Title: The value of endoscopically-placed metal clips for transcatheter arterial embolization in
the treatment of recurrent acute non-variceal upper gastrointestinal bleeding
Version: 1 Date: 08 Oct 2023
Reviewer:  David L. Carr-Locke
Reviewer's report:
General Comments
This is an excellent report demonstrating the benefit of placing an endoscopic clip at the site
of non-variceal upper GI bleeding either as treatment or as a deliberate marker for guiding
subsequent arterial embolization when this is necessary.
There are a number of typographical and grammatical errors as detailed below.
Specific Comments
1   The title should read: "The value of endoscopically-placed metal clips for transcatheter arterial
embolization in the treatment of recurrent acute non-variceal upper gastrointestinal bleeding"
2   Introduction, para 2 should read: "Before embolization, angiography is required to find the
bleeding site where the contrast agent extravasates. However, it may not be possible to see the
contrast agent spill if bleeding was due to venous hemorrhage or if  bleeding has stopped. In this
circumstance, empiric embolization of the left gastric artery or gastroduodenal artery is usually
undertaken. However, the blood supply of the pylorus and duodenum is complicated, and the
collateral circulation between the celiac trunk and the superior mesenteric artery branches varies
greatly. Empiric embolization is often ineffective. In the study of Kim et al.4, the rebleeding rate
after TAE was up to 16% in patients with negative angiographic results. Since most ANVUGIB
patients undergo endoscopy before TAE, it has been proposed that a metal clip can be placed at
the site or edge of bleeding points during endoscopy to guide embolism during TAE based on
the radiopacity of the metal clip.(Figure-1)"
3   Introduction, para 3 should read: "Currently, there are several case reports about the role of
metal clips in the TAE of ANVUGIB patients marked with metal clips. No controlled studies
on the value of metal clips in TAE have been reported. (For details, see Table 1: Research status
of metal clips in TAE operations in patients with ANVUGIB.) These studies have preliminarily
suggested that marking the bleeding site with a metal clip can help locate the bleeding point
and guide embolization in patients with ANVUGIB who have failed endoscopic treatment.
Metal clip marking could also reduce the occurrence of complications (organ ischemia, necrosis,
dislocation of coils, etc.)."
4   M&M, Patients should read: "The inclusion criteria for the study population were patients
who had been diagnosed with ANVUGIB by clinical features and  a bleeding site found at
endoscopy and subsequently treated with TAE. Exclusion criteria were patients who had biliary
or pancreatic duct hemorrhage, hemodynamically unstable patients who were dependent on
intensive care support, and digestive tract bleeding due to malignant tumors. According to the
presence or absence of preplaced metal clips, they were divided into two groups."
5   Why were ICU patients excluded?
6   M&M Variables should read: "Clinical success refers to a follow-up up to 30 days after
discharge, complete hemostasis, and no need for additional endoscopic treatment, repeated
embolization or invasive treatment such as surgery. Mortality was recorded within 30 days after
TAE.
The baseline information included gender, age, history of surgery or trauma within 30 days, the
use of antithrombotics, the Rockall score, the hemorrhage site, intervals from hemorrhage to
TAE, angiography result, blood transfusion before TAE, hemoglobin before TAE, coagulation
disorders (PLT#80×109/L or international normalized ratio, INR#1.5, or activated partial
thromboplastin time, APTT#45 s)5 and embolization materials."
7   Subheading should read: "TAE Technical approach" and  change all "is" to "was"
8   Change "bucrylate" to N-butyl cyanoacrylate"
9   Results, para 1 should read: "According to the inclusion criteria,  172 patients were screened
out, and 70 patients were excluded.  102 patients were included in the study. There were 73 cases
in the metal clip group and 29 cases in the no metal clip group. For the flow chart, see Fig. 2."
Please clarify the difference between 'screened out' and 'excluded'
10 Change all use of 'nonmetal clip' in the text to 'no metal clip'
11 Discussion para 1 should read: " The clinical treatment of ANVUGIB may be challenging.
Endoscopic examination is always required  with hemostasis implemented if necessary and
possible. However, there is a rebleeding rate after endoscopic treatment and patients who have
failed endoscopic hemostasis are likely to be treated by TAE. However, it is often difficult
to locate the responsible blood vessel during TAE. Previous case reports have shown that
previously-placed endoscopic metal clips can play a role in locating the responsible blood vessels
during TAE. There have been no controlled studies evaluating the effect of endoscopic metal clip
marking on rebleeding rates and clinical outcomes after TAE. This study is the first controlled
study to assess the impact of endoscopically-placed metal clips placed at the bleeding site of
ANVUGIB patients on the clinical effect of TAE....."
