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J Chest Surg
J Chest Surg
Journal of Chest Surgery
2765-1606
2765-1614
The Korean Society for Thoracic and Cardiovascular Surgery

39115198
10.5090/jcs.24.021
jcs-57-5-484
Clinical Research
Recurrence-Free Survival after Postoperative Hormone Therapy for Catamenial Pneumothorax
https://orcid.org/0009-0008-1120-2923
Kim Ji Hoon M.D.
https://orcid.org/0000-0002-0053-4470
Woo Won-Gi M.D.
https://orcid.org/0000-0001-7696-1236
Jung Yong-Ho M.D.
https://orcid.org/0000-0003-1388-2471
Moon Duk Hwan M.D.
https://orcid.org/0000-0001-8998-9510
Lee Sungsoo M.D., Ph.D.
Department of Thoracic and Cardiovascular Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
Corresponding author Duk Hwan Moon Tel 82-2-2019-3381 Fax 82-2-3461-8282 E-mail pupupuck@yuhs.ac ORCID https://orcid.org/0000-0003-1388-2471
See Commentary page 490.

5 9 2024
8 8 2024
8 8 2024
57 5 484489
28 2 2024
29 5 2024
18 6 2024
Copyright © 2024, The Korean Society for Thoracic and Cardiovascular Surgery
2024
https://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Background

Catamenial pneumothorax (CP) is a rare form of spontaneous pneumothorax that is linked to endometriosis; thus, it predominantly manifests in women of reproductive age. Considerable research has explored the potential benefits of postoperative hormone therapy following various surgical interventions. This study was performed to examine the clinical implications of postoperative hormone treatment in patients with CP.

Methods

The study included patients who underwent surgical intervention for CP between November 2009 and February 2023. These procedures included wedge resection, diaphragm resection, and total pleural coverage. Recurrence-free survival was analyzed using the Kaplan-Meier log-rank test to assess the impact of hormone therapy. Additionally, Cox proportional hazards analysis was employed to identify risk factors associated with postoperative CP recurrence.

Results

The study included 41 patients, with a median age of 38.4 years. Among them, 27 individuals received hormone therapy, 8 of whom experienced recurrence during a median follow-up period of 1 year. Patients who received hormone therapy exhibited a lower rate of recurrence than those who did not; however, the difference was not statistically significant, likely due to the small sample size. Side effects of hormone therapy included depression (6.8%), excessive sweating (3.4%), and headache (3.4%). In the analysis of risk factors for postoperative recurrence, diaphragm resection emerged as a protective factor (hazard ratio, 0.16; 95% confidence interval, 0.03–0.77; p=0.022).

Conclusion

Hormone treatment combined with surgery did not significantly impact recurrence in patients with CP. The application of diaphragm resection was the sole factor that displayed significance in preventing CP recurrence.

Catamenial pneumothorax
Hormone therapy
Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
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pmcIntroduction

Catamenial pneumothorax (CP) is a rare condition that predominantly affects women of reproductive age during the perimenstrual period, which is 72 to 96 hours before or after the onset of the menstrual cycle [1]. This condition is characterized by diaphragmatic defects and the presence of endometrial implants [2].

Treatment for CP is focused on managing the condition and preventing its recurrence [3]. Over the past decade, surgical interventions for pneumothorax have shifted toward minimally invasive thoracoscopic approaches. These procedures typically involve the excision of alveolar or endometrial nodules and the application of oxidized regenerated cellulose to achieve complete pleural coverage, which minimizes recurrence [4]. Additionally, surgeons must address diaphragmatic pores by performing diaphragmatic resection, given the distinctive presence of endometrial deposits or perforations associated with this type of pneumothorax.

Postoperative hormone therapy has been repeatedly identified as an adjunctive treatment to surgery for CP [5]. Administered for 6 to 12 months postoperatively, this therapy has been considered essential for preventing recurrence. Hormone therapy induces hypogonadotropic hypogonadism and amenorrhea, allowing the ovaries to rest and suppressing the activity of ectopic endometrial tissue [6]. Additionally, these medications may help prevent pneumothorax caused by cyclic hormonal fluctuations [6].

