Second Opinion in the Italian Organ Procurement Transplantation: The Pathologist Is In

Round 1

Reviewer 1 Report

Abstract: 1) The authors mention that the consultations provided by the second opinion service led to safer and homogenous management of donors with history of malignancy or ongoing neoplasm by transplant centres. 

-Data to substantiate the claim may kindly be provided.

                2)  Aim of the paper is to discuss the role of the Italian Second opinion during organ procurement, highlighting the critical issues and the areas of improvement.

 -  It may kindly be specified whether this would be restricted to donors with history of neoplasm or  with a neoplastic process discovered at the time of donor evaluation alone or it would it encompass  all aspects of donor asessment.

Introduction: 

1)Availability of images simplifies protocols of consultation in radiology and also in  pathology.

  - However, presently, in the absence of digital pathology and IT infrastructure and the system of communication by telephone, the methodology of  obtaining second opinion may be defined.

History, Role and Advantages:

The english language requires editing. This may kindly be looked into.

For eg., Lines 54-55 may be written as: The consultation requests are managed by a pathologist , who is a pivotal figure in the process which leads to defining the risk profile of the donor......

Critical issues and room for improvemnet:

The goal of digital pathology is ideal.

- The proposed timeline for achievement would make the article more objective and result oriented. Adding the facilities of Artificial intelligence and machine learning would give a punch to the program but would escalate costs. Their feasibility and estimated time for implementation may also be indicated to make it a comprehensive and realistic perspective.

Standardization: is of utmost importance for reproducibility and harmonization-

-References may be given for guidelines, if any, for standardization of second opinion to make it thorough and accurate. 

Data integration: Auto processing is an useful suggestion.

-References for mechanisms to improve data integration and interoperability to review relevant information and provide accurate second opinionmay be listed.

Communication: 

It is effectively brought out in the paragraph on standardization that unwanted social interactions and unrelated conversations defy the objective. Effective communication is vitalfor successful second opinion.

- However the existing system of referral and the specialists available at the transplant centre and the National second opinion service and their heirarchy are not defined. Under such circumstances when possibly a junior person at the national centre would be providing a second opinion over that of a senior person at the transplant centre, the problems anticipated in the implementation of des=cision and hoew they would be sorted in the short time available for organ donation would need addressing.

Checklists: Extremely useful.

If any checklists have been created, they may be quoted.

Transplant outcome tracking: an effective scientific tool to assess the utility of second opinion. 

- The procedure for co;llection and communication to the pathologist may be defined.

Future direction: of telepathology is crucial to achieve optimal results. But digital pathology comes at a cost. It would be wise to have joint radiology- pathology programs ( being image intensive) AS DESCRIBED BY THE AUTHORS. aLSO TO CARRY ON WITH CHEAPER OPTION OF PORTABLE TABLETS  till the complete infrastructure is established is a good option.

Second opinion , being not so well established for donor assessment, pilot projects if any, may be cited.Application of AI and MLwill give a boost. Big Data may be added if deemed fit.

Conclusion: Editing the english language would enable better comprehensibility in the conclusion as also in the article as a whole.

Harmoization of centres is a noble objective. However implementation strategies are of importance.It would be wonderful to know how these are proposed to be achieved in Italy/

Author Response

We thank the Editor and Reviewer for the comments, which substantially helped us to further improve our manuscript.

All comments have been taken into full consideration and the appropriate changes made. All of the changes are made with use of “track change” and both a marked and a clean copy of manuscript are provided.

Furthermore, as recommended, the manuscript has been edited by an Editing Professional Service.

Please find below our responses to the comments.

Comments and Suggestions for Authors

Abstract: 1) The authors mention that the consultations provided by the second opinion service led to safer and homogenous management of donors with history of malignancy or ongoing neoplasm by transplant centres. 

-Data to substantiate the claim may kindly be provided.

Thank for this recommendation.

Specific experience from 2006 to 2015 has showed that use of neoplastic donors is safe, as no cases of transmission were recorded from this donor pool, and expands the pool of organs to transplant. This has been added to Paragraph 2 (ref n .15).