12 Discussion, para 2 should read: "Compared with the no clips group, the group with metal
clips had a higher clinical success rate (82.2% vs. 45.0%, P<0.001), a lower rebleeding rate
(8.2% vs 27.6%, P=0.039) and a lower additional surgery rate (11.0% vs 20.7%, P<0.001).
Consistent with these results, metal clip marking was also shown to improve overall clinical
success (OR=3.750, 95CI=1.456-9.659, P=0.004) of TAE in multivariate analysis. Compared
with patients without metal clips, patients marked with metal clips were 3.75 times more likely
to achieve successful hemostasis by TAE. These results indicated that a metal clip placed at
the bleeding site was a facilitating factor for the success of hemostasis by TAE by locating the
bleeding vessels and guiding embolization during TAE procedures......."
13  Discussion, para 4 should read: "Although no consensus has been reached, the overall view
of these studies is basically the same. Combined with the results of our study, we recommend
that lesions with a Forrest classification of Ia-IIb and a Rockall score #5 should be marked with
metal clips when conditions permit. Metal clip marking  could be performed either by direct
metal clip hemostasis or by marking at the edge of the lesion without hemostasis.(Figure 3)"
The remainder of this para may be deleted as well as the next paragraph.
14 The 'Conclusions' para may be deleted.
Title: The value of endoscopically-placed metal clips for transcatheter arterial embolization in
the treatment of recurrent acute non-variceal upper gastrointestinal bleeding
Version: 1 Date: 08 Oct 2023
Reviewer:  David L. Carr-Locke
Reviewer's report:
General Comments
This is an excellent report demonstrating the benefit of placing an endoscopic clip at the site
of non-variceal upper GI bleeding either as treatment or as a deliberate marker for guiding
subsequent arterial embolization when this is necessary.
There are a number of typographical and grammatical errors as detailed below.
Specific Comments
1   The title should read: "The value of endoscopically-placed metal clips for transcatheter arterial
embolization in the treatment of recurrent acute non-variceal upper gastrointestinal bleeding"
2   Introduction, para 2 should read: "Before embolization, angiography is required to find the
bleeding site where the contrast agent extravasates. However, it may not be possible to see the
contrast agent spill if bleeding was due to venous hemorrhage or if  bleeding has stopped. In this
circumstance, empiric embolization of the left gastric artery or gastroduodenal artery is usually
undertaken. However, the blood supply of the pylorus and duodenum is complicated, and the
collateral circulation between the celiac trunk and the superior mesenteric artery branches varies
greatly. Empiric embolization is often ineffective. In the study of Kim et al.4, the rebleeding rate
after TAE was up to 16% in patients with negative angiographic results. Since most ANVUGIB
patients undergo endoscopy before TAE, it has been proposed that a metal clip can be placed at
the site or edge of bleeding points during endoscopy to guide embolism during TAE based on
the radiopacity of the metal clip.(Figure-1)"
3   Introduction, para 3 should read: "Currently, there are several case reports about the role of
metal clips in the TAE of ANVUGIB patients marked with metal clips. No controlled studies
on the value of metal clips in TAE have been reported. (For details, see Table 1: Research status
of metal clips in TAE operations in patients with ANVUGIB.) These studies have preliminarily
suggested that marking the bleeding site with a metal clip can help locate the bleeding point
and guide embolization in patients with ANVUGIB who have failed endoscopic treatment.
Metal clip marking could also reduce the occurrence of complications (organ ischemia, necrosis,
dislocation of coils, etc.)."
4   M&M, Patients should read: "The inclusion criteria for the study population were patients
who had been diagnosed with ANVUGIB by clinical features and  a bleeding site found at
endoscopy and subsequently treated with TAE. Exclusion criteria were patients who had biliary
or pancreatic duct hemorrhage, hemodynamically unstable patients who were dependent on
intensive care support, and digestive tract bleeding due to malignant tumors. According to the
presence or absence of preplaced metal clips, they were divided into two groups."
5   Why were ICU patients excluded?
6   M&M Variables should read: "Clinical success refers to a follow-up up to 30 days after
discharge, complete hemostasis, and no need for additional endoscopic treatment, repeated
embolization or invasive treatment such as surgery. Mortality was recorded within 30 days after
TAE.
