A Reverse Thymic Fat Pad Flap to Cover the Anastomosis of an Extended Tracheal Resection Following Induction Chemotherapy: A Challenging Case Report

Round 1

Reviewer 1 Report

This case report presents an interesting technique of using the thymus to protect a tracheal anastomosis after neoadjuvant chemotherapy and tracheal resection.  This patient was briefly mentioned in a previous article reviewing a single-center experience by the same authors.  Although the strategy of using the thymus as a pedicled flap to cover a tracheal anastomosis is an intriguing one, it is not novel.  This has been reported as far back as 1990 by LoCicero et al, as you have referenced.  I would recommend that you highlight the aspects of this case that make it unique, including the need for neoadjuvant chemotherapy, prior neck surgery and need for extended tracheal resection.  Additional questions to address include:

1.    You mention that the value of induction chemotherapy is uncertain.  Since this is the one aspect of your case that makes it most unique, please explain in more detail why you chose to take this approach rather then proceed directly with resection.

2.    Did you utilize any tracheal release maneuvers?

3.    Please describe the technique of harvesting the thymic fat pad.  Did you create a pedicled flap using the internal mammary artery?

4.    The patient was in the hospital for 11 days.  Is this because you kept the patient in neck flexion using a “Grillo stitch?”

5.    Please briefly describe your technique for apneic hyperoxygenation

Author Response

Dear Reviewer,

Thank you for your time and your stimulating comments that enhance us to improve the quality of our manuscript. We have highlighted the most interesting aspects of our case in lines 168-174 of REVISED MANUSCRIPT.

1) We decided upon neoadjuvant chemotherapy rather than upfront surgery because of tumour longitudinally extension of more than 5 cm and cartilaginous rings infiltration. Patient history of prior neck surgery was another key point in our decision making: tumour shrinkage was the goal of multimodal treatment to minimize surgical complications of a redo procedure. Our strategy has revealed successfully to reduce the tumour load and lessen the extent of tracheal resection. (REVISED MANUSCRIPT lines 168-174).

2) No further tracheal release maneuvers were needed. Neck flexion and dissection of the pretracheal plane typically provide enough relief of anastomotic tension, according to Mulliken and Grillo. In cadaveric experiments, they showed that with 15° to 35° of neck flexion, a 4.5 cm length of trachea can be resected with a tension-free primary anastomosis (REVISED MANUSCRIPT lines 138-142).

3)  Technique of harvesting the thymic fat pad: Dissection of the thymus was begun at the inferior margin of the gland and it was carried laterally to within 2 cm of the phrenic nerve and superiorly to above the innominate vein, until the entire gland was freed. The flap was pedicled on thymic branches arising from the internal mammary artery. (REVISED MANUSCRIPT lines 86-89).

4) Yes, a “guardian stitch” was placed to maintain neck flexion for the first post-operative week. (REVISED MANUSCRIPT lines 91-93)

5) Tracheal anastomosis was completed in 38 minutes of apnoeic hyperoxygenation with mild hypercapnia (PaCO2 48-50 mmHg), that has promptly been solved in less than 2 minutes. The patient had been pre-oxygenate to a PaO2of 400 mmHg at the beginning of surgical procedure; the Near Infrared Spectroscopy (NIRS) was used to monitor cerebral oxygenation and serial blood gases analysis were performed to control pH during apnoeic hyperoxygenation. (REVISED MANUSCRIPT lines 80-84).

Reviewer 2 Report

I reviewed the manuscript entitled "Reverse thymic fat pad flap to cover anastomosis of extended tracheal resection following induction chemotherapy: a challenging case report" by Mastromarino et al. (surgeries-1883901).

The authors presented a really interesting case report regarding a difficult and challenging surgical procedure. They performed an extended tracheal resection with subsequent tracheal anastomosis, which was covered by a reversed thymic fat pad flap to prevent erosion of adjacent brachiocephalic vessels in a 67-year-old patient with squamous-cell carcinoma of the trachea, who previously underwent neo-adjuvant chemotherapy and had a major surgery in the neck in the past. The authors describe the procedure in detail and they present great images. 

Minor issues:

1) It would be better, if the authors described more specifically the "potentially severe anastomotic complications" in the "Introduction" section.

2) The authors should explain why did they prefer apnoeic oxygenation via iLA and not traditional ECMO and how did they monitored the patient during this period (for example did they use capnography?). Furthermore, they should define mild hypercapnia and mention the precise duration that it was observed.

3) In my opinion, the authors should discuss whether the reverse thymic fat pad could prevent the formation of tracheoesophageal fistula.  

Author Response

Dear Reviewer,

Thank you for your time and your stimulating comments.

1) "Potentially severe anastomotic complications": Specifically, anastomotic leak, erosion of the brachiocephalic vessels and tracheoesophageal fistula could be life-threatening conditions (REVISED MANUSCRIPT lines 31-33)

2) We prefered apnoeic hyperoxygenation rather than ECMO because of a lower risk of peri-operative complications (REVISED MANUSCRIPT lines 154-163). ECMO is used in the management of severe cardiopulmonary failure, but the indication in the oncologic population has not been clearly established. Moreover, our team (included anesthesiologists) is well experienced in apnoeic hyperoxygenation, with a considerable reduction in operating times compared to the use of ECMO. Tracheal anastomosis was completed in 38 minutes of apnoeic hyperoxygenation with mild hypercapnia (PaCO2 48-50 mmHg), that has promptly been solved in less than 2 minutes. The patient had been pre-oxygenate to a PaO2of 400 mmHg at the beginning of surgical procedure; the Near Infrared Spectroscopy (NIRS) was used to monitor cerebral oxygenation and serial blood gases analysis were performed to control pH during apnoeic hyperoxygenation. (REVISED MANUSCRIPT lines 80-84).

3) (REVISED MANUSCRIPT lines 197- 205) When properly harvested, the lobes of the thymus generate two pedicles which are versatile enough to be applied to any part of the cervical or thoracic trachea. They may represent a suitable option to wrap tracheal anastomosis both anteriorly and posteriorly, to prevent tracheoesophageal fistula. This feared complication is a consequence of breakdown of the membranous wall of the anastomosis. The interposition of a well-vascularized and angiogenetic flap may lead to a better membranous repair and, consequently, this phenomenon may reveal effective in preventing posterior anastomotic leakage, cause of tracheoesophageal fistula. 

Reviewer 3 Report

Dear author. I commend you for this nice case illustrating that good clinical judgement and technical skills resulting in good results even in borderline cases. 

Can you describe if additional release maneuvers were performed and if not why you didn't use release maneuvers as recommended by previous authors that you cited.

Author Response

Dear Reviewer,

Thank you for your time and your positive comments.

No additional release maneuvers were performed. Neck flexion and dissection of the pretracheal plane typically provide enough relief of anastomotic tension, according to Mulliken and Grillo. In cadaveric experiments, they showed that with 15° to 35° of neck flexion, a 4.5 cm length of trachea can be resected with a tension-free primary anastomosis. (REVISED MANUSCRIPT lines 138-142)