Liver Transplantation for Colorectal Liver Metastases: Current Management and Future Perspectives
, Guillaume Rossignol 4, Teresa Antonini 2, Domitille Erard 2, Sylvie Radenne 2,5, Marielle Guillet 5, Jean-Christophe Souquet 5, Kayvan Mohkam 1,3 and Mickael Lesurtel 1,3,*Round 1
Reviewer 1 Report
Congratulations for your work. This is very concise and informative review. It would be better to readers that you summarize more details about protocol of LF for unresectable CRLM, especially chemotherapy and regimens before and after LT. Is there any report about hepatic arterial chemotherapy like LT for bile duct cancer?
Author Response
Our reply to Reviewer 1:
We thank the reviewer for taking the time to review our manuscript.
In general, there is no clear recommendation of chemotherapy regimens in patients with nonresectable CRLM before potential LT. Indeed, in all studies, chemotherapy regimens were left at the discretion of oncologists to achieve the best control of the metastatic disease. In this setting, doublets or triplets associated with biological agents should be selected according to tumor biology including mutations. In this setting, several lines of chemotherapy including intra-arterial chemotherapy may be necessary.
Regarding adjuvant chemotherapy after liver transplantation, there is no consensus in the literature. From the 8 ongoing trials on liver transplantation for nonresectable CRLM, only one (TRANSMET) implies the administration of adjuvant chemotherapy.
Reviewer 2 Report
The manuscript “Liver Transplantation for colorectal liver metastases: Current management and future perspectives” presents data and perspectives about liver transplantation for nonresectable liver metastases from colorectal cancer.
This is an interesting topic of great interest for the scientific community.
My comments for the authors are the following:
Table 1: the title is missing
TRANSMET NCT02597348 : in which city or cities has performed this study?
Abbreviations in table 1 are missing
Extended criteria donors (e.g., steatotic, aged, small size, etc) grafts are more susceptible to ischemia-reperfusion injury. In my view, this point should be discussed since these organs plus the basal state of the cancer patient could deeply decrease the success of the transplantation. In this sense, the donors' characteristics should be considered.
Most of the references are not recent (older than 5 years).
Author Response
Our reply to Reviewer 2:
We thank the reviewer for his constructive remarks on our manuscript.
- Table 1: the title is missing
We do not understand this remark since in our manuscript send to the editor, the title is included before the first line of the table
Table 1: Ongoing trials on liver transplantation for CRLM
2.TRANSMET NCT02597348: in which city or cities has performed this study?
Transmet is a French prospective randomized trial and patients were included from 14 centers in France, 2 centers in Italy, and 4 centers in Belgium. For the sake of space, I did not include all the names of the centers in table 1.
- Abbreviations in table 1 are missing
We are sorry for this oversight. We have now completed the list of abbreviations at the bottom of table 1.
- Extended criteria donors (e.g., steatotic, aged, small size, etc) grafts are more susceptible to ischemia-reperfusion injury. In my view, this point should be discussed since these organs plus the basal state of the cancer patient could deeply decrease the success of the transplantation. In this sense, the donors' characteristics should be considered.
According to Eurotransplant, because of the scarcity of donors, 50% of liver transplantations in Europe are performed with liver grafts from extended criteria donors (also called marginal grafts). Although those marginal grafts are usually used in ill patients with severe portal hypertension and liver insufficiency, outcomes are not significantly worse than after liver transplantation with optimal grafts. Since patients with nonresectable CRLM may have more physiological resources because they do not suffer from liver insufficiency, but are considered as not validated indications, it seems reasonable to propose marginal liver grafts to those patients.
Page 11, we added the following sentence in the paragraph about extended criteria donors:
“Indeed, recipients with nonresectable CRLM do not suffer from portal hypertension nor liver insufficiency and may therefore tolerate better those marginal grafts.”
- Most of the references are not recent (older than 5 years).
We would like to point out that the literature on liver transplantation for colorectal metastases is limited and mostly monocentric reports. After 2010, the Oslo team elaborated the majority of papers on the subject. The current review includes all the latest papers of the Oslo team (Dueland Am J Transplant 2020, Smedman BJS 2020, Dueland Ann Surg 2020). The only recent paper outside the Oslo group covering this topic is also included (Toso Liver Transpl 2017).
Reviewer 3 Report
The authors described Liver Transplantation for colorectal liver metastases in recent era.
With development of chemotherapy, liver transplantation for unresectable colorectal liver metastases has been reconsidered. It is one of the most important issue in recent era. The authors reviewed carefully and well described.
Author Response
Our reply to Reviewer 3:
We thank the reviewer for his encouraging comments.
Reviewer 4 Report
I enjoyed your work and felt it was a good summary of disparate studies and is helpful to those who have not read a great deal about this topic. The paper flows well and is easy to follow.
My only quibbles have to do with wording and grammar. My suggestions are as follows:
1.) Line 21: Replace "with" with "and".
2.) Line 21-22: Rewrite the second sentence to read "for this indication has historically a poor reputation,"
3.) Line 57: Replace "unsatisfactory" with "disappointing".
4.) Line 68: Replace "reconsidering" with "reconsider".
5.) Line 73: Replace "2000'" with "2000's".
6.) Line 76: Replace "2000'" with "2000's".
7.) Line 81: Replace "1980'" with "1980"s".
8.) Line 102: Replace "of the" with "at".
9.) Line 125: Reorder "negatively" so it comes after "survival".
10.) Line 145: Rewrite the sentence to read "with at least a 10% response rate".
11.) Line150: Replace "The" with "Their" and remove the "the" prior to "arm".
12.) Line 152: Replace "applied" with "used".
13.) Line 153: Rewrite the sentence to read "including having a steatosis of over 60%, coming from donation after circulatory death donors, "
14.) Line 174: Replace "within" with "with" and "criteria" with "patients" and "arguments" with "support".
15.) Line 177: Replace "bear" with "have".
16.) Line 192: Start the first sentence with "In one pattern, pulmonary..."
17.) Line 192: Rewrite the second sentence to read, “They occurred early, 4 months after LT, had an indolent course,..”
18.) Line 194: Rewrite the second sentence to read, “In the second pattern, hepatic metastases occurred as multi-site recurrences while the liver was never the first site.”
19.) Line 204: Rewrite the sentence to read, “most common site of recurrence, but these lesions…”.
20.) Line 206: Replace “compassioned” with “compassionate”.
21.) Line 207: Replace “tumor profile” with “cancer”.
22.) Line 220: Replace “mature” with “long” and “An” with “A”.
23.) Line 228: Add a space after “13” and before “month”.
24.) Line 238: Add an “and” after “CRM,” and before “assessment”.
25.) In the Inclusion Criteria of the SECA II trial, I believe you meant to say “-2 years or more between the diagnosis”, i.e., replacing “before” with “between”.
26.) In the Inclusion Criteria of the Toronto Study, replace “of” with “or”.
27.) Line 255: Replace “mostly” with “often”.
28.) Line 270: Replace “0,8%” with “0.8%”.
29.) Line 283: Remove “of all”.
30.) Line 284: Remove “of all”.
31.) Line 284-285: Rewrite “offers a more precise control” to “allows more precise timing,”.
32.) Line 294: Replace “solid” with “acceptable”.
33.) Line 298: Replace “guaranty” with “guarantee” and ”in” with “for”.
Author Response
Our reply to Reviewer 4:
We thank the reviewer for his/her positive remarks and we much appreciate his/her suggestions regarding wording and grammar. We have modified the manuscript accordingly.
