture technology, and 2) wireless surface electromyography (EMG), in pre-clinical setting.
1) The multiple motion capture assessment
The control section of standard flexible endoscope (GIF-Q260J; Olympus, Tokyo, Japan), from the boot to the angulation knobs, was marked with 6 optical reflective markers. These markers were traced using a motion capture system (OptiTrack Flex13; NaturalPoint, OR) and the data were processed to generate 3-D coordinate data (The sternum manubrium of the endoscopist was setup as the coordinate origin; X: left-right axis, Y: cranio-caudal axis, Z: antero-posterior axis). EGD and ESD were performed with this motion capture system using live porcine models. For each endoscopist, mean±2SD for plotted coordinates from the origin was calculated in the three axes and described as a range of his/her arm/hand movement. The data were compared between EGD and ESD.
2) EMG assessment
Muscle activation of the left biceps brachii muscle, trapezius muscle, extensor carpi ulnaris muscle, flexor carpi radialis muscle, pronator teres muscle, thenar muscle, back neck muscle, and erector spinae muscle were recorded during endoscopic procedures using wireless surface EMG (BioLog DL-5500, DL-510A; S&ME, Tokyo, Japan). The maximal voluntary contraction (MVC) was obtained to normalize root-mean-square muscle activation as %MVC. We compared differences in muscle activity between EGD and ESD using %MVC.

Results

1) The motion capture was performed on 15 board-certified endoscopists conducting EGD (n=13) and ESD (n=12). The movement range of endoscopist’s left hand/arm holding endoscope is shown in the Table. On all three axes, the range of movement was significantly narrower during ESD than during EGD (X, p<0.001; Y, p=0.015; Z, p<0.001).

	EGD			ESD
	X axis	Y axis	Z axis	X axis	Y axis	Z axis
Mean ± 2SD (cm)	-0.32±14.2	-24.3±11.0	12.8±11.6	-1.3±9.9	-22.8±9.8	7.9±8.9

2) The EMG was recorded during 15 EGDs and 8 ESDs. The %MVC was higher during ESD than EGD in an analysis including all muscles (LS-mean±SE; EGD, 28.9±1.5%; ESD, 34.1±2.6%; p=0.078). The comparison by each specific muscle showed that the extensor carpi ulnaris muscle (EGD, 34.6±3.5%; ESD, 47.8±5.8%; p=0.093) and the pronator teres muscle (EGD, 42.8±6.6%; ESD, 67.6±10.9%; p=0.092) had significantly larger %MVC during ESD (p<0.1 was considered statistically significant).

Conclusion

Our study has first shown that the range of endoscopis’s movement was significantly narrower in therapeutic endoscopy than in diagnostic endoscopy. Furthermore, it was demonstrated that muscle activity, especially in left forearm muscles, was larger during therapeutic endoscopy. These data may help understanding the ergonomics in flexible endoscopy, and potentially contribute to optimize its working environment and further development of relevant medical devices.

Clinical Case Summary

A 40-year-old male came to our emergency department referring worsening jaundice, mental status deterioration, epigastric pain and anorexia over the past week. Four weeks earlier he presented odynophagia, myalgias, and hand pruritus but didn’t seek medical attention.
Patient’s clinical background included cognitive impairment due to peripartum anoxia and type 2 Diabetes Mellitus. At admission, he had elevated liver enzymes (R value=2,7), coagulopathy (INR 1.3), pancreatic enzymes >3 times the upper normal level and hyperbilirubinemia (mostly conjugated).
The CT-scan revealed pancreatic tail globosity, diffuse abdominal and retroperitoneal peri-centimetric lymph nodes and excluded biliary lithiasis.
After common causes of acute hepatitis and pancreatitis were ruled out, and since patient was at risk of acute liver failure despite supportive treatment, a liver biopsy was performed. Autoimmune hepatitis, drug-induced liver injury or lymphoproliferative disease were held as potential differentials. Hepatitis E Virus (HEV) RNA was then found and genotyped in the serum (genotype 3). HEV infection was assumed as the cause for both hepatitis and pancreatitis. Histological pattern was inconclusive and epidemiological source wasn’t found.

