Efficacy and safety of three-dimensional magnetically assisted capsule endoscopy for upper gastrointestinal and small bowel examination

Dong Jun Oh; Yea Je Lee; Sang Hoon Kim; Joowon Chung; Hyun Seok Lee; Ji Hyung Nam; Yun Jeong Lim

doi:10.1371/journal.pone.0295774

Peer Review History

Original SubmissionJuly 13, 2023
4 Sep 2023 Decision Letter - Thomas Lui Ka Luen, Editor PONE-D-23-18486Efficacy and safety of three-dimensional magnetically assisted capsule endoscopy for upper gastrointestinal and small bowel examinationPLOS ONE Dear Dr. Lim, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Please submit your revised manuscript by Oct 19 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. 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Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes Reviewer #2: Partly ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes ****** 3. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: No ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: Yes ****** 5. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: This is a well-designed study to show the potential application of 3D MACE in evaluating upper GI and small bowel lesions. The strong point is that to have the endoscopy result to compare. The similarity in results suggested further application of this technique in the future for the patients not tolerating to endoscopy. However, due to the small number of patients, the data analysis is simple with descriptive methods mainly. I have some suggestions for the authors: - Clarify more in the results besides detection, is it possible for the doctors to evaluate the characteristics of the lesions using the standardized classification? For the inflammatory lesions, can 3D MACE detect both the lesions with focal and spreading areas? If possible adding more characteristics of the lesions and endoscopists' evaluations will make the data more interesting. - For the cases with mucosal injury and minor bleeding, in fact what is the origin of the bleeding? EGD is safe so it is a bit confusing why patients have post-procedure bleeding? Reviewer #2: Congratulation to Lim et al on their proof of concept study utilising a novel 3D enhanced MACE for examination of stomach and small bowel in 55 patients. The efficacy and safety appears to be comparable with conventional upper endoscopy. My comments on the manuscript are listed as following: Financial disclosure - Intromedic is mentioned as clinical sponsor in the study protocol which is not stated in the financial disclosure. Please clarify Intromedic's role in the study Method - Further description on manipulation of the MACE after ingestion should be provided. - Please define unsuccessful examination of anatomical structure or suspected lesions eg. length of time or number of attempts in assessment of a structure or lesion of concern Result and discussion - Photos taken by MACE vs. 3D MACE vs. conventional endoscopy on selected case should be provided for better appreciation by the readers - For figure 5 regarding lesions detected, please comment on whether further assessment of lesions ie. image magnification, image enhancement is possible. Also, how to decide on need for conventional upper endoscopy with biopsy if the 3D-MACE is to be used independently. - Image on small bowel examination including detected pathology should be provided - Regarding the 3 inflamed lesions and 1 polyps detected by 3D MACE but not upper endoscopy, how are the cases managed ? Are they considered as false positive or follow up assessment is arranged to confirm the lesion ? - Additional limitation of the study is no gastric cancer cases being recruited, therefore efficacy in detecting potential malignant lesion cannot be inferred ****** 6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: Yes: Dao Viet Hang Reviewer #2: No ******** [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0295774.r001
Revision 1
6 Oct 2023 Author Response Thank you very much for giving the opportunity of revision. The authors appreciate the reviewer’s critical and thoughtful comments. We did our best to write the reply for your comments. We also used the "Track Changes" feature to make revision to the manuscript and make them easily visible to editors and reviewers. [Reviewer 1] 1. Clarify more in the results besides detection, is it possible for the doctors to evaluate the characteristics of the lesions using the standardized classification? For the inflammatory lesions, can 3D MACE detect both the lesions with focal and spreading areas? If possible adding more characteristics of the lesions and endoscopists' evaluations will make the data more interesting. : This is an important point. Of course, 3D MACE operator and endoscopist each classified the characteristics of the inflamed lesion such as erosive, hyperemic, and edematous. However, subgroup analysis was not performed because there were differences between 3D MACE operator and endoscopist in distinguishing whether an inflamed lesion was hyperemic or erosive. Additionally, this distinction was thought to be minor and insignificant, and was not relevant to the outcome of this study. : The extent of the inflamed lesion could be confirmed similarly for both 3D MACE and upper endoscopy. This information added to the “Result; Table 2” and “Discussion; Limitations” section. 2. For the cases with mucosal injury and minor bleeding, in fact what is the origin of the bleeding? EGD is safe so it is a bit confusing why patients have post-procedure bleeding? : Most procedure related bleeding involved belching in this study. The bleeding was spontaneously stopped without any additional procedure. We added this content to the “Result; Safety and patient satisfaction” section. ===================================================================================================== [Reviewer 2] 1. Financial disclosure - Intromedic is mentioned as clinical sponsor in the study protocol which is not stated in the financial disclosure. Please clarify Intromedic's role in the study : Intromedic company only developed 3D MACE for a research project and we did the research independently. The company had no research or financial involvement in this study. Additionally, the authors have no financial or personal relationship with Intromedic. We added this content in the “Acknowledgments” section. 2. Method - Further description on manipulation of the MACE after ingestion should be provided. : We added a description of the manipulation of 3D MACE in “Method; Study protocol; 3D MACE for upper GI and small bowel examination” section → “When the 3D MACE stopped at the esophagus, the controller was moved up and down to observe the esophagus.” “Once the 3D MACE landed on the stomach, the cardia and fundus were observed by rotating and tilting the controller in the left lateral position. Then, the patient was placed upright, and the controller was placed in the left upper quadrant and left flank area to observe the fundus and body. After that, the operator moved the controller to right upper quadrant and right flank area to observe the antrum and pylorus. If necessary, the patient was changed to the right lateral position and the antrum was observed.” 