However, the current literature reveals inconsistent results regarding the efficacy of adjunctive hormone therapy for CP, which can be attributed to the low incidence of this condition and the scarcity of available studies. Therefore, we sought to identify risk factors associated with the recurrence of CP and to explore the clinical implications of postoperative hormone treatment in patients with this condition.

Methods

Patients

From November 2009 to February 2023, 41 patients with CP at Gangnam Severance Hospital received surgical treatment and hormone therapy. Clinically, CP was suspected when chest pain or pneumothorax was detected on chest radiography, coinciding with or preceding menstruation, and when the pain or extent of the pneumothorax spontaneously subsided after menstruation. Prior to surgery, all patients with suspected menstrual pneumothorax underwent pelvic examination and ultrasonography. Postoperatively, the resected lung and diaphragm tissues were stained with hematoxylin and eosin. A diagnosis of CP was confirmed if endometrial glands and stroma were identified. If confirmation of endometrial tissue was difficult, CD10 staining was used to facilitate the process.

The study protocol was approved by the institutional review board (IRB) of Severance Hospital, Yonsei University Health System (IRB approval no., 3-2022-0061; approval date: April 15, 2022). Informed consent was obtained from all individual participants included in the study.

Surgical techniques

All patients underwent video-assisted thoracoscopic surgery (VATS). A 12-mm camera port was inserted through the seventh intercostal space (ICS) at the anterior axillary line, a 5-mm working port through the seventh ICS at the posterior axillary line, and a wound retractor through the ninth ICS at the posterior axillary line. When endometrial tissues were identified around the lungs, wedge resection of the lung and total pleural coverage were performed (Fig. 1). Total pleural coverage involved wrapping the entire visceral pleura with sheets of oxidized regenerated cellulose mesh, reinforcing the affected pleura and helping to prevent recurrence [7]. Additionally, when diaphragmatic defects were present, diaphragm resection and plication were conducted, followed by the removal of intraperitoneal endometrial tissue. The tendon of the diaphragm was resected using 2 or 3 tri-staples from an Endo GIA endoscopic linear stapler (Medtronic, Minneapolis, MN, USA). After resection, the stapled area of the diaphragm was reinforced with deep bite sutures using V-Loc 1-0 thread (Covidien, Mansfield, MA, USA) [8]. Following surgery, a 28F chest tube was inserted.

Follow-up and hormone therapy

The chest tube was removed on postoperative day 2, and patients were discharged on the same day. One week after discharge, patients underwent a follow-up chest X-ray examination and had their stitches removed. Hormone therapy, primarily consisting of oral progesterone, was initiated to prevent recurrence. However, patients who experienced side effects of continuous medication, such as weight gain, depression, nausea, bruising, or discomfort, had the option to switch to monthly gonadotropin-releasing hormone (GnRH) agonist injections.

Statistical analysis

Continuous variables are presented as medians with interquartile ranges. Cox proportional hazards analysis was employed to identify risk factors associated with recurrence-free survival, and survival curves were generated using the Kaplan-Meier log-rank test. Statistical analyses were performed using R ver. 4.0.4 (R Core Team, R Foundation for Statistical Computing, Vienna, Austria). A 2-tailed p-value of less than 0.05 was considered to indicate statistical significance.

Results

A total of 41 patients were clinically diagnosed with CP and subsequently received surgical intervention. The mean age of the patients was 38.4 years (Table 1). Pneumothorax was predominantly observed on the right side (39/41, 95%). All patients underwent thoracoscopic surgery (Table 2), and wedge resection was performed in 34 of the 41 patients (83%). Diaphragm resection was conducted in 39 patients (95%) and was followed by diaphragmatic reinforcement. Total pleural coverage was achieved in 28 patients (68%), while partial pleural coverage was performed in 6 (15%). Among the 41 patients, 28 (68%) underwent a comprehensive surgical approach that included wedge resection, diaphragm resection, and total pleural coverage. These patients were discharged after an average of approximately 4 days postoperatively without any complications. Notably, within the first 6 months after surgery, 29 of the 41 patients (71%) experienced no recurrence. Of these individuals without recurrence, 21 (72%) had received hormone therapy.

