Introduction

Hepatocellular carcinoma (HCC) is a global problem being fourth in terms of cancer-related deaths¹. Contrast-enhanced ultrasound (CEUS) is used as an add-on test to confirm focal liver lesions suspected as HCC at prior diagnostic tests such as ultrasound or alpha-foetoprotein, or both^2,3. According to guidelines^4,5,6, a single contrast-enhanced imaging techniques, with either computed tomography (CT) or magnetic resonance imaging (MRI) showing the typical hallmarks is sufficient to diagnose HCC in cirrhotic patients. However, a significant number of HCC show atypical imaging features, and therefore, are missed at imaging.
The advantages of CEUS over CT and MRI is the use of contrast agents not containing iodine and that are not nephrotoxic, and quick image acquisition. Despite the advantages, the use of CEUS in the diagnostic algorithm for HCC remains controversial, with disagreement on relevant guidelines.

Aims & Methods

The aim was to assess the diagnostic accuracy of CEUS for the diagnosis of HCC of any size and at any stage in adults with chronic liver disease, in a surveillance programme or in a clinical setting and to assess the diagnostic accuracy of CEUS for the diagnosis of resectable HCC in people with chronic liver disease and identify potential sources of heterogeneity in the results.
We included studies assessing the diagnostic accuracy of CEUS for the diagnosis of HCC in adults with chronic liver disease, with cross-sectional designs, using one of the acceptable reference standards, such as pathology of the explanted liver, and histology of resected or biopsied focal liver lesion with at least a six-month follow-up.
Standard Cochrane methods ⁷ were used to screen studies, extract data, and assess the risk of bias and applicability concerns, using the QUADAS-2 checklist⁸. We used the bivariate model and provided estimates of summary sensitivity and specificity. We assessed the certainty of the evidence using GRADE^9,10. We presented uncertainty-of-the-accuracy estimates using 95% confidence intervals (CIs).

Results

We included 23 studies with 6546 participants. Studies were published between 2001 and 2021. We judged all 23 studies at high-risk of bias in at least one domain, and 13/23 studies at high concern for applicability. Most studies used different reference standards to exclude the presence of the target condition. The time interval between the index test and the reference standard was rarely defined. We also had major concerns on their applicability due to the participant characteristics.
CEUS for HCC of any size and stage: sensitivity 77.8% (95% CI 69.4% to 84.4%) and specificity 93.8% (95% CI 89.1% to 96.6%) (23 studies, 6546 participants; very low-certainty evidence).
CEUS for resectable HCC: sensitivity 77.5% (95% CI 62.9% to 87.6%) and specificity 92.7% (95% CI 86.8% to 96.1%) (13 studies, 1257 participants; low-certainty evidence).
The observed heterogeneity in the results remains unexplained.

Conclusion

Using CEUS, as an add-on test following abdominal ultrasound, to diagnose HCC of any size and stage, 22% of people with the tumor would be missed, and 6% of people without would unnecessarily undergo further testing or inappropriate treatment. As to resectable HCC, we found that 23% of people with resectable tumor would incorrectly be unresected, while 8% of people without HCC would undergo further inappropriate testing or treatment. The uncertainty resulting from the high risk of bias of the included studies, heterogeneity, and imprecision of the results and concerns on their applicability limit our ability to draw confident conclusions.

References

1) Forner A et al. Hepatocellular carcinoma. Lancet 2018;391(10127):1301-14.
2) Niu Y, et al. Contrast-enhanced ultrasonography for the diagnosis of small hepatocellular carcinoma: a metaanalysis and meta-regression analysis. Tumour Biology
2013;34(6):3667-74.
3) VogelA, et al. Hepatocellular carcinoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Annals of Oncology2019;30(5):871-3.
4) Galle PR, et al. EASL clinical practice guidelines: management of hepatocellular carcinoma. Journal of Hepatology 2018;69(1):182-236.
5) Omata M, et al.Asia–Pacific clinical practice guidelines on the management of hepatocellular carcinoma: a 2017 update. Hepatology International 2017;11:317-70
6) HeimbachJK,, et al. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology 2018;67:358-80.
7) Macaskill P, et al. Chapter 10: Understanding meta-analysis Draft version (13 May 2022) for inclusion in: Deeks JJ, Bossuyt PM, Leeflang MM, TakwoingiY, editor(s). Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy Version 2. London: Cochrane.
8) Whiting PF, Ret al. QUADAS-2 Group. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Annals of Internal Medicine 2011;155(8):529-36.
9) McMaster University (developed by Evidence Prime) GRADEpro GDT. Version accessed 26 January 2022. Hamilton (ON): McMaster University (developed by Evidence Prime). Available at gradepro.org.