The baseline information included gender, age, history of surgery or trauma within 30 days, the
use of antithrombotics, the Rockall score, the hemorrhage site, intervals from hemorrhage to
TAE, angiography result, blood transfusion before TAE, hemoglobin before TAE, coagulation
disorders (PLT#80×109/L or international normalized ratio, INR#1.5, or activated partial
thromboplastin time, APTT#45 s)5 and embolization materials."
7   Subheading should read: "TAE Technical approach" and  change all "is" to "was"
8   Change "bucrylate" to N-butyl cyanoacrylate"
9   Results, para 1 should read: "According to the inclusion criteria,  172 patients were screened
out, and 70 patients were excluded.  102 patients were included in the study. There were 73 cases
in the metal clip group and 29 cases in the no metal clip group. For the flow chart, see Fig. 2."
Please clarify the difference between 'screened out' and 'excluded'
10 Change all use of 'nonmetal clip' in the text to 'no metal clip'
11 Discussion para 1 should read: " The clinical treatment of ANVUGIB may be challenging.
Endoscopic examination is always required  with hemostasis implemented if necessary and
possible. However, there is a rebleeding rate after endoscopic treatment and patients who have
failed endoscopic hemostasis are likely to be treated by TAE. However, it is often difficult
to locate the responsible blood vessel during TAE. Previous case reports have shown that
previously-placed endoscopic metal clips can play a role in locating the responsible blood vessels
during TAE. There have been no controlled studies evaluating the effect of endoscopic metal clip
marking on rebleeding rates and clinical outcomes after TAE. This study is the first controlled
study to assess the impact of endoscopically-placed metal clips placed at the bleeding site of
ANVUGIB patients on the clinical effect of TAE....."
12 Discussion, para 2 should read: "Compared with the no clips group, the group with metal
clips had a higher clinical success rate (82.2% vs. 45.0%, P<0.001), a lower rebleeding rate
(8.2% vs 27.6%, P=0.039) and a lower additional surgery rate (11.0% vs 20.7%, P<0.001).
Consistent with these results, metal clip marking was also shown to improve overall clinical
success (OR=3.750, 95CI=1.456-9.659, P=0.004) of TAE in multivariate analysis. Compared
with patients without metal clips, patients marked with metal clips were 3.75 times more likely
to achieve successful hemostasis by TAE. These results indicated that a metal clip placed at
the bleeding site was a facilitating factor for the success of hemostasis by TAE by locating the
bleeding vessels and guiding embolization during TAE procedures......."
13  Discussion, para 4 should read: "Although no consensus has been reached, the overall view
of these studies is basically the same. Combined with the results of our study, we recommend
that lesions with a Forrest classification of Ia-IIb and a Rockall score #5 should be marked with
metal clips when conditions permit. Metal clip marking  could be performed either by direct
metal clip hemostasis or by marking at the edge of the lesion without hemostasis.(Figure 3)"
The remainder of this para may be deleted as well as the next paragraph.
14 The 'Conclusions' para may be deleted.
Please review this paper.
user
Title: The value of endoscopically-placed metal clips for transcatheter arterial embolization in
the treatment of recurrent acute non-variceal upper gastrointestinal bleeding
Version: 1 Date: 08 Oct 2023
Reviewer:  David L. Carr-Locke
Reviewer's report:
General Comments
This is an excellent report demonstrating the benefit of placing an endoscopic clip at the site
of non-variceal upper GI bleeding either as treatment or as a deliberate marker for guiding
subsequent arterial embolization when this is necessary.
There are a number of typographical and grammatical errors as detailed below.
Specific Comments
1   The title should read: "The value of endoscopically-placed metal clips for transcatheter arterial
embolization in the treatment of recurrent acute non-variceal upper gastrointestinal bleeding"
2   Introduction, para 2 should read: "Before embolization, angiography is required to find the
bleeding site where the contrast agent extravasates. However, it may not be possible to see the
contrast agent spill if bleeding was due to venous hemorrhage or if  bleeding has stopped. In this
circumstance, empiric embolization of the left gastric artery or gastroduodenal artery is usually
undertaken. However, the blood supply of the pylorus and duodenum is complicated, and the
collateral circulation between the celiac trunk and the superior mesenteric artery branches varies
greatly. Empiric embolization is often ineffective. In the study of Kim et al.4, the rebleeding rate
after TAE was up to 16% in patients with negative angiographic results. Since most ANVUGIB
patients undergo endoscopy before TAE, it has been proposed that a metal clip can be placed at
the site or edge of bleeding points during endoscopy to guide embolism during TAE based on
the radiopacity of the metal clip.(Figure-1)"
3   Introduction, para 3 should read: "Currently, there are several case reports about the role of
metal clips in the TAE of ANVUGIB patients marked with metal clips. No controlled studies
on the value of metal clips in TAE have been reported. (For details, see Table 1: Research status
of metal clips in TAE operations in patients with ANVUGIB.) These studies have preliminarily
suggested that marking the bleeding site with a metal clip can help locate the bleeding point
and guide embolization in patients with ANVUGIB who have failed endoscopic treatment.