Following surgery, 27 patients underwent postoperative hormone therapy. Among them, 9 selected oral progesterone, while 16 opted for agonist therapy. However, oral progesterone can result in complications such as weight gain, depression, nausea, and bruising. Those who exhibited these side effects or experienced discomfort with continuous medication use were transitioned to GnRH injections. The side effects of oral progesterone were depression in 3 patients, weight gain in 2, bruising in 1, and breast pain in 1. In comparison, the side effects reported from GnRH agonist injections were insomnia in 3 patients, headache in 1, amnesia in 1, and sweating in 1.

The group receiving postoperative hormone therapy demonstrated a lower recurrence rate than the patients who did not receive this therapy, as indicated by Kaplan- Meier analysis (Fig. 2). However, this finding did not achieve statistical significance (p=0.117), which may be attributed to the limited number of cases. Analysis of risk factors for postoperative recurrence identified diaphragm resection as a protective factor against recurrence (hazard ratio, 0.16; 95% confidence interval, 0.03–0.77; p=0.022) (Table 3, Fig. 3).

Discussion

Thoracic endometriosis syndrome is a rare condition characterized by the presence of ectopic endometrial tissue within the thoracic cavity. It typically manifests as spontaneous pneumothorax, with symptoms that may include chest pain, dyspnea, and cough. A high degree of clinical suspicion and a thorough gynecological history are essential for diagnosis. Although imaging studies can be helpful, VATS is considered the gold-standard diagnostic tool. Surgical intervention, followed by at least 6 months of hormone therapy, has been shown to improve the prognosis and reduce the recurrence rate of this condition [9]. In general, recurrence represents the most common complication after surgery for CP. The general recurrence rate after VATS for spontaneous pneumothorax ranges from 10% to 20% [10], but for CP, it is markedly higher, between 20% and 40% [1]. Therefore, minimizing recurrence should be a primary focus of all post-thoracic surgical interventions.

In cases of CP, endometrial tissues migrate from the abdominal cavity to the thoracic cavity through an opening in the diaphragm. Since 2021, laparoscopy has been performed for all patients with CP at our institution in collaboration with gynecological surgeons, enabling the diagnosis of pelvic endometriosis. Considering the systemic nature of CP, exclusive reliance on localized treatments, such as wedge resection similar to that used for spontaneous pneumothorax, is associated with an increased rate of recurrence.

In one systematic review and meta-analysis, the recurrence rate among patients who received postoperative hormone therapy was 17.3%, compared to a 53% rate in those who did not receive such therapy [1]. Notably, this meta-analysis indicated inconsistency in the surgical approaches and hormone therapy protocols used. At our center, recurrence was observed in 6 of 27 patients (22.2%) who received hormone therapy and in 6 of 14 patients who did not. Currently, in the landscape of CP surgical treatments, growing emphasis is placed on procedures such as diaphragm resection, excision of parietal pleural endometrial tissue, and total pleural coverage. As surgical treatments continue to evolve, the role of postoperative hormone therapy is expected to become increasingly vital in reducing the recurrence rate.

The analysis identified diaphragm resection as a significant factor that may influence recurrence. When CP is suspected, a thorough examination of the diaphragm during surgery is crucial. At our center, we have found that diaphragm resection, followed by muscular layer reinforcement with barbed suture, is an effective technique to minimize operative time. In cases of re-exploratory thoracoscopy due to recurrence, diaphragmatic examination revealed no abnormalities. We expect improved outcomes to be realized with continuous follow-up and hormone therapy in patients who have undergone this standardized surgical approach.

Despite not achieving statistical significance regarding postoperative hormone therapy, this retrospective study holds value as the largest single-center evaluation of CP to date, including 41 patients under continuous follow-up. Furthermore, since November 2020, our center has adopted a standardized surgical approach. This includes wedge resection, diaphragm resection and plication, and total pleural coverage, complemented by postoperative hormone therapy administered by 2 specialized thoracic surgeons. With a sufficiently large sample size, we anticipate obtaining statistically significant results with the established treatment protocols at our center.

