Gastroenterology Today Summer 2024

Gastroenterology Today Summer 2024

Gastroenterology Today Summer 2024


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Volume 34 No. 6 <strong>Summer</strong> <strong>2024</strong><br />

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<strong>Gastroenterology</strong> <strong>Today</strong><br />


9 CASE STUDY Epiploic Appendagitis: An Under-recognised<br />

Cause of the Acute Abdomen<br />

This issue edited by:<br />

Aaron Bhakta<br />

c/o Media Publishing Company<br />

Greenoaks, Lockhill<br />

Upper Sapey, Worcester, WR6 6XR<br />

12 CASE STUDY Leicester nurses leading the way in capsule<br />

sponge testing<br />

15 FEATURE Endoscopic Ultrasonography-Guided Fine-<br />

Needle Biopsy for Patients with Resectable<br />

Pancreatic Malignancies<br />

24 FEATURE Texture and color enhancement imaging improves<br />

the visibility of gastric neoplasms: clinical trial with<br />

image catalogue assessment using conventional and<br />

newly developed endoscopes<br />



Media Publishing Company<br />

Greenoaks, Lockhill<br />

Upper Sapey, Worcester, WR6 6XR<br />

Tel: 01886 853715<br />

E: info@mediapublishingcompany.com<br />

www.ambulanceukonline.com<br />


March, June, September and December.<br />


Media Publishing Company<br />

Greenoaks<br />

Lockhill<br />

Upper Sapey, Worcester, WR6 6XR<br />


Opportunities in Endoscopy: Join Our 18WS Team in the Midlands and East of England<br />

We’re healthcare providers supporting elective care backlogs in NHS trusts, and we are<br />

looking for talented individuals to join our elite team of Endoscopy Consultants, Nurses,<br />

HCAs, and Decontamination Technicians in the Midlands and the East of England.<br />


The views and opinions expressed in<br />

this issue are not necessarily those of<br />

the Publisher, the Editors or Media<br />

Publishing Company<br />

Next Issue Autumn <strong>2024</strong><br />

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GASTROENTEROLOGY TODAY – SUMMER <strong>2024</strong><br />




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articles.”<br />

Evidence-based practice (EBP) has been the gold standard in healthcare for nearly three centuries and<br />

aims to assist physicians in providing the safest and most effective healthcare for their patients. The wellestablished<br />

hierarchy of evidence lists systematic reviews and meta-analyses at the top however these<br />

methodologies are not always appropriate or possible and in these instances case-control studies, case<br />

series and case reports are utilised to support EBP.<br />

Case series and reports are particularly useful in the study of rare diseases and also as an educational<br />

opportunity to remind us all of conditions not frequently encountered in clinical practise but conditions that<br />

need to be on our clinician radar.<br />

Case reports are often difficult to publish but here at <strong>Gastroenterology</strong> <strong>Today</strong> we want to support this type<br />

of publication. We are open to all types of article. Any potential articles can be submitted to:<br />

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Published quarterly, with a well established distribution list and no processing charges we look forward to<br />

receiving potential articles.<br />

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St George’s Hospital<br />

<strong>Gastroenterology</strong> <strong>Today</strong><br />

GASTROENTEROLOGY TODAY – SUMMER <strong>2024</strong><br />

Publishers Comment<br />

On behalf of everyone involved with the publishing of <strong>Gastroenterology</strong> <strong>Today</strong> I would like to say a big<br />

thank you to our contributors for their input and a special thank you to our advertisers as without their<br />

ongoing support we would not be able to print and despatch copies of this very unique publication to all<br />

<strong>Gastroenterology</strong> Departments and Endoscopy Units. Wishing you all a prosperous <strong>2024</strong>.<br />

Terry Gardner<br />

Publisher<br />


Octasa ® 1600mg<br />

delivers mesalazine<br />

throughout the<br />

entire colon 1<br />

Octasa ® 1600mg<br />

releases mesalazine<br />

in the caecum<br />

which spreads<br />

throughout<br />

the colon<br />

even distally 2,3<br />

Octasa ® 1600mg was equally effective at inducing endoscopic remission in patients<br />

with different disease extents, even distal mild to moderate UC 4<br />

See how<br />

it works<br />

Get your mild to moderate UC patients<br />

into remission with Octasa ® 1600mg,<br />

3 tablets (4.8g) once-daily* 1<br />

OCTASA 400mg, 800mg & 1600mg Modified Release Tablets<br />

(mesalazine) - Prescribing Information<br />

Presentation: Modified Release tablets containing 400mg, 800mg or 1600mg<br />

mesalazine. Indications: All strengths: Ulcerative Colitis - Treatment of mild to<br />

moderate acute exacerbations. Maintenance of remission. 400mg & 800mg<br />

only: Crohn’s ileocolitis - Maintenance of remission. Dosage and<br />

administration: 400mg & 800mg tablets – Adults: Mild acute disease: 2.4g<br />

once daily or in divided doses, with concomitant steroid therapy where indicated.<br />

Moderate acute disease: 2.4g – 4.8g daily. 2.4g may be taken once daily or in<br />

divided doses, higher doses should be taken in divided doses. Maintenance<br />

therapy: 1.2g – 2.4g once daily or in divided doses. 1600mg tablets – Adults:<br />

Acute exacerbations: up to 4.8g, once daily or in divided doses. Maintenance:<br />

1600mg daily. Tablets must be swallowed whole. Elderly: 400mg & 800mg -<br />

normal adult dose may be used unless liver or renal function is severely<br />

impaired. 1600mg - no studies in elderly patients have been conducted.<br />

Children: 400mg & 800mg - limited documentation of efficacy in children >6<br />

years old. Dose to be determined individually. Generally recommended that half<br />

the adult dose may be given to children up to a body weight of 40 kg; and the<br />

normal adult dose to those above 40 kg. 1600mg – safety and efficacy not<br />

established in children. Contra-indications: Hypersensitivity to salicylates,<br />

mesalazine or any of the excipients, severe impairment of hepatic or renal<br />

function (GFR less than 30 ml/min/1.73m 2 ). Warnings and Precautions:<br />

Urinary status (dip sticks) should be determined prior to and during treatment, at<br />

discretion of treating physician. Caution in patients with raised serum creatinine<br />

or proteinuria. Stop treatment immediately if renal impairment is evident. Cases<br />

of nephrolithiasis have been reported with mesalazine treatment. Ensure<br />

adequate fluid intake during treatment. Severe cutaneous adverse reactions<br />

(SCARS), including Drug reaction with eosinophilia and systemic symptoms<br />

(DRESS), Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis<br />

(TENS) have been reported. Stop treatment immediately if signs and symptoms<br />

of severe skin reactions are seen. Haematological investigations are<br />

recommended prior to and during treatment, at discretion of treating physician.<br />

Stop treatment immediately if blood dyscrasias are suspected or evident.<br />

Caution in patients with impaired hepatic function. Liver function should be<br />

determined prior to and during treatment, at the discretion of the treating<br />

physician. Do not use in patients with previous mesalazine-induced cardiac<br />

hypersensitivity and use caution in patients with previous myo- or pericarditis of<br />

allergic background. Monitor patients with pulmonary disease, in particular<br />

asthma, very carefully. In patients with a history of adverse drug reactions to<br />

sulphasalazine, discontinue immediately if acute intolerance reactions occur<br />

(e.g. abdominal cramps, acute abdominal pain, fever, severe headache and<br />

rash). Use with caution in patients with gastric or duodenal ulcers. Intact<br />

400mg & 800mg tablets in the stool may be largely empty shells. If this occurs<br />

repeatedly patients should consult their physician. Use with caution in the<br />

elderly, subject to patients having normal or non-severely impaired renal and<br />

liver function. Patients with rare hereditary problems of galactose intolerance,<br />

the Lapp lactase deficiency or glucose-galactose malabsorption, should not<br />

take the 400mg or 800mg tablets. Mesalazine may produce red-brown urine<br />

discoloration after contact with sodium hypochlorite bleach (e.g. in toilets<br />

cleaned with sodium hypochlorite contained in certain bleaches). Interactions:<br />

No interaction studies have been performed. May decrease the anticoagulant<br />

activity of warfarin. Caution when used with known nephrotoxic agents such as<br />

NSAIDs, methotrexate and azathioprine. May increase the myelosuppressive<br />

effects of azathioprine, 6-mercaptopurine or thioguanine. Monitoring of blood<br />

cell counts is recommended if these are used concomitantly. Fertility,<br />

pregnancy and lactation: Only to be used during pregnancy and lactation<br />

when the potential benefit outweighs the possible risk. No effects on fertility<br />

have been observed. Adverse reactions: Common: dyspepsia, rash.<br />

Uncommon: eosinophilia (as part of an allergic reaction), paraesthesia, urticaria,<br />

pruritus, pyrexia, chest pain. Rare: headache, dizziness, myocarditis,<br />

pericarditis, abdominal pain, diarrhoea, flatulence, nausea, vomiting,<br />

photosensitivity. Very rare: altered blood counts (aplastic anemia,<br />

agranulocytosis, pancytopenia, neutropenia, leucopenia, thrombocytopenia),<br />

blood dyscrasia, hypersensitivity reactions (such as allergic exanthema, drug<br />

fever, lupus erythematosus syndrome, pancolitis), peripheral neuropathy,<br />

allergic and fibrotic lung reactions (including dyspnoea, cough, bronchospasm,<br />

alveolitis, pulmonary eosinophilia, lung infiltration, pneumonitis), interstitial<br />

pneumonia, eosinophilic pneumonia, lung disorder, acute pancreatitis, changes<br />

in liver function parameters (increase in transaminases and cholestasis<br />

parameters), hepatitis, cholestatic hepatitis, alopecia, myalgia, arthralgia,<br />

impairment of renal function including acute and chronic interstitial nephritis and<br />

renal insufficiency, renal failure which may be reversible on withdrawal,<br />

nephrotic syndrome, oligospermia (reversible). Not known: Drug reaction with<br />

eosinophilia and systemic symptoms, Stevens-Johnson Syndrome, toxic<br />

epidermal necrolysis, pleurisy, lupus-like syndrome with pericarditis and<br />

pleuropericarditis as prominent symptoms as well as rash and arthralgia,<br />

nephrolithiasis, intolerance to mesalazine with C-reactive protein increased and/<br />

or exacerbation of symptoms of underlying disease, blood creatinine increased,<br />

weight decreased, creatinine clearance decreased, amylase increased, red<br />

blood cell sedimentation rate increased, lipase increased, BUN increased.<br />

Consult the Summary of Product Characteristics in relation to other adverse<br />

reactions. Marketing Authorisation Numbers, Package Quantities and<br />

basic NHS price: 400mg - PL36633/0002; packs of 90 tablets (£19.50) and<br />

120 tablets (£26.00). 800mg - PL36633/0001; packs of 90 tablets (£40.38)<br />

and 180 tablets (£80.75). 1600mg – PL36633/0009; packs of 30 tablets<br />

(£30.08). Legal category: POM. Marketing Authorisation Holder: Tillotts<br />

Pharma UK Ltd, The Larbourne Suite, The Stables, Wellingore Hall, Wellingore,<br />

Lincolnshire, LN5 0HX, UK. Octasa is a trademark. © 2022 Tillotts Pharma UK<br />

Ltd. Further Information is available from the Marketing Authorisation Holder.<br />

Date of preparation of PI: November 2022<br />

Adverse events should be reported. Reporting forms and<br />

information can be found at https://yellowcard.mhra.gov.uk.<br />

Adverse events should also be reported to Tillotts Pharma<br />

UK Ltd. (address as above) Tel: 01522 813500.<br />

* Octasa ® 1600mg tablets can be administered in divided doses if required or if this aids adherence.<br />

References: 1. Octasa ® 1600mg Modifi ed Release Tablets – Summary of Product Characteristics. 2. Varum F et al. Int J Pharm 2022;<br />

625: 122055. 3. Data on fi le, Tillotts Pharma UK Limited. [OPTICORE ® scintigraphy data from Varum et al. 2022 visualised as cyan<br />

heatmap – December 2023]. 4. D’Haens GR et al. Infl amm Intest Dis 2023; 8: 51–59.<br />

Date of preparation: May <strong>2024</strong>. PU-01740.




The surveillance of Barrett’s oesophagus represents a significant<br />

opportunity to identify and treat oesophageal cancer earlier. However,<br />

challenges in targeting necessary endoscopies have led to a heavily<br />

resource-intensive pathway that needs support.<br />

Challenges exacerbated by the COVID-19 pandemic and pre-existing<br />

issues within the GI endoscopy landscape, such as inefficient patient<br />

selection, rising demand, and workforce challenges, resulted in an<br />

approximate 95% reduction in surveillance activities and routine<br />

gastroscopies in that period. 1 There are currently over 17,056 people<br />

waiting over six weeks for a gastroscopy procedure across England,<br />

with 54% of those waiting over 13 weeks. 2<br />

Early cancer detection and treatment with capsule sponge testing<br />

A pioneering diagnostic tool, Cyted’s EndoSign ® capsule sponge<br />

test offers a minimally invasive way to identify patients who are at an<br />

increased risk of developing oesophageal cancer, particularly those<br />

with chronic reflux symptoms or diagnosed with Barrett’s oesophagus.<br />

Identifying at-risk patients who need further endoscopic investigation,<br />

and diverting those who don’t, eases the pressure on endoscopy<br />

services, and releases resources across the patient care pathway.<br />

How it works:<br />

• Swallowing the capsule: The patient swallows a capsule, similar in<br />

size to a vitamin pill, which is tethered to a strong, thin thread.<br />

• Capsule dissolves: Once the capsule reaches the stomach, its<br />

outer layer dissolves to release a small sponge.<br />

From a provider perspective, the test is efficient and practical, requiring<br />

only about 10 minutes to complete in any outpatient setting, from GPs<br />

and Community Diagnostics Centres, to hospital outpatient clinics.<br />

This cost-effective and simple process helps healthcare providers<br />

boost the number of sites and clinical staff that can offer the test,<br />

supporting improved clinical capacity and lower waiting times.<br />

Early detection is another pivotal advantage; by catching Barrett’s<br />

oesophagus and oesophageal cancer early, the capsule sponge test<br />

greatly improves the likelihood of successful treatment outcomes<br />

and patient survival rates. This is particularly important in the case<br />

of oesophageal cancer, where 81% of patients are diagnosed late (at<br />

stages 3-4) when less than 20% of patients survive beyond the year<br />

of diagnosis. 3<br />

Piloting sponge capsule testing<br />

In January 2021, NHSE launched a pilot of the capsule sponge test<br />

for triaging patients with low-risk reflux symptoms on a routine referral<br />

pathway in secondary care settings. Eligible patients waiting for a<br />

routine endoscopy on the standard diagnostic pathway were offered a<br />

capsule sponge test as an alternative to their endoscopy. Patients who<br />

accepted the offer were subsequently diverted from the endoscopy<br />

pathway and placed on an alternative pathway with the capsule<br />

sponge test. The pilot;<br />

• Reduced endoscopy pressures by 78% by diverting<br />

unnecessary endoscopies 4<br />

• Saved at least £420 per patient for NHS England 5<br />

GASTROENTEROLOGY TODAY – SUMMER <strong>2024</strong><br />

• Sponge expansion and retrieval: The clinician pulls the string, and<br />

the sponge collects cells as it passes through the oesophagus.<br />

• Cell analysis: The retrieved sponge containing a sample of<br />

oesophageal cells is sent to Cyted Health’s laboratory and analysed<br />

for any abnormalities and indications of oesophageal cancer or its<br />

precancerous condition, Barrett’s oesophagus.<br />

This minimally invasive approach avoids sedation, significantly<br />

enhancing patient comfort and convenience. This makes it a preferable<br />

option for many, mitigating the discomfort and anxiety associated with<br />

conventional endoscopic examinations to help improve uptake.<br />

• The capsule sponge testing pathway increased the prevalence of<br />

Barrett’s diagnosis by around 40% compared to the counterfactual<br />

group with the standard-of-care. 6<br />

“Thousands of people have now benefitted from this incredibly efficient<br />

test on the NHS – while the sponge on a string is small in size, it can<br />

make a big difference for patients – they can conveniently fit the test<br />

into their day and it can often replace the need for an endoscopy while<br />

also helping to reduce waiting lists by freeing up staff and resources.”<br />

Amanda Pritchard, Chief Executive, NHS<br />

1<br />

Rutter et al. “Impact of the COVID-19 pandemic on UK endoscopic activity and cancer detection: a National Endoscopy Database Analysis.” Gut<br />

vol. 70,3 (2021): 537-543.<br />

2<br />

NHS England. Diagnostic Waiting Times and Activity (DM01). February <strong>2024</strong>.<br />