HEV infection paradigm has changed and is now considered an endemic zoonotic infection in most high-income countries (Portuguese seroprevalence is 16.3%)¹. Infection occurs due to ingestion of undercooked pig or boar meat and should be suspected in every acute hepatitis, mostly with a cholestatic pattern.
The setting of acute HEV hepatitis complicated with acute pancreatitis (AP) is uncommon². AP usually starts after a median of 10 days of jaundice onset³. Literature only reports association between AP and HEV caused by genotype 1 from Southeast Asia^{3 4}, and genotype 3 was only related to gallstone-related pancreatitis, according to current knowledge⁵. This might be the first form of HEV genotype 3 infection with hepatitis and pancreatitis.

References

1. Nascimento MSJ, Pereira SS, Teixeira J, et al. A nationwide serosurvey of hepatitis E virus antibodies in the general population of Portugal. Eur J Public Health 2018;28(4):720-24. doi: 10.1093/eurpub/ckx213 [published Online First: 2017/12/14]
2. Debnath P, Datta AK, Chakraborty U, et al. Acute viral hepatitis E complicated with acute pancreatitis in an immunocompetent adult. BMJ Case Rep 2021;14(2) doi: 10.1136/bcr-2020-239684 [published Online First: 2021/02/06]
3. Haffar S, Bazerbachi F, Garg S, et al. Frequency and prognosis of acute pancreatitis associated with acute hepatitis E: A systematic review. Pancreatology 2015;15(4):321-6. doi: 10.1016/j.pan.2015.05.460 [published Online First: 2015/06/08]
4. European Association for the Study of the Liver. Electronic address eee, European Association for the Study of the L. EASL Clinical Practice Guidelines on hepatitis E virus infection. J Hepatol 2018;68(6):1256-71. doi: 10.1016/j.jhep.2018.03.005 [published Online First: 2018/04/04]
5. Karlsson M, Norder H, Bergstrom M, et al. Hepatitis E virus genotype 3 is associated with gallstone-related disease. Scand J Gastroenterol 2019;54(10):1269-73. doi: 10.1080/00365521.2019.1666163 [published Online First: 20190925]

Introduction

Filgotinib is an oral Janus kinase 1 selective inhibitor licensed for the treatment of moderate to severe ulcerative colitis (UC) following the successful UC-SELECTION registration trials.¹ However, no real-world data have been published since filgotinib first received marketing authorisation in November 2021.

Aims & Methods

The aim of this study was to assess the short-term safety and effectiveness of filgotinib for the treatment of UC. The primary outcome was post-induction clinical remission, defined as a Simple Clinical Colitis Activity Index (SCCAI) of ≤2. A retrospective, observational cohort study was conducted at a tertiary IBD referral centre using prospectively maintained records between August 2022 and February 2023. Clinical disease activity was assessed at baseline and following induction at week 10 using paired SCCAI scores, faecal calprotectin (FCAL), and C-reactive protein (CRP). Quality of life was assessed using the IBD-Control questionnaire. Non-responder imputation was used for analyses.

Results

Thirty-four patients were initiated on filgotinib during the study period, with post-induction outcome data available for 32 patients; 56% male, median age 38 (IQR range 26–53), 41% with prior biologic and/or tofacitinib exposure. Patients were treated for a median duration of 20 weeks (IQR 13–25) with treatment persistence of 69% at the time of analysis; eight patients were switched to alternative treatments due to non-response and two patients underwent colectomy.
At the end of induction, nine patients (28%) were in clinical remission; all patients were corticosteroid-free. Median SCCAI decreased significantly from a baseline of 7 (IQR 4-10) to 1 (IQR 0-6) at week 10, p<0.01, n=25. Median FCAL fell numerically from a baseline of 464 mcg/g (IQR 183-1245) to 125mcg/g (IQR 30-502) following induction, p=0.06, n=20. There was no significant change in CRP, haemoglobin, serum albumin, or lipid profile components following induction. There was a significant improvement in pre- and post-treatment quality of life scores from a median of 5 (IQR 2-9) to 16 (IQR 4-16), p<0.01.
Thirteen patients described a mild self-resolving coryzal illness, sore throat, or headaches during treatment. There was one reported case of oral herpes simplex infection requiring treatment interruption. There were no serious adverse events.

Conclusion

Filgotinib was well tolerated and clinically effective in the short term with improvements in quality of life but larger prospective cohorts with longer follow up are needed.

References

1. Feagan BG, Danese S, Loftus EV, et al. Filgotinib as induction and maintenance therapy for ulcerative colitis (SELECTION): a phase 2b/3 double-blind, randomised, placebo-controlled trial. The Lancet. 2021 Jun 19;397(10292):2372–84.

