Relationship between Catamenial Pneumothorax or Non-catamenial Pneumothorax and Endometriosis

Accepted Manuscript Title: Relationship between Catamenial Pneumothorax or Non-Catamenial Pneumothorax and Endometriosis Author: Togas Tulandi, Christian Sirois, Hussein Sabban, Aviad Cohen, Ally Murji, Sukhbir S. Singh, Innie Chen, Liane Belland PII: DOI: Reference:

S1553-4650(17)31236-0 https://doi.org/doi:10.1016/j.jmig.2017.10.012 JMIG 3309

To appear in:

The Journal of Minimally Invasive Gynecology

Received date: Revised date: Accepted date:

13-9-2017 4-10-2017 6-10-2017

Please cite this article as: Togas Tulandi, Christian Sirois, Hussein Sabban, Aviad Cohen, Ally Murji, Sukhbir S. Singh, Innie Chen, Liane Belland, Relationship between Catamenial Pneumothorax or Non-Catamenial Pneumothorax and Endometriosis, The Journal of Minimally Invasive Gynecology (2017), https://doi.org/doi:10.1016/j.jmig.2017.10.012. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Tulandi et al

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Relationship between Catamenial Pneumothorax or Non-Catamenial Pneumothorax and

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Endometriosis

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Togas Tulandi, MD, MHCM1, Christian Sirois MD2, Hussein Sabban, MD3, Aviad Cohen MD1,

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Ally Murji MD, MPH4, Sukhbir S. Singh MD5, Innie Chen MD, MPH5, Liane Belland MD6.

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Department of Obstetrics and Gynecology1 and Department of Thoracic Surgery2, McGill

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University, Montreal, QC; Department of Obstetrics and Gynecology, King Abdul Aziz

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University, Saudi Arabia; University of Toronto, Toronto, ON4; University of Ottawa and the

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Ottawa Hospital Research Institute, Ottawa, ON5; University of Calgary6, Calgary, AB Canada

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Financial Disclosure

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Dr. Tulandi is an ad-hoc advisor for Allergan, Sanofi-Genzyme, and AbbVie; Dr. Singh:

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advisory board, research grants and speaker honorarium with Bayer, AbbVie and Allergan; Dr

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Murji and Dr. Belland advisory board and speaker honorarium with AbbVie, Bayer, Allergan.

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Other authors declared no conflict of interest.

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Corresponding author:

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Togas Tulandi, MD, MHCM

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McGill University Health Center

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1001 Decarie Boulevard, Room D05.2519

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Montreal, QC H4A 3J1

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E-mail: [email protected]; Tel: 514 934 1934; Fax: 514 843 1496

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Study objectives: To evaluate the clinical characteristics of women presenting with catamenial

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pneumothorax and compare them with those with non-catamenial pneumothorax.

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Design: Case control study (Canadian Task Force II-2).

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Setting: Multicenter study

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Patients: 42 women with pneumothorax; 21 women had catamenial pneumothorax (study group)

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and 21 age-matched women with non-catamenial pneumothorax (control group).

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Interventions: All patients underwent video-assisted thoracoscopy (VATS) and pleural biopsy.

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We also evaluated the presence and stage of pelvic endometriosis in 16 women with catamenial

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pneumothorax who had undergone laparoscopic surgery.

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Measurements and Main Results: The number of known episodes of catamenial pneumothorax

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before treatment was between 2 to 8 episodes. Symptoms were mainly chest pain, shortness of

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breath, and one patient had hemoptysis. The prevalence of right sided pneumothorax was 95.2%

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in the study group and 57.1% in the control group (P: 0.004). Beside two cases with complete

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collapse of the right lung, most of the cases in the study group had apical pneumothorax. Pelvic

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endometriosis was found in 15 of 16 women (93.7%) mainly stage 3 or 4 and thoracic

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endometriosis in 12 of 20 women (60%). None of the patients in the control group had thoracic

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endometriosis.

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Conclusion: Thoracic endometriosis is found in over a half of women with catamenial

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pneumothorax but absent in those with non-catamenial pneumothorax. Right apical

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pneumothorax is predominant in women with catamenial pneumothorax. Endometriosis plays an

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important role in the mechanism of catamenial pneumothorax.

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Key Words: catamenial pneumothorax; thoracic endometriosis; pulmonary endometriosis;

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pleural endometriosis

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Précis: Thoracic endometriosis is found in over of a half of women with catamenial

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pneumothorax but is absent in those with non-catamenial pneumothorax.

