{"paper_id":"68c45a17-6413-457e-91aa-829fd9de90fd","body_text":"Clinical characteristics of catamenial and non-catamenial thoracic \nendometriosis-related pneumothorax \n \n(月経随伴性気胸およびその他の時期に発症する \n胸腔内子宮内膜症関連気胸の臨床的特徴) \n \n \n \n \n \n \n \n \n \n \n \n千葉大学大学院医学薬学府 \n先端医学薬学専攻 \n (主任：巽浩一郎教授) \n福岡みずき \n\n \n \nABSTRACT \nBackground and Objectives \nA major pathogenic factor for catamenial pneumothorax is thoracic endometriosis. On \nthe other hand, thoracic endometriosis-related pneumothorax (TERP) can develop as \neither catamenial or non-catamenial pneumothorax. Therefore, the aim of this study was \nto elucidate the clinical differences between catamenial and non-catamenial TERP. \nMethods \nThe clinical and pathological data in female patients who underwent video-assisted \nthoracoscopic surgery at the Pneumothorax Research Center during an eight-year period \nwere retrospectively reviewed. This study included 150 females with \nsurgico-pathologically confirmed TERP. The subjects were divided into two groups, \nthose having all of the pneumothorax episodes in the catamenial period (CP group) and \nthose who did not (non-CP group). We compared the clinical characteristics and \nsurgico-pathological findings between these two groups. \nResults \nOf the 150 TERP patients, 55 (36.7%) were classified in the CP group, and 95 (63.3%) \nin the non-CP group. In regard to the locations of endometriosis, all TERP patients had \ndiaphragmatic endometriosis, while pleural implantation was recognized in 34 of the 55 \n\n \n \n(61.8%) patients in the CP group and 42 of the 95 (44.2%) patients in the non-CP group \n(p<0.05).  \nConclusions \nA significant difference in the proportion of patients with pleural endometriosis was \nobserved between catamenial and non -catamenial TERP.  The ectopic site s of the \nendometriosis may be responsible for the timing of the pneumothorax episodes.  \n \nKey words:  \nCatamenial pneumothorax , endometriosis, pneumothorax , spontaneous pneumothorax, \nVideo Assisted Thoracoscopic Surgery \n \nShort title: \nEndometriosis-related pneumothorax \n \nAbbreviations:  \nthoracic endometriosis-related pneumothorax (TERP) \ncatamenial pneumothorax (CP) \nvideo-assisted thoracoscopic surgery (VA TS) \n\n \n \nINTRODUCTION \n   Catamenial pneumothorax (CP) had been considered to be an unusual \ncondition, but with increasing interest in the disease, it has been reported more \nfrequently, and is now considered to account for 20-30% of the cases with primary \nspontaneous pneumothorax in females of reproductive age [1-2]. CP is generally \ndefined simply as a recurrent pneumothorax occurring between the day before and \nthree days after the onset of menstruation [3-4]. A major part of the pathogenesis of CP \nis thoracic endometriosis [5-6]. Thoracic endometriosis-related pneumothorax (TERP) \nis the term used to refer to a pneumothorax accompanied with thoracic endometriosis. \n Until recently, TERP had been considered to develop only as catamenial \npneumothorax. However, Alifano et al. reported that one-third of TERP cases presented \nin the intermenstrual period [7]. Thus, TERP can develop as a catamenial pneumothorax \nas well as a non-catamenial pneumothorax. There have been only a few reports of \nnon-catamenial TERP (the report by Alifano’s group and our group), thus the clinical \ncharacteristics of non-catamenial TERP have not been clarified [7-9]. The purpose of \nthis study was to clarify the characteristics of this condition and to speculate on the \npathogenic mechanism underlying non-catamenial TERP by comparing it with \ncatamenial TERP. \n\n \n \nMATERIALS AND METHODS \nStudy population \nThe clinical and pathological files of all female patients who underwent \nvideo-assisted thoracoscopic surgery (VA TS) in the Pneumothorax Research Center for \nthe surgical treatment of a spontaneous pneumothorax during the eight-year period from \nJanuary 2005 to December 2012 were reviewed retrospectively. The surgery was \nperformed as a VA TS procedure under general anesthesia. No patients underwent \nthoracotomy. We included 150 females who had surgico-pathologically confirmed TERP. \nDuring surgery, we searched the thoracic cavity systematically with a thoracoscope to \nfind bulla e and blebs, diaphragmatic abnormalities (holes and nodular lesions) and \nnodular lesions in the thoracic wall (Figure 1). We resected the abnormalities of the  \ndiaphragm, lung, and thoracic wall where  possible. In addition, a cellulosic mesh \n(Surgicel Johnson and Johnson, Inc., New Brunswick, NJ, USA) was inserted to cover \nthe diaphragm.  