3<br />

Cancer Research UK. Early Diagnosis Data Hub: Incidence by Stage. Oesophageal Cancer, Stage 1, 2, 3 and 4 (England, excluding unknown<br />

stage). 2023.<br />

4<br />

IQVIA, NHS England. NHS England Cytosponge evaluation for routine referrals: final report. 2023.<br />

5<br />

IQVIA, NHS England.<br />

6<br />

IQVIA, NHS England.<br />



Capsule sponge testing success in Scotland<br />

How it works:<br />

Faced with disrupted endoscopy services following the pandemic,<br />

NHS Scotland was an early adopter of the capsule sponge test,<br />

a strategic shift to alleviate the strain on endoscopic services by<br />

introducing a non-endoscopic, clinically robust alternative for<br />

monitoring patients with Barrett’s oesophagus.<br />

The deployment of the capsule sponge test across NHS Scotland for<br />

Barrett’s surveillance procedures has yielded promising outcomes,<br />

resulting in;<br />

• A 77% reduction in demand for surveillance endoscopies. 7<br />

• Median waiting list times reduced from 9 to 5 months. 8<br />

Triage: Identify patients with chronic reflux or under Barrett’s<br />

Oesophagus surveillance from the NHS backlog for routine endoscopy<br />

referrals, excluding those unsuitable for the capsule sponge test.<br />

Capsule sponge procedure: Eligible patients undergo the capsule<br />

sponge test managed by Xyla, involving swallowing a capsule that<br />

collects oesophageal cell samples.<br />

EndoSign ® diagnostic test at Cyted Health: Samples are sent<br />

to Cyted Health for the EndoSign® diagnostic test to detect<br />

abnormalities.<br />

Follow-Up: Acacium Group clinicians follow up with patients based on<br />

pathology reports.<br />

• The detection of concerning pathologies at endoscopy increased<br />

from 10% to 50% of patients. 9<br />

NHS Scotland’s efforts have set a new standard of care for Barrett’s<br />

surveillance. The success of this programme has not only informed<br />

clinical teams throughout the UK and Europe but has also spurred<br />

audits and the optimisation of endoscopic resources. This has freed up<br />

staff and facilities for other critical procedures, such as colonoscopies<br />

and bowel screenings.<br />

“This technology has been easy to use, very acceptable for patients<br />

and closely audited to ensure we learn and are able to share as much<br />

as we can from our experience. It is now established as a key tool in<br />

how we use our endoscopic resource for assessment of patients and<br />

surveillance of Barrett’s oesophagus.”<br />

Mr Paul Glen, Upper GI Surgeon, NHS Greater Glasgow & Clyde (GGC)<br />

Compounding the benefits of capsule sponge testing with a<br />

managed service<br />

Over the last 15 years, endoscopy has consistently ranked among the<br />

top three clinical specialities sought for insourcing. This model requires<br />

trusts to maintain operational and clinical oversight while utilising their<br />

premises and equipment with external teams.<br />

To mitigate these issues, Cyted Health has partnered with Xyla, part of<br />

Acacium Group, the UK’s leading healthcare delivery partner, to deliver<br />

an outsourced managed service that provides capacity, flexibility and<br />

access to specialist workforce and equipment.<br />

This service is an alternative pathway for patients who require<br />

endoscopic evaluation, particularly due to chronic reflux symptoms or<br />

surveillance of Barrett’s oesophagus.<br />

Outcome-based actions: Positive results (15-20% of cases) lead to<br />

an endoscopy referral. Negative results (80% of cases) ensure patients<br />

are safely managed without endoscopy based on symptoms.<br />

This fully managed service streamlines the patient journey by<br />

integrating triage, testing, analysis, and follow-up. It effectively<br />

addresses the backlog while ensuring patients receive the appropriate<br />

level of care based on their test results.<br />

The future of oesophageal health<br />

The deployment of the capsule sponge test in over 60 hospitals and 20<br />

community care-based clinics throughout the UK has demonstrated<br />

substantial benefits. The ease of implementation and integration<br />

into current healthcare pathways underscores its potential as a<br />

transformative tool in managing gastrointestinal diseases. Cyted Health<br />

and Acacium Group’s co-developed service offers a promising avenue<br />

for reducing costs and waiting lists while improving cancer surveillance<br />

and patient care at scale.<br />

For more information, contact Charlene Tang, Head of Growth,<br />

hello@cytedhealth.com<br />

7<br />

Scottish Health Technologies Group Assessment. Capsule sponge technologies for the detection of Barrett’s oesophagus and early stage<br />

oesophageal cancer. November 2023.<br />

8<br />

Siobhan Chien, et al National adoption of an esophageal cell collection device for Barrett’s esophagus surveillance: impact on delay to investigation<br />

and pathological findings. Diseases of the Esophagus (Online). <strong>2024</strong><br />

9<br />

Natalie Tse et al. Impact of introduction of a cytosponge barrett’s oesophagus surveillance service on the endoscopic pathology pattern. Gut<br />

2023;72:A7-A8.<br />

A fully managed capsule sponge service<br />

Triage of those with chronic<br />

reflux symptoms<br />

Surveillance of those with<br />

Barrett’s Oesophagus<br />

NHS backlog for routine<br />

endoscopy referrals<br />

Not suitable for<br />

capsule sponge test<br />

Nurse led triage<br />

EndoSign® diagnostic<br />

procedure with Xyla<br />

EndoSign ® diagnostic test at Cyted<br />

Negative result (75-85%)<br />

Xyla follow up with patient<br />

following pathology report<br />

Safely manage according<br />

to symptoms<br />

Positive result<br />

(15-20%)<br />

Patient referred<br />

for Endoscopy<br />

GASTROENTEROLOGY TODAY – SUMMER <strong>2024</strong><br />



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K Jacob, M Colwill & A Poullis<br />

Department of <strong>Gastroenterology</strong>, St George’s Hospital, London<br />