Metal clip marking could also reduce the occurrence of complications (organ ischemia, necrosis,
dislocation of coils, etc.)."
4   M&M, Patients should read: "The inclusion criteria for the study population were patients
who had been diagnosed with ANVUGIB by clinical features and  a bleeding site found at
endoscopy and subsequently treated with TAE. Exclusion criteria were patients who had biliary
or pancreatic duct hemorrhage, hemodynamically unstable patients who were dependent on
intensive care support, and digestive tract bleeding due to malignant tumors. According to the
presence or absence of preplaced metal clips, they were divided into two groups."
5   Why were ICU patients excluded?
6   M&M Variables should read: "Clinical success refers to a follow-up up to 30 days after
discharge, complete hemostasis, and no need for additional endoscopic treatment, repeated
embolization or invasive treatment such as surgery. Mortality was recorded within 30 days after
TAE.
The baseline information included gender, age, history of surgery or trauma within 30 days, the
use of antithrombotics, the Rockall score, the hemorrhage site, intervals from hemorrhage to
TAE, angiography result, blood transfusion before TAE, hemoglobin before TAE, coagulation
disorders (PLT#80×109/L or international normalized ratio, INR#1.5, or activated partial
thromboplastin time, APTT#45 s)5 and embolization materials."
7   Subheading should read: "TAE Technical approach" and  change all "is" to "was"
8   Change "bucrylate" to N-butyl cyanoacrylate"
9   Results, para 1 should read: "According to the inclusion criteria,  172 patients were screened
out, and 70 patients were excluded.  102 patients were included in the study. There were 73 cases
in the metal clip group and 29 cases in the no metal clip group. For the flow chart, see Fig. 2."
Please clarify the difference between 'screened out' and 'excluded'
10 Change all use of 'nonmetal clip' in the text to 'no metal clip'
11 Discussion para 1 should read: " The clinical treatment of ANVUGIB may be challenging.
Endoscopic examination is always required  with hemostasis implemented if necessary and
possible. However, there is a rebleeding rate after endoscopic treatment and patients who have
failed endoscopic hemostasis are likely to be treated by TAE. However, it is often difficult
to locate the responsible blood vessel during TAE. Previous case reports have shown that
previously-placed endoscopic metal clips can play a role in locating the responsible blood vessels
during TAE. There have been no controlled studies evaluating the effect of endoscopic metal clip
marking on rebleeding rates and clinical outcomes after TAE. This study is the first controlled
study to assess the impact of endoscopically-placed metal clips placed at the bleeding site of
ANVUGIB patients on the clinical effect of TAE....."
12 Discussion, para 2 should read: "Compared with the no clips group, the group with metal
clips had a higher clinical success rate (82.2% vs. 45.0%, P<0.001), a lower rebleeding rate
(8.2% vs 27.6%, P=0.039) and a lower additional surgery rate (11.0% vs 20.7%, P<0.001).
Consistent with these results, metal clip marking was also shown to improve overall clinical
success (OR=3.750, 95CI=1.456-9.659, P=0.004) of TAE in multivariate analysis. Compared
with patients without metal clips, patients marked with metal clips were 3.75 times more likely
to achieve successful hemostasis by TAE. These results indicated that a metal clip placed at
the bleeding site was a facilitating factor for the success of hemostasis by TAE by locating the
bleeding vessels and guiding embolization during TAE procedures......."
13  Discussion, para 4 should read: "Although no consensus has been reached, the overall view
of these studies is basically the same. Combined with the results of our study, we recommend
that lesions with a Forrest classification of Ia-IIb and a Rockall score #5 should be marked with
metal clips when conditions permit. Metal clip marking  could be performed either by direct
metal clip hemostasis or by marking at the edge of the lesion without hemostasis.(Figure 3)"
The remainder of this para may be deleted as well as the next paragraph.
14 The 'Conclusions' para may be deleted.
assistant