LITHUANIAN UNIVERSITY OF HEALTH SCIENCES MEDICAL ACADEMY
CLINIC OF RADIOLOGY
DANIEL ZILBERMAN
The role of interventional radiology as treatment
of upper gastrointestinal ulcer bleeding
2
DEDICATION
3
DECLARATION
I, Daniel Zilberman hereby declare that this thesis on ‘The role of interventional radiology as management and treatment of upper gastrointestinal ulcer bleeding’ is original, and has been written by me. It is a record of my research work and has not been presented before in any previous publication.
Name: _________________________________ Signature: ____________
4
TABLE OF CONTENTS
SUMMARY
... 5
CONFLICTS OF INTERESTS
... 6
ETHICS COMMITTEE APPROVAL
... 75
SUMMARY
Master’s thesis written and presented by Daniel Zilberman; “The role of interventional radiology as management and treatment of upper gastrointestinal ulcer bleeding”.
Aim: To produce an overview about the methods used in Interventional Radiology to control ulcerative UGI bleeding, and comparison of those methods to traditional treatment strategies
Objectives: 1. Analysis of methods used to manage upper Gastrointestinal bleeding 2. Analysis of the role of Interventional Radiology as definitive treatment after unsuccessful endoscopic strategy 3. Comparison between endoscopic and interventional methods, their indications, technical pearls, possible complications, and outcomes.
Methodology: Literature review of scientific articles published in English language from PubMed and PubMed Central, eLABA system, New England Journal of Medicine, ResearchGate, BMJ Journals and Oxford Academic data bases from the years 2008-2019, with over 70% of the analysed articles are from the year 2014 and onward. For complete evaluation of the article’s eligibility PICO criteria were implicated: 1. Population/Problem: patients who are suffering from ulcerative GI bleed, with/without previous endoscopic treatment. 2. Intervention: the studied intervention is embolization of the artery which supplies the area of bleeding. 3. Comparison: Endoscopic treatment versus Interventional radiology procedure. Outcome: all possible outcomes were analysed- rate of successful procedures, rate of complications (early and late) and patient’s death as the direct outcome of the procedures.
Results: Nine hundred and forty seven abstracts were found. Only 12 studies were included. All selected papers were non-randomized studies: eleven were single centre, longitudinal observational studies, while only one was a multi-centre prospective cohort study. No comparative randomized clinical trial is proposed in the literature.
Conclusions: The role of interventional radiology can be considered as vital in patients whose upper GI bleeding remains resistant and non responsive to medical and endoscopic therapies, therefore the role of the interventional radiological procedures becomes crucial. Radiology offers diagnostic imaging studies and endovascular therapeutic interventions that can be done safely and effectively with successful clinical outcomes. TAE is a safe method of intervention for acute non-variceal UGIB and a potential alternative to surgery for patients who are at high risk.
6
CONFLICTS OF INTERESTS
7
ETHICS COMMITTEE APPROVAL
8
ABREVIATIONS
IR Interventional Radiology UGI Upper Gastrointestinal tract UGIB Upper gastrointestinal bleeding CI Confidence interval
CT Computed tomography
NSAIDs Non-steroidal anti-inflammatory drugs NVUGIB Non-variceal upper gastrointestinal bleeding OD Odds ratio
OR Operating room
PICO Population/Problem, Intervention, Comparison, Outcome
PRISMA Preferred Reporting Items for Systematic Reviews and Meta-Analyses RCTs Randomized controlled trials
9
INTRODUCTION
Upper gastrointestinal bleeding is defined as bleeding originating at the level of the distal oesophagus, stomach, and the duodenum (proximal to the ligament of Treitz).[1] Nonvariceal UGI bleeding has the occurrence of 30-100 cases per 100 000 population per year, which is two to four times more common finding than lower GI bleeding, since peptic ulcer disease is the number one etiological factor which is causative for UGI bleeding.[2]
The Indicated 1st line therapy for an un-complicated case of UGI bleeding is by endoscopic measures. But in
cases of 1st line treatment failure the mortality rate can reach 5-10%.[3] There are several important factors
which may influence the outcome of such procedure; the main factors are: advanced age, hematologic abnormalities (as coagulation impairments and abnormalities, abnormal blood counts, cancers and etc.,). Laparotomic and laparoscopic measures are also mentioned in literature, but in practice they are rarely used due to three-fourfold increased risk of complications.[4]
When endoscopic therapy fails, contraindicated or the bleeding lesion(ulcer) is resistant to conventional endoscopic measures, surgery or IR procedure of embolization (TAE) are treatment options. As mentioned before, TAE is considered a relatively safe alternative, mostly because of the vast collateral supply in the areas above the ligament of Treitz, but this can be said as long as the procedure is performed by an experienced radiologist. [5]
10
Following the first report of selective arterial embolization of acute gastric bleeding, improvements in interventional radiological technological means and embolic materials together with a wider availability of skilled IR specialists have expanded the effectiveness of such practices in management of UGI bleeding. [8] The UGIB's diagnosis and management depends on its site, nature and aetiology. The role of radiological interventions becomes especially essential in patients whose UGIB remains resistant to conventional medical and endoscopic treatment. The radiological measures which are in use offer diagnostic imaging studies and endovascular therapeutic interventions that can be performed safely and effectively.
The aim of this study is to produce an overview about the methods used in Interventional Radiology to control ulcerative UGI bleeding, and comparison of those methods to traditional treatment strategies.