appendage or a sub-serosal lymphatic channel that loops through their<br />

base while travelling to mesenteric nodes. The average adult colon<br />

contains 50 to 100 appendages that vary considerably in size, shape<br />

and contour. They are more abundant and larger in the transverse<br />

and sigmoid colon and on average tend to be 1 to 2 cm thick and 2 to<br />

5cm long, although can rarely measure up to 15cm. 1 They are typically<br />

larger in obese patients and in those who recently lost weight. 2,3 The<br />

role of epiploic appendages is unknown, but they are theorised to<br />

serve a function in protection similar to the greater omentum, possibly<br />

acting as a cushion to protect colonic blood supply during peristalsis<br />

and may contribute to colonic absorption. 2<br />

Epiploic Appendagitis<br />

Figure 1. An axial frame from our patient’s CT scan. The area circled<br />

demonstrates an area of inflammatory change related to the fat<br />

overlying the anti-mesenteric aspect of the sigmoid colon in the left<br />

iliac fossa is identified, representing epiploic appendigitis.<br />

Epiploic appendagitis is an ischaemic infarction of an epiploic<br />

appendage. Primary epiploic appendagitis is caused by torsion<br />

of the epiploic appendage or venous thrombosis of the draining<br />

appendageal vein. Secondary epiploic appendagitis is associated with<br />

inflammation of adjacent organs, for example diverticulitis, appendicitis<br />

or cholecystitis.<br />

Case<br />

A 64 year old male with no significant past medical history presented<br />

with a 7 day history of left lower quadrant pain and fevers without an<br />

associated change in bowel habit, haematochezia or vomiting. On<br />

examination he was tender throughout the left lower quadrant but not<br />

peritonitic and there was no guarding. Initial blood tests revealed a<br />

normal full blood count and biochemistry including C-reactive protein<br />

and stool cultures were negative. He was managed initially with simple<br />

analgesia but his symptoms did not resolve. Following this a Computed<br />

Tomography (CT) scan of the abdomen revealed epiploic appendagitis<br />

(Fig 1). He was treated with non-steroidal anti-inflammatories and his<br />

symptoms completely resolved within 5 days.<br />

Discussion<br />

Pathophysiology<br />

Epiploic appendages are small pouches of fat and small blood vessels<br />

that protrude from the serosal surface of the colon into the peritoneal<br />

cavity. Each appendage contains branches of the circular artery and<br />

vein that supply the corresponding segment of the colon. Appendages<br />

also contain lymphatic channels either with a lymph node within the<br />

The incidence of epiploic appendagitis is not known but has been<br />

reported in 2-7% of patients who were initially suspected of having<br />

acute diverticulitis, and 0.3-1% of patients suspected of having acute<br />

appendicitis. 4 It most commonly presents second to fifth decades of<br />

life, with a mean age of diagnosis of 40 ears. The incidence of epiploic<br />

appendagitis has been reported to be up to four times higher in men<br />

compared to women. 4,5,6 Obesity, increased abdominal adipose tissue<br />

and strenuous exercise may be contributing risk factors. 4,7,8<br />

Epiploic appendagitis can occur throughout the colon, with a surgical<br />

case series showing 57% of cases occurred in the rectosigmoid<br />

junction, 26% in the ileocaecal region, 9% in the ascending colon, 6%<br />

in the transverse colon and 2% in the descending colon. 4,7,9<br />

Presentation<br />

Epiploic appendagitis typically presents with localised abdominal<br />

pain, more commonly on typically normal but can be mildly elevated.<br />

Differential diagnosis can include appendicitis, diverticulitis, omental<br />

infarction, pelvic inflammatory disease or a ruptured ovarian cyst.<br />

Diagnosis<br />

Pathological confirmation of diagnosis is uncommon. Diagnosis is<br />

typically based on CT scanning of the abdomen and pelvis. Epiploic<br />

GASTROENTEROLOGY TODAY – SUMMER <strong>2024</strong><br />



appendagitis appears as an oval-shaped, 2-3 cm paracolic fatty mass<br />

with thickened peritoneal lining and peri-appendigeal fat stranding<br />

(known as a ring sign). 11 It is typically of slightly higher attenuation<br />

than peritoneal fat and may contain a central dot of high attenuation<br />

(known as the ‘dot sign’) possibly representing a thrombosed vessel in<br />

the epiploic appendage. 10 CT changes of acute epiploic appendagitis<br />

completely resolved in all patients undergoing a follow up CT scan 6<br />

months after the initial presentation. 11-13 Magnetic resonance imaging<br />

findings of epiploic appendagitis have not been well studied but appear<br />

to be the left side (60 to 80%). Pain can be of variable intensity and<br />

duration and exacerbated by coughing, deep inspiration, or stretching<br />

(as the infarcted appendage is adherent to the parietal peritoneum).<br />

It typically does not radiate. Patients may also present with a mild<br />

fever, rebound tenderness and an abdominal mass. More rarely,<br />

there may be associated nausea, vomiting and weight loss. White cell<br />

count, erythryocyte sedimentation rate and C-reactive protein are in<br />

congruence with CT findings. 14<br />

Alternatively, abdominal ultrasound may be used demonstrating<br />

a non-compressible, hyperechoic, solid oval mass with a subtle<br />

hypoechoic rim located at the point of maximal tenderness. 7 Doppler<br />

studies typically reveal absence of blood flow with the appendage,<br />

with normal blood flow in the hyperechoic inflamed fat surrounding<br />

the appendage. 15 Adding contrast shows a central area of no<br />

enhancement with moderately increased vascularisation around the<br />

avascular necrotic appendage. 16<br />

Disease Course<br />

Epiploic appendagitis is a self-limiting disease with signs and<br />

symptoms normally resolving within 3 to 14 days. 7,17,18 It should be<br />

treated conservatively with analgesia. Patients do not usually require<br />

hospitalisation or antibiotics and surgery is typically reserved for<br />

patients who fail to improve with conservative management or develop<br />

complications (intussusception, abscess or bowel obstruction)<br />

that cannot be managed nonoperatively. At surgery, the inflamed<br />

appendage is typically ligated and resected. Recurrence is not well<br />

studied but is likely very low.<br />

4. Schnedl WJ, Krause R, Tafeit E, et al. Insights into epiploic<br />

appendagitis. Nat Rev Gastroenterol Hepatol 2011; 8:45.<br />

5. Ozdemir S, Gulpinar K, Leventoglu S, et al. Torsion of the primary<br />

epiploic appendagitis: a case series and review of the literature.<br />

Am J Surg 2010; 199:453.<br />

6. Sand M, Gelos M, Bechara FG, et al. Epiploic appendagitis--<br />

clinical characteristics of an uncommon surgical diagnosis. BMC<br />

Surg 2007; 7:11.<br />

7. Rioux M, Langis P. Primary epiploic appendagitis: clinical, US, and<br />

CT findings in 14 cases. Radiology 1994; 191:523.<br />

8. Nugent JP, Ouellette HA, O’Leary DP, et al. Epiploic appendagitis:<br />

7-year experience and relationship with visceral obesity. Abdom<br />

Radiol (NY) 2018; 43:1552.<br />

9. Macari M, Laks S, Hajdu C, Babb J. Caecal epiploic appendagitis:<br />

an unlikely occurrence. Clin Radiol 2008; 63:895.<br />

10. Giannis D, Matenoglou E, Sidiropoulou MS, et al. Epiploic<br />

appendagitis: pathogenesis, clinical findings and imaging clues of<br />

a misdiagnosed mimicker. Ann Transl Med 2019; 7:814.<br />

11. Singh AK, Gervais DA, Hahn PF, et al. CT appearance of acute<br />

appendagitis. AJR Am J Roentgenol 2004;183:1303-7. 10.2214/<br />

ajr.183.5.1831303.<br />

12. Rao PM, Wittenberg J, Lawrason JN. Primary epiploic<br />

appendagitis: evolutionary changes in CT appearance. Radiology<br />

1997;204:713-7. 10.1148/radiology.204.3.9280248.<br />

13. Mollà E, Ripolles T, Martinez MJ, et al. Primary epiploic<br />

appendagitis: US and CT findings. Eur Radiol 1998;8:435-8.<br />

10.1007/s003300050408.<br />

14. Sirvanci M, Balci NC, Karaman K, et al. Primary epiploic<br />

appendagitis: MRI findings. Magn Reson Imaging 2002; 20:137.<br />

15. Deceuninck A, Danse E. Primary epiploic appendagitis: US and CT<br />

findings. JBR-BTR 2006; 89:225.<br />

16. Görg C, Egbring J, Bert T. Contrast-enhanced ultrasound of<br />

epiploic appendagitis. Ultraschall Med 2009; 30:163.<br />

17. Desai HP, Tripodi J, Gold BM, Burakoff R. Infarction of an epiploic<br />

appendage. Review of the literature. J Clin Gastroenterol 1993;<br />

16:323.<br />

18. Legome EL, Belton AL, Murray RE, et al. Epiploic appendagitis:<br />

the emergency department presentation. J Emerg Med 2002;<br />

22:9.<br />

Key Points<br />

GASTROENTEROLOGY TODAY – SUMMER <strong>2024</strong><br />

• Epiploic appendigitis is a rare pathology that can cause abdominal<br />

pain and mimic several other acute abdominal pathologies including<br />

appendicitis, colitis and diverticulitis<br />

• It is benign and self-limiting and usually can be managed with<br />

conservative measures<br />

• Cross-sectional imaging is the gold-standard in diagnosis to assess<br />

for ring sign or dot sign<br />

References:<br />

1. Linkenfeld F. Deutsche Ztschr f Chir. 1908;92:383 10.1007/<br />

BF02799591.<br />

2. Pines BR, Beller J. Primary torsion and infarction of the<br />

appendices epiploicae. Arch Surg 1941; 42:775.<br />

3. Ghahremani GG, White EM, Hoff FL, et al. Appendices epiploicae<br />

of the colon: radiologic and pathologic features. Radiographics<br />

1992; 12:59.<br />




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Introduction<br />

University Hospitals of Leicester NHS Trust (UHL) has transformed<br />

patient access to diagnostics for Barrett’s oesophagus, a risk factor<br />

for cancer, through the roll out of capsule sponge testing. The team’s<br />

creation of a new nurse-led diagnostic pathway has allowed them to<br />

cut gastroscopy waiting times, improve clinical capacity and deliver a<br />

better experience for both patients and clinical staff.<br />

The challenge<br />

The team at UHL had an ambition to reduce wait times and improve<br />

survival chances for a lesser-known group of patients with Barrett’s<br />

oesophagus that affects around 1 million adults in Britain. 1 The<br />

incidence of oesophageal adenocarcinoma in this group has increased<br />

dramatically since the 1970s, 2 yet survival remains poor despite<br />

advances in surgery and chemotherapy. In the UK, 81% are diagnosed<br />

at stage 3 or 4, of which only ~20% survive for 1 year or more. 3<br />

The only way of improving survival chances for this patient group is to<br />

ensure early diagnosis and surveillance of Barrett’s Oesophagus.<br />

However, the team were facing all-time high waits for gastroscopy and<br />

saturated 2-week wait pathways, placing these patients at increased<br />

risk of late diagnosis.<br />

• Average patient wait time for this group: 6-12 months<br />

• Number of staff able to perform the initial diagnostic test: 1<br />

• Number of locations the initial diagnostic test was available from:1<br />

The solution<br />

The Trust joined the national capsule sponge testing pilot programme<br />

and came to see the benefits of the simple, minimally-invasive<br />

capsule sponge test. Testing was undertaken by a range of clinical<br />

professionals from nurses to consultants – widening the possible<br />

delivery of the service - which provided the potential to reduce<br />

the wait associated with traditional endoscopist-led endoscopy<br />

procedures. The team also improved their triaging process for the<br />

test, adding electronic forms to improve the speed and accuracy of<br />

patient selection.<br />

Capsule sponge testing offered the opportunity for nurses to be<br />

upskilled, providing improved career pathways which the team felt<br />

would strengthen both their attraction and retention. By improving their<br />

capacity to deliver the service, and upskilling their team, the Trust was<br />

able to create a nurse-led clinic that could see more Barrett’s patients,<br />

more quickly.<br />

Customer testimonial<br />

“What started as two nurses with an idea has become a key part of<br />

our pathway and now my full time job! The training opportunity alone<br />

has helped position ourselves as an innovative service that people<br />

are excited to join. Our staff retention has improved and we’re already<br />

hiring for more as we plan to roll out capsule sponge testing for other<br />

patient groups, and look to GP referrals to reach even more people.<br />

Our vision is that in time, all patients for Barrett’s surveillance and<br />

investigation for GORD will be offered capsule sponge testing as a first<br />

line diagnostic procedure.”<br />

“Our nurse-led approach means we have more people that can deliver<br />

the test, meaning each patient has a dedicated contact that supports<br />

them through the entire process, from testing at their community<br />

hospital to sending their diagnosis. It’s more convenient for them and<br />

helps them feel personally looked after. They clearly prefer the test, and<br />

so do we; all I want to do now is capsule sponge tests!”<br />

Vanessa deVivian<br />

Capsule Sponge Lead Nurse Specialist<br />

“In selecting what improvement to pursue, we collectively agreed<br />

that any new approach needed to help us recruit and retain more<br />

diagnostic staff, to build more capacity and be able to rapidly reduce<br />

the overall patient wait time.The testing process has delivered on all of<br />

those targets!”<br />

“The benefits to the patients have been huge. We proved the<br />

effectiveness of the capsule sponge by first showing the waiting<br />

times reductions for our Barrett’s patients, and then showing how<br />

we’ve been able to catch cancer earlier. For the team, we’ve been<br />

able to save endoscopy resources and give staff an exciting training<br />

opportunity. The test has been a big hit here and we’re hoping our<br />

nurse-led model can be an inspiration to other services to just go<br />

for it!”<br />

Colette J Green<br />

Endoscopy team lead<br />

1<br />

Dymedex Market Development Consulting, GERD Sizing, 2015<br />

2<br />

Pohl H, Welch HG. The role of overdiagnosis and reclassification in the marked increase of esophageal adenocarcinoma incidence. J Natl Cancer<br />

Inst. 2005;97(2):142-6.<br />

3<br />

Cancer Research UK. Early Diagnosis Data Hub: Incidence by Stage. Oesophageal Cancer, Stage 1, 2, 3 and 4 (England, excluding unknown<br />

stage). Available at: https://crukcancerintelligence.shinyapps.io/EarlyDiagnosis/ Accessed 14 March 2023. 2023.<br />



Outcomes<br />

Following the success of the pilot, the Trust is aiming to expand both<br />

the scope and the setting of its capsule sponge testing.<br />

Vanessa (left), Dr Kadri, Colette and Rachel<br />

To offer the test to even more at-risk patients, UHL is now looking at<br />

ways to sustainably expand the offer to reflux patients who have had<br />

at least 6-8 weeks of proton pump inhibitors (PPI). Another group that<br />

UHL is looking to diagnose is patients with Gastroesophageal reflux<br />

disease (GORD). Early intervention using capsule sponge testing would<br />

detect undiagnosed Barrett’s oesophagus in this group of patients,<br />

potentially decreasing mortality, improving patient experience and<br />

reducing costs to the NHS.The cost savings per patient can be reinvested<br />

in further service improvements through hiring dedicated staff<br />

or pathway innovations in the wider service. The Trust’s ambition is to<br />

accept direct GP referrals for patients with suspected GORD to further<br />

reduce pressure on gastroscopy pathways.<br />

Key findings<br />

• 20-week reduction in patient waiting times.<br />

• Increased capacity, with 3 staff able to perform the test. One<br />

dedicated full-time nurse and two other part-time.<br />

• Testing now available to more sites across the Trust and expanding<br />

into community care.<br />

Testing in the community is another area that UHL is planning to<br />

explore. The team found that 99% of patients expressed a preference<br />

for testing in a community hospital instead of the acute setting. In<br />

response to this, the Trust is aiming to secure additional funding to<br />

expand the service at St Luke’s Community Hospital to offer four full<br />

lists per week (48 capsule sponge procedures). It is hoped that in time<br />

this will become a site for referrals from neighbouring counties and will<br />

support expansion into a further three community sites.<br />

Conclusion<br />

• The early detection of Barrett’s Oesophagus has helped to prevent<br />

the occurrence of oesophageal cancers.<br />

• Positive impact on staff retention and acquisition, with colleagues<br />

expressing how valued they feel.<br />

The Trust’s nurse-led model demonstrates a clear way for other<br />

services to reduce the pressure on endoscopy teams, while still<br />

offering exciting training opportunities and autonomy to those that<br />

want to innovate. By expanding the deliverability of the testing, UHL is<br />

leading the way in developing cost-effective, nurse-led services that<br />

can provide better access, experience, and outcomes for patients.<br />

• Cost reduction of around 50% compared with gastroscopy, due to<br />

the different skill mix, setting and product.<br />

The capsule sponge testing programme has also improved patient<br />

experience by providing patient-centric care, closer to home. This more<br />

focused approach has created less anxiety for patients throughout<br />

their journey and greater patient satisfaction.<br />

• 100% of patients who previously had gastroscopy said they would<br />

prefer to have a capsule sponge testing in the future.<br />

• Patients reported better tolerance to the procedure and lower<br />

anxiety levels versus a gastroscopy.<br />

• 99% of patients said they experienced little to no discomfort during<br />

or after their capsule sponge test.<br />

• “Dealing with the same person throughout the journey is<br />

very reassuring.”<br />

• “A lovely, relaxed experience, felt very cared for (strange for a<br />

medical procedure).”<br />

UHL’s vision is that in time, all patients for Barrett’s surveillance and<br />

investigation for GORD will be offered capsule sponge testing as a firstline<br />

diagnostic procedure. The determination of the UHL team means<br />

that this vision will no doubt become reality.<br />

GASTROENTEROLOGY TODAY – SUMMER <strong>2024</strong><br />



GASTROENTEROLOGY TODAY – SUMMER <strong>2024</strong><br />







Ming-Sheng Chien 1 , Ching-Chung Lin 1,2 and Jian-Han Lai 1,2,3,*<br />

Gastroenterol. Insights <strong>2024</strong>, 15, 375–385. https://doi.org/10.3390/gastroent15020026<br />


Abstract: Clinicians often use endoscopic ultrasonography to survey<br />

pancreatic tumors. When endoscopists conduct this examination and<br />

find the tumor to be unresectable, a fine-needle biopsy is subsequently<br />

performed for tissue confirmation. However, if the tumor is deemed<br />

resectable, the necessity of a pre-operative fine-needle biopsy remains<br />

debatable. Therefore, we performed a retrospective analysis of a<br />

single-center cohort of patients with pancreatic tumors who underwent<br />

an endoscopic ultrasound-guided fine-needle biopsy or aspiration<br />

(EUS-FNB or FNA) between 2020 and 2022. This study focused on<br />

patients diagnosed with resectable malignant pancreatic tumors.<br />

The exclusion criteria included individuals diagnosed with benign<br />

pancreatic lesions and those with unresectable tumors. A total of 68<br />

patients were enrolled in this study. Histological examination revealed<br />

that pancreatic adenocarcinoma was the predominant type of tumor<br />

(n = 42, 61.8%), followed by neuroendocrine tumors (n = 22, 32.3%),<br />

and metastasis (n = 4, 5.9%). Notably, 17 patients had a history of other<br />

cancers, with 23.5% being diagnosed with a metastatic tumor rather<br />

than primary pancreatic cancer. Therefore, EUS-FNA/FNB is crucial in<br />

patients with a resectable pancreatic tumor and a history of cancer to<br />

differentiate between a primary and a metastatic tumor.<br />

Keywords: endoscopic ultrasonography; fine-needle biopsy; malignant<br />

pancreatic tumor; resectable tumor; pancreatic surgery<br />

1. Introduction<br />

Pancreatic cancer stands as a lethal malignancy, ranking among the<br />

leading contrib-utors to cancer-related deaths [1,2]. Surgical resection<br />

is the only curative approach for resectable pancreatic cancer. Imaging<br />

examinations such as computed tomography (CT) and magnetic<br />

resonance imaging (MRI) are valuable tools in identifying malignancy<br />

and determining whether tumors are resectable or non-resectable<br />

by assessing their interaction with nearby vascular structures, such<br />

as the superior mesenteric artery and vein, portal vein, and celiac<br />

artery. However, these imaging studies are unable to differentiate<br />

between primary and metastatic tumors. The definitive determination<br />

of the tumor type and origin relies on histological examination and<br />

immunohistochemical staining.<br />

In cases where tumors are deemed unresectable, tissue confirmation<br />

is imperative to guide subsequent systemic treatment. The decision<br />

making process regarding subsequent fine-needle aspiration or<br />

biopsy (FNA or FNB) for tissue confirmation becomes pivotal when<br />

endoscopists perform EUS in patients with pancreatic tumors.<br />

Conversely, when tumors are considered resectable, surgical<br />

resection is the primary recommendation for curative therapy.<br />

Consequently, pre-operative tissue confirmation through FNB may not<br />

be perceived as necessary for the majority of patients unless there is<br />

disagreement among surgeons regarding the pre-operative imaging<br />

study results, such as distinguishing between benign and malignant<br />

conditions. However, certain studies have documented cases in which<br />

patients underwent surgery only owing to the final diagnosis, which<br />

unexpectedly revealed pancreatic metastasis [3]. In such instances,<br />

if a pre-operative FNB was performed, unnecessary surgeries would<br />

avoided, thereby emphasizing the significance of judicious decision<br />

making in the diagnostic process.<br />

This study aimed to examine patients diagnosed with resectable<br />

pancreatic cancer based on pre-EUS evaluations, including CT,<br />

magnetic resonance imaging (MRI), and abdominal US. The<br />

objective of this study was to determine whether pre-operative tissue<br />

confirmation using FNA or FNB influenced the subsequent treatment<br />

plan, particularly the choice between surgical intervention and<br />

systemic treatment. Additionally, we reviewed several studies published<br />

in English to identify the distinct characteristics and features that<br />

differentiate between primary and secondary pancreatic tumors.<br />

2. Materials and Methods<br />

This retrospective cohort study was conducted at a medical center in<br />

Taiwan. We per-formed a retrospective analysis of a cohort of patients<br />

with pancreatic tumors, specifically focusing on those who underwent<br />

EUS-FNA and FNB between January 2020 and December 2022.<br />

Patients diagnosed with benign tumors or unresectable malignancy<br />

1<br />

Division of <strong>Gastroenterology</strong>, Department of Internal Medicine, MacKay Memorial Hospital, Taipei 104217, Taiwan; lineage2728@gmail.com<br />

(M.-S.C.); sunny.lin56@msa.hinet.net (C.-C.L.)<br />

2<br />

Department of Medicine, MacKay Medical College, New Taipei City 25245, Taiwan<br />