The re sected lesions were histopathologically diagnosed as thoracic \nendometriosis when the endometrial glands or stroma were positively stained for \nestrogen/progesterone receptors or CD10. \nWe asked all of the patients with TERP about  the temporal relationship \nbetween the pneumothorax episodes and menses in order to divide them into a CP group \n\n \n \nand a non -CP group. We defined the date of pneumothorax as the date of the  onset of \nchest symptoms (chest pain, difficulty of breathing, or some respiratory discomfort). We \nwere sure to ask patients about the date of pneumothorax on ea ch clinic visit. The data \nof the patients with recurrence after surgery were not included in the analysis. We \ndefined the CP group as those having all of the pneumothorax episodes during the \ncatamenial period (i.e. from the day before to within three days after the onset of \nmenstruation [7-9]), with the remaining patients classified as the non-CP group. \nFor the patients with catamenial and non -catamenial TERP, we compared the \nage, pneumothorax side, height, body weight, smoking habits, history of pelvic \nendometriosis, value of serum CA125, number of pneumothorax episodes before \nsurgery, duration of follow -up after surgery and the postoperative recurrence rate. \nFurthermore, we compared the locations of endometrial implants in the thoracic cavity \nbetween the c atamenial and non -catamenial TERP.  The study was approved by the \ninstitutional review board of Nissan Tamagawa Hospital (approval number 14-015). \n \nStatistical analysis \nThe quantitative data are presented as the means ± SD. The differences \nbetween the patients with catamenial and non-catamenial TERP were analyzed using the \n\n \n \nChi-square test for categorical variables and Student’s t-test for quantitative variables. A \nvalue of p < 0.05 was considered to be significant. A statistical software package (JMP \nversion 10.0.2; SAS Institute; Cary, NC, USA) was used for the statistical analysis.  \n\n \n \nRESULTS \nDuring the eight -year period, a total of 714 females with a spontaneous \npneumothorax underwent V A TS in our center. One hundred and fifty (21.0%) of the 714 \npatients were diagnosed as having TERP.  \nA total of 570 pneumothorax episodes had occurred in the patients with TERP \nbefore the surgery , giving a mean of 3.8 ±2.3 episodes per patient. Figure 2 shows the \ndistribution of the pneumothorax episodes  according to the menstrual cycle. The \nrelationship between the day of episodes and menstruation was available for 288 \nepisodes (50.5%). A total of 180 (59.4%) of the 288 episodes developed during the \ncatamenial period.  \nOf the 150 patients with TERP,  55 (36.7%) were classified as being in the CP \ngroup, and the remainder (95/150, 63.3%) were classified as the non-CP group. Table 1 \nshows the clinical characteristics of each group. It should be noted that all but one of the \npatients developed a right -sided pn eumothorax. The patients with catamenial and \nnon-catamenial TERP showed similar clinical features. \nTable 2 shows the ectopic sites of thoracic endometriosis in each group. All of \nthe TERP patients had endometrial implants in the diaphragm. Thirty -four of t he 55 \n(61.8%) patients in the CP group and 42 of the 95 (44.2%) patients in the non -CP group \n\n \n \nhad implants not only in diaphragm, but also in the pleura. This difference was \nstatistically significant (p < 0.05). Endometriosis in the visceral pleura was obse rved in \n22 of the 55 (40%) patients in the CP group and 30 of the 95 (31.5%) patients in the \nnon-CP group (p=0.30).  \n\n \n \nDISCUSSION \nWe found that diaphragmatic endometriosis w as detected in all of the patients \nwith TERP, and that pleural endometriosis w as also  detected in some of them. It is \nimportant that the proportion of patients with endometriosis in both the diaphragm and \npleura was significantly higher in the CP group than in the non -CP group, because the \nectopic sites of endometriosis may be related to the timing of pneumothorax episodes. \nThe pathogenesis of thoracic endometriosis has been explained by the \nfollowing three theories . 1) Migration: the migration of pelvic endometriosis through \nthe peritoneum to the diaphragm [9]. 2) Embolization: t ransplantation of pelvic \nendometriosis through lymphatic or vascular embolization  [10]. 3)  Metaplasia: \ncoelomic metaplasia of epithelium in the thorax [11]. The fact that most of the cases of \nTERP develop in the right -side lung supports the mig ration theory [12 -14]. T he \npresence of intrapulmonary endometriosis supports the embolization theory [10]. \nMetaplasia to endometrial tissue has been reported in patients with ectopic \nendometriosis other than in the thorax [11]. Therefore, this phenomenon i s also \nconsidered to occur in the thoracic cavity. In the present study, a laterality of the right \nlung and the specialized distribution of endometriosis were recognized in the location \nof thoracic endometriosis. Recently, Legras et al. reported 229 female patients with \n\n \n \npneumothorax, including 54 TERP patients. T his study showed a similar distribution \nof thoracic endometriosis to our own study , i.e. 53 (98.1%) had a right -sided \npneumothorax, 52 (96.3%) had endometrial implants in the diaphragm, and 11 \n(12.2%) had endometrial implants in  the pleura [ 8]. Thus, TERP was speculated to \ndevelop largely due to the  migration of pelvic endometriosis through defects in the \nright diaphragm. Furthermore, endometrial cells do not stay still on the diaphragm, but \nprogress to disseminate to the dorsal thoracic wall or pleura.  \n  Our study showed that catamenial TERP tended to be detected with pleural \nendometriosis more frequently than non-catamenial TERP. We thought that the timing \nof pneumothorax episodes with TERP probably varied because air from outside entered \nthrough two different passages; the transdiaphragmatic passage and transpleural passage. \nEndometriosis in the visceral pleura may cause a pneumothorax to occur during the \nearly menstrual period, because the lung surface with sloughing endometriosis is \ndirectly broken [15-16]. To cause transdiaphragmatic passage, air from outside needs to \novercome three different blockades; the cervix of the uterus, ovarian tubes and \ndiaphragm [17]. All three of these are ordinarily closed, but when these blockades fail \nfor sort reason at the same time or one after another, TERP can develop in the \nintermenstrual period. Another possible explanation for the development of \n\n \n \nnon-catamenial TERP is as follows. 1) Non-catamenial TERP may be a milder disease, \nhence the onset of chest symptoms may be delayed. 2) For the patients with \npneumothorax due to the transdiaphragmatic passage of air, it seems likely that the \npneumothorax developed more gradually than in patients in whom pneumothorax \ndeveloped due to the transpleural passage of air, hence the date of presentation may be \nless precise.  \nAlifano et al. speculated that when air from outside enters into the peritoneum \nthrough the genital tract due to uterine contractions, physical activity or sexual \nintercourse, this air can enter into the thorax in the intermenstrual period [10]. We \ndoubted this hypothesis, because we have not experienced any cases of pneumothorax \ncaused by physical activity or sexual intercourse based on our patient interviews. Most \nof the patients were at their office jobs at the time of onset.  \nWe discovered that the only significant difference between the CP and non -CP \ngroups was the proportion of the patients with pleura l endometriosis . We could not \nfind any significant difference in the rates of visceral pleural endometriosis. This result \nis probably due to the difficulty of inspecting for thoracic endometriosis, because these \nendometriotic implants are very small, as we reported previou sly [18]. When ectopic \nendometrial sites are found in the parietal or visceral pleura, the endometrial tissues \n\n \n \nmay extend to both the parietal and visceral pleural surfaces. Thus, TERP patients with \npleural endometriosis are likely to develop pneumothorax due to  transpleural air \npassage.  \nThis study is associated with  several limitations. First, our subjects were \nlocated at the Pneumothorax Research Center, which  specializes in the treatment of \npneumothorax. M any patients with intractable pneumothorax are r eferred to this \nfacility. Accordingly, the clinical features for TERP may be biased. Second, this was a \nretrospective cohort study, as such we may  have failed to detect the temporal \nrelationship between the pneumothorax episodes and menses in some cases. A  \nprospective study to confirm our results is needed. Finally, because it was difficult to \ninspect all of the sites of thoracic cavity, especially in the fissure s, small endometrial \nimplants may have been missed. This could have led to bias.  \nThere have rarely been reviews or large series of case reports of TERP because \nit is a relatively unusual disorder.  However, we have extensive experience with the \ntreatment of TER P, including surgery for TERP. As a result, w e were able to perform \ndetailed interviews and evaluations of TERP in our cases. \n\n \n \nCONCLUSION: \nWe have clarified the precise distribution of thoracic endometriosis in TERP \npatients. Furthermore, the ectopic site s of endometriosis differed between the CP \ngroup and non -CP group. This study provides a good basis for considering the \npathogenesis of TERP. \n \nACKOWLEDGEMENTS:  \nWe thank Brian Quinn (Japan Medical Communication)  for excellent assistance in the \nreview of English. \n\n \n \nREFERENCES \n1) Alifano M, Roth T, Broet SC, Schussler O, Magdeleinat P, Regnard JF.  Catamenial \npneumothorax; a prospective study. Chest 2003; 124: 1004-1008. \n2) Joseph J, Sahn SA. Thoracic endometriosis syndrome: new observation from an \nanalysis of 110 cases. Am J Med 1996; 100: 164-170. \n3) Alifano M, Trisolini R, Cancellieri A, Regnard JF . Thoracic endometriosis: current \nknowledge. Ann Thorac Surg 2006; 81: 761-769. \n4) Korom S, Canyurt H, Missbach A, Schneiter D, Kurrer MO, Haller U,  Keller PJ, \nFurrer M, Weder W .  Catamenial pneumothorax revisited: clinical approach and \nsystematic review of the literature. J Thorac Cardiovasc Surg 2004; 128: 502-508. \n5) Channabasavaiah AD, Joseph JV . Thoracic endometriosis: revisiting the association \nbetween clinical presentation and thoracic pathology based on thoracoscopic findings in \n110 patients. Medicine (Baltimore) 2010; 89: 183-188. \n6) Bagan P, Barthes FL, Assouad J, Souilamas R, Riquet M. Catamenial pneumothorax: \nretrospective study of surgical treatment. Ann Thorac Surg 2003; 75: 378-381. \n7) Alifano M, Jablonski C, Kadiri H, Falcoz P, Gompel A, Camilleri -Broet S, Regnard \nJF. Catamenial and noncatamenial, endometriosis -related or nonendometriosis -related \npneumothorax referred for surgery. Am J Respir Crit Care Med 2007; 176: 1048-1053. \n\n \n \n8) Legras A, Mansuet-Lupo A, Rousset-Jablonski C, Bobbio A, Magdeleinat P, Roche N,  \nRegnard JF, Gompel A, Damotte D, Alifano M. Pneumothorax in women of \nchild-bearing age: An update classification based on clinical and pathologic findings. \nChest. 2014; 145:354-360. \n9) Haga T, Kataoka H, Otsuji M, Seyama K, Tatsumi K, Kurihara M. Thoracic \nendometriosis-related pneumothorax distinguished from primary spontaneous \npneumothorax in females. Lung 2014; 192: 583-587. \n9) Kirschner PA.  Porous diaphragm synd romes. Chest Surg Clin N Am  1998; 8 : \n449-472. \n10) Flieder DB, Moran CA, Travis WD, Koss MN, Mark EJ.  Pleuropulmonary \nendometriosis and pulmonary ectopic deciduosis: A clinicopathologic and \nimmunohistochemical study of 10 cases with emphasis on diagnostic p itfalls. Hum \nPathol 1998; 29: 1495-1503. \n11) Nguessan KL, Nguessan E, Mian DB, Guie P, Boni S.  Spontaneous cutaneous \numbilical endometriosis: a rare variant of extragenital endometriosis. Clin Exp Obstet \nGynecol. 