Objectives of this study:
1. Analysis of methods used to manage upper gastrointestinal bleeding.
2. Analysis of the role of Interventional Radiology as definitive treatment unsuccessful endoscopic management.
11
RESEARCH METHODOLOGY
Review Construction:
To ensure a standardized approach to the development of this review, the PRISMA protocol was utilized [34]. The PRISMA protocol is a standard set of entities used for reporting data particularly in systematic reviews and meta-analyses. This study takes the form of a concise- descriptive analysis, since the studies offer epidemiological evidence, of a cross-sectional design.
Records identified through database searching (n = 947) Sc re en in g In cl ud ed El ig ib ili ty Id en tif ic at io n
Additional records identified through other sources
(n = 3)
Records after duplicates removed (n = 780)
Records screened (n = 780)
Records excluded (n = 682)
Full-text articles assessed for eligibility
(n = 98)
Full-text articles excluded, with reasons
(n = 86)
Studies included in systematic review
12
Search Strategy:
Electronic databases PubMed, NCBI, Elsevier, UpToDate, ResearchGate, Medline, Embase, CINAHL, Cochrane and Web of Science were evaluated. The search strategy expanded and involved key terms pertaining to the concepts; to reach maximum sensitivity, a combination of the terms “upper gastrointestinal bleeding”; “upper gastrointestinal haemorrhage”; “embolization”; “angiography”; and “interventional radiology” were involved. Studies were retrieved and relevant studies were involved after reading the title and abstract of the study. Any additional studies were analysed by the author further via the reference lists of selected articles for research of additional beneficial studies.
Selection criteria
This study used the guidelines for PRISMA (Preferred Reporting Products for Systematic Evaluations and Meta-Analysis) to base selection criteria using the PICO (P - Populations/People/Patient/Problem, I - Intervention(s), C - Comparison, O - Outcome) worksheet and search strategy as shown in table 1.
Randomized controlled trials, case-control studies, and cohort studies fulfilling the following criteria were included: (1) English language, (2) considering adult patients’ population with refractory UGIB (3) studies from the last 10 years (4) studies conducted on Humans only, and (5) report of any considered outcomes (mortality, re-bleeding, complications, need for further intervention). If multiple trials or studies were published by the same centre, only the most complete one was included. Studies that were excluded include: (1) studies with more than 10 years of publication (unless publication has extreme relevance up to this day) (2) Non relevant articles by abstract and content and (3) Case reports, editorials, letters, and studies having duplicate data or already published data.
Other prevalent exclusion criteria
Most of the articles which were excluded from this review were excluded due to irrelevance; as the vast majority of the articles found in the various databases were concluding venous bleeding in the upper gastrointestinal tract (hence ‘Variceal bleeding’). although variceal bleeding is a highly prevalent issue, it’s essence, pathophysiology and the causative mechanisms are completely different than arterial bleeding, and although there are IR techniques which might be used for the treatment of this ailment, they differ from the methods of treatment of arterial UGI bleeding.
13
Data collection, Evaluation of study quality, and risk of bias
Studies were selected by the author himself. Studies that were not in the public domain were not included. Studies generated by the search were assessed for relevance. Potentially relevant papers were retrieved in full and evaluated by the author to minimize the risk of developing bias to the results reviewed.The full text of the included studies was thoroughly reviewed to assess the relevance and the quality of the paper. Risk of bias evaluation was considered according to the Newcastle–Ottawa Quality Assessment Scale criteria.
Table 1
PICO (Patients, Intervention, Comparison, Outcome) worksheet
Population Adult patients with upper gastrointestinal bleeding
Intervention Transcatheter Arterial Embolization of bleeding area
Comparison Direct comparison with non-radiological management methods. If multiple trials or studies were published by the same centre, only the most complete one was included.
14
Statistical analysis
Statistical analysis was performed using RevMan software (Review Manager Version 5.3). Odds ratio (OR) with a 95% confidence interval (CI) was used to compare outcomes. A fixed effect model was utilized in case of low heterogeneity, while a random effects model was utilized when significant heterogeneity was noticed. Heterogeneity was evaluated using the Cochrane Q square test (P < 0.1 was considered an indicator of significant heterogeneity) and the I2 estimates (< 25% moderate, 25–50% moderate, > 50% high
heterogeneity).