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Disclosure

nothing to disclose

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.

Introduction

Finite nucleos(t)ide analog (NA) therapy has been proposed as an alternative strategy for chronic hepatitis B (CHB), but data on optimal biomarkers for post-treatment monitoring is limited.

Aims & Methods

With the aim to investigate whether measuring hepatitis B core-related antigen (HBcrAg) after NA cessation may stratify the risk of subsequent clinical relapse (CR), this retrospective multicenter analysis enrolled adults with CHB who were prospectively monitored after discontinuing entecavir or tenofovir with negative HBeAg and undetectable HBV DNA at the end of treatment (EOT). Patients with cirrhosis or malignancy were excluded. CR was defined as serum alanine aminotransferase (ALT) > 80 U/L with recurrent viremia. During follow-up, serum HBcrAg was evaluated as a time-varying variable in the Cox proportional hazard model.

Results

The cohort included 203 patients (median age, 49.8 years; 76.8% male; 60.1% entecavir) who had been treated for a median of 36.9 months (interquartile range [IQR], 36.5-40.1). During a median post-treatment follow-up of 31.7 months (IQR, 16.7-67.1), CR occurred in 104 patients with a 5-year cumulative incidence of 54.8% (95% confidence interval [CI], 47.1% ‐ 62.4%). Time-varying HBcrAg levels were a significant risk factor for subsequent CR (adjusted hazard ratio [aHR], 1.43 per log U/mL; 95% CI, 1.16-1.76) in the multivariable model adjusted for EOT HBsAg level, anti-HBe antibody, and EOT ALT. During follow-up, HBcrAg < 1,000 U/mL predicted a low risk of subsequent CR (aHR, 0.31; 95% CI, 0.17-0.57).

Conclusion

Dynamic measurement of HBcrAg after NA cessation is predictive of subsequent CR and may be used to guide posttreatment monitoring.

References

1. Mak LY, Wong DK, Cheung KS, Seto WK, Lai CL, Yuen MF. Review article: Hepatitis B core-related antigen (HBcrAg): an emerging marker for chronic hepatitis B virus infection. Aliment Pharmacol Ther. 2018;47(1):43-54.
2. Hsu YC, Nguyen MH, Mo LR, Wu MS, Yang TH, Chen CC, et al. Combining hepatitis B core-related and surface antigens at end of nucleos(t)ide analogue treatment to predict off-therapy relapse risk. Aliment Pharmacol Ther. 2019;49(1):107-15.
3. Sonneveld MJ, Park JY, Kaewdech A, Seto WK, Tanaka Y, Carey I, et al. CREATE Study Group. Prediction of Sustained Response After Nucleo(s)tide Analogue Cessation Using HBsAg and HBcrAg Levels: A Multicenter Study (CREATE). Clin Gastroenterol Hepatol. 2022 Apr;20(4):e784-e793

Introduction

Thermal ablative methods (such as argon plasma coagulation (APC) and soft tip snare coagulation (STSC) are commonly used to treat polyp margins.

Aims & Methods

We aim to appraise the current literature and compare clinical outcomes between patients with treated (with APC vs STSC) and non-treated EMR margins.
We searched major databases from inception until November 2023 for RCTs comparing EMR of large non-pedunculated colorectal polyps with and without treated margins. Pooled data was analyzed for the primary outcome of recurrence at first screening colonoscopy, as well as adverse events. Analysis was performed using a random effects model and data was reported using 95% confidence intervals (CI).

Results

A total of five RCTs were found which included 1020 polyps (577 in treatment and 443 in control groups). Three studies included treatment with STSC and three studies used APC as the modality for margin ablation. Of included patients, 53% were female and average age was similar between treatment and control groups (65.9 vs 66.1 years). Overall, 71% of lesions were proximal to the splenic flexure. Mean follow up to first colonoscopy and average polyp size were comparable (6.3 vs 6.2 months; 28.2 mm vs 28.0 mm, respectively). Pooled analysis showed that margin ablation was associated with significantly lower rates of recurrence (OR = 0.267, 95% CI 0.18 - 0.4, P< 0.001) with low heterogeneity between studies (I²=0%, P = 0.47). Pooled analysis showed no significant difference between STSC and APC in terms of recurrence (OR = 0.6, 95% CI 0.27 - 1.7, I²=0%, P=0.3) or adverse events (OR = 0.67, 95% CI 0.3 - 1.6, I² 13%, P = 0.46).