3<br />

MacKay Medicine Nursing and Management, Taipei 11260, Taiwan<br />

GASTROENTEROLOGY TODAY – SUMMER <strong>2024</strong><br />

* Correspondence: jiannhann@gmail.com; Tel.: +886-2-25433535<br />



beyond stage III according to the American Joint Committee on Cancer<br />

8th edition were excluded. The definitive diagnosis relied on both<br />

cytopathological and imaging findings, and not solely on the images.<br />

The criteria for imaging in the differential diagnosis of benign and<br />

malignant tumors were established based on previous studies [4,5]. In<br />

the EUS images, the tumor presented as a hypoechoic heterogeneous<br />

pattern, accompanied by an upstream pancreatic duct dilatation and<br />

distal pancreas atrophy, raising suspicion of malignancy. The diagnosis<br />

of background chronic pancreatitis was made using EUS based on the<br />

proposed Rosemont criteria [6].<br />

The adequacy of the obtained tissue was determined by the presence<br />

of well-defined pancreatic ductal epithelium or stromal cells in the<br />

retroperitoneal mass. An unsuccessful FNA/B cytopathological<br />

diagnosis was defined as either a false negative or atypical result,<br />

whereas a successful FNA/B diagnosis was defined as a suspicious<br />

or positive finding of malignancy. Specimens categorized as<br />

“atypical” exhibit a spectrum of architectural and/or cellular changes<br />

that exceed the parameters of normal or reactive conditions. Nevertheless,<br />

these alterations lack adequate quantitative or qualitative<br />

criteria to categorize them as neoplastic (benign/other), suspicious,<br />

or indicative of malignancy [7]. If a patient had an unsuccessful<br />

FNA/B cytopathological diagnosis, further surgical tissue-proof or<br />

transabdominal echo-guided metastatic lesion biopsy was arranged to<br />

obtain a final histo-logical diagnosis. Patients who were diagnosed with<br />

benign lesions underwent diagnostic imaging follow-up for at least 6<br />

months to rule out the possibility of a missed diagnosis of malignancy.<br />

For the analysis, we extracted the following personal and clinical data<br />

from patient records: age, sex, presentation of chronic pancreatitis,<br />

EUS findings (tumor location and size and number of FNA or FNB<br />

passes), and cytopathological results. Because CT imaging data were<br />

available for most patients, we opted to evaluate and incorporate CT<br />

findings in our study. We also recorded whether the patients had a<br />

history of other cancers before undergoing EUS.<br />

2.1. Study Design<br />

2.2. EUS-FNB<br />

All EUS-FNA/FNB procedures were performed with the patients in<br />

the left lateral decubitus position, under conscious sedation using<br />

midazolam and fentanyl. Additional sedatives were administered by<br />

endoscopists to achieve moderate conscious sedation. All EUS-<br />

FNA/B procedures were performed by three endoscopists who had<br />

completed the FNA learning curve [9]. The procedures were performed<br />

using a GF-UCT260 curvilinear echoendoscope (Olympus Optical Co.,<br />

Ltd., Tokyo, Japan). A 22-gauge FNA needle (EZ Shot 3 Plus, Olympus,<br />

Tokyo, Japan) or a 22-gauge FNB needle (TopGain ® , Medi-Globe,<br />

Achenmühle, Germany; Acquire TM, Boston Scientific, Natick, MA,<br />

USA) was employed.<br />

A fanning method was used for FNA/B, involving aspiration from at<br />

least four different areas within the target lesion using a stylet slow-pull<br />

or low negative suction technique. Subsequently, the endoscopists<br />

preserved the acquired tissues in ethanol and formalin to prepare<br />

cytological smears and pathological samples, respectively. Rapid<br />

onsite cytological evaluation was not available in our hospital setting,<br />

and the decision regarding the requisite number of FNA/FNB passes<br />

for each case was individually made by the endoscopists, considering<br />

the condition of the patient and the volume of tissue obtained<br />

(macroscopic onsite quality evaluation) [10].<br />

2.3. Statistical Analysis<br />

Continuous variables were presented as the mean ± standard<br />

deviation, and cate-gorical variables were expressed as frequencies<br />

and percentages. The baseline clinical characteristics of the two<br />

comparison groups were assessed using independent samples t-test,<br />

Chi-square test, and crosstabs statistics, depending on the data<br />

type. Student’s t-test for continuous variables was applied for the<br />

comparison between two groups, and Chi-square or Fisher’s exact<br />

test (when cell had an expected frequency less than 5) for categorical<br />

variables was applied for measures of association. Statistical analyses<br />

were performed using SPSS software (version 27.0; SPSS, Chicago,<br />

IL, USA), with a significance level set at a two-sided p-value of 0.05.<br />

GASTROENTEROLOGY TODAY – SUMMER <strong>2024</strong><br />

Patients were initially classified into two groups: those with benign<br />

and malignant tumors. If malignant tumors were suspected in the<br />

initial imaging, it was necessary to assess the possibility of a tumor<br />

resection based on evidence of large vessel invasion and regional<br />

lymph node metastasis [8]. The characteristics of patients who had<br />

resectable malignant pancreatic tumors were recorded, such as age,<br />

sex, and history of cancer. Details of EUS and FNB procedures were<br />

documented, including the FNB pass number and the success rate of<br />

cytopathological diagnoses. Tumor characteristics, including location<br />

and final histological diagnosis, were also recorded. We further<br />

analyzed patients with a history of cancer and those without, with a<br />

particular focus on comparing the rates of primary and metastatic<br />

tumors between these two subgroups of patients. Furthermore, this<br />

retrospective chart review received approval from the Institutional<br />

Review Board of Mackay Memorial Hospital, Taiwan. The Ethics<br />

Committee waived the requirement for informed consent, and the<br />

medical records of each patient were anonymized and de-identified<br />

before access.<br />

To estimate the required sample size for our study, G*Power 3.1<br />

software was utilized, employing Fisher’s exact test to compare two<br />

independent proportions. The underlying assumptions included a<br />

Type I error (α) set at 0.05 and a desired statistical power of 0.80. The<br />

proportions of interest, denoted as p1 and p2, were assumed to be<br />

0.65 and 0.95, respectively, with a ratio of the sample sizes between<br />

the two groups (N2:N1) maintained at 3:1. Based on these parameters,<br />

the calculated adequate sample size necessary to detect a statistically<br />

significant difference between the two proportions with the specified<br />

power and Type I error rate was determined to be 64 participants.<br />

3. Results<br />

A total of 180 patients with pathologically confirmed pancreatic<br />

tumors were retro-spectively reviewed. Among them, 112 patients<br />

were excluded from the analysis because they were diagnosed with<br />

either benign (n = 6) or unresectable (n = 106) tumors. A flow diagram<br />

of the participant selection is presented in Figure 1. The clinical<br />

characteristics of the patients are shown in Table 1. Patients diagnosed<br />



with resectable malignant pancreatic tumors and undergoing EUS- pheochromocytoma, and carcinoid tumors of the mediastinum. The<br />

FNB comprised 27 men and 41 women, with a mean age of 64.53 ± diagnosis of pancreatic metastatic tumors was confirmed by tissue<br />

13.5 years. Seventeen patients had a history of cancer, accounting proof via EUS-FNB/A and pathohistology, which included IHC staining.<br />

hts <strong>2024</strong>, 15, for FOR 25% PEER of all cases. REVIEW FNB tissue confirmation achieved a success The patient with solitary fibrous lung tumors was the oldest, 4 at 68 years<br />

rate of 88.4%, with an average of 3.01 passes. The most common old, while the patient with lung adenocarcinoma was the youngest,<br />

sites of tumor occurrence were the uncinate process and head (n =<br />

47, 69.1%), followed by the body and tail (n = 21, 30.8%). The most<br />

frequent histological types of pancreatic malignancies were pancreatic<br />

adenocarcinoma (n = 42, 61.8%), neuroendocrine tumors (n = 22,<br />

32.3%), and metastases (n = 4, 5.9%).<br />

with secondary cases, with a mean size of 3.2 ± 2.60 cm (p = 0.07).<br />

hts <strong>2024</strong>, 15 with an average of 3.01 passes. The most common sites of tumor occurrence were the<br />

The patients were divided into two groups: those with a history of In our study, the incidence of metastatic pancreatic tumors 378 tended to<br />

cancer (n = 17) and those without (n = 51), as shown in Table 2. Of the<br />

patients with a history of cancer, three had lung cancer, seven had<br />

breast cancer, one had esophageal cancer, and six had other types<br />

of cancer, such as hepatocellular carcinoma, endometrial carcinoma,<br />

at 58 years old. These cases presented without typical features,<br />

consistent with their respective primary origins and, in general, posed<br />

malignant pancreatic tumors and undergoing EUS-FNB comprised 27 men and 41<br />

women, with a mean age of 64.53 ± 13.5 years. Seventeen patients had a history of cancer,<br />

accounting for 25% of all cases. FNB tissue confirmation achieved a success rate of 88.4%,<br />

diagnostic challenges. There was no significant difference in the mean<br />

age (p = 0.27) or sex (p = 0.66) between the two groups. The mean<br />

size of primary pancreatic tumors was 2.25 ± 0.86 cm, compared<br />

uncinate process and head (n = 47, 69.1%), followed by the body and tail (n = 21, 30.8%).<br />

The most frequent histological types of pancreatic malignancies were pancreatic<br />

adenocarcinoma histological types(n of = pancreatic 42, 61.8%), malignancies neuroendocrine were tumors pancreatic (n = 22, adenocarcinoma 32.3%), and metastases (n = 42,<br />

(n adenocarcinoma or neuroendocrine tumors).<br />

61.8%), = 4, 5.9%). neuroendocrine tumors (n = 22, 32.3%), and metastases (n = 4, 5.9%).<br />

be higher in patients with a history of malignancy (23.5%) than in those<br />

with no cancer history (p < 0.001). Notably, all patients without a history<br />

of cancer were diagnosed with primary pancreatic cancer (either<br />

Figure 1. Flowchart of patients considered for inclusion in the study.<br />

Table 1. Patients with resectable malignant pancreatic tumors who underwent EUS-FNB (n = 68).<br />

Age (year) 64.53 ± 13.5<br />

Figure Male 1. Flowchart of patients considered for inclusion in the study. 27 (39.7%)<br />

Table<br />

History<br />

1. Patients<br />

of cancer<br />

with<br />

(n, %)<br />

resectable malignant pancreatic tumors who underwent<br />

17 (25%)<br />

EUS-FNB (n = 68).<br />

EUS-suspected malignancy 68<br />

Age (year) 64.53 ± 13.5<br />

Pass number (n) 3.01<br />

Male 27 (39.7%)<br />

Successful FNB tissue proof (n, %)<br />

History of cancer (n, %)<br />

61 (88.4%)<br />

17 (25%)<br />

EUS-suspected Location of tumormalignancy 68<br />

Pass -Uncinate number (n) process and head 47 (69.1%) 3.01<br />

Successful -Body and FNB tail tissue proof (n, %) 21 (30.8%) 61 (88.4%)<br />

Location Kinds of tumor of tumor (PDAC/NET/Metastasis) (n, %)<br />

-PDAC -Uncinate process and head 42 (61.8%) 47 (69.1%)<br />

-Body and tail 21 (30.8%)<br />

-NET 22 (32.3%)<br />

Kinds of tumor (PDAC/NET/Metastasis) (n, %)<br />

-Metastasis 4 (5.9%)<br />

-PDAC 42 (61.8%)<br />

EUS, endoscopic ultrasound; FNB, fine-needle biopsy; PDAC, pancreatic ductal adenocarcinoma; NET, neuroendocrine-NET<br />

tumor.<br />

22 (32.3%)<br />

-Metastasis 4 (5.9%)<br />

EUS, The endoscopic patients ultrasound; were divided FNB, into fine-needle two groups: biopsy; those PDAC, withpancreatic a historyductal of cancer adenocarcinoma;<br />

(n = 17) and<br />

NET, thoseneuroendocrine without (n = 51), tumor. as shown in Table 2. Of the patients with a history of cancer, three had<br />

lung cancer, seven had breast cancer, one had esophageal cancer, and six had other types<br />

GASTROENTEROLOGY TODAY – SUMMER <strong>2024</strong><br />


ghts <strong>2024</strong>, 15 379<br />


history (p

Figure 2. (A) The computed tomography scan revealing a well-defined resectable tumor in the<br />

Figure 2. (A) The computed tomography scan revealing well-defined resectable tumor in the<br />

Figure pancreatic 2. (A) body, The computed accompanied tomography by pancreatic scan revealing duct dilatation a well-defined (arrow). resectable (B) During tumor inthe pancreatic<br />

examination, body, accompanied the tumor exhibits by pancreatic a hypoechoic duct dilatation and heterogeneous (arrow). (B) During appearance. the EUSSubsequently, examination, the an<br />

EUS<br />

pancreatic body, accompanied by pancreatic duct dilatation (arrow). (B) During the EUS<br />

examination, the tumor exhibits hypoechoic and heterogeneous appearance. FEATURE Subsequently, an<br />

tumor FNB was<br />

FNB was<br />

exhibits performed,<br />

performed,<br />

a hypoechoic confirming<br />

confirming<br />

and heterogeneous it to be a metastatic<br />

it to be metastatic<br />

appearance. tumor<br />

tumor<br />

Subsequently, originating from<br />

originating from<br />

an FNB the<br />

the<br />

was previous<br />

previous<br />

performed, lung<br />

lung<br />

confirming adenocarcinoma<br />

adenocarcinoma it to be (arrow).<br />

(arrow). a metastatic tumor originating from the previous lung adenocarcinoma (arrow).<br />

Figure 3. (A) The positron Figure<br />

Figure emission 3. 3.<br />

(A)<br />

(A) (A) tomography The<br />

The The<br />

positron positron scan revealing emission emission a malignant tomography tomography tumor located scan<br />

scan scan at revealing the revealing pancreatic a malignant malignant ahead malignant (arrow). tumor<br />

tumor tumor<br />

located<br />

located located<br />

at the<br />

the at<br />

(B) Magnetic resonance pancreatic imaging discloses head an (arrow). ill-defined (B) mass Magnetic in the pancreatic resonance head region, imaging leading discloses to pancreatic an duct ill-defined mass in the<br />

the pancreatic head head (arrow). (B) (B) Magnetic resonance imaging disclosesan an ill-defined mass in the<br />

dilatation (arrow). (C) In pancreatic the EUS examination, head region, a hypoechoic leading tumor to pancreatic was identified, duct leading dilatation to pancreatic (arrow). duct dilatation. (C) In the A EUS examination, a<br />

pancreatic head region, leading to pancreatic duct dilatation (arrow). (C) In the EUS examination, a<br />

subsequent FNB confirmed hypoechoic it to be a pancreatic tumor was lesion identified, metastasized leading from lung adenocarcinoma to pancreatic (arrow). duct dilatation. A subsequent FNB<br />

hypoechoic tumor was identified, leading to pancreatic duct dilatation. subsequent FNB<br />

confirmed it tumor to be was a pancreatic identified, lesion leading metastasized to pancreatic from duct lung dilatation. adenocarcinoma A subsequent (arrow). FNB confirmed<br />

it<br />

confirmed<br />

to be a pancreatic<br />

it to be lesion<br />

pancreatic<br />

metastasized<br />

lesion metastasized<br />

from lung adenocarcinoma<br />

from lung adenocarcinoma<br />

(arrow).<br />

(arrow).<br />

nonhematologic neo-plasms that exhibited pancreatic metastasis,<br />

4. Discussion<br />

4.<br />

4. Discussion<br />

Discussion<br />

including renal cell carcinoma, melanoma, pulmonary small-cell<br />

Pancreatic lesions, primarily pancreatic Pancreatic Pancreatic ductal adenocarcinomas, lesions, carcinoma, breast carcinoma, and sporadic cases of prostate carci-<br />