Outcomes
15
LITERATURE REVIEW
Upper Gastro-intestinal bleeding:
Upper gastro-intestinal bleeding (UGIB) is defined as bleeding stemming proximally from the Treitz ligament and is usually subdivided into two important categories: variceal and non-variceal. Hematemesis and melena are the most common presentations.[1]
Aetiology:
The most common aetiologies in the presented cases are ulcerative bleeding-with some articles which discuss the aetiology of NVUGIB attribute approximately 50% to them. [2]
16
figure 1: Description of both common and rare causes of UGIB
Source: Oxford handbook of clinical medicine v.10 p.256
Epidemiology
A detailed review on the epidemiology of arterial UGIB found that peptic ulcer disease was by far the most common cause, with an annual recorded occurrence of haemorrhage in the general population ranging from 19.4 cases per 100,000 to 57 cases per 100,000 population, with an estimated sample size weighted 30-day mortality of 8.6 percent. This high incidence of complicated peptic ulcer could be related to an increased usage of ASA and NSAIDs and due to the increasing number of elderly population. It is easy to understand how this complication remains a great health-care problem, with a relatively large overall population health and financial impact. [11]
Vascular Anatomy
A complicated network of anastomotic vessels provides a rich blood supply to the upper part of the gastrointestinal tract (GIT). Blood supply to the oesophagus, stomach and duodenum is relatively rich and collateral, this is both a point of strength and a point of weakness for the TAE procedure; in cases of widespread area of bleeding as it might occur in malignancies or AVM’s, embolization of a single artery might not be enough for cessation of the bleeding, while on the other hand this might be a factor why a complication of post-TAE ischemia in UGI is not common. [12] The chances of successful embolization procedure vastly depend on the location of the bleeding lesion. For vascular supply of bleedings in the lesser curvature of the stomach or the distal oesophagus we will need to look for the Left Gastric Artery (LGA), and embolization of this blood vessel is a good management option for bleedings arising from that region. The LGA In 90% of the anatomic variants is the first branch of the celiac trunk, but in other anatomic variants it may also be seen to be branched directly from the aorta- where it might be referred to as spleno-gastric (lienogastric) or
hepato-COMMON CAUSES RARE CAUSES
Peptic ulcers Bleeding disorders
Mallory-Weiss tears Portal hypertensive gastropathy
Gastritis/gastric erosions Aorto- enteric fistula
Drugs (NSAID’s, aspirin, steroids..) Angiodysplasia
Oesophagitis Haemobilia
Duodenitis Dieulafoy lesion
Malignancy Meckel’s diverticulum
17
gastric trunk [13] as the LGA reaches its point of termination, in most anatomical variants it anastomoses with the RGA (Right gastric artery) and lesser branches may also anastomose with the short gastric arteries and also with the inferior phrenic artery dex. The RGA (commonly referred as Pyloric Artery) arises from the proper hepatic artery, though on the lesser amount of cases it may arise from the common, middle or left hepatic arteries, and in rare cases from the right hepatic artery or even the gastro-duodenal artery; Generally, it’s a small diameter vessel travelling in proximity to the hepato-gastric ligament and supplies the distal part of the lesser curvature of the stomach and pylorus. The greater curvature is vastly supplied by the gastro-epiploic artery (GEA- sometimes referred to as arch), which follows the greater curvature of the stomach, and it’s point of origin is from right and left gastroepiploic arteries (RGEA & LGEA). In some anatomic variants the arch may be in an ‘incomplete’ presentation where supply from one of it’s origins is lacking, though complete presentation occurs at approximately 65 percent of individuals. [14]
Duodenal supply mostly relies on pancreatico-duodenal arch (arcade) where the supplying vessels are the GDA(gastroduodenal artery) and SMA(superior mesenteric artery)- though when it comes to duodenal arterial supply, it presents much less anatomical variants then gastric supply in the majority of reviewed cases. Anatomic variations in the celiac anatomy, most importantly in the origins of the hepatic arteries, occur in at least 50% of the patients.Such variations should always be taken into account when assessing NVUGIB patients angiographically [15].
Historical background
18
a specific set of complications including access site thrombosis or haemorrhage, contrast reactions, damage to target vessels (such as dissection and distal embolization), and ischemic injury following embolization.[20] The common use of proton pump inhibitors, as well as the development and advancement of efficient endoscopic practices, has significantly altered the approach to non-variceal upper GI bleeding, shifting the therapeutic path from surgical technique to a more conservative radiological approach.
Symptoms
Classic presentations of UGIB usually involves hematemesis or melena. Although commonly attributed to lower gastrointestinal bleedings, haematochezia may also occur with high dependence on the rate of bleeding and the time of blood stasis and/or transmit through the intestine. Individuals with variceal bleeding are likely to experience cirrhosis signs, uncomplicated hematemesis, and a greater degree of hemodynamic dysfunction. Non-variceal bleeding is more commonly associated with coffee-ground emesis and NSAIDs use. [21] Endoscopy
Endoscopy would be the primary intervention as it allows bleeding site localization and cause identification by visual inspection and biopsy taking. It is useful in identifying arterial and venous sources of haemorrhage. Beyond its diagnostic application, endoscopy also offers several therapeutic options. Endoscopic haemostasis can be perfected by thermo-coagulation, injection of sclerosing agent, and/or clips/banding. [22] Epinephrine injection is sub-optimal. Even if not successful, the placement of endoscopic clips will aid concurrent endovascular intervention by guiding the interventional radiologist to the region of concern. [23]. Endoscopy conducted within the first twenty-four hours after presentation is linked to an improved patient morbidity and shortened stay at the hospital. At first endoscopy, however, the source of haemorrhage may not be found in up to 24 percent of individuals. Endoscopic treatment is shown to be effective in 85 percent to 90 percent of individuals. However, re-bleeding after endoscopic treatment occurs in 15% to 20%. Endoscopic predictors of re-bleeding include visualized active bleeding, non-bleeding visible vessel, adherent clot, ulcer size >2 cm, and ulcer location in the posterior mid-gastric body or posterior duodenal bulb. Persistent bleeding should be accompanied by a second endoscopic intervention before considering endovascular therapy. [25]
Computed Tomographic Angiography
19
an intra-venous (IV) contrast-enhanced series in arterial and delayed phases. A positive CTA study will show hyper-dense contrast material (>90 HU) within the bowel lumen on the arterial phase that enhances on the delayed phase. [26]
Angiography Indications
Angiography involves visualisation of blood vessel with contrast material, therefore CTA is an angiographic measure. CTA is the right choice of Angio-imaging when endoscopic visualization fails.