2014; 41: 486-8. \n12) Lee CY , Diloreto PC, Beaudoin J. Catamenial pneumothorax. Obstet Gynecol 1974; \n44: 407–411. \n\n \n \n13) Laws HL, Fox LS, Y ounger B. Bilateral catamenial pneumothorax. Arch Surg 1977; \n112: 627–628. \n14) Wilhelm JL, Scommegna A. Catamenial pneumothorax:  bilateral occurrence while \non suppressive therapy. Obstet Gynecol 1977; 50: 227–231. \n15) Rossi NP, Goplerud CP. Recurrent catamenial pneumothorax. Arch Surg 1974; 109:  \n173-176. \n16) Lillington GA, Mitchell SP, Wood GA. Catamenial pneumothorax. JAMA 1972; \n219: 1328-1332. \n17) Maurer CR, Schaal JA, Mendez FL. Chronic recurring spontaneous pneumothorax \ndue to endometriosis of the diaphragm. JAMA 1958; 168: 2013-2014. \n18) Haga T, Kumasaka T, Kurihara M, Kataoka H, Miura M. Immunohistochemical \nanalysis of thoracic endometriosis. Pathol Int 2013; 63: 429-434. \n\n                                                       \nTable 1. The characteristics of the study population \nThere were no missing data for any of these variables. The data are presented as no (%) \nor the mean ± SD. The P values were calculated by comparing the patients with \ncatamenial and non-catamenial TERP. \n \nPatients with \nTERP \nn=150 \nPatients with \ncatamenial  \nTERP \nn=55 \nPatients with \nnon-catamenial  \nTERP \nn=95 \np \nvalue* \nAge (years old) (range) \n38.3 ± 5.2 \n(24-50) \n38.4 ± 4.8 \n(29-47） \n38.3 ± 5.6 \n(24-50) \n0.91 \nSide of pneumothorax \nRight \nLeft \n \n149 (99.3%) \n1 (0.7%) \n \n55 (100%) \n0 \n \n94 (98.9%) \n1 (1.1%) \n \n0.45 \nHeight (cm) 159.3 ± 5.3 159.3 ± 5.4 159.3 ± 5.2 0.96 \nWeight (kg) 49.5 ± 5.8 50.6 ± 5.3 49.0 ± 6.0 0.10 \nSmoking habit \nCurrent/former smoker \nNon-smoker \n \n13 (8.7%) \n137 (91.3%) \n \n7 (12.7%) \n48 (87.3%) \n \n6 (6.3%) \n89 (93.7%) \n \n0.18 \nThe number of patient with a \nhistory of pelvic endometriosis \n83 (55.3%) 31 (56.4%) 52 (54.7%) 0.85 \nThe value of serum CA125 (U/mL) 31.1 ± 34.8 29.0 ± 30.6 33.1 ± 37.8 0.51 \nThe number of preoperative \npneumothorax episodes \n3.7 ± 2.4 3.4 ± 2.3 4.0 ± 2.4 0.13 \nPostoperative follow-up period \n(months) \n28.4 ± 20.0 26.0 ± 18.1 29.4 ± 22.0 0.33 \nThe number of patients with \nrecurrence after surgery \n51 (34.0%) 20 (36.4%) 31 (32.6%) 0.84 \n\n \n \nTable 2. The ectopic sites of thoracic endometriosis in patients with catamenial and \nnon-catamenial TERP \n \n \nAll of the patients had thoracic endometriosis in the diaphragm, while some of them \nalso had endometriosis in the pleura (visceral, parietal or both). The P values were \ncalculated by comparing the patients with catamenial and non-catamenial TERP. \n \nPatients with \ncatamenial  \nTERP \nn=55 \nPatients with \nnon-catamenial  \nTERP \nn=95  \np \nvalue \nThoracic endometriosis in the diaphragm \nThoracic endometriosis in the diaphragm and \npleura \n21 (38.2%) \n34 (61.8%) \n53 (55.8%) \n42 (44.2%) \n<0.05 \nThoracic endometriosis in the diaphragm and \nvisceral pleura \n16 (29.1%) 18 (18.9%) 0.15 \nThoracic endometriosis in the diaphragm and \nparietal pleura \n12 (21.8%) 12 (12.6%) 0.14 \nThoracic endometriosis in the diaphragm, \nvisceral and parietal pleura \n6 (10.9%) 12 (12.6%) 0.75 \n\n \n \nFigure Legends \nFigure 1. \nThe thoracoscopic views of endometrial implants on the te ndinous part of the right \ndiaphragm [A], on the visceral pleura [D], and on the parietal pleura [ G]. Blue-brown \nimplants [A], small bulla [D], and tiny lucent nodules [G] were detected. Endometrial \nglands and/or stroma were detected in the resected specimens (hematoxylin-eosin) [B, E, \nH]. These glands and/or stroma exhibited nuclear staining for estrogen receptors [ C, F, \nI].  \n \n\n\n                                                       \n \n \nFigure 2.  \nThe distribution of pneumothorax episodes in the TERP patients. The r ed bars indicate \ncatamenial pneumothorax; the pneumothorax that occurs between 24 hours before and \n72 hours after the initiation of menses . Day 1 means the day of onset of menstruation. \nDay -1 means the day before the onset of menstruation.  \n \n \n \n \n \n \n \n \n\n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \nRespirology vol. 20 No. 8 \n平成 27 年 11 月 20 日 公表済","source_license":"CC0","license_restricted":false}