3. Method - Please define unsuccessful examination of anatomical structure or suspected lesions eg. length of time or number of attempts in assessment of a structure or lesion of concern : This is a good point. Mucosal visualization for each structure was also assessed. Failure to structure confirmation was defined as a case where the structure was not visible during examination or was not clearly photographed. There were no restrictions on length of time or number of attempts. We added this content in the “Method; Outcomes and Safety” section. 4. Result and discussion - Photos taken by MACE vs. 3D MACE vs. conventional endoscopy on selected case should be provided for better appreciation by the readers : MACE and 3D MACE are completely different models. And since this study was approved for clinical research only using 3D MACE, there is no data regarding MACE. Therefore, MACE and 3D MACE could not be compared in this study. Instead, we will post here images of MACE published in other articles, for comparison with 3D MACE. 5. Result and discussion - For figure 5 regarding lesions detected, please comment on whether further assessment of lesions ie. image magnification, image enhancement is possible. Also, how to decide on need for conventional upper endoscopy with biopsy if the 3D-MACE is to be used independently. : Image brightness and definition was enhanced using a reading viewer. We added this content in the “Figure 5” section. Gastric examination using a magnetic capsule is still in the challenging stage. Therefore, it is considered premature to separate 3D MACE from upper endoscopy. The need for biopsy in 3D MACE is also considered to be the same as the indications for upper endoscopy such as gastric ulcer and suspected gastric cancer. We added this content in the “Discussion; Limitation” section. 6. Result and discussion - Image on small bowel examination including detected pathology should be provided : Images of small bowel ulcers were included in S4 Fig. 7. Result and discussion - Regarding the 3 inflamed lesions and 1 polyps detected by 3D MACE but not upper endoscopy, how are the cases managed? Are they considered as false positive or follow up assessment is arranged to confirm the lesion? : Thank you for your thoughtful comment. In the case of missed lesions, the authors reviewed the 3D MACE images and concluded that the lesions were insignificant. The endoscopist explained that the patients needed periodic follow-up endoscopy. We added this information in the “Result” section. 8. Result and discussion - Additional limitation of the study is no gastric cancer cases being recruited, therefore efficacy in detecting potential malignant lesion cannot be inferred : I agree with your comment. We added to the “Discussion” section the limitation that we could not confirm the efficacy of gastric cancer detection because we did not have gastric cancer patients. Attachments Attachment Submitted filename: Response to reviewers.docx https://doi.org/10.1371/journal.pone.0295774.r002
13 Nov 2023 Decision Letter - Thomas Lui Ka Luen, Editor PONE-D-23-18486R1Efficacy and safety of three-dimensional magnetically assisted capsule endoscopy for upper gastrointestinal and small bowel examinationPLOS ONE Dear Dr. Lim, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Please submit your revised manuscript by Dec 28 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. Please include the following items when submitting your revised manuscript: A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'. A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'. An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter. If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols. We look forward to receiving your revised manuscript. Kind regards, Thomas Lui Ka Luen Academic Editor PLOS ONE Journal Requirements: Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation. Reviewer #3: (No Response) ******** 2. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #3: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #3: Yes ****** 4. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #3: Yes ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #3: Yes ****** 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #3: On the overall, the authors were able to address the previous round of comments. Some inconsistencies are still present in the statistical section: (a) The power/sample size stab does not mention the statistical test that was used. (b) It is not clear what the authors meant by "Kapp" in "Kapp, sensitivity, and specificity were used to assess..." ****** 7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #3: No ******** [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0295774.r003
Revision 2
26 Nov 2023 Author Response Response to reviewer Thank you very much for giving the opportunity of revision. The authors appreciate the reviewer’s critical and thoughtful comments. We did our best to write the reply for your comments. We also used the "Track Changes" feature to make revision to the manuscript and make them easily visible to editors and reviewer. On the overall, the authors were able to address the previous round of comments. Some inconsistencies are still present in the statistical section: 1. The power/sample size stab does not mention the statistical test that was used. : Thank you for the helpful suggestion. We revised the sentence as follows in relation to mention of power/sample size stability: ‘To ensure the power and stability of the sample size in our study, we conducted a Power Analysis, setting the level of significance (α) at 0.05 and the power of the test (β) at 80%. This involved considering a standard deviation of 4.0 based on the successful visualization of gastric structures from the previous study [5], and an effect size of 0.8 in the t-test for the Power Analysis. 2. It is not clear what the authors meant by "Kapp" in "Kapp, sensitivity, and specificity were used to assess..." : Kapp is a misspelling of kappa (k), and I apologize for the mistake. We revised the sentence as follows: ‘Kappa (κ), sensitivity, and specificity were used to evaluate the agreement and assess each part of upper GI anatomy and gastric lesions between two groups. Attachments Attachment Submitted filename: Response to reviewer - 2nd revision.docx https://doi.org/10.1371/journal.pone.0295774.r004
29 Nov 2023 Decision Letter - Thomas Lui Ka Luen, Editor Efficacy and safety of three-dimensional magnetically assisted capsule endoscopy for upper gastrointestinal and small bowel examination PONE-D-23-18486R2 Dear Dr. Lim, We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements. Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication. An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Thomas Lui Ka Luen Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0295774.r005

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