There are two main indications for conventional angiography: the bleeding site cannot be located by endoscopy or CTA, or the source of bleeding cannot be controlled by endoscopic measures. Angiography is favoured over surgery as the treatment of choice after failed endoscopic intervention, particularly in high-risk surgical patients. It is less invasive, associated with lower mortality and morbidity, and there has been shown to be no difference in results between patients managed with surgery versus arterial embolization. [27]
Transcatheter Arterial Embolization:
Trans-catheter arterial embolization (TAE) is an effective intervention for controlling acute UGIB. Studies show that TAE is better than surgical intervention for the high risk patient population and has a lower 30-day mortality rate. [28] TAE is a feasible procedure and temporizing tool in conditions where there is no endoscopic and/or surgical solution. The goal of transcatheter arterial embolization is super-selective embolization of the blood vessels to alleviate the pressure of arterial perfusion while ensuring sufficient collateral blood flow in order to minimize the risk of possible intestinal infarction. A five F(French) angiographic catheter is commonlyused to reach the celiac or superior mesenteric depending on the suspected location of bleeding and its supplying blood vessels. Smaller guide-wires, such as 0,018 or smaller are used to guide the micro-catheters as close as possible to the bleeding vasculature. Caution must be taken to move the guide-wire and micro-catheter as carefully and smoothly as possible to avoid vessel perforation, dissection, and vasospasm while accessing the site of bleeding. For UGIB, bleeding visualized in the stomach fundus is managed by left gastric artery embolization and bleeding in the gastric antrum or proximal duodenum by gastro-duodenal embolization. [29]
20
Coils come in various sizes and lengths, ranging from submillimetre to centimetre. Coils are made up of a metal component that acts as a physical occlusion and a fibre component that enhance the thrombogenic process. Coils can be visualized under fluoroscopy after placement which is an important benefit when compared to Gel-foam or PVA. [31]
Gel-foam (absorbable compressed sponge) is a temporary embolic agent consisting of subcutaneous porcine adipose tissue that remains effective for weeks to months before recanalization process occurs. For this reason, Gel-foam is not recommended as a single embolic agent. Advantages of gel-foam involves: large availability, cost-effectiveness, and allows future access to embolized vessels after resorption. Disadvantages include that the preparation of particles can be time consuming and recanalization of vessels is un-predictable [32]. In addition, because Gel-foam is made of small particulates, it is difficult to place and can reach more distally than intended, which may result in increased risk of bowel infarction from embolization of nearby collateral vessels.
Ethylene-vinyl alcohol co-polymer (Onyx®, Micro Therapeutics) is a promising newer embolic agent to control UGIB. [32]
Vasopressin Infusion
21
RESULTS
The search strategy resulted in an initial yield of 950 abstracts, of which 170 were duplicates. The title and abstracts were reviewed, and 98 articles were found to be of relevance. The full texts of 98 articles were retrieved and examined. The majority of studies were excluded because they were irrelevant. Of the remaining 98 studies, 86 were excluded using the exclusion criteria. Only 12 studies were selected (Figure 1, Table 2) for inclusion: all the selected papers were non-randomized studies, published between January 2010 and January 2020. Finally, 12 articles were analysed in this systematic review.
The characteristics of all the studies are shown in table 2. The studies were heterogeneous in terms of sample size, type of radiological intervention, variables examined, and tools used for measuring variables.
Table 2:
First author Country Year of publication Study population (n) Study Design Defreyene et al. [20]
Belgium 2008 46 Single centre, retrospective
Greenspoon et al. [15]
Canada 2010 98 Single centre, retrospective
Wong et al. [36] Hong Kong 2011 88 Single centre, retrospective Schenker et al. [37] UK 2002 72 Single centre, retrospective
Poultsides et al.
[38]
New Zealand
2018 129 Single centre, retrospective
Rondonotti at al.
[39]
22
Mirsadraee et al.
[40]
UK 2011 35 Single centre, retrospective
Loffroy at al. [2]* UK 2010 819 Multicentre, prospective Yata et al. [41] Japan 2013 37 Single centre, retrospective Lenhart et al. [42] Germany 2010 16 Single centre, retrospective Laursen et al. [43] Denmark 2015 118 Single centre, retrospective
TOTAL: 1488
*study by Loffroy is discussed and presented separately- as a reference article
Some variations are present in the material and methods utilized for UGIB among the selected articles. These studies have utilized different radiological interventions ranging from endoscopy to TAE.
In a study, Greenspoon [15] reported the role of arterial TAE in the management of acute non-variceal UGIB and provides the literature evidence on the outcomes of endovascular therapy. In his studies, Yata [19,41] reported the patients’ risk factors and patients’ clinical condition influencing the role IVR. Defreyene and colleagues [20] considered that making decisions after failure of endoscopic intervention was significantly affected by the presence of a peptic ulcer disease(PUD), they did not involve any specific criteria to refer individuals to surgical or angiographic managementIn an analysis produced by Mirsadraee [30] the individual basis was considered whether the patient would benefit from emergency laparotomy or TEA intervention and embolization therapy was taken when the individual was at potential risk of surgery.Beggs[16] stated that after transarterial embolization, there is a substantial high risk of rebleeding as compared with surgery; however, mortality rates did not differ substantially. According to Rondonotti [22] availability of the interventional radiological means and the haemodynamic stability has had a significant influence on outcome, with no other specific considerations. A total of Eight studies focused on bleeding deriving exclusively from a duodenal or gastric peptic ulcer. The remaining four studies include different aetiologies that lead to non- vericeal UGIB such as anastomotic ulcer, Dieulafoy ulcers(lesions) of the stomach and duodenum, post-operative pseudo-aneurysm and angiodysplastic lesions, leiomyomas.