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Introduction

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Catamenial pneumothorax was first described in 1958 by Maurer et al (1). It usually presents as a

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recurrent pneumothorax occurring within 72 hours after the onset of menstruation (2). The

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pathophysiology of catamenial pneumothorax is unclear. However, it has been associated with

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thoracic endometriosis, where the endometrial tissue is found in the lung or on the pleural

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surface. The most common presentation of thoracic endometriosis is pneumothorax followed by

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hemothorax, hemoptysis and lung nodule (3). Catamenial hemothorax is an infrequent

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manifestation of thoracic endometriosis, occurring in 14% of the cases (3). Cyclical hemoptysis

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is even rarer (4). Catamenial chest pain is almost always related to catamenial pneumothorax or

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catamenial hemothorax. Yet, cases of diaphragmatic endometriosis diagnosed at laparoscopy in

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which chest pain without pneumothorax was the only clinical complaint have also been reported

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(5,6).

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The purpose of our study was to evaluate the clinical characteristics of women presenting with

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catamenial pneumothorax and compare them with those with non-catamenial pneumothorax.

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Materials and Methods

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We conducted a case-control study of 42 women with pneumothorax; 21 women had catamenial

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pneumothorax (study group) and 21 age-matched women with non-catamenial pneumothorax

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(control group). A patient in the study group had a hysterectomy and bilateral salpingo-

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oophorectomy and did not undergo pleural biopsy. Others underwent video-assisted

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thoracoscopic surgery (VATS) and a biopsy of the pleura. All cases in the study group had at 4 Pneumothorax and endometriosis Page 4 of 13

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least 2 episodes of pneumothorax during menses. The institutional research and ethics board

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approved the study (Study #CODIM-MBM-CR16-34). Data of the study group were obtained

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from gynecologists who participated in the national gynecologic collaborative study on

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catamenial pneumothorax. We excluded pneumothorax that was related to malignancy, trauma or

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tuberculosis. The control group was obtained from the thoracic database with no information on

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gynecologic condition. Accordingly, we could not calculate the prevalence of pelvic

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endometriosis in this group.

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The outcome measures were the presence of endometriosis on histopathology of the pleural

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biopsy and the location of pneumothorax. In the study group, we also evaluated whether the

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patients had had pelvic endometriosis and the stage of the disease. We used Student t test for

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continuous variables and Fisher exact test for proportions. P-values less than 0.05 were

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considered significant. Data are presented as mean ± SD and proportion (%).

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Results

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Table 1 shows the characteristics of patients in the study group. Symptoms were mainly chest

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pain, shortness of breath, and one patient had hemoptysis. Beside two cases with complete

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collapse of the right lung, most of the cases had apical pneumothorax. Of the total 20 cases with

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pleural biopsy, thoracic endometriosis was found in 16 patients (80%) and among 16 cases who

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had had laparoscopic surgery, 15 patients had pelvic endometriosis (93.7%) and 14 of them had

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stage 3 or 4 endometriosis. None of the patients was found to have diaphragmatic endometriosis

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on laparoscopic examination. Besides pneumothorax, operative findings included blebs,

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diaphragmatic defect, and brownish black lesions or brown discoloration on the diaphragm or

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pleural surface. VATS consisted of talc pleurodesis and other procedures including blebectomy

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or apical wedge pleurectomy.

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Histopathology of the pleural biopsy in the study group revealed 3 cases of classical

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endometriosis with endometrial glands and stroma, 9 cases with hemosiderin laden macrophages

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suggestive of endometriosis, and 8 with pleuritis. Endometriosis or findings suggestive of

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endometriosis was not encountered on the pleural biopsy in the control group. Bronchiolectasis

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and normal pathology were found in one patient each.

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Most cases of catamenial pneumothorax were treated with hormonal suppression after thoracic

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surgery with gonadotropin releasing hormone agonist (GnRHa, 15 cases), continuous oral

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contraceptive pills (OCP, 1 case) and dienogest (1 case). Dienogest was given to a patient who

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could not tolerate the side effects of GnRHa even with addback treatment. GnRHa was given

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with add back treatment; the choice of addback hormones varied with physician’s preference.

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Four patients did not undergo hormonal suppression due several reasons (wishes to conceive,

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refused hormonal treatment, after oophorectomy and premenopausal). Three patients

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subsequently conceived.

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Table 2 demonstrates that right pneumothorax is predominant in women with catamenial

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pneumothorax (95.2%) compared to those with non-catamenial pneumothorax (57.1%).

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Endometriosis or findings suggestive of endometriosis was found in 12 of 20 women with

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catamenial pneumothorax (60%). Those findings were absent in those with non-catamenial

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pneumothorax.