90%<br />

lesions, primarily pancreatic ductal adenocarcinomas, constitute over 90%<br />

constitute over 90% of pancreatic<br />

of neoplasms, pancreatic and despite neoplasms, surgical and noma, despite colon adenocarcinoma, surgical interventions, pulmonary squamous the cell prognosis carcinoma, remains<br />

pancreatic neoplasms, and and despite despite surgical surgical interventions, interventions, the prognosis the prognosis remains remains challenging<br />

challenging [1,11,12]. The<br />

and gastrointestinal stromal tumors [16–18]. Notably, pancreatic<br />

interventions, the prognosis remains The incidence of pancreatic metastasis from cancers of other origins<br />

challenging [1,11,12]. [1,11,12]. The incidence incidence of pancreatic of pancreatic metastasis metastasis from from cancers cancers of other of other origins origins is<br />

incidence of pancreatic metastasis<br />

notably notably<br />

from cancers<br />

low,<br />

of other<br />

ranging<br />

origins<br />

from<br />

is metastases predominantly target the pancreatic head, followed by 3% to 12% [13]. rare, it is notably low, low, ranging ranging from from 3% 3% to to 12% 12% [13]. [13]. Although rare, rare, it it poses a significant challenge<br />

notably low, ranging from 3% to 12% [13]. Although rare, it poses pancreatic body and tail [17]. Contrary to a previous study that focused<br />

a significant challenge for clinics in terms of diagnosis, and even on renal cell carcinoma (RCC), our analysis suggested that lung cancer<br />

surgeons have expressed concerns, as they are reluctant to perform is more commonly linked to secondary pancreatic tumors (50%).<br />

unnecessary pancreatectomies and risk unexpected diagnoses. However, considering the limited number of patients and the inclusion<br />

of only resectable tumors in this study, it is important to acknowledge<br />

Initially, secondary pancreatic tumors are often asymptomatic. In the potential for bias.<br />

typical cases, an asymptomatic patient may exhibit evidence of<br />

prior surgical interventions, such as nephrec-tomy, lobectomy, or The presentation timeframe of pancreatic metastasis varies, with<br />

colon resection, during CT or abdominal US examinations. As the instances docu-mented to manifest long after the initial diagnosis and<br />

disease progresses, symptoms such as epigastric pain, jaundice, treatment of the primary tumor averaging more than 8 years, with a<br />

and weight loss may manifest, mirroring those observed in primary maximum duration of 17 years [19]. On average, in our study, the onset<br />

pancreatic tumors. CT and MRI are instru-mental in providing a<br />

of a second pancreatic cancer occurred approximately 42 months after<br />

general assessment of the disease and evaluating the surrounding the initial cancer diagnosis, with the longest duration extending up to<br />

lymphadenopathy, distal metastasis, and potential resection [14]. 120 months. The most common locations of secondary pancreatic<br />

EUS plays a crucial role in offering a final diagnosis through tissue tumors were the pancreatic head and body. These findings are<br />

proofing and aids in the selection of the most effective treatment for consistent with those of previous studies [17].<br />

the patient [15].<br />

In CT and MRI, some secondary pancreatic tumors may present<br />

Analysis of autopsies and surgical cases identified prevalent<br />

with characteristics of the original malignancy. RCC is the most<br />

GASTROENTEROLOGY TODAY – SUMMER <strong>2024</strong><br />



GASTROENTEROLOGY TODAY – SUMMER <strong>2024</strong><br />

common cancer to metastasize to the pan-creas [19]. It typically<br />

shows either intense homogeneous enhancement in small lesions<br />

or rim enhancement in large lesions. In contrast, the outer regions<br />

of colorectal metastases showed no difference from the normal<br />

pancreatic tissue, whereas the inner area showed hypo-enhancement<br />

due to central necrosis [20]. Additionally, a distinctive lesion may<br />

be present in the pancreas that lacks the classic double duct sign<br />

typically observed in primary pancreatic cancers. This is because,<br />

quite often (approximately one-third of the time), tumors are initially<br />

thought to be primary pancreatic tumors upon imaging stud-ies [12].<br />

Hence, if a patient has a history of cancer and is newly diagnosed<br />

with a pancreatic mass, the possibility of metastasis should be fully<br />

evaluated. It can either initiate the most effective treatment or decrease<br />

mortality and morbidity resulting from unnecessary surgery.<br />

In EUS, the morphology of metastatic pancreatic tumors varies. They<br />

are typically located at the head of the pancreas with regular borders,<br />

although they are occasionally irregular. Hypoechogenic tumors are<br />

predominant; however, hyperechoic metastases from bladder cancer<br />

and anechoic metastases from melanoma have also been observed.<br />

Mixed characteristics of metastatic pancreatic tumors are common,<br />

such as renal cell carcinoma, in which echogenicity can vary. Similarly,<br />

the consistency of metastatic pancreatic tumors may vary from solid<br />

to cystic or heterogeneous [20,21]. In our study, the four metastatic<br />

pancreatic tumors exhibited a hypoechoic heterogeneous pattern on<br />

EUS images, similar to the primary tumors. Consequently, relying solely<br />

on imaging for an accurate diagnosis in these cases is challenging.<br />

Emphasizing the importance of a thorough history taking, particularly<br />

regarding cancer, before performing EUS is crucial. It is highly likely<br />

that the history of cancer was the sole piece of information hinting the<br />

possibility of metastasis to the endoscopist.<br />

A contrast-enhanced ultrasound (CE-EUS) was not employed in this<br />

study because at our hospital, patients must pay for it out of pocket,<br />

and not every patient agreed to its use. Although CE-EUS has been<br />

recognized as useful for diagnosing primary pancreatic tumors, its<br />

efficacy in detecting metastasis remains a subject of debate. A recent<br />

study suggested its potential usefulness in the diagnosis of pancreatic<br />

metastases [22]. RCC metastasis typically exhibits a hyperenhanced<br />

pattern, which distinguishes it from primary adenocarcinoma, which<br />

typically displays a hypoenhanced pattern. However, it can still be<br />

challenging to differentiate it from a neuroendocrine tumor, which<br />

also presents with a hyperenhanced pattern. In contrast, metastases<br />

from other origins, such as the stomach, colon, and ovaries, exhibit<br />

a hypoenhanced pattern [23]. Therefore, the use of contrast to<br />

distinguish between primary and metastatic pancreatic tumors has no<br />

value. Tissue acquisition remains the gold standard for diagnosis.<br />

In accordance with the current guidelines, including the ESMO and<br />

NCCN, if a patient presents with a suspected malignant pancreatic<br />

tumor, lacks a history of cancer, and imaging studies suggest a<br />

resectable tumor. Non-diagnostic biopsy should not delay surgical<br />

resection when the clinical suspicion for pancreatic cancer is high<br />

[24,25]. However, when a patient has a history of cancer, it becomes<br />

crucial to consider the possibility of metastatic pancreatic cancer<br />

originating from various organs. While rare, pancreatic metastases<br />

pose a considerable clinical challenge due to their potential to influence<br />

treatment decisions and affect patient outcomes. In such cases, a<br />

biopsy is necessary to differentiate between a primary and metastatic<br />

lesion before initiating treatment. EUS with an FNA/FNB is preferred<br />

for this purpose due to its superior diagnostic yield, safety profile, and<br />

potential to mitigate the risk of peritoneal seeding compared to the CTguided<br />

approach [26–28].<br />

In addition to tumor morphology, cytological and immunohistochemical<br />

staining (IHC) were performed to confirm the final diagnosis. In this<br />

comprehensive single-center study, EUS-guided tissue sampling<br />

proved to be valuable and had a significant clinical impact [21]. EUS-<br />

FNA was developed to acquire tissues using negative pressure for<br />

cytological analyses. Cytological samples acquired using EUS-FNA<br />

exhibit a relatively high diagnostic accuracy. Nonetheless, reliance<br />

solely on cytological evaluation is insufficient to diagnose metastatic<br />

pancreatic cancer. Recently, the introduction of FNB needles has<br />

been aimed at enhancing the quality of tissue sampling, and they<br />

are generally considered more effective in obtaining tissue cores,<br />

compared with traditional FNA needles [7,29]. Tissue cores obtained<br />

through an FNB allow for the preservation of architectural features and<br />

facilitate the implementation of an IHC, which is a critical component in<br />

the diagnosis of secondary pancreatic tumors. Moreover, an FNB is a<br />

safe procedure for obtaining tissue samples even from older patients<br />

who often have comorbidities and are undergoing anticoagulation<br />

therapy [30]. Therefore, an FNB is the primary choice for pancreatic<br />

tumor tissue sampling. A surgical biopsy is considered an alternative<br />

method if an FNB is unsuccessful.<br />

Notably, in this study, all the patients with no history of cancer<br />

had primary pancreatic malignancies. Therefore, in daily practice,<br />

when endoscopists encounter a pancreatic tumor during an EUS<br />

that appears malignant (Figure 4), they should initially differentiate<br />

between resectable and unresectable tumors. If the tumor is<br />

deemed an unresectable malignancy, a subsequent FNB should be<br />

performed for tissue sampling. Conversely, if the tumor is resectable,<br />

a subsequent FNB should only be performed in patients with a<br />

history of cancer. An FNB may not provide additional information or<br />

influence the subsequent surgical plan in patients without a history of<br />

cancer. Therefore, an FNB should be avoided in these patients and<br />

surgical resection should be performed without pre-operative tissue<br />

confirmation. This approach ensures a more efficient and tailored<br />

diagnostic process based on individual patient profiles.<br />

Pancreatic surgery is a possible curative management strategy not<br />

only for primary pancreatic tumors, but also metastatic tumors.<br />

However, the incidence of major complications is more than 40%.<br />

These complications may arise from inherent risks associated with<br />

pancreatectomy or preexisting comorbidities. Due to the associated<br />

risks of morbidity and mortality in pancreatic surgery, it is advisable to<br />

perform pancreatic resection when clinically necessary. Notably, when<br />

dealing with a pancreatic mass, it is crucial to consider its potential as<br />

a metastatic lesion, among other diagnostic possibilities. Hence, the<br />

clinical background and pathological confirmation are necessary prior<br />

to tumor resection. They can not only detect the involvement of major<br />

vessels, such as the celiac artery, splenic artery, splenic vein, and<br />

superior mesenteric artery, but can also provide tissue confirmation for<br />

a definitive diagnosis [31,32].<br />

The advantage of a surgical resection in terms of the overall survival<br />



troenterol.<br />

troenterol.<br />

Insights<br />

Insights<br />

<strong>2024</strong>,<br />

<strong>2024</strong>,<br />

15,<br />

15<br />


383<br />

has not yet been demonstrated, and the introduction of tyrosine<br />

kinase inhibitors (TKIs) has changed the outcomes of patients with<br />

unresectable metastatic disease. The median overall survival from<br />

a pancreatic metastatic RCC diagnosis was more than 7 years for<br />

both resected and unresected patients. Specifically, in patients who<br />

underwent pancreatic surgery for pancreatic metastasis–RCCs, the<br />

median overall survival was 103 months, with 43% still alive and 42%<br />

of the resected patients without disease recurrence. For patients with<br />

an unresected pancreatic metastatic RCC, the median overall survival<br />

was 86 months, with 75% still alive at the time of analysis. However,<br />

the difference in the overall survival between resected and unresected<br />

patients was not significant (p = 0.201) [33]. Based on the results of<br />

this study, the efficacy of surgery for pancreatic metastases remains<br />

a topic of debate and surgery should not be the primary option, with<br />

systemic treatment being the preferred choice. Therefore, an accurate<br />

diagnosis through EUS tissue sampling is crucial.<br />

In this study, we aimed to assist endoscopists in making decisions<br />

during EUS examinations, including whether to perform an FNB<br />

when a resectable pancreatic malignancy is encountered. As a result,<br />

our focus was solely on patients who underwent EUS with an FNB,<br />

and we did not include those who did not undergo a pre-operative<br />

FNB. Therefore, separate and more extensive studies are needed to<br />

evaluate resectable tumors across the entire patient population. Other<br />

limitations of this study are its retrospective study design and relatively<br />

small number of patients.<br />

5. Conclusions<br />

Imaging tests such as CT and EUS assess malignancy and tumor<br />

resectability based on vascular involvement but cannot distinguish<br />

between primary and metastatic tumors. EUS with an FNA/B is<br />

crucial as it provides a definitive histological diagnosis for patients,<br />

especially those with a prior history of cancer, helping differentiate<br />

between metastatic and primary pancreatic tumors. This strategy not<br />

only aids in avoiding unnecessary surgeries, but also facilitates the<br />

prompt initiation of appropriate treatments, thereby optimizing patient<br />

outcomes through a timely intervention.<br />

Figure 4. The decision making process of EUS management in pancreatic tumors.<br />

Pancreatic surgery is is a possible curative management strategy not only for primary<br />

pancreatic tumors, but but also also metastatic metastatic Author<br />

tumors.<br />

Contributions: tumors. However, However, Conceptualization,<br />

the incidence the M.-S.C. incidence and<br />

of major<br />

J.-H.L.; of formal<br />

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writing— risks<br />

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associated with pancreatectomy with pancreatectomy or preexisting or preexisting comorbidities. review and editing, C.-C.L.<br />

comorbidities. Due to and the J.-H.L.; associated supervision,<br />

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associated ofAll morbidity<br />

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are necessary<br />

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Institutional Review Board Statement: Ethical review and approval to<br />

can not only detect the involvement of major vessels, such as the celiac artery, splenic artery,<br />

tumor resection. They can not only were detect waived the for involvement this study due to the of utilization major vessels, of anonymous such clinical as the<br />

splenic vein, and superior mesenteric<br />

celiac artery, splenic artery, splenic data<br />

artery,<br />

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but<br />

and presentation.<br />

can also provide tissue confirmation for a<br />

superior mesenteric artery, but can also<br />

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provide tissue confirmation for a definitive diagnosis [31,32].<br />

The advantage of a surgical resection Informed inConsent termsStatement: of the overall Patient consent survival was has waived not due yet to been the<br />

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demonstrated, and the introductionutilization of tyrosine of anonymous kinase clinical inhibitors data for image (TKIs) presentation. has changed the<br />

demonstrated, and the introduction of tyrosine kinase inhibitors (TKIs) has changed the<br />

outcomes of patients with unresectable metastatic disease. The median overall survival<br />

outcomes of patients with unresectable metastatic disease. The median overall survival<br />

from a pancreatic metastatic RCCData diagnosis<br />

Availability<br />

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more<br />

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from a pancreatic metastatic RCC diagnosis was more than 7 years for both resected and<br />

and unresected patients. Specifically, in patients who underwent pancreatic surgery for<br />

unresected patients. Specifically, in Conflicts patients of Interest: who The underwent authors declare pancreatic no conflicts of surgery interest. for<br />

pancreatic metastasis–RCCs, the median overall survival was 103 months, with 43% still<br />

pancreatic metastasis–RCCs, the median The funders overall had no survival role in the design was 103 of the months, study; in the with collection, 43% still<br />