23
been effective. The causes of endovascular management failure included: variable vascular and especially arterial anatomy, arterial dissection, vasospasms, false negative angiograms, repeated bleedings and malignant haemorrhage. Several specific embolic materials have been utilized.Sandwich technique with positioning of embolic material on both sides of the bleeding site was used to minimize the risk of repeated bleeding due to collateral vessels. In fifty four percent of the patients, active extravasation was present form blood vessels of patients. As a result, forty six percent of patients underwent blind embolization, guided by the findings of endoscopy or banding at the bleeding site. Gelatine sponge or coils were utilized for embolization in most of the cases. Sixty seven percent of the patients responded well clinically with cessation of bleeding. This procedure has failed with 33% of the total amount of patients but almost half of them were treated by repeated embolization. Twenty percent of patients underwent open surgical procedure to definitively manage the bleeding source. A number of major and minor complications were developed in nine percent of patients and included access site complications, dissection of the target vessel, along with liver and spleen infarction. In a study by Lang [36], the most significant complication was found to be partial or complete duodenal stenosis (duodenal atresia), although in other studies this complication was less prevalent. Overall 30-day mortality was twenty eight percent. Most of the deaths were due to underlying conditions.
24
Table 3. Outcomes in main published studies radiological intervention for UGIB.
First author Clinical success
(%) Rebleeding rate (%) Need for surgery (%) Complication rate (%) 30-day mortality (%) Defreyene et al. 60 26 37 26 3 Greenspoon et al. 70 15 7 34 04 Wong et al. 77 14 14 13 8
Schenker et al. 58 29 N/A 33 10
Poultsides et al. 51 47 21 26 21 Rondonotti et al. 62 11 17 17 45 Mirsadraee et al. 30 05 05 08 - Yata et al. 72 28 12 10 07 Lenhart et al. 16 03 02 06 - Laursen et al. 72 09 30 08 17 AVERAGE (%) 56.8 18.7 16.1 18.1 12 Loffroy et al.* 94 17 14 6 21
25
DISCUSSION
Upper GI bleeding is defined by a bleeding source proximal to the Treitz ligament. Upper GI bleeding is responsible for 76 percent of cases of GI bleeding.[1] The incidence of UGIB in the US is estimated at 102 per 100,000 per year, with a mortality rate of fifty .[2] Upper GI bleeding can be classified into arterial (non-variceal) and venous ((non-variceal) causes; this is an essential point of differentiation and a vital branch in the management of UGIB. Acute variceal bleeding is linked with a high early mortality rate of up to 30%.[3,4] Causes of UGIB include peptic ulcer disease (up to 40%), Mallory-Weiss tear (15%), haemorrhagic gastritis, pancreatitis-related pseudo-aneurysms, neoplasm, haemobilia, AV fistula, and trauma. Venous causes include variceal bleeding secondary to portal venous hypertension (e.g., due to cirrhosis or Budd-Chiari syndrome) or splenic vein thrombosis.[5]
26
heparin to localize bleeding sites. [20, 21]While empirical embolization is a technique taken as a preventative measure for re-bleeding [9]. However, it is known that its role is controversial because of the enhanced possibility of complications [23].
Trans-arterial embolization in the upper gastrointestinal tract above the Treiz ligament has low possibility to cause intestinal infarction because of the extensive collateral circulation to these parts. However, with the wide range of trans-arterial embolization, rates of duodenal stenosis may increase. [27,28] On the other hand, TAE in the lower GI tract may cause intestinal infarction unless TAE was performed in the vasa recta. This is because lower GI tract is characterized by poorer collateral circulation and anastomoses compared to upper GI tract.
Embolization agents are mainly selected by the site of involved vessels. Gelfoam, microcoils, N-butyl cyanoacrylat, and/or the combination of these materials are commonly used when involved vessels are occluded.
Re-bleeding after TAE occurs in a rate ranging from 21 percent to 34.4 percent, most likely due to collateral circulation development. [29]. Once upper gastrointestinal bleeding is controlled by TAE, gastrointestinal neoplasms should be excised surgically as soon as possible or frequent follow-ups by endoscopy should be considered.
When medical and endoscopic treatment remains unsuccessful in the case of non-variceal UGIB, trans-catheter embolization is the available management option. The number of individuals requiring surgical intervention has decreased massively over the past few years. In the past decade, up to thirteen percent of patients required surgery to control bleeding from peptic ulcer disease [30], but with better endoscopic haemostatic techniques and IV proton pump inhibitor infusions, the rate of surgical procedures has dropped to less than 2% in the present day [15,19]. Endoscopic therapy is highly effective in controlling upper GI bleeding, but refractory bleeding can occur in up to twenty four percent of high-risk patients. [20]
27
A recent systematic review on TAE for upper gastrointestinal bleeding proposed a success rate of 85 percent; while mean re-bleeding rate, mean complication rate, and mean 30-day all-cause mortality were 28, 7, and 8 percent, respectively [32]. The study assessed the factors related to angio-embolization failure and found that the presence of coagulopathy and/or multiorgan deterioration has the worst effect on the outcome of TAE. Another point which can explain this higher rate of rebleeding is the intermittent character of this kind of haemorrhage that makes it difficult to identify the bleeding site during the angiographic study and could lead to significant modifications in vessel diameters thus making the embolic agent too small to completely occlude the circulation.