Conclusion

Our study shows that ablation of EMR margins is very effective at preventing recurrence at first surveillance colonoscopy. We found no difference between STSC or APC in terms of polyp recurrence or adverse outcomes.

Introduction

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease in which muscle weakness develops insidiously. In advanced stages of the disease dysphagia, weight loss and malnutrition occur in the majority of patients. Thus, the consideration of Percutaneous Endoscopic Gastrostomy (PEG) tube placement is common. However, the optimal timing and setting for the procedure as well desired spirometry results are either are not stated in most guidelines or debated. Previous studies have suggested greater procedural risk for patients whose forced vital capacity (FVC) was less than 50% than predicted

Aims & Methods

The aim of this study was to assess the safety of our tertiary center simplified approach to PEG tube placement in patients with ALS.
The electronical records of patients who underwent percutaneous endoscopic gastrostomy (PEG) placement between 1.1.2020 to 1.1.2023 were retrospectively reviewed. All adult patients diagnosed with ALS who underwent ambulatory PEG tube placement were included. Patients who underwent PEG tube placement during hospitalization due to acute illness were excluded. The common practice of our center regarding PEG placement in patients with ALS is as follows: initial evaluation at the Gastroenterology clinic of patients referred by the neurology clinic, followed by ambulatory PEG placement under sedation by an anesthesiologist. We collected baseline information from the neurology and gastroenterology clinic visits regarding comorbidities and baseline FVC and the functional rating score [ALS-FRS, 0-48 points, lower score indicating a more severe disease). The data concerning the procedure and possible complications were collected from endoscopy reports, emergency department visits and clinic visits after the procedure.

Results

Six hundred and sixty patients had underwent PEG tube placement in our center during study period. Of them, 67 patients had an established diagnosis of ALS (10.2%). One patient was excluded due to PEG placement in the setting of an acute illness during admission, thus 66 patients were included (mean age at PEG placement 63.5±12.7 years and 37.8% were females). Mean ALS-FRS score was 23.6±8.81 and mean FVC was 49.8±19.45% of predicted. More than half (54.7%) of the patients were using non-invasive ventilation support device at home prior to the procedure and 12.1% of patients had underwent endotracheal tube placement prior to PEG tube placement.
The averaged duration of PEG tube placement was 11.96±5.3 minutes. All PEG procedures were completed successfully. Complications were documented during two PEG placements (3%): one patient suffered from aspiration and was hospitalized and later diagnosed with aspiration pneumonia and the second patient suffered from gastric perforation and peritonitis which was diagnosed a few hours after the procedure. During the 30 days following PEG placement, 3 (4.5%) complications were documented: Two patients (3%) suffered from PEG site infections and were treated with antibiotics and one (1.5%) was diagnosed with aspiration pneumonia. No deaths occurred during the procedure or during the 30 days that followed.

Conclusion

The simple straight forward approach to PEG placement in our institution was successful and safe in the vast majority of cases. The complications rate in our cohort is comparable to other studies, even though the patients in our cohort had significantly reduced lung function and functional scores then accepted in the common practice.

References

1. Miller R G, Jackson C E, Practice parameter update: the care of the patient with amyotrophic lateral sclerosis: drug, nutritional, and respiratory therapies (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology, Neurology, 2009 Oct 13;73(15):1218-26
2. EFNS Task Force on Diagnosis and Management of Amyotrophic Lateral Sclerosis: Andersen P M, Abrahams S, EFNS guidelines on the clinical management of amyotrophic lateral sclerosis (MALS)--revised report of an EFNS task force, Eur J Neurol 2012 Mar;19(3):360-75.
3. Korner S, Hendricks M, Weight loss, dysphagia and supplement intake in patients with amyotrophic lateral sclerosis (ALS): impact on quality of life and therapeutic options, BMC Neurol 13, 84 (2013).
4. Russ K B, Phillips MC, Percutaneous Endoscopic Gastrostomy in Amyotrophic Lateral Sclerosis, Am J Med Sci . 2015 Aug;350(2):95-7.
5. Gregory S, Siderowf A, Gastrostomy insertion in ALS patients with low vital capacity: respiratory support and survival, Neurology . 2002 Feb 12;58(3):485-7.
6. Thomas K, Schrager J, Percutaneous endoscopic gastrostomy tube placement in amyotrophic lateral sclerosis: a case series with a multidisciplinary, team-based approach, Ann Gastroenterol 2020 Sep-Oct;33(5):480-484