Disclosure

FD has received honoraria for educational meetings and speaker fees for Dr Falk. Received advisory board/nurse consultation fees for for Dr Falk, Galapagos, Pfizer and Takeda. Travel grants received from Pharmacosmos, Celtrion, and Tillotts.
KP has received honoraria for educational meetings and speaker fees from AbbVie, Janssen, Takeda, Pfizer, DrFalk, PredictImmune and Ferring and has received advisory board fees from AbbVie, Galapagos, Pfizer and Janssen.
SH served as a speaker, a consultant, and/or an advisory board member for Pfizer, Janssen, AbbVie, and Takeda. Travel grants received from Ferring, Falk Pharma, and Pharmacosmos.
RH, AA and SK have no disclosures.

Introduction

Gastric adenoma is recognized as a premalignant lesion.¹Much of the literature lumps all adenomas together with different classifications. These are few western reports regarding the prevalence, associated risk factors and outcomes of endoscopic management of different subtypes of gastric adenoma.

Aims & Methods

Aims: The aim of this study is to determine the prevalence, potential predictors, and outcomes of endoscopic management of the different subtypes of gastric adenoma.
Methods: Of 162 consecutive patients who underwent endoscopic resection for gastric lesions between 2017 and 2022 at our center, 79 patients were enrolled. All the hyperplastic polyps (n=37) and subepithelial lesions (n=46) were excluded. The patient clinical characteristics, endoscopic and histopathological features of gastric lesions were retrospectively collected. Patients were divided according to the histological types of gastric adenoma into 4 groups: intestinal group (n= 49), foveolar group (n= 23),pyloric group (n= 6) and oxyntic group (n=1). We statistically compared the clinical and endoscopic features of the three groups. In addition to the analysis of the outcomes of endoscopic resection of gastric adenomas.

Results

Of the 79 patients with a mean follow-up of 2622 months, 51 patients were males (65 %) and 28 patients were females (35%). Forty-nine patients (49/79,62%) had intestinal adenoma, 23 patients (29%) showed foveolar adenoma, 6 patients (8%) developed pyloric adenoma and only 1 patient (1%) had oxyntic adenoma. The mean age was significantly older in the intestinal group (71 ± 13 years vs. 64 ± 16 years vs. 58 ± 18 years, p = 0.03). Intestinal adenomas were significantly associated with family history of gastric adenocarcinoma (14% vs. 4% vs. 0%, p = 0.01) and history of statin intake (39% vs. 26% vs. 0%, p = 0.04).Foveolar adenomas were significantly associated with multiple lesions (≥3 lesions) (p < 0.001) and 0-IIa+IIc Paris classification (6/23, 26%). the size of largest polyp was significantly higher among pyloric group (28 ±15, p= 0.00). Among intestinal group, 33/49 patients (67%) had atrophic gastritis. 82% of the adenomas were resected by ESD with histologically complete resection (R0) in 72/79 patients (91%). Although the difference was not statistically significant (p = 0.4), adenocarcinoma was most frequently encountered among the intestinal adenoma group (17/49, 35%). The post endoscopic resection outcome was comparable among 3 groups with overall recurrence rate (group1:8% vs. group 2:17% vs group 3:17%, P = 0.07) with a comparable mean time to recurrence among three groups (21 ± 17 months vs. 20±17months vs. 14 months, p=0.8). Family history of gastric adenocarcinoma (HR=1.33, p< 0.001) and active helicobacter pylori infection (HR=1.14, p < 0.001) were identified as independent predictors of recurrence after endoscopic resection of different gastric adenoma. Among baseline endoscopic characteristics, polyp size ³ 30mm(HR= 2.04, p< 0.001), more than 3 polyps (HR=1.51, p<0.001), lesser curvature as lesion location (HR=1.72, p< 0.001) and morphology as Paris classification IIc are potential predictors of post resection recurrence. In addition to specimen size ³ 15mm (HR=2.19, p< 0.001) and T1b as lesion histology (HR=2.07, p< 0.001), in the histopathological examination.

Conclusion

The present study clarifies the endoscopic and histopathological characteristics of different gastric adenomas, in addition to the potential predictive factors for each subtype. Potential predictors of recurrence after endoscopic resection emphazie the importance of endoscopic follow up.

References

1. Fujiwara, Y. et al. Diagnosis of borderline adenomas of the stomach by endoscopic mucosal resection. Endoscopy 28, 425–430 (1996).