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Discussion 6 Pneumothorax and endometriosis Page 6 of 13

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In our series, most of the cases of catamenial pneumothorax had endometriosis in the pelvis or in

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the thorax and 95% of the cases had the pneumothorax on the right side. The pelvic

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endometriosis was mainly stage 3 or 4. The prevalence of thoracic endometriosis was 60%. This

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is in contrast to those with non-catamenial pneumothorax where we did not encounter any

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endometriosis. In a systematic review of 229 cases of catamenial pneumothorax, Korom et al

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reported right pneumothorax in 91.7% of cases, left pneumothorax in 4.8%, and bilateral

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pneumothoraces in 3.5% of cases (7). We did not encounter bilateral pneumothoraces.

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There are a few theories that may explain the presence of endometriosis in the thorax

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including coelomic metaplasia, lymphatic or hematogenous spread or retrograde menstruation

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with subsequent transperitoneal-transdiaphragmatic migration of the endometrial cells (2,3). Due

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the right predisposition of thoracic endometriosis and the movement of peritoneal fluid, the last

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theory is plausible. The movement of the diaphragm and peristalsis of the intestines create the

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flow of the peritoneal fluid. The fluid moves from the pelvis into the paracolic gutters. Due to the

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anatomical difference between the right and left abdominal cavity, the flow predominantly

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reaches the supramesocolic space and further cranially until the right suprahepatic and

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subphrenic spaces. The peritoneal surface of the diaphragm has lymphatic lacunae that

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communicate with the abdominal cavity. During expiration, the peritoneal fluid enters these

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lacunae (8). Diaphragmatic defects predominantly on the right side can also be found and

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contributes to the development of thoracic endometriosis.

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The occurrence of catamenial pneumothorax could be explained by the increase in

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prostaglandin F2 (PGF2) during menses (9). This potent bronchial and vascular constrictor

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causes rupture of subpleural blebs. The findings of “hemosiderin laden macrophages suggestive

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of endometriosis” is consistent with those previously published (10, 11). 7 Pneumothorax and endometriosis Page 7 of 13

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Management of catamenial pneumothorax varies from simple rest for mild symptoms to

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surgery (12,13) and thoracentesis or chest tube for symptomatic relief (8, 14). Tube

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thoracostomy has been used in the treatment of some patients (2). Similar to treatment of pelvic

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endometriosis, ovarian suppression is one of the treatments (15). In fact, in most of our patients,

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medical treatment and chest tube insertion was the first line of treatment. Video-assisted

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thoracoscopy was performed in women who wished to conceive, had failed conservative

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treatment or for recurrences. VATS will allow patients to conceive early without prolonged

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hormonal suppression treatment.

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In most cases, pleurodesis (mechanical or chemical) is needed. Other procedures includes

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blebectomy or apical wedge pleurectomy (16). Due to endometriosis recurrence, postoperative

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hormonal suppression is usually required. In our series, the predominant medical treatment was

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GnRHa with add back treatment. We also used dienogest in 2 patients. It is steroidal progestin of

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the 19-nortestosterone group that has been used for endometriosis. Continuous oral contraceptive

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pill was prescribed to another patient. Laparoscopic excision of pelvic endometriosis is indicated

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in infertile women or in those with symptomatic endometriosis (16). However, whether

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laparoscopy should be performed in women with catamenial pneumothorax with or without

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excision of diaphragmatic endometriosis (if any) is still unclear (5,6,17).

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The limitations of our study includes lack of information on abdominal surgery in some

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cases in the study group and especially in the control group. In addition, the site of pleural biopsy

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in the control group might not be at the diaphragmatic site. However, our study represents the

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largest series of catamenial pneumothorax with a control group. It suggests for the first time that

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unlike catamenial pneumothorax, non-catamenial pneumothorax is not or rarely associated with

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endometriosis. 8 Pneumothorax and endometriosis Page 8 of 13

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We conclude that right pneumothorax is especially predominant in women with

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catamenial pneumothorax. Thoracic endometriosis could be found in over a half of women with

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catamenial pneumothorax, but is absent in those with non-catamenial pneumothorax. Our

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findings suggest that endometriosis plays an important role in the mechanism of catamenial

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pneumothorax.

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References 1. Maurer ER, Schaal JA, Mendez FL Jr. Chronic recurring spontaneous pneumothorax due to endometriosis of the diaphragm. J Am Med Assoc. 1958;168:2013-4. 2. Alifano M, Roth T, Broet SC, Schussler O, Magdeleinat P, Regnard JF. Catamenial pneumothorax: a prospective study. Chest. 2003;124:1004-8. 3. Joseph J, Sahn SA. Thoracic endometriosis syndrome: new observations from an analysis of 110 cases. Am J Med. 1996;100:164-70. 4. Terada Y, Chen F, Shoji T, Itoh H, Wada H, Hitomi S. A case of endobronchial endometriosis treated by subsegmentectomy. Chest. 1999;115:1475-8. 5. Nezhat C, Seidman DS, Nezhat F, Nezhat C. Laparoscopic surgical management of diaphragmatic endometriosis. Fertil Steril. 1998;69:1048-55. 6. Redwine DB. Diaphragmatic endometriosis: diagnosis, surgical management, and long-term results of treatment. Fertil Steril. 2002;77:288-96. 7. Korom S, Canyurt H, Missbach A, et al. Catamenial pneumothorax revisited: clinical approach and systematic review of the literature. J Thorac Cardiovasc Surg. 2004;128:502-8. 8. Bricou A, Batt RE, Chapron C. Peritoneal fluid flow influences anatomical distribution of endometriotic lesions: why Sampson seems to be right. Eur J Obstet Gynecol Reprod Biol. 2008;138:127-34. 9. Rossi NP, Goplerud CP. Recurrent catamenial pneumothorax. Arch Surg. 1974;109:173-6. 10 Pneumothorax and endometriosis Page 10 of 13