Although the upper GI tract usually has an extensive collateral blood supply, previous studies have demonstrated ischemic complications to occur in 8 to 18% of cases [29] and they can either present acutely, with gastrointestinal necrosis, or later, with ischemic duodenal changes which might develop into stenosis. It is worth noting that numerous factors, such as previous surgery, pancreatitis, and radiotherapy, can interfere with the collateral circulation and eventually cause ischemia.
Another important notice, is that the study which reflects the most similar results to real-life practice in the Lithuanian University of Health Sciences (LUHS- Kauno Klinikos) is the study by Loffroy et al. [2], which concludes fifteen studies on endovascular management of intractable UGIB.The majority of patients treated with endovascular therapy had significant comorbidities and were considered high risk for surgical procedure. Endovascular embolization has been clinically effective in 93 per cent of cases. Thirty-three percent of patients remained bleeding, but nearly half responded to repeated embolization. Finally, twenty percent of patients underwent surgical management to definitively treat the bleeding site. Major and minor embolization-related complications developed in nine percent of patients and involved access site complications, dissection of the target vessel with apparent extravasation, and liver and spleen infarction. The mortality rate reported was twenty-eight percent. Factors influencing survival reported by other studies are early recurrent bleeding, coagulopathy, cirrhosis and malignancy.
28
the same region, and with that comes along a similarity in their social-economic history, ethnical origins with a lesser amount of genetic diversity, and the level of previous medical care, as patients from the same region are probably being treated in the same centres- taking into account budget and facilities, and as noted below, the methodology and the choice of TAE for treatment varies between different medical care centres and specialists, as a definitive protocol for its use in NVUGIB is yet to be established. As reported by Dechartres[51] in a meta-epidemiologic study to evaluate the differences between single and multicentre studies, it was found that in single centre studies the effect size differs with 26% larger results, as Dechartres also suggests that this deviation might be due to the factors discussed above, and generally suggests that multicentre trials provide a closer estimate of the intervention effect, but conclusive evidence is lacking to validate this assumption, as her study (2011) is the only one done in the field since 1986.
29
or surgeon, and therefore a study which specifically defines the role of IR is required- a conclusion that also Beggs [44] has reached.
30
LIMITATION
The study has few limitations.
First of all, the retrospective nature of the most of included studies leads to an inevitable selection bias. Secondly, decision of choice of radiological intervention was made on an individual case-by-case basis by the attending physician, making group allocation and randomization difficult to achieve. It can cause reduced external validity.
Thirdly, although the most common cause of refractory UGIB is a peptic ulcer, there remain a variety of causes. Choice of radiological intervention also varies among the included studies.
Fourthly, regarding complications, only a few studies showed a complication rate for the analysed procedures and several researches reported intervention rates only for bleeding after initial procedure; thus, re-intervention analysis and outcomes do not reflect the reality of everyday life.
31
CONCLUSIONS
Although many cases of UGIB resolve spontaneously or respond to medical treatment, patients with UGIB refractory to such treatment are at higher risk for poor outcome. Upper gastrointestinal bleeding is an emergency medical condition that leads to haemorrhagic shock or haemodynamic instability if left untreated. Various subspecialties participate to the care of bleeding patients. Patients with acute UGIB should be considered for prompt radiologic imaging studies and endovascular intervention to prevent morbidity and mortality.
Endoscopy is the initial diagnostic intervention that can localize and determine the aetiology of an upper GI bleed as well as offer several treatment options. Endoscopic therapy is an important procedure for treating UGIB; more than 90% of UGI bleeding can be controlled by endoscopic haemostasis. However, patients with unstable haemodynamics or UGIB that cannot be managed by endoscopic measures might require trans-catheter embolization or other interventions. The development of several devices and embolization agents that are used in interventional radiology (IR) cause safe and accessible management via IR. If endoscopic treatment fails, TAE is an optional choice of treatment strategy.
CTA can localize lesions and gives information helpful for endovascular intervention and management. Stabilization of upper GI bleeding can be acquired effectively with endovascular angiography and trans-catheter embolization.Coagulopathy has been considered to adversely affect the rate of success for TAE, every measure should be made to control coagulopathy before, during, and after procedure. A variety of factors have been reported as having an effect on mortality following embolization. The absence of an early persistent UGIB is one of the most significant and frequently encountered. There has been a strong correlation, after interventional procedures, between coagulopathy, clinical failure and mortality.
32
REFERENCES
1. Lu Y, Loffroy R, Lau JY, Barkun A. Multidisciplinary management strategies for acute non-variceal upper gastrointestinal bleeding. Br J Surg. 2014;101:e34-50.
2. Loffroy R, Rao P, Ota S, et al. Embolization of acute nonvariceal upper gastrointestinal hemorrhage resistant to endoscopic treatment: results and predictors of recurrent bleeding. Cardiovasc Intervent Radiol. 2010;33:1088-100.