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pancreatic<br />

at the time<br />

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of analysis.<br />

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patients<br />

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References was not significant (p =0.201) [33]. Based on the<br />

between<br />

results of<br />

resected<br />

this study,<br />

and<br />

the<br />

unresected<br />

efficacy<br />

patients<br />

of surgery<br />

was<br />

for<br />

not<br />

pancreatic<br />

significant<br />

metastases<br />

(p = 0.201)<br />

remains<br />

[33]. Based<br />

a topic<br />

on the<br />

of<br />

results debate of and this surgery study, should the efficacy not beof the 1. surgery primary Siegel, for R.L.; option, pancreatic Miller, K.D.; with Fuchs, metastases systemic H.E.; Jemal, treatment remains A. Cancer Statistics, a being topic the of<br />

debate and surgery should not be the primary 2021. CA Cancer option, J. Clin. with 2021, systemic 71, 7–33.<br />

preferred choice. Therefore, an accurate diagnosis through EUS tissuetreatment [CrossRef]<br />

samplingbeing is crucial. the<br />

2. Grossberg, A.J.; Chu, L.C.; Deig, C.R.; Fishman, E.K.; Hwang,<br />

preferred In this choice. study, Therefore, we aimedan to accurate assist W.L.; diagnosis Maitra, A.; through inMarks, making D.L.; EUS Mehta, decisions tissue A.; Nabavizadeh, sampling during EUS N.; is crucial. examinations,<br />

In this including study, whether we aimed to perform to assist Simeone,<br />

anendoscopists D.M.; et al.<br />

FNB when a resectable in Multidisciplinary making pancreatic decisions standards of care<br />

malignancy during and recent EUS is<br />

progress in pancreatic ductal adenocarcinoma. CA Cancer J. Clin.<br />

examinations, encountered. As including a result, whether our focusto was perform<br />

2020, solely 70, 375–403. on an patients FNB<br />

[CrossRef]<br />

when who underwent a resectable EUS pancreatic with malignancy FNB, and weis did encountered. not includeAs those a result, 3.<br />

whoZ’graggen, our didfocus notK.; undergo was Fernández-del solely a pre-operative<br />

Castillo, on patients C.; Rattner, who FNB.<br />

D.W.; underwent Therefore,<br />

Sigala,<br />

H.; Warshaw, A.L. Metastases to the Pancreas and Their Surgical<br />

EUS separate with and FNB, more extensive and we did studies not include are needed those towho evaluate did not resectable undergo tumors a pre-operative<br />

Extirpation. Arch. Surg. 1998, 133, 413–418. [CrossRef] across [PubMed] the<br />

FNB. entireTherefore, patient population. separate and Other more limitations 4. extensive Lai, J.-H.; of this Lee, studies study K.-H.; are Chang, areneeded its C.-W.; retrospective Chen, to evaluate M.-J.; Lin, study C.-C. resectable design<br />

Predicting Factors for Pancreatic Malignancy with Computed<br />

tumors and relatively across small the entire number patient of patients. population. Other limitations of this study are its<br />

Tomography and Endoscopic Ultrasonography in Chronic<br />

retrospective study design and relatively Pancreatitis. small number Diagnostics of 2022, patients. 12, 1004. [CrossRef] [PubMed]<br />

5. Conclusions<br />

5. Srisajjakul, S.; Prapaisilp, P.; Bangchokdee, S. CT and MR features<br />

that can help to differentiate between focal chronic pancreatitis<br />

5. Conclusions Imaging tests such as CT and EUSand assess pancreatic malignancy cancer. Radiol. and Med. tumor 2020, 125, resectability 356–364. based<br />

on vascular Imaging involvement tests such as but CT cannot and EUS distinguish<br />

[CrossRef] [PubMed]<br />

assess malignancy between primary and tumor andresectability metastatic tumors. based<br />

on EUS vascular with aninvolvement FNA/B is crucial but cannot as it provides distinguish a definitive between histological primary and diagnosis metastatic for patients, tumors.<br />

EUS especially with an those FNA/B withis acrucial prior history as it provides of cancer, a definitive helping differentiate histological between diagnosis metastatic for patients, and<br />

especially primary pancreatic those with tumors. a prior This history strategy of cancer, not only helping aids indifferentiate avoiding unnecessary between metastatic surgeries,<br />

GASTROENTEROLOGY TODAY – SUMMER <strong>2024</strong><br />



GASTROENTEROLOGY TODAY – SUMMER <strong>2024</strong><br />

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M.N.; Neukamm, M.; Kleeff, J.; Hallscheidt, P. Metastasis to<br />

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A.H.; et al. Endoscopic ultrasound- guided fine needle aspiration<br />

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resulting from any ideas, methods, instructions or products referred to<br />

in the content.<br />


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GASTROENTEROLOGY TODAY – SUMMER <strong>2024</strong><br />









Toshiki Futakuchi 1 , Akira Dobashi 1* , Hideka Horiuchi 1 , Hiroto Furuhashi 1 , Hiroaki Matsui 1 , Yuko Hara 1 ,<br />

Masakuni Kobayashi 1 , Shingo Ono 1 , Naoto Tamai 1 , Kazutaka Gomisawa 2 , Takashi Yamauchi 3 , Machi Suka 3<br />

and Kazuki Sumiyama 1<br />

Futakuchi et al. BMC <strong>Gastroenterology</strong> (2023) 23:389 https://doi.org/10.1186/s12876-023-03030-9<br />


Abstract<br />

Background Texture and color enhancement imaging (TXI) enhances<br />

the changes in endoscopic features caused by gastric neoplasms,<br />

such as redness/whiteness and elevation/depression. This study<br />

aimed to demonstrate the effectiveness of TXI in improving the visibility<br />

of gastric neoplasms compared with white light imaging (WLI) using<br />

conventional (CE) and newly developed endoscopes (NE).<br />

scores of NE were superior to those of CE in all modalities. In the<br />

secondary outcome, there was no factor affected the differences of<br />

visibility scale scores between TXI-1/TXI-2 and WLI.<br />

Conclusions This study demonstrated that TXI-1 and TXI-2 enhanced<br />

the visibility scale scores of gastric neoplasms compared with that<br />

of WLI. Moreover, newly developed endoscope has the potential to<br />

improve visibility compared to conventional endoscope.<br />

Trial Registration This study was registered with the University<br />

Hospital Medical Information Network (UMIN000042429, 16/11/2020).<br />

GASTROENTEROLOGY TODAY – SUMMER <strong>2024</strong><br />

Methods We recruited patients who were histologically diagnosed with<br />

gastric neoplasms; endoscopy was performed, and gastric neoplasms<br />

photographed using three imaging modalities, including WLI, TXI mode<br />

1 (TXI-1) and TXI mode 2 (TXI-2). Two different endoscopes (CE and<br />

NE) were used for the same patients. Six endoscopists provided the<br />

visibility scale scores ranging from 1 (poor) to 4 (excellent) for gastric<br />

neoplasms. The primary outcome was the visibility scale scores based<br />

on each modality and endoscope. The secondary outcome was the<br />

identification of factors including H. pylori infection, atrophy, location,<br />

size, morphology, histological diagnosis and intestinal metaplasia that<br />

affect the differences in visibility scale scores between TXI-1/TXI-2<br />

and WLI.<br />

Results Fifty-two gastric neoplasms were analyzed. The mean visibility<br />

scale scores with the NE were 2.79 ± 1.07, 3.23 ± 0.96 and 3.14 ± 0.92<br />

for WLI, TXI-1 and TXI-2, respectively. The mean visibility scales with<br />

the CE were 2.53 ± 1.10, 3.04 ± 1.05 and 2.96 ± 1.92 for WLI, TXI-1<br />

and TXI-2, respectively. For both endoscopes, significant differences<br />

were observed in visibility scale scores between WLI and TXI-1 (p<br />

< 0.001) and between WLI and TXI-2 (p < 0.001). The visibility scale<br />

*Correspondence:<br />

Akira Dobashi<br />

akira.dobashi1980@gmail.com<br />

Full list of author information is available at the end of the article<br />

Keywords Gastric neoplasms, Image enhanced endoscopy, Texture<br />

and color enhancement imaging<br />

Background<br />

Gastric cancer was the fifth most common cancer and the third<br />

most common cause of cancer-related deaths worldwide in 2020 [1].<br />

Surgery is the mainstay of gastric cancer treatment; however, with early<br />

detection, endoscopic treatment can be expected to provide a radical<br />

cure through minimally invasive treatment. Endoscopic screening<br />

for gastric cancer has allowed for a 30% reduction in gastric cancer<br />

mortality [2–4]. Macroscopic types of early gastric cancer (EGC) show<br />

elevation or depression, whereas the tumor color changes exhibit<br />

redness or whiteness. However, early detection of gastric cancer can<br />

be difficult, because changes in morphology and color are subtle,<br />

and endoscopists may encounter difficulty in recognizing a lesion.<br />

Moreover, EGC is highly associated with Helicobacter pylori (H. pylori)<br />

infection, and map-like redness and mucosal changes caused by<br />

H. pylori eradication make EGC detection difficult. Most diffuse type<br />



gastric cancers comprise an endoscopically depressed type [5];<br />

therefore, considering these characteristics of EGC, it is important that<br />

slight changes in color and structure are detected during endoscopy.<br />

Image-enhanced endoscopy (IEE), including narrow band imaging<br />

(NBI), blue laser imaging (BLI) and linked color imaging (LCI), was<br />

developed to improve the visibility of EGC and is currently clinically<br />

available; LCI enhances red and white hues during endoscopy and has<br />

been reported to improve gastric cancer detection and visibility [6–13].<br />

As for the other IEEs, Yoshida et al. compared between secondgeneration<br />

NBI and white light imaging (WLI) in EGC detection and<br />

found no significant differences in the characteristics of the detected<br />

lesions [14]. Nagashima reported that low magnifying NBI was able to<br />

detect gastric neoplasm overlooked by WLI [15]. Dohi et al. reported<br />

that BLI-bright had a higher real-time detection rate for EGC than<br />

WLI [16].<br />

Texture and color enhancement imaging (TXI) is a new IEE technology<br />

that has been available in clinical practice since 2020. TXI can enhance<br />

brightness, color contrast and texture changes during endoscopic<br />

observation, and has been reported to improve the visibility and color<br />

difference of gastric cancer compared with WLI [17–22]. Since the<br />

previous studies on TXI were conducted on a small number of cases or<br />

had retrospective study design, we attempted to prove the significance<br />

of TXI by a prospective case collection with sample size calculation.<br />

This study aimed to demonstrate that TXI—which was prospectively<br />

corrected—improved the visibility of EGC compared with WLI<br />

using conventional and newly developed endoscopes. Additionally,<br />

we analyzed the effect of TXI on lesion characteristics and the<br />

improvement in visibility for EGC.<br />

Methods<br />

Charge Coupled Device (CCD), while the NE uses a high-sensitivity<br />

Complementary Metal-Oxide-Semiconductor (CMOS) which is<br />

expected to improve image quality. The EVIS X1 system can promptly<br />

change the image modalities (WLI, TXI, and NBI) via a button on the<br />

scope holder.<br />

Texture and color enhancement imaging<br />

TXI is a newly developed IEE that enhances the texture, brightness<br />

and color of endoscopic images obtained using WLI. First, the RGB<br />

input image is classified into a base and a detail layer. Second, the<br />

base layer is adjusted for brightness, followed by dynamic range<br />

compression (tone mapping). Subsequently, texture enhancement<br />

is applied to the detail layer to enhance subtle contrast. TXI mode 2<br />

(TXI-2) is displayed by stacking the two layers, while the processing<br />

designed to expand the difference between red and white hues yields<br />

TXI mode 1 (TXI-1). TXI-1 is more tonally enhanced, while TXI-2 is more<br />

similar to WLI [23]; TXI is thought to enhance subtle morphological<br />

or color changes on the gastrointestinal surface caused by gastric<br />

neoplasms.<br />

Endoscopic procedure<br />

All endoscopic examinations were performed under sedation with<br />

intravenous midazolam (2–5 mg; Maruishi Pharmaceutical Co, Ltd.,<br />

Osaka, Japan) or midazolam and pethidine hydrochloride (35 mg,<br />

pethidine; Takeda Pharmaceutical Company, Tokyo, Japan). Prior<br />

to treatment, an expert endoscopist performed an endoscopic<br />

examination, and the unmagnified endoscopic images of the lesion<br />

were stored in a middle-distant view with CE or NE using the three<br />

modalities (WLI, TXI-1 and TXI-2). On the day of treatment, images of<br />

the same lesion were stored in the same view as those in the other<br />

endoscope using the three modalities (Fig. 1). In total, we obtained six<br />

endoscopic images of each lesion using the three modalities and two<br />

endoscopes.<br />

Patients and study design<br />

This was a single-center, prospective trial. We prospectively enrolled<br />

patients who were diagnosed with gastric neoplasms (including<br />

adenoma and adenocarcinoma) through endoscopic and histological<br />

diagnosis, and who were referred to our hospital for treatment. Patients<br />

were enrolled as consecutive cases in this study to eliminate selection<br />

bias. Written informed consent was obtained from all patients.<br />

The recruitment period was between August 2021 and July 2022.<br />

The exclusion criteria were as follows: age < 20 years, pregnancy,<br />

large lesions (> 8 cm) that did not fit in one endoscopic field of view,<br />

and being evaluated as inappropriate by the attending doctor for this<br />

study considering general condition. This study was approved by the<br />

Institutional Review Board of the Jikei University School of Medicine<br />

on 14 September 2020 (32–156(10,237)) and is registered with the<br />

University Hospital Medical Information Network (UMIN000042429,<br />

16/11/2020).<br />

Endoscopic system and setting<br />

We used the EVIS X1 (Olympus Corporation, Tokyo, Japan)<br />

endoscopic system and high-definition endoscopes, which include<br />

a conventional endoscope (CE) (GIF-H290Z; Olympus Corporation,<br />

Tokyo, Japan) and a newly developed endoscope (NE) (GIF-XZ1200;<br />

Olympus Corporation). Regarding the image sensor, the CE uses a<br />

Evaluation of endoscopic images<br />

We created an image catalogue where each gastric neoplasm had<br />

six different images. The images were randomly arranged based<br />

on a randomized table created using Excel software (Microsoft<br />

Corporation, Redmond, Washington, USA). Six endoscopists provided<br />

the visibility scales [9, 24]. All reviewers were instructed how to<br />

apply and interpret the visibility scales by an organizer (A.D.), who<br />

was not an image reviewer in this study. Visibility scale was scored<br />

based on previous reports as follows: 1, poor (not detectable without<br />

repeated careful examination); 2, fair (hardly detectable without<br />

careful examination); 3, good (detectable with careful observation);<br />

and 4, excellent (easily detectable) [10, 25]. The reviewers comprised<br />

three expert endoscopists who were certified by the board of the<br />

Japan Gastroenterological Endoscopy Society and had experience<br />

with > 100 cases of endoscopic submucosal dissection for early<br />

gastric cancer and three novices who had experience with < 100<br />

esophagogastroduodenoscopies.<br />

Outcomes<br />

The primary outcome was the visibility scale score based on each<br />

modality and endoscope. The secondary outcome was the effect of<br />

lesion characteristics on the improvement of the visibility scale score<br />

for EGC. The status of H. pylori infection was defined as follows:<br />

positive (positive rapid urease test, anti-H. pylori antibody assay, or<br />

GASTROENTEROLOGY TODAY – SUMMER <strong>2024</strong><br />



fecal H. pylori antigen assay, before eradication), eradicated (negative<br />

urease breath test or anti‐H. pylori antibody assay, post eradication),<br />

and negative (negative rapid urease test, anti‐H. pylori antibody assay,<br />

or fecal H. pylori antigen assay, without eradication) [26]. Atrophy<br />

was graded as open type, closed type, or negative according to the<br />

Kimura–Takemoto Classification [27]. The location of the neoplasm was<br />

defined as U (upper third), M (middle third) and L (lower third) according<br />

to the Japanese Classification of Gastric Carcinoma [28]. Morphology<br />

was classified according to the Paris classification [29], and histological<br />