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10. Flieder DB, Moran CA, Travis WD, Koss MN, Mark EJ. Pleuro-pulmonary endometriosis and pulmonary ectopic deciduosis: a clinicopathologic and immunohistochemical study of 10 cases with emphasis on diagnostic pitfalls. Hum Pathol. 1998;29:1495-503. 11. Ghigna MR; Mercier O; Mussot S; Fabre D; Fadel E; Dorfmuller P; de Montpreville VT. Thoracic endometriosis: clinicopathologic updates and issues about 18 cases from a tertiary referring center. Ann Diagnostic Pathol 2015;19:320-5. 12. Hinson JM Jr, Brigham KL, Daniell J. Catamenial pneumothorax in sisters. Chest. 1981;80:634-635. 13. Carter EJ, Ettensohn DB. Catamenial pneumothorax. Chest. 1990;98:713-716. 14. Shearin RP, Hepper NG, Payne WS. Recurrent spontaneous pneumothorax concurrent with menses. Mayo Clin Proc. 1974;49:98-101. 15. Bagan P, Le Pimpec Barthes F, Assouad J, Souilamas R, Riquet M. Catamenial pneumothorax: retrospective study of surgical treatment. Ann Thorac Surg. 2003;75:378-81 16. Ottolina J, De Stefano F, Viganò P, Ciriaco P, Zannini P, Candiani M. Thoracic Endometriosis Syndrome: Association With Pelvic Endometriosis and Fertility Status. J Minim Invasive Gynecol. 2017;24:461-5. 17. Härkki P1, Jokinen JJ, Salo JA, Sihvo E. Menstruation-related spontaneous pneumothorax and diaphragmatic endometriosis. Acta Obstet Gynecol Scand. 2010;89:1192-6. 168 11 Pneumothorax and endometriosis Page 11 of 13

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Table 1. Profile of 21 women with catamenial pneumothorax. Case 1 2

Age (years) 34 29

Site of pneumothorax Right Right

Stage of pelvic endometriosis 3 3

3

43

Right

3

4 5

30 34

Right Right

NA 4

6

41

Right

NA

7 8 9

33 44 34

Right Left Right

3 4 3

10

29

Right

4

11

31

Right

12 13 14

38 27 29

Right Right Right

No endometriosis 4 4 3

15 16

45 29

Right Right

NA 3

17 18

36 29

Right Right

4 3

19 20 21

39 44 49

Right Right Right

NA NA 2

Histopathology of pleural biopsy Endometriosis Suggestive of endometriosis Suggestive of endometriosis Chronic pleuritis Suggestive of endometriosis Suggestive of endometriosis Chronic pleuritis Chronic pleuritis NA

Suggestive of endometriosis Suggestive of endometriosis Chronic pleuritis Endometriosis Suggestive of endometriosis Endometriosis Suggestive of endometriosis Chronic pleuritis Suggestive of endometriosis Chronic pleuritis Chronic pleuritis Interstitial fibrosis and pleuritis

Additional hormonal treatment None GnRHa Continuous OCP GnRHa GnRHa; then Dienogest None GnRHa GnRHa None (underwent hysterectomy and oophorectomy) GnRHa GnRHa GnRHa GnRHa GnRHa Dienogest GnRHa GnRHa GnRHa GnRHa GnRHa None

170 171 172

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173 174

Table 2. Comparison of women with catamenial pneumothorax and non-catamenial pneumothorax. Catamenial pneumothorax Number of patients Mean age ± SD (years) Right pneumothorax Suggestive of endometriosis or endometriosis on pleural biopsy

175 176 177

P value

21

Non-catamenial pneumothorax (control) 21

35.6±6.6

33.9±7.4

NS

20/21 (95.2%)

12 (57.1%)

0.005

12/20 (60%)*

0%

<0.0001

*One case underwent hysterectomy and bilateral salpingo-oophrectomy and did not undergo VATS.

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