CP remains a substantial challenge for clinicians. Among women of reproductive age who present with chest pain, dyspnea, or pneumothorax, the potential for diaphragmatic or thoracic endometriosis should be a key consideration. An integrated approach that includes both hormone therapy and surgery should be recognized as the optimal strategy for managing patients with thoracic endometriosis.

Acknowledgments

The authors express their sincere gratitude for the artistic support received in relation to this work.

Article information

Fig. 1 (A) Thoracoscopic view of a diaphragm pore on the tendinous portion of the right diaphragm. (B) Resection of the diaphragm using a tri-staple from an Endo GIA endoscopic linear stapler (Medtronic, USA). (C) Reinforcement with a deep bite suture using V-Loc 1-0 thread (Covidien, USA). (D) Total pleural coverage achieved with an oxidized regenerated cellulose mesh.

Fig. 2 Recurrence-free survival of patients who underwent surgery for catamenial pneumothorax, according to the use of postoperative hormone therapy.

Fig. 3 Recurrence-free survival of patients who underwent surgery for catamenial pneumothorax, according to the use of diaphragm resection.

Table 1 Baseline characteristics of patients who underwent surgery for catamenial pneumothorax

Clinical variable	No postoperative recurrence	Postoperative recurrence	p-value	
No. of patients	29	12		
Age (yr)	41.0±4.0	38.5±2.3	0.080	
Body mass index (kg/m2)	22.0±2.0	21.0±1.0	0.478	
Height (cm)	163.0±3.0	160.5±2.0	0.374	
Weight (kg)	56.4±4.0	54.5±2.0	0.359	
Duration of hospitalization (day)	3.0±0.5	3.0±0.5	0.569	
Values are presented as number or mean±standard deviation.

Table 2 Operative findings in patients who underwent surgery for catamenial pneumothorax

Clinical variable	Postoperative recurrence (n=12)	No postoperative recurrence (n=29)	p-value	
Laterality (right)	11/12 (91.7)	28/29 (96.6)	0.505	
Pelvic endometriosis	2/12 (16.7)	15/29 (51.7)	0.079	
Previous hormone therapy	2/12 (16.7)	2/29 (6.9)	0.567	
Diaphragm resection	10/12 (83.3)	29/29 (100.0)	0.08	
Intraoperative pleurodesis	0/12 (0)	3/29 (10.3)	0.543	
Total pleural coverage	10/12 (83.3)	18/29 (62.1)	0.276	
Wedge resection	10/12 (83.3)	24/29 (82.8)	1	
Postoperative hormone therapy	6/12 (50.0)	21/29 (72.4)	0.278	
Side effects of hormone therapy	0	5/21 (23.8)	0.283	
Gynecologic ultrasound findings				
Ovarian cyst	9/12 (75.0)	14/29 (48.3)	0.234	
Not applicable	2/12 (16.7)	5/29 (17.2)		
Normal	1/12 (8.3)	3/29 (10.3)		
Pathological finding of diaphragmatic endometriosis	10/12 (83.3)	22/29 (75.9)	0.555	
Pathological finding of lung endometriosis	6/12 (50.0)	5/29 (17.2)	0.13	
Values are presented as number/total number (%), unless otherwise stated.

Table 3 Multivariate risk factor analysis for postoperative recurrence among patients who underwent surgery for catamenial pneumothorax

Factor	HR (95% CI)	p-value	
Postoperative hormone therapy	0.41 (0.13–1.29)	0.130	
Age over 40 yr	0.48 (0.15–1.52)	0.210	
Laterality (right)	0.42 (0.05–3.29)	0.410	
Pelvic endometriosis	0.33 (0.07–1.54)	0.160	
Diaphragm resection	0.16 (0.03–0.77)	0.022	
Total pleural coverage	4.18 (0.9–19.51)	0.069	
HR, hazard ratio; CI, confidence interval.

Author contributions

Conceptualization: JHK, DHM. Methodology: JHK, DHM. Data curation: JHK, YHJ. Investigation: JHK. Formal analysis and software: WW. Validation: DHM. Supervision: DHM, SL. Project administration: DHM, SL. Writing–original draft: JHK. Writing–review and editing: JHK, YHJ, DHM, SL. Final approval of the manuscript: all authors.

Conflict of interest

No potential conflict of interest relevant to this article was reported.
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