Trends in Lymphadenectomy for Esophageal/Esophagogastric Junction Cancer

Round 1

Reviewer 1 Report

The authors present a well-researched review of lymph node metastasis and lymphadenectomy in esophageal cancer. The review is well organized and addresses both the challenges of lymph node metastasis quantification, dissection, and side effects, and the possible surgical approaches that can tackle these problems. The comments I have are minor.

1. “System for classifying lymph node…” Can the authors include a paragraph or two here, describing how lymph node metastasis is usually quantified in these cases?
2. Line 131 – “Applicating” should be “Applying”.
3. Table 1 – Replace “Our Study” with “Nishimura”
4. Line 236 – “Transition” – I am unsure why the authors used the term transition here. I think saying “Surgical approaches to eliminate…” should suffice here.
5. Line 254 – “Replace “retrieved” with “received”.
6. Line 297 – “Multivalley” – did the authors mean “universally”?

The authors do need the manuscript proofread, since the grammar and usage of certain words were incorrect at multiple points.

Author Response

We are grateful for your insightful comments, which have helped us improve the manuscript significantly. We agree with your suggestions and have revised the manuscript accordingly to the best of our ability. Please find below our responses to your comments in a point-by-point manner.

Reviewer: 1

1. “System for classifying lymph node…” Can the authors include a paragraph or two here, describing how lymph node metastasis is usually quantified in these cases?

Response:

Thank you for your valuable comment. The largest difference between the 2 classifications is the definition of cervical lymph nodes. By the AJCC system, cervical lymph nodes, except for station 1 and level VI and VII (Head and Neck AJCC cancer staging) are not considered as locoregional lymph node metastases but as extraregional lymph node as M-disease regardless to the location of the tumor. The latest JES system has attempt to unify with the AJCC classification and has defined supraclavicular lymph nodes as M1a lymph node when the tumor is located at the thoracic part. In clinical practice in Japan, treatment strategy would be determined by the classification of JES. I have added this paragraph to the same section.

2. Line 131 – “Applicating” should be “Applying”.

Response:

We are sorry for the confusion. We have corrected the word as you pointed out.

3. Table 1 – Replace “Our Study” with “Nishimura”

Response:

We have changed the label as your suggestion.

4. Line 236 – “Transition” – I am unsure why the authors used the term transition here. I think saying “Surgical approaches to eliminate…” should suffice here.

Response:

Thank you for your comment. We wanted to propose 3 field lymph node dissection by minimally invasive trans-thoracic esophagectomy as a modern lymphadenectomy in this section. However, we believe it is more simple and easier for readers to understand the context as you suggested. Therefor, we changed the title as your propose. 

5. Line 254 – “Replace “retrieved” with “received”.

Response:

We have changed the word as your suggestion.

6. Line 297 – “Multivalley” – did the authors mean “universally”?

Response:

We meant “multiply”. We again apologize for the confusion.  

Reviewer 2 Report

LINE 53: Postoperative complicationS

LINE 78: radiation THERAPY.

LINE 116: classificationS

LINE 140: "percentage" may be changed by the word "percent"

LINE 168: % OF tumors

LINE 232: in the table change "decresaed" for "decreased"

LINE 236: change TSANSITION for TRANSITION

Author Response

We are grateful for your insightful comments, which have helped us improve the manuscript significantly. We agree with your suggestions and have revised the manuscript accordingly to the best of our ability. Please find below our responses to your comments in a point-by-point manner.

Thank you for revising this review. I have changed the typo that you have pointed out.

Reviewer 3 Report

1.     “Table previous statements of resection of TD”, please mark “Table 1”

2.     The author should explain “EC showed SLN in the abdominal areas, and SLNs in 20% of those with lower thoracic EC were identified around the right recurrent nerve. This may suggest that the extended esophagectomy with 3-field lymphadenectomy may be a reasonable procedure for the wide SLN distribution and unpredictable metastatic patterns.” more detailed. (Lines 141-144)

3.     Again, the author should explain “The decrease of body fat mass were statistically greater with patients who underwent TD resection. However, the change of skeletal muscle mass did not differ after TD resection.” more detailed. (Lines 285-287)

Minor editing of English language required. 

Author Response

We are grateful for your insightful comments, which have helped us improve the manuscript significantly. We agree with your suggestions and have revised the manuscript accordingly to the best of our ability. Please find below our responses to your comments in a point-by-point manner.

Reviewer: 2

1. “Table previous statements of resection of TD”, please mark “Table 1”

Response: Thank you for your comment. I have changed the label of Table as Table1.

2. The author should explain “EC showed SLN in the abdominal areas, and SLNs in 20% of those with lower thoracic EC were identified around the right recurrent nerve. This may suggest that the extended esophagectomy with 3-field lymphadenectomy may be a reasonable procedure for the wide SLN distribution and unpredictable metastatic patterns.” more detailed. (Lines 141-144)

Response:

Thank you for your valuable comment. SLNs are usually predicted to be identified at the closest LN region of the tumor. In upper thoracic esophageal cancer, the lymph nodes along bilateral recurrent laryngeal nerve chain were identified most frequently. However, 25% of those showed SLN along the left gastric artery. As for lower thoracic EC, SLN was mainly detected in the abdominal area but 20% of cases identified SLNs in the right recurrent nerve. This may indicate that the lymphatic flow of EC is abundant and LN metastasis can be found to other regional LN stations. As so, the extended esophagectomy with 3-field lymphadenectomy may be a reasonable procedure for the wide SLN distribution and unpredictable metastatic patterns. We have made this change to the main manuscript.

3. Again, the author should explain “The decrease of body fat mass were statistically greater with patients who underwent TD resection. However, the change of skeletal muscle mass did not differ after TD resection.” more detailed. (Lines 285-287)

Response:

Thank you for the valuable comment. The decrease of body fat mass were statistically greater 1 year after surgery with patients who underwent TD resection (TD preserved – 33.14% vs TD resected – 41.9%, p = 0.021). However, the change of skeletal muscle mass did not differ after TD resection (TD preserved – 4.19% vs TD resected – 3.76%, p = 0.858). They speculated that because TD plays an important role in transporting digestive fat, TD resection may have interfered this function. On the contrary, muscle mass could be influenced by many factors such as perioperative rehabilitation and nutrition counseling, and TD resection may not be a strong factor to deteriorate skeletal muscle mass.

Because TD plays an important role in transporting digestive fat, TD resection may have interfered this function. However, there are few studies that have examined the physiological changes after TD resection which makes it difficult to prove this speculation. On the contrary, muscle mass could be influenced by many factors such as perioperative rehabilitation and nutrition counseling. Thus, TD resection may not be a strong factor to deteriorate skeletal muscle mass. It is difficult to verify how TD resection can influence body composition. However, we have previously examined the change of body composition by TD resection and the results were similar. We have added changes to the main manuscript.

Round 2

Reviewer 2 Report

None