                2)  Aim of the paper is to discuss the role of the Italian Second opinion during organ procurement, highlighting the critical issues and the areas of improvement.

 -  It may kindly be specified whether this would be restricted to donors with history of neoplasm or  with a neoplastic process discovered at the time of donor evaluation alone or it would it encompass  all aspects of donor asessment.

Thank you for the comment.

As a rule, second opinion expert confronts and assists the network of colleagues required to evaluate the risk of a donor with neoplasm and also guides with recognized expertise the entire team of healthcare professionals involved in potential donor management. The consultation is not restricted only to donors with history of neoplasm or with newly discovered neoplasm. Aim of the consultation is helping in defining the risk profile of donor, helping centers to evaluate medical history of donors and to plan clinical, radiological or pathological investigations. This concept/definition has been rephrased in order to improve clarity.

Introduction: 

1)Availability of images simplifies protocols of consultation in radiology and also in pathology.

  - However, presently, in the absence of digital pathology and IT infrastructure and the system of communication by telephone, the methodology of  obtaining second opinion may be defined.

 Thank you for the valuable comment.

Nowadays the operating method of the second opinion expert is an available 24 hours service by telephone. This is still a reliable medium in a country like Italy with geographical and logistic difficulties and differences among regions. The development of an adequate infrastructure is a primary objective for services that base diagnostic reports on images such as pathology and radiology. This has been better rephrased in Paragraph 3.

History, Role and Advantages:

The english language requires editing. This may kindly be looked into.

As recommended, after the revision the manuscript has been edited by an Editing Professional Service.

For eg., Lines 54-55 may be written as: The consultation requests are managed by a pathologist , who is a pivotal figure in the process which leads to defining the risk profile of the donor......

Thank you for reporting this. The sentence has been rephrased as recommended.

Critical issues and room for improvemnet:

The goal of digital pathology is ideal.

- The proposed timeline for achievement would make the article more objective and result oriented. Adding the facilities of Artificial intelligence and machine learning would give a punch to the program but would escalate costs. Their feasibility and estimated time for implementation may also be indicated to make it a comprehensive and realistic perspective.

Thank for this valuable suggestion on which we strongly agree.

Considering the digital transition authors are fully committed with several literature evidences and running projects in order to promote Digital Pathology and to develop and validate dedicated AI tools.

Unfortunately the question on when digital pathology and machine learning algorithms will be ready for use in this setting, we are aware that the application of artificial intelligence tools depends on two main factors: the first is the implementation of digital pathology networks, the second is the development of solid and validated artificial intelligence tools, which should not only replicate experts, but should rather be directly trained to predict the desired transplant outcome endpoints.

We have added this perspective to the text.

Furthermore, the question of cost has been discussed into the manuscript as our ref. n 36 (Lujan G, Quigley JC, Hartman D, Parwani A, Roehmholdt B, Meter BV, et al. Dissecting the Business Case for Adoption and Implementation of Digital Pathology: A White Paper from the Digital Pathology Association. J Pathol Inform. 2021;12:17).

Standardization: is of utmost importance for reproducibility and harmonization-

-References may be given for guidelines, if any, for standardization of second opinion to make it thorough and accurate. 

Data integration: Auto processing is an useful suggestion.

-References for mechanisms to improve data integration and interoperability to review relevant information and provide accurate second opinion may be listed.

Thank you for the comment and recommendation. In order to further support, References n 32-33 have been added to the reference list.

Communication: 

It is effectively brought out in the paragraph on standardization that unwanted social interactions and unrelated conversations defy the objective. Effective communication is vitalfor successful second opinion.

- However the existing system of referral and the specialists available at the transplant centre and the National second opinion service and their heirarchy are not defined. Under such circumstances when possibly a junior person at the national centre would be providing a second opinion over that of a senior person at the transplant centre, the problems anticipated in the implementation of decision and how they would be sorted in the short time available for organ donation would need addressing.