diagnosis was based on Lauren’s classification [30]. A pathologist who<br />

did not know the result of visibility scale scores evaluated the degree<br />

Futakuchi et al. BMC <strong>Gastroenterology</strong> (2023) 23:389<br />

of intestinal metaplasia classified as complete, incomplete, or negative<br />

according to the previous report [31].<br />

Sample size calculation<br />

The mean visibility scale scores for EGC were reported to be 2.54 ±<br />

1.10 (mean ± standard deviation) and 3.28 ± 0.97 for WLI and LCI,<br />

respectively [9]. TXI was expected to improve the visibility of gastric<br />

neoplasms to the same extent as that of LCI; therefore, we calculated<br />

the sample size with an α value of 0.05 and a power of 0.90 using<br />

a two-sided test. The required number of lesions was 42. Finally,<br />

considering dropout or exclusion, we set the number of cases to 50.<br />

Statistical analysis<br />

All statistical analyses were performed using STATA (version 14.0;<br />

Stata Corp., College Station, Texas, United States). Quantitative<br />

parameters were compared using Student’s t test or the Mann- Page 4 of 9<br />

Whitney U test. The normal distribution was analyzed using Shapiro-<br />

Wilk test. For the secondary outcome, a two-way ANOVA was<br />

GASTROENTEROLOGY TODAY – SUMMER <strong>2024</strong><br />

Fig. 1 Example of early gastric cancer detected during this study. A depressed-type early gastric cancer in the lesser curvature lower body is detected<br />

using the newly developed endoscope (GIF-XZ1200, Olympus). The diagnosis of lesion margins followed the pathology finding. a. Arrows indicate lesion<br />

margins of gastric cancer in monochrome image. b. The lesion is difficult to detect in white light imaging. c. Texture and color enhancement imaging (TXI)<br />

mode 1 enhances the color and texture, and the whole image turns pinkish compared to WLI in this image. The visibility of gastric cancer is improved. d.<br />

TXI mode 2 enhances the texture, and the color tone is similar to that of WLI. The depression in the gastric cancer is enhanced<br />

26<br />

Bonferroni adjustment was used when testing for repetition<br />

in ANOVA.<br />

were male. H. pylori infection was positive, eradicated<br />

and negative in 16, 24 and 12 lesions, respectively. Atrophy<br />

was open type, closed type and negative in 42, 7 and 3

Futakuchi et et al. al. BMC <strong>Gastroenterology</strong> (2023) (2023) 23:389 23:389<br />

Page 5 Page of 9 5 of 9<br />


Fig. 2 Flow chart of this study participants<br />

Fig. 2 Flow chart of this study participants<br />

Table 1 Demographics of the patients and characteristics of the modalities (WLI, p = 0.002; TXI-1, p = 0.025; and TXI-2,<br />

lesions<br />

Table 1 Demographics of the patients and characteristics of the p = modalities excluded 0.004). after (WLI, the first p endoscopic = 0.002; TXI-1, examination p = 0.025; because and the gastric TXI-2,<br />

Patients<br />

lesions<br />

Among<br />

p cancer = 0.004). was experts, diagnosed visibility as advanced scale scores cancer. were Finally, 3.04 49 patients ± 1.00, met<br />

(n = 49)<br />

Patients<br />

3.34 the ± 0.90 and 3.27 ± 0.90 with the NE, and 2.89 ± 1.02,<br />

Sex Male/Female 37/12<br />

Among inclusion experts, criteria, and visibility we obtained scale 312 scores endoscopic were images 3.04 ± (6 1.00,<br />

(n = 49)<br />

3.15 ± 1.00 and 3.04 ± 1.02 with the CE for WLI, TXI-1<br />

Age, years<br />

70.8 (33–86) 3.34 images ± 0.90 per lesion) and from 3.2752 ± 0.90 lesions with (Fig. the 2). NE, and 2.89 ± 1.02,<br />

Sex Male/Female 37/12 and TXI-2, respectively. Significant differences were<br />

(range)<br />

3.15 ± 1.00 and 3.04 ± 1.02 with the CE for WLI, TXI-1<br />

observed in the visibility scale scores between WLI and<br />

Lesions<br />

Age, years<br />

(n = 52)<br />

70.8 (33–86)<br />

and Demographics TXI-2, of respectively. the patients and Significant characteristics differences of the lesions were are<br />

(range)<br />

TXI-1 (p = 0.008 for NE, 0.020 for CE); however, not<br />

H. Pylori Positive/Eradicated/Negative 16/24/12 observed summarized in the Table visibility 1. The median scale age scores of the patients between was WLI 72.5 and<br />

infection Lesions (n = 52)<br />

between WLI and TXI-2 (p = 0.056 for NE, 0.175 for CE).<br />

Among<br />

TXI-1<br />

(range: 33–86)<br />

novices,<br />

(p = 0.008<br />

years,<br />

visibility<br />

for<br />

and 75.5%<br />

NE,<br />

scale<br />

0.020<br />

(37/49) were<br />

scores<br />

for<br />

male.<br />

were<br />

CE);<br />

H.<br />

2.54<br />

however,<br />

pylori infection<br />

± 1.07,<br />

not<br />

Atrophy H. Pylori Open Positive/Eradicated/Negative type/Closed type/Negative 42/7/3 16/24/12<br />

was positive, eradicated and negative in 16, 24 and 12 lesions,<br />

Location<br />

infection<br />

3.12<br />

between<br />

± 1.01 and<br />

WLI<br />

3.01<br />

and<br />

± 0.92<br />

TXI-2<br />

with<br />

(p =<br />

the<br />

0.056<br />

NE,<br />

for<br />

and<br />

NE,<br />

2.16<br />

0.175<br />

± 1.06,<br />

for CE).<br />

U/L/M 6/15/31<br />

respectively. Atrophy was open type, closed type and negative in 42,<br />

Size(mm) Atrophy ≥ Open 10, < 10 type/Closed type/Negative 32/20 42/7/3 2.92 ± Among 1.09 and novices, 2.71 ± 1.11 visibility with scale the CE scores for WLI, were TXI-1 2.54 ± 1.07,<br />

7 and 3 lesions, respectively; however, all lesions without atrophy<br />

Morphology Location 0-I/0-IIa/0-IIb/0-IIc/0-III U/L/M 3/13/0/36/0 6/15/31 and 3.12 TXI-2, ± 1.01 respectively. and 3.01 ± For 0.92 both with types the NE, of endoscopes, and 2.16 ± 1.06,<br />

were negative for H. pylori infection. Regarding location, 6, 15 and<br />

Histological Size(mm) Diffuse ≥ 10, < type/Intestinal 10 type/Adenoma 7/43/2 32/20 significant 2.92 ± 1.09 differences and 2.71 were ± 1.11 observed with the in CE visibility for WLI, scale TXI-1<br />

31 lesions were in U, M and L, respectively. The median (range) size<br />

diagnosis Morphology 0-I/0-IIa/0-IIb/0-IIc/0-III 3/13/0/36/0 scores and between TXI-2, respectively. WLI and TXI-1 For (p both < 0.001 types for both of endoscopes, endoscopes),<br />

significant and between differences WLI were and TXI-2 observed (p < 0.001 in visibility for both scale<br />

of the lesions was 12.5 (1–75) mm, including 32 lesions ≥ 10 mm and<br />

Intestinal Histological Complete/Incomplete/Negative Diffuse type/Intestinal type/Adenoma 20/28/4 7/43/2<br />

20 lesions < 10 mm. The morphology was 0-I, 0-IIa and 0-IIc in 3,<br />

metaplasia diagnosis<br />

endoscopes). scores between WLI and TXI-1 (p < 0.001 for both endoscopes),<br />

the secondary and between outcome, WLI no and factors TXI-2 were (p < 0.001 found for to both<br />

U, upper third; M, middle third; L, lower third; H. pylori, Helicobacter pylori<br />

13 and 36 lesions, respectively. Histological diagnoses were diffuse<br />

Intestinal Complete/Incomplete/Negative 20/28/4 In<br />

type, intestinal type and adenoma in 7, 43 and 2 lesions, respectively.<br />

metaplasia<br />

significantly endoscopes). affect the improvement in visibility of gastric<br />

U, upper third; M, middle third; L, lower third; H. pylori, Helicobacter pylori<br />

Intestinal metaplasia were complete, incomplete and negative in 20, 28<br />

The mean visibility scale scores based on the endoscopes<br />

and modalities are shown in Fig. 3. The mean visi-<br />

and significantly WLI (Table affect 2). the improvement in visibility of gastric<br />

neoplasms In the between secondary TXI-1 outcome, and WLI, no and factors between were TXI-2 found to<br />

and 4 lesions, respectively.<br />

performed bility The scale mean because scores visibility the with visibility the scale NE scale were scores 2.79 was based ± 1.07, evaluated on 3.23 the repeatedly ± 0.96 endoscopes<br />

the 3.14 same and ± 0.92 reviewer. modalities for We WLI, used are TXI-1 the shown visibility and in TXI-2, scale Fig. 3. score The respectively. differences mean visi-<br />

Discussion and<br />

neoplasms between TXI-1 and WLI, and between TXI-2<br />

The mean visibility scale scores based on the endoscopes and<br />

by and<br />

modalities<br />

WLI<br />

are<br />

(Table<br />

shown<br />

2).<br />

in Fig. 3. The mean visibility scale scores with the<br />

between Visibility scale TXI-1 scale scores and WLI scores with of NE, the with between NE the were TXI-2 CE 2.79 and were ± WLI 1.07, 2.53 of 3.23 NE, ± 1.10, and ± 0.96 This study showed that TXI improved the visibility scale<br />

NE were 2.79 ± 1.07, 3.23 ± 0.96 and 3.14 ± 0.92 for WLI, TXI-1 and<br />

the 3.04 and following ± 3.14 1.05 ± lesion 0.92 and 2.96 for characteristics WLI, ± 1.92 TXI-1 for for WLI, ANOVA: and TXI-1 TXI-2, status and of respectively.<br />

H. TXI-2, pylori scores Discussion of gastric neoplasms compared with WLI using<br />

TXI-2, respectively. Visibility scale scores with the CE were 2.53 ± 1.10,<br />

infection, respectively. Visibility atrophy, scale For location, both scores types size, with of morphology, endoscopes, the CE histological were significant 2.53 diagnosis ± differences<br />

1.10, an This image catalogue comprising 52 consecutive gastric<br />

3.04 ± study 1.05 and showed 2.96 ± that 1.92 for TXI WLI, improved TXI-1 and TXI-2, the visibility respectively. scale<br />

and 3.04 intestinal ± 1.05<br />

were metaplasia. and<br />

observed<br />

2.96 ± We 1.92<br />

in set visibility the for scale WLI,<br />

scale score TXI-1<br />

scores differences and<br />

between as TXI-2, the neoplasms<br />

scores<br />

in clinical practice. Moreover, visibility scale<br />

For both of types gastric of endoscopes, neoplasms significant compared differences with were WLI observed using<br />

dependent WLI<br />

respectively.<br />

and TXI-1 variables, For<br />

(p<br />

both and < 0.001 reviewers types<br />

for<br />

of<br />

both and endoscopes,<br />

endoscopes), each lesion significant characteristics and WLI<br />

differences<br />

were observed in visibility scale scores between neoplasms endoscopes), in and clinical WLI and practice. TXI-2 (p < 0.001 Moreover, for both visibility endoscopes). scale<br />

scores<br />

an<br />

with the NE were significantly better than those<br />

in visibility image scale catalogue scores between comprising WLI and 52 TXI-1 consecutive (p < 0.001 for gastric both<br />

as and independent TXI-2 (p variables. < 0.001 for The both size was endoscopes). analyzed in two When groups, comparing<br />

the lesions endoscopes, ≥ 10 mm or visibility < 10 mm. scale The significance scores with level the was NE set neoplasms, and selection bias was eliminated as much<br />

with CE. This study included > 50 consecutive gastric<br />

including WLI and TXI-1 (p < 0.001 for both endoscopes), and WLI scores When comparing with the the NE endoscopes, were significantly visibility scale better scores than with the those NE<br />

at were p < 0.05, significantly and Bonferroni higher adjustment than those was with used when the CE testing for for all as possible. Visibility scale scores of TXI-1 were better<br />

and TXI-2 (p < 0.001 for both endoscopes). When com-<br />

with were significantly CE. This higher study than included those with > the 50 CE consecutive for all modalities gastric (WLI,<br />

repetition in ANOVA.<br />

than those of TXI-2; however, there was no significant<br />

p = 0.002; TXI-1, p = 0.025; and TXI-2, p = 0.004).<br />

paring the endoscopes, visibility scale scores with the NE<br />

were significantly higher than those with the CE for all<br />

Results<br />

Endoscopic examinations were performed in 50 patients; 1 was<br />

neoplasms, and selection bias was eliminated as much<br />

as possible. Visibility scale scores of TXI-1 were better<br />

than Among those experts, of visibility TXI-2; scale however, scores were there 3.04 was ± 1.00, no 3.34 significant ± 0.90<br />

and 3.27 ± 0.90 with the NE, and 2.89 ± 1.02, 3.15 ± 1.00 and 3.04<br />

± 1.02 with the CE for WLI, TXI-1 and TXI-2, respectively. Significant<br />

GASTROENTEROLOGY TODAY – SUMMER <strong>2024</strong><br />


Futakuchi et al. BMC <strong>Gastroenterology</strong> (2023) 23:389<br />


Page 6 of 9<br />

Fig. 3 Mean visibility scale scores for the GIF-XZ1200 and GIF-H290Z endoscopes. * p < 0.05. WLI, white light imaging; TXI, texture and color enhancement<br />

imaging ; NS, not significant<br />

GASTROENTEROLOGY TODAY – SUMMER <strong>2024</strong><br />

difference. The encouraging outcomes from this benchmark<br />

test were suggest observed that in TXI the visibility may enhance scale scores lesion between visibility, WLI<br />

differences<br />

and regardless TXI-1 (p = of 0.008 the for prevailing NE, 0.020 for conditions. CE); however, A not randomized<br />

between WLI<br />

and controlled TXI-2 (p = trial 0.056 is for warranted NE, 0.175 for to CE). evaluate whether TXI can<br />

enhance the detection or delineation of EGC.<br />

Among Recently, novices, LCI visibility was scale developed scores were as a 2.54 new ± 1.07, IEE 3.12 to assist ± 1.01 in<br />

and detecting 3.01 ± 0.92 gastrointestinal with the NE, and neoplasms. 2.16 ± 1.06, 2.92 LCI ± 1.09 enhances and 2.71 the ±<br />