3. Loffroy R, Favelier S, Pottecher P, et al. Transcatheter arterial embolization for acute nonvariceal upper gastrointestinal bleeding: indications, techniques and outcomes. Diagn Interv Imaging. 2015;96:731-744.
4. Gralnek IM, Dumonceau JM, Kuipers EJ, et al. Diagnosis and management of nonvariceal upper gastrointestinal hemorrhage: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy. 2015;47:a1-46.
5. Loffroy R, Guiu B, D’Athis P, et al. Arterial embolotherapy for endoscopically unmanageable acute gastroduodenal hemorrhage: predictors of early rebleeding. Clin Gastroenterol Hepatol. 2009;7:515-523.
6. Huang YS, Chang CC, Liou JM, et al. Transcatheter arterial embolization with N-butyl cyanoacrylate for nonvariceal upper gastrointestinal bleeding in hemodynamically unstable patients: results and predictors of clinical outcomes. J Vasc Interv Radiol. 2014;25:1850-1857.
7. Loffroy R, Guiu B, Cercueil JP, et al. Refractory bleeding from gastroduodenal ulcers: arterial embolization in high-operative-risk patients. J Clin Gastroenterol. 2008;42:361-367
8. Lu Y, Loffroy R, Lau JY, Barkun A. Multidisciplinary management strategies for acute non-variceal upper gastrointestinal bleeding. Br J Surg. 2014;101:e34-50.
9. de Franchis R. Evolving consensus in portal hypertension. Report of the Baveno IV consensus workshop on methodology of diagnosis and therapy in portal hypertension. J Hepatol. 2005;43(1):167– 176.
10. Garcia-Tsao G, Sanyal A J, Grace N D, Carey W. Practice Guidelines Committee of the American Association for the Study of Liver Diseases; Practice Parameters Committee of the American College of Gastroenterology. Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis. Hepatology. 2007;46(3):922–938.
33
12. Frisoli J.K., Sze D.Y., Kee S. Transcatheter embolization for the treatment of upper gastrointestinal bleeding Tech Vasc Interv Radiol 2004 ; 7 : 136-142)
13. Kadir S., Lundell C., Saeed M. Celiac, superior, and inferior mesenteric arteries Atlas of normal and variant angiography anatomy Philadelphia: WB Saunders (1991). 297-308)
14. Vreeburg E M, Snel P, de Bruijne J W, Bartelsman J F, Rauws E A, Tytgat G N. Acute upper gastrointestinal bleeding in the Amsterdam area: incidence, diagnosis, and clinical outcome. Am J Gastroenterol. 1997;92(2):236–243.
15. Greenspoon J, Barkun A. A summary of recent recommendations on the management of patients with nonvariceal upper gastrointestinal bleeding. Pol Arch Med Wewn. 2010;120(9):341–346.
16. Beggs AD, Dilworth MP, Powell SL, et al. A systematic review of transarterial embolization versus emergency surgery in treatment of major nonvariceal upper gastrointestinal bleeding. Clin Exp Gastroenterol. 2014;7:93–104.
17. Lau J Y, Sung J J, Lam Y H. et al.Endoscopic treatment compared with surgery in patients with recurrent bleeding after initial endoscopic control of bleeding ulcers. N Engl J Med. 1999;11(340):751–756.
18. Laine L Jensen D M Management of patients with ulcer bleeding Am J Gastroenterol 20121073345– 360.; quiz 361
19. Yata S, Ihaya T, Kaminou T, Hashimoto M, Ohuchi Y, Umekita Y, Ogawa T. Transcatheter arterial embolization of acute arterial bleeding in the upper and lower gastrointestinal tract with N-butyl-2-cyanoacrylate. J Vasc Interv Radiol. 2013;24:422–431.
20. Defreyne L, De Schrijver I, Decruyenaere J, Van Maele G, Ceelen W, De Looze D, Vanlangenhove P. Therapeutic decision-making in endoscopically unmanageable nonvariceal upper gastrointestinal hemorrhage. Cardiovasc Intervent Radiol. 2008;31:897–905. doi: 10.1007/s00270-008-9320-x. 21. Yann G, Rodallec M H, Boulay-Coletta I. et al.Multidetector CT angiography in acute gastrointestinal
bleeding: why, when and how. Radiographics. 2011;31:E35–46.
22. Rondonotti E, Marmo R, Petracchini M, de Franchis R, Pennazio M. The American Society for Gastrointestinal Endoscopy (ASGE) diagnostic algorithm for obscure gastrointestinal bleeding: eight burning questions from everyday clinical practice. Dig Liver Dis. 2013;45:179–185.
23. . Eriksson L G, Ljungdahl M, Sundbom M, Nyman R. Transcatheter arterial embolization versus surgery in the treatment of upper gastrointestinal bleeding after therapeutic endoscopy failure. J Vasc Interv Radiol. 2008;19(10):1413–1418.
34
25. Defreyne L, Vanlangenhove P, De Vos M. et al.Embolization as a first approach with endoscopically unmanageable acute nonvariceal gastrointestinal hemorrhage. Radiology. 2001;218(3):739–748. 26. Loffroy R, Rao P, Ota S, De Lin M, Kwak B K, Geschwind J F. Embolization of acute nonvariceal
upper gastrointestinal hemorrhage resistant to endoscopic treatment: results and predictors of recurrent bleeding. Cardiovasc Intervent Radiol. 2010;33(6):1088–1100.