Thank for this important comment.

The second opinion is an advisory tool and consultation and answers provided by second opinion expert guarantee the best achievable rapidity in reliable risk assessment. The potential “junior vs senior” question can be configured but experience and competence are predominant values. It is necessary to specify that it is always and ultimately the responsibility of the clinician who manages the potential recipient to evaluate the risk differential between remaining on the waiting list for an indeterminate time and receiving an organ potentially capable of to transmit a neoplasm.

Checklists: Extremely useful.

If any checklists have been created, they may be quoted.

Thank for this valuable recommendation indeed we are working on a checklist in order to manage a Second Opinion on a donor.

Transplant outcome tracking: an effective scientific tool to assess the utility of second opinion. 

Thank your for the comment.

Specific experience from 2006 to 2015 has showed that use of neoplastic donors is safe, as no cases of transmission were recorded from the donor pool subject of a Second Opinion. This has been rephrased in Paragraph 2 (ref n .15).

- The procedure for collection and communication to the pathologist may be defined.

The operating method of the second opinion expert is by telephone followed by an email summarizing the discussion. This has been better rephrased in Paragraph 3.

Future direction: of telepathology is crucial to achieve optimal results. But digital pathology comes at a cost. It would be wise to have joint radiology- pathology programs ( being image intensive) AS DESCRIBED BY THE AUTHORS. aLSO TO CARRY ON WITH CHEAPER OPTION OF PORTABLE TABLETS  till the complete infrastructure is established is a good option.

Second opinion , being not so well established for donor assessment, pilot projects if any, may be cited.Application of AI and MLwill give a boost. Big Data may be added if deemed fit.

Thank for this valuable comment on the importance of share “images”

We are aware that the application of digital pathology and then AI depends on two main factors: the first is the implementation of digital pathology networks, the second is the development of solid and validated artificial intelligence tools.

Conclusion: Editing the english language would enable better comprehensibility in the conclusion as also in the article as a whole.

The whole manuscript, after the Revision, has been edited by an Editing Professional Service.

Harmoization of centres is a noble objective. However implementation strategies are of importance.It would be wonderful to know how these are proposed to be achieved in Italy/

Thank you for your comment.

The role of the Second Opinion also wants to be to participate in the drafting of the national guidelines, to indicate shared procedures to standardize the preparation methods of the preparations in the various pathological anatomy laboratories, to standardize as much as possible the "forms" for histological reporting both of morpho-functional biopsies which, in cases of neoplasia or suspected neoplasia. This part has been added to Paragraph 2.

Reviewer 2 Report

The manuscript entitled “Second Opinion in the Italian Organ Procurement Transplantation: The Pathologist is In” aimed to discuss the role and future of the Italian second opinion consultation service during organ procurement, highlighting the critical issues and areas of improvement. 

The authors are to be commended for an interesting manuscript on the relevant topic of management and use of donors with history of malignancy or ongoing neoplasm discovered at the time of donor evaluation.

Errors and recommendations for the manuscript are detailed below. All page numbers refer to page position of the PDF submission.

Errors/Recommendations:

1)     History, Role and Advantages, Lines 62-68: I would suggest to rephrase this sentence as too long and difficult to read. 

2)     Future Direction, Lines 137-139: Please rephrase this sentence as difficult to read.

3)     Future Direction, Line 152: Please be consistent in using the abbreviations (for example, artificial intelligence).

4)     Conclusions, Lines 161-164: Please rephrase this sentence to improve clarity. 

5)     I would suggest to use a comma after adverbs such as ‘However’ or ‘Furthermore’ throughout the manuscript.

Author Response

Comments and Suggestions for Authors

The manuscript entitled “Second Opinion in the Italian Organ Procurement Transplantation: The Pathologist is In” aimed to discuss the role and future of the Italian second opinion consultation service during organ procurement, highlighting the critical issues and areas of improvement. 

 The authors are to be commended for an interesting manuscript on the relevant topic of management and use of donors with history of malignancy or ongoing neoplasm discovered at the time of donor evaluation.