Introduction

Atrophic gastritis(AG) is mainly caused by Helicobacter pylori(Hp)infection or autoimmunity. Hp-related AG affects both corpus and antral mucosa resulting in multifocal AG(MF-AG), whereas AG driven by autoimmunity is corpus-restricted(CR-AG).
Corpus mucosa gastric atrophy carries an increased risk of gastric dysplasia(GD) and cancer(GC);the neoplastic risk in CR-AG is considered lower, but still debated. GD-GC lesions in AG may arise in the antrum, incisura angularis or, less frequently,the corpus.Data on characteristics and potential differences of GD-GC lesions between MF-AG and CR-AG are lacking.

Aims & Methods

This study aimed to assess clinical,endoscopic,and histological characteristics of GD-GC in MF-AG and CR-AG pts.
A multicenter,cross-sectional study was conducted across 14 Italian GI centers. Data on GD-GC in patients with MF-AG or CR-AG(2001-2023) were retrospectively collected based on clinical,endoscopic, and histological charts: site,dimension,endoscopic,and histologic features of GD-GC, perilesional gastric antral and corpus mucosa(updated Sydney system),and patients’ clinical data (age,sex,outcome after GD-GC diagnosis,Hp infection, parietal cell antibodies(PCA), family history for GC). Inclusion criteria were:patients with MF-AG or CR-AG and GD or GC diagnosis,aged>18 years, availability of endoscopic and histological description of GD-GC and perilesional gastric mucosa, completeness of clinical data.Data were stratified for MF-AG/CR-AG and the GD-GC, perilesional mucosa, and clinical characteristics were compared.

Results

A total of 84 pts[(F46[54.8%];age 70(33-90yrs)] were included. MF-AG and CR-AG were observed in 45(53.6%) and 39(46.4%) pts,respectively. High-grade(HG)-GD,low-grade(LG)-GD,and non-cardia GC were diagnosed in 6(7.1%),31(36.9%), and 47(56.0%)pts.
Age, GC family history,smoking habits, and PCA positivity were similar between MF-AG and CR-AG.Women(69.2% vs 42.2%,p=0.01) and pernicious anemia(29% vs 9.1%,p=0.04) were more frequent in CR-AG than in MF-AG.
The proportion of GD and GC in MF-AG and CR-AG pts was similar:HG-GD was present in 4(8.9%) vs 2(5.1%),LG-GD in 17(37.8%) vs 14(35.9%),GC in 24(53.5%) vs 23(59.0%)pts(p>0.05).
Compared to MF-AG,in CR-AG pts GD-GC were more frequently polypoid lesions (51.6% vs 27.3%,p=0.048) and more frequent in the corpus (55.3% vs 28.6%,p=0.02), but also occurred in the antrum(34.2%) and incisura(10.5%).The intestinal-type GC was the most prevalent and was more frequent in MF-AG than in CR-AG (87%vs60.9%,p>0.046), while diffuse GC was 2 times more frequent in CR-AG than in MF-AG, albeit not reaching statistical significance (26.1% vs 13%, p=0.27).
Concerning GC differentiation grade and staging, no significant differences were observed between MF-AG and CR-AG.Endoscopic treatment of GD-GC was similar in both groups. CR-AG patients underwent surgery more frequently than MF-AG(48.6% vs 23.1%,p=0.0207), but outcome was similar with 90.7% MF-AG and 92.1% CR-AG pts being alive.
Histopathological features of corpus mucosa (acute-chronic inflammation, severity of atrophy,pseudopyloric and intestinal metaplasia) were similar between MF-AG and CR-AG(p>0.05). The histological evidence of Hp in the antrum and corpus was low in both groups (2.3% vs 2.9%,p=0.87).

Conclusion

Non-cardia GC and GD may occur in both,MF-AG and CR-AG, displaying differences in topography and endoscopic presentation, but similarities in perilesional gastric corpus mucosa, differentiation, staging and outcome.
Endo-histological surveillance should be considered in pts with gastric corpus atrophy, irrespective of its etiology and extension.

References

Lahner E, et al. Dig Liver Dis. 2019 Dec;51(12):1621-1632.
Lenti MV, et al. Nat Rev Dis Primers. 2020 Jul 9;6(1):56.
Rugge M, et al. Gut. 2023 Jan;72(1):30-38.