1.11 color with change the CE for in WLI, endoscopic TXI-1 and images TXI-2, respectively. obtained For using both WLI. types<br />

of<br />

Some<br />

endoscopes,<br />

reports<br />

significant<br />

have shown<br />

differences<br />

that<br />

were<br />

LCI<br />

observed<br />

enhances<br />

in visibility<br />

the<br />

scale<br />

visibility<br />

of gastric neoplasms, and three randomized con-<br />

scores between WLI and TXI-1 (p < 0.001 for both endoscopes), and<br />

between WLI and TXI-2 (p < 0.001 for both endoscopes).<br />

trolled trials revealed that LCI improved the detection<br />

rate of upper gastrointestinal neoplasms [11, 13, 32]. As<br />

In the secondary outcome, no factors were found to significantly affect<br />

expected, it was demonstrated that focusing on color<br />

the improvement in visibility of gastric neoplasms between TXI-1 and<br />

change was effective for detecting upper gastrointestinal<br />

WLI, and between TXI-2 and WLI (Table 2).<br />

neoplasms during endoscopy. Although LCI enhances<br />

the brightness and visibility of red and white hues, TXI-1<br />

Discussion<br />

and TXI-2 can enhance the morphological changes in the<br />

gastrointestinal mucosa. Considering that the mean visibility<br />

scale scores in TXI-2 were significantly higher than<br />

This study showed that TXI improved the visibility scale scores of<br />

gastric neoplasms compared with WLI using an image catalogue<br />

those in WLI, endoscopists should monitor the change in<br />

comprising 52 consecutive gastric neoplasms in clinical practice.<br />

elevation/depression to detect EGC.<br />

Moreover, visibility scale scores with the NE were significantly<br />

TXI-1 had the highest visibility scale scores compared<br />

better than those with CE. This study included > 50 consecutive<br />

to those of TXI-2 and WLI. These results may be owing<br />

gastric neoplasms, and selection bias was eliminated as much as<br />

to several reasons. First, completely flat type (0-IIb) EGC<br />

possible. Visibility scale scores of TXI-1 were better than those of<br />

is rare [29, 33], and no lesions were classified as 0-IIb<br />

TXI-2; however, there was no significant difference. The encouraging<br />

outcomes<br />

in this study.<br />

from this<br />

Second,<br />

benchmark<br />

some<br />

test<br />

EGCs<br />

suggest<br />

do<br />

that<br />

not<br />

TXI may<br />

exhibit<br />

enhance<br />

color<br />

lesion changes, visibility, and regardless it may of be the difficult prevailing conditions. to identify A randomized the lesion<br />

controlled despite color trial is warranted enhancement to evaluate in whether the endoscopic TXI can enhance image. the<br />

detection Therefore, delineation it would of be EGC. reasonable to improve the visibility<br />

of EGC by enhancing both the texture and color, as<br />

Recently, LCI was developed as a new IEE to assist in detecting<br />

gastrointestinal neoplasms. LCI enhances the color change in<br />

in TXI-1. However, it remains unknown whether color or<br />

morphological endoscopic images changes obtained using are more WLI. Some effective reports in have improving shown<br />

the that LCI visibility enhances of the EGC. visibility of gastric neoplasms, and three<br />

randomized An analysis controlled of color trials revealed changes that between LCI improved the the inside detection and<br />

outside rate of upper of a gastrointestinal lesion with neoplasms L* a* b* values [11, 13, was 32]. As used expected, to objectively<br />

demonstrated evaluate that visibility focusing on [34]. color change Using was L* a* effective b* values, for detecting Abe<br />

it was<br />

et upper al. gastrointestinal [17] reported neoplasms a significant during color endoscopy. difference Although between LCI<br />

the enhances inside the and brightness outside and of visibility lesions of red for and WLI white and hues, TXI TXI-1 (both and<br />

TXI-1 TXI-2 can and enhance − 2), the whereas morphological Ishikawa changes et in al. the gastrointestinal<br />

[18] reported<br />

a<br />

mucosa.<br />

significant<br />

Considering<br />

color<br />

that<br />

difference<br />

the mean visibility<br />

between<br />

scale<br />

WLI<br />

scores<br />

and<br />

in TXI-2<br />

TXI-1.<br />

were<br />

Moreover,<br />

significantly higher<br />

Koyama<br />

than those<br />

et al.<br />

in<br />

[19]<br />

WLI,<br />

also<br />

endoscopists<br />

reported<br />

should<br />

that<br />

monitor<br />

color difference<br />

between EGCs and non-neoplastic mucosa was<br />

the<br />

change in elevation/depression to detect EGC.<br />

significantly higher in TXI than in WLI in all patients.<br />

TXI-1 had the highest visibility scale scores compared to those of<br />

We did not analyze the color difference using L* a* b*<br />

TXI-2 and WLI. These results may be owing to several reasons. First,<br />

values since a similar result was likely to be obtained<br />

completely flat type (0-IIb) EGC is rare [29, 33], and no lesions were<br />

in our study. As reported in our previous clinical study<br />

classified as 0-IIb in this study. Second, some EGCs do not exhibit<br />

using esophageal neoplasms, the L* a* b* values and visibility<br />

scale scores may not completely correspond to one<br />

color changes, and it may be difficult to identify the lesion despite<br />

color enhancement in the endoscopic image. Therefore, it would be<br />

another [35]. In addition to color differences, other information—such<br />

as morphological changes and mucosal or<br />

reasonable to improve the visibility of EGC by enhancing both the<br />

texture and color, as in TXI-1. However, it remains unknown whether<br />

microvascular patterns—may affect the visibility of EGC.<br />

color or morphological changes are more effective in improving the<br />

We analyzed characteristics whereby TXI significantly<br />

visibility of EGC.<br />

improved visibility scale scores of EGC by considering<br />

the impact among endoscopists who evaluated the<br />

An analysis of color changes between the inside and outside of a<br />

endoscopic<br />

lesion with L* a*<br />

images;<br />

b* values<br />

however,<br />

was used to<br />

we<br />

objectively<br />

could<br />

evaluate<br />

not extract<br />

visibility<br />

the<br />

characteristics.<br />

[34]. Using L* a* b* values,<br />

The results<br />

Abe et<br />

showed<br />

al. [17] reported<br />

a tendency<br />

a significant<br />

for TXI<br />

color<br />

to<br />

always difference be between superior the to inside WLI, and regardless outside of lesions of the for lesion WLI and characteristics<br />

(both TXI-1 and or − endoscopist’s 2), whereas Ishikawa experience. et al. [18] reported Particularly, a significant TXI<br />

TXI<br />

can color enhance difference between the visibility WLI and of TXI-1. EGC Moreover, regardless Koyama of et lesion al. [19]<br />

color, morphological type, location, the status of H. pylori<br />

also reported that color difference between EGCs and non-neoplastic<br />

mucosa was significantly higher in TXI than in WLI in all patients.<br />

We did not analyze the color difference using L* a* b* values since a<br />



similar result was likely to be obtained in our study. As reported in our<br />

previous clinical study using esophageal neoplasms, the L* a* b* values<br />

and visibility scale scores may not completely correspond to one<br />

another [35]. In addition to color differences, other information—such<br />

as morphological changes and mucosal or microvascular patterns—<br />

may affect the visibility of EGC.<br />

We analyzed characteristics whereby TXI significantly improved<br />

visibility scale scores of EGC by considering the impact among<br />

endoscopists who evaluated the endoscopic images; however,<br />

we could not extract the characteristics. The results showed a<br />

tendency for TXI to always be superior to WLI, regardless of the lesion<br />

characteristics or endoscopist’s experience. Particularly, TXI can<br />

enhance the visibility of EGC regardless of lesion color, morphological<br />

type, location, the status of H. pylori infection, atrophic gastritis,<br />

and histology and intestinal metaplasia. This result was similar to<br />

that previously reported in studies examining the visibility of gastric<br />

neoplasms using LCI [9, 10].<br />

Futakuchi et al. BMC <strong>Gastroenterology</strong> (2023) 23:389<br />

In this study, TXI resulted in better gastric neoplasms visibility scale<br />

scores than WLI; however, it remains unclear whether TXI actually<br />

improved EGC detection. The effectiveness of NBI in the detection of<br />

EGC is still controversial. The usefulness of LCI in detecting neoplasm<br />

in the upper gastrointestinal tract has been reported in a randomized<br />

controlled trials, and further studies should be conducted to determine<br />

which IEE is most effective. The improved resolution may also<br />

contribute to the detection rates, because this study demonstrates that<br />

the visibility scale scores of NE was significantly better than that of CE.<br />

Although 0-IIb lesions with minimal color changes are rare, TXI has<br />

limited visibility enhancement for these lesions. Thus, other modalities,<br />

such as magnifying endoscopy and NBI, may be superior for detecting<br />

0-IIb lesions [36].<br />

This study had some limitations. First, the modalities were not<br />

completely blinded while scoring the visibility scale. Therefore, it is<br />

undeniable that reviewers may have rated TXI higher than WLI. Second,<br />

endoscopic examinations were conducted by expert endoscopists at a<br />

single center. Since it is necessary to maintain highquality examinations<br />

Page 7 of 9<br />

and obtain appropriate endoscopic images, we included endoscopists<br />

with experience in the protocol. Third, the images captured with each<br />

Table 2 Visibility scale difference between WLI and TXI-mode 1 and between WLI and TXI-mode 2 and results of two-way ANOVA in<br />

endoscopists and the six endoscopic features of gastric neoplasms<br />

Scale score p value Scale score p value<br />

difference<br />

(TXI mode1-WLI),<br />

mean ± SD<br />

TXI<br />

mode1<br />

difference<br />

(TXI mode2-WLI),<br />

mean ± SD<br />

TXI<br />

mode2<br />

H. pylori infection 0.618 0.382<br />

Positive 0.34 ± 0.79 0.28 ± 0.79<br />

Eradicated 0.53 ± 0.94 0.44 ± 0.83<br />

Negative 0.38 ± 0.81 0.24 ± 0.72<br />

Atrophy 0.07 0.175<br />

Positive 0.45 ± 0.87 0.36 ± 0.81<br />

Open type 0.44 ± 0.86 0.34 ± 0.81<br />

Closed type 0.50 ± 0.93 0.48 ± 0.79<br />

Negative 0.22 ± 0.79 0.06 ± 0.40<br />

Location 0.915 0.337<br />

U 0.17 ± 0.69 0.08 ± 0.89<br />

M 0.38 ± 1.00 0.35 ± 0.78<br />

L 0.51 ± 0.81 0.39 0.78<br />

Size 0.372 0.14<br />

10 mm 0.40 ± 0.85 0.26 ± 0.76<br />

Morphology 0.924 0.954<br />

0-I 0.28 ± 0.45 0.1 ± 0.31<br />

0-IIa 0.55 ± 0.94 0.40 ± 0.82<br />

0-IIc 0.41 ± 0.86 0.34 ± 0.81<br />

Pathology diagnosis 0.762 0.931<br />

Diffuse type 0.21 ± 0.71 0.17 ± 0.48<br />

Intestinal type 0.47 ± 0.89 0.38 ± 0.85<br />

Adenoma 0.58 ± 0.64 0.25 ± 0.43<br />

Intestinal metaplasia 0.682 0.966<br />

Complete 0.30 ± 0.89 0.43 ± 0.82<br />

Incomplete 0.51 ± 0.88 0.34 ± 0.83<br />

Negative 0.56 ± 0.81 0.29 ± 0.82<br />

The visibility scale scores of newly developed endoscope are used for the analysis. Significance is calculated as < 0.0083 according to Bonferroni adjustment. There<br />

is no factor which affected the improvement of visibility of gastric neoplasms in TXI-1 and TXI-2.<br />

U, upper third; M, middle third; L, lower third.<br />

GASTROENTEROLOGY TODAY – SUMMER <strong>2024</strong><br />

infection, atrophic gastritis, and histology and intestinal<br />

metaplasia. This result was similar to that previously<br />

reported in studies examining the visibility of gastric<br />

modalities, such as magnifying endoscopy and NBI, may<br />

be superior for detecting 0-IIb lesions [36].<br />

This study had some limitations. First, the modalities<br />



GASTROENTEROLOGY TODAY – SUMMER <strong>2024</strong><br />

endoscope and modality differed; six images were acquired per lesion<br />

at different times, and the conditions varied slightly depending on gastric<br />

peristalsis, air insufflation and endoscope stability.<br />

Conclusions<br />

TXI improved the visibility scale scores of gastric neoplasms compared<br />

with those of WLI. Moreover, NE has the potential to improve visibility<br />

compared to CE.<br />

Abbreviations<br />

ANOVA Analysis of variance<br />

CE Conventional endoscope<br />

EGC Early gastric cancer<br />

IEE Image-enhanced endoscopy<br />

LCI Linked color imaging<br />

NBI Narrow-band imaging<br />

NE Newly developed endoscope<br />

TXI Texture and color enhancement imaging<br />

WLI White light imaging<br />

Acknowledgements<br />

Not applicable.<br />

Authors’ contributions<br />

TF and AD designed and wrote this study; HH, HF, HM, YH, MK,<br />

SO, and NT performed image collection and image evaluation; KG<br />

was pathologically evaluated for intestinal metaplasia; TY and MS<br />

contributed to statistical analysis; KS was the supervisor and all<br />

authors read and approved the final manuscript.<br />

Funding<br />

There was no funding for this study.<br />

Data availability<br />

The datasets used and/or analyzed during the current study are<br />

available from the corresponding author on reasonable request.<br />

Declarations<br />

Ethics approval and consent to participate<br />

This study was conducted in accordance with the ethical principles<br />

and guidelines of the Declaration of Helsinki and was approved by the<br />

Institutional Review Board of the Jikei University School of Medicine<br />

on 14 September 2020 (32–156(10237)). All participants provided<br />

written informed consent prior to enrollment in this study. This study<br />

is registered with the University Hospital Medical Information Network<br />

(UMIN000042429, 16/11/2020).<br />

Consent for publication<br />

Not applicable.<br />

Competing interests<br />

The authors declare no competing interests.<br />

Author details<br />

1<br />

Department of Endoscopy, The Jikei University School of Medicine,<br />

3-25-8, Nishi-shimbashi, Minato-ku, Tokyo 105-8461, Japan<br />

2<br />

Department of Pathology, The Jikei University School of Medicine,<br />

Tokyo, Japan<br />

3<br />

Department of Public Health and Environmental Medicine, The Jikei<br />

University School of Medicine, Tokyo, Japan<br />

Received: 4 May 2023 / Accepted: 5 November 2023<br />

Published online: 13 November 2023<br />

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