Errors and recommendations for the manuscript are detailed below. All page numbers refer to page position of the PDF submission.

 Errors/Recommendations:

1)     History, Role and Advantages, Lines 62-68: I would suggest to rephrase this sentence as too long and difficult to read. 

Thank your for the comment.

The sentence has been rephrased to improve clarity and readability.

2)     Future Direction, Lines 137-139: Please rephrase this sentence as difficult to read.

Thank you for the comment.

The sentence has been rephrased.

3)     Future Direction, Line 152: Please be consistent in using the abbreviations (for example, artificial intelligence).

Thank you for the comment.

The use of abbreviations has been checked and improved (e.g line 152).

4)     Conclusions, Lines 161-164: Please rephrase this sentence to improve clarity. 

Thank you for the valuable suggestion.

The Conclusions have been rephrased.

5)     I would suggest to use a comma after adverbs such as ‘However’ or ‘Furthermore’ throughout the manuscript.

Thank you for this recommendation.

After the Revision the manuscript has been edited by an Editing Professional Service in order to meet the required improvement and standard.

Reviewer 3 Report

The article highlights the role of second opinion consultation in transplantation medicine, specifically in the centralized assessment of donors, and aims to address the areas of improvement based on the Italian Transplant Centers expertise.  

1.     It is suggested that the use of second opinion consultations can lead to a safer and more standardized approach to the management of donors with a history of malignancy or an ongoing neoplasm. This is an essential aspect of transplantation medicine, as the presence of cancer in a donor can have serious consequences for the recipient outcome. To improve the readability and clarity of the text, it would be beneficial to use shorter sentences and simplify the language (e.g. lines 62-67, conclusion paragraph). This would make the text more accessible to a wider audience and help ensure that the message is conveyed clearly and effectively. 

2.     The article shortly addresses the use of AI to improve transplantation practices. This represents a contemporary topic and a promising application of the technology. AI based algorithms can analyze large amounts of data, including the donor/recipient medical history and genetic information to identify the best match for the organ transplant. One of the main advantages of using AI in this context is that it can also factor in data from previous transplants to improve outcomes. However, an essential step towards implementation of AI in organ transplant is the need for AI algorithms to be trained on large and diverse datasets to avoid biases and ensure accurate predictions. I would recommend expanding the paragraph on AI as this is of high interest nowadays. 

Author Response

Comments and Suggestions for Authors

The article highlights the role of second opinion consultation in transplantation medicine, specifically in the centralized assessment of donors, and aims to address the areas of improvement based on the Italian Transplant Centers expertise.  

1. It is suggested that the use of second opinion consultations can lead to a safer and more standardized approach to the management of donors with a history of malignancy or an ongoing neoplasm. This is an essential aspect of transplantation medicine, as the presence of cancer in a donor can have serious consequences for the recipient outcome. To improve the readability and clarity of the text, it would be beneficial to use shorter sentences and simplify the language (e.g. lines 62-67, conclusion paragraph). This would make the text more accessible to a wider audience and help ensure that the message is conveyed clearly and effectively. 

We thank the reviewer for this important recommendation.

The manuscript has been fully reviewed and edited by an editing service, to improve readability and clarity, with particular reference to the conclusion, which as been fully rephrased, as recommended.

2. The article shortly addresses the use of AI to improve transplantation practices. This represents a contemporary topic and a promising application of the technology. AI based algorithms can analyze large amounts of data, including the donor/recipient medical history and genetic information to identify the best match for the organ transplant. One of the main advantages of using AI in this context is that it can also factor in data from previous transplants to improve outcomes. However, an essential step towards implementation of AI in organ transplant is the need for AI algorithms to be trained on large and diverse datasets to avoid biases and ensure accurate predictions.I would recommend expanding the paragraph on AI as this is of high interest nowadays.

We thank the reviewer for this comment.

The paragraph on AI has been improved and expanded in order to better define the role and perspective of artificial intelligence in the context of transplant pathology.