27. Sandhu C, Buckenham T M, Belli A M. Using CO2-enhanced arteriography to investigate acute gastrointestinal hemorrhage. AJR Am J Roentgenol. 1999;173(5):1399–1401.
28. Aina R, Oliva V L, Therasse E. et al.Arterial embolotherapy for upper gastrointestinal hemorrhage: outcome assessment. J Vasc Interv Radiol. 2001;12(2):195–200
29. Padia S A, Geisinger M A, Newman J S, Pierce G, Obuchowski N A, Sands M J. Effectiveness of coil embolization in angiographically detectable versus non-detectable sources of upper gastrointestinal hemorrhage. J Vasc Interv Radiol. 2009;20(4):461–466.
30. Mirsadraee S, Tirukonda P, Nicholson A, Everett S M, McPherson S J. Embolization for non-variceal upper gastrointestinal tract haemorrhage: a systematic review. Clin Radiol. 2011;66(6):500–509. 31. Kurihara N, Kikuchi K, Tanabe M. et al.Partial resection of the second portion of the duodenum for
gastrointestinal stromal tumor after effective transarterial embolization. Int J Clin Oncol. 2005;10(6):433–437.
32. Fidelman N, Freed R C, Nakakura E K, Rosenberg J, Bloom A I. Arterial embolization for the management of gastrointestinal hemorrhage from metastatic renal cell carcinoma. J Vasc Interv Radiol. 2010;21(5):741–744.
33. Lee C W, Liu K L, Wang H P, Chen S J, Tsang Y M, Liu H M. Transcatheter arterial embolization of acute upper gastrointestinal tract bleeding with N-butyl-2-cyanoacrylate. J Vasc Interv Radiol. 2007;18(2):209–216.
34. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med. 2009;6:e1000100.
35. R. Loffroy, B. Guiu, J.P. Cercueil, et al. Refractory bleeding from gastroduodenal ulcers: arterial embolization in high-operative risk patients J Clin Gastroenterol, 42 (2008), pp. 361-367
36. Wong TCL, Wong KT, Chiu PWY, Teoh AYB, Yu SCH, Au KWL, Lau JYW. A comparison of angiographic embolization with surgery after failed endoscopic hemostasis to bleeding peptic ulcers. Gastrointest Endosc. 2011;73:900–908.
35
38. Poultsides GA, Kim CJ, Orlando R, Peros G, Hallisey MJ, Vignati PV. Angiographic embolization for gastroduodenal hemorrhage: safety, efficacy, and predictors of outcome. Arch Surg. 2008;143(5):457– 461.
39. Rondonotti E, Marmo R, Petracchini M, de Franchis R, Pennazio M. The American Society for Gastrointestinal Endoscopy (ASGE) diagnostic algorithm for obscure gastrointestinal bleeding: eight burning questions from everyday clinical practice. Dig Liver Dis. 2013;45:179–185.
40. Mirsadraee S, Tirukonda P, Nicholson A, Everett SM, McPherson SJ. Embolization for non-variceal upper gastrointestinal tract haemorrhage: a systematic review. Clin Radiol. 2011;66:500–509.
41. Yata S, Ihaya T, Kaminou T, Hashimoto M, Ohuchi Y, Umekita Y, Ogawa T. Transcatheter arterial embolization of acute arterial bleeding in the upper and lower gastrointestinal tract with N-butyl-2-cyanoacrylate. J Vasc Interv Radiol. 2013;24:422–431.
42. Larssen L, Moger T, Bjornbeth BA, Lygren I, Klow NE. Transcatheter arterial embolization in the management of bleeding duodenal ulcers: a 5.5-year retrospective study of treatment and outcome. Scand J Gastroenterol. 2008;43:217–222.
43. Laursen SB, Jakobsen M, Nielsen MM, Hovendal C, Schaffalitzky de Muckadell OB. Transcatheter arterial embolization is the first-line therapy of choice in peptic ulcer bleeding not responding to endoscopic therapy. Scand J Gastroenterol. 2015;50:264–271.
44. Beggs AD, Dilworth MP, Powell SL, Atherton H, Griffiths EA. A systematic review of transarterial embolization versus emergency surgery in treatment of major nonvariceal upper gastrointestinal bleeding. Clin Exp Gastroenterol. 2014;7:93–104. doi: 10.2147/CEG.S56725.
45. Jairath, V., & Barkun, A. N. (2011, October). The Overall Approach to the Management of Upper Gastrointestinal Bleeding. Gastrointestinal Endoscopy Clinics of North America, Vol. 21, pp. 657– 670. https://doi.org/10.1016/j.giec.2011.07.001
46. Budgeting for Radiology Practices. (n.d.). Retrieved April 18, 2020, from https://www.radiologytoday.net/archive/rt0811p10.shtml
47. Facilities for diagnostic imaging and interventional radiology DESIGN & BRIEFING. Retrieved from www.dh.gov.uk/en/Publicationsandstatistics/
48. Tarasconi, A., Baiocchi, G. L., Pattonieri, V., Perrone, G., Abongwa, H. K., Molfino, S., … Catena, F. (2019). Transcatheter arterial embolization versus surgery for refractory non-variceal upper gastrointestinal bleeding: A meta-analysis. World Journal of Emergency Surgery, 14(1). https://doi.org/10.1186/s13017-019-0223-8
36
50. Radiology and primary care in Europe. (2010). Insights into Imaging, 1(2), 46–52. https://doi.org/10.1007/s13244-010-0024-9
