{"paper_id":"f43c6b72-daef-447d-9d81-aaf8897d3348","body_text":"Thoracic endometriosis-related pneumothorax distinguished from primary \nspontaneous pneumothorax in females \n \n(女性の原発性自然気胸と胸腔内子宮内膜症関連気胸の鑑別) \n \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芳賀高浩\n\nThoracic endometriosis-related pneumothorax distinguished from primary \nspontaneous pneumothorax in females \n \nTakahiro Haga MD1, 2, 5, Hideyuki Kataoka MD1, 5, Hiroki Ebana MD1, 3, 4, 5, Mizuto \nOtsuji MD, PhD 1, 4, 5, Kuniaki Seyama MD, PhD3, 5, Koichiro Tatsumi MD, PhD2, \nMasatoshi Kurihara MD, PhD1, 5 \n \n1Pneumothorax Research Center and Division of Thoracic Surgery, Nissan Tamagawa \nHospital; 4-8-1 Seta; Setagaya-ku; Tokyo 158-0095, Japan \n2Department of Respirology, Graduate School of Medicine, Chiba University ; 1-8-1 \nInohana; Chuo-ku; Chiba 260-8670, Japan \n3Division of Respir atory Medicine, Juntendo University Faculty of Medicine and \nGraduate School of Medicine; 2-1-1 Hongo; Bunkyo-ku; Tokyo 113-8421, Japan \n4Division of Thoracic and Cardiovascular Surgery, Tokyo Metropolitan Bokutoh \nHospital; 4-23-15 Koto-bashi; Sumida-ku; Tokyo 130-8575, Japan \n5The Study Group of Pneumothorax and Cystic Lung Diseases: 4 -8-1 Seta ; \nSetagaya-ku; Tokyo 158-0095, Japan. \n \n \n\nCorresponding Author: Masatoshi Kurihara MD, PhD  \nPneumothorax Research Center and Division of Thoracic Surgery, Nissan Tamagawa \nHospital; 4-8-1 Seta; Setagaya-ku; Tokyo 158-0095, Japan  \nTel: +81-3-3700-1151 \nFax: +81-3-3700-2090 \nE-mail: kuri@tf6.so-net.ne.jp \n\n \n \nABSTRACT \nPurpose: Thoracic endometriosis -related pneumothorax (TERP) is a secondary \ncondition specific for females, but in a  clinical setting, TERP is often difficult to \ndistinguish from primary spontaneous pneumothorax (PSP)  based on a relationship \nbetween the dates of pneumothorax and menstruation. The aim of this study is to clarify \nthe clinical features of TERP as compared with PSP.  \nMethods: We retrospectively reviewed the clinical and histopathological files of female \npatients with pneumothorax who underwent video -assisted thoracoscopic surgery in the \nPneumothorax Research Center during the six -year period from January 200 5 to \nDecember 2010. We analyzed the clinical differences between TERP and PSP. \nResults: The study included a total of 393 female patients with spontaneous \npneumothorax, of whom 92 (23.4%) were diagnosed as having TERP and 33.6% \n(132/393) as having PSP. We identified four factors ( right-sided pneumothorax, history \nof pelvic endometriosis , age ≥ 31 years old  and no smoking history) that were \nstatistically significant for predicting TERP  and assigned 6, 5, 4, and 3 points,  \nrespectively, to establish a scoring system with a calculated score from 0 to 18 . The \ncut-off values of a calculated score ≥ 12 yielded the highest positive predictive value \n(86.0% with a 95% confidence interval (CI)  of 81.5% - 90.5%) for TERP and negative \npredictive value (95.2% with 95% CI of 92.3% - 98.0%) for PSP.  \n\n \nConclusions: TERP has several distinct clinical features from PSP. O ur scoring system \nconsists of only four clinical variables that are easily obtainable and enable s us to \nsuspect TERP in female patients with pneumothorax. \n \nKey words: primary spontaneous pneumothorax, thoracic endometriosis-related \npneumothorax, thoracic endometriosis, pneumothorax  \n \n \n \n \n\n \n \nINTRODUCTION \nSpontaneous pneumothorax is classified into primary (PSP) and secondary \ncategories. PSP refers to a spontaneously occurring air leakage into the pleural space in \npatients with no clinically apparent underlying lung disease  [1]. The diagnosis of PSP is \nconfirmed histopathologically with subpleural blebs and bullae and no obvious \nabnormality in pulmonary parenchyma  [2]. Catamenial pneumothorax is a condition \nlimited to females and reported to account for about 20 to 30% of women with \npneumothorax [3, 4] . It is defined simply by the onset of pneumothorax during a \nmenstrual cycle: the pneumothorax that occurs between 24 ho urs before and 72 hours \nafter the initiation of menses  [5]. Because catamenial pneumothorax is usually caused \nby thoracic endometriosis [6, 7], a large part of catamenial pneumothorax is diagnosed \nas thoracic endometriosis -related pneumothorax (TERP) after  thoracic surgery. \nHowever, catamenial pneumothorax may include female patients with PSP that happens \nto occur in the peri-menstrual period. \nTERP is defined as pneumothorax due to thoracic endometriosis, and the \ndiagnosis of TERP requires histopathological  confirmation [5]. Generally, ectopic \nendometrial tissues are found in the diaphragm in TERP, whereas no abnormality in \npulmonary parenchyma is apparent. The mechanism of TERP has been speculated as \nfollows: 1) Air enters into the thoracic cavity from the peritoneum through a \n\n \ndiaphragmatic defect caused by the implantation of endometrial tissues. This a ir in the \nperitoneum may be from outside the body and pass through ovarian tubes  [8]. 2) \nAlternatively, air enters into the thoracic cavity from the airway through a defect of \nvisceral pleura caused by the implantation of endometrial tissues [9, 10].  \nUntil recently, TERP had been thought to develop only as catamenial \npneumothorax. However, Alifano et al. recently reported that 37.9% of TERP cases \ndeveloped as  non-catamenial pneumothorax  [11]. Accordingly, TERP is difficult to \ndistinguish from PSP based on the relationship between the calendar dates of \npneumothorax and menstruation; theoretically, catamenial TERP, non-catamenial TERP, \ncatamenial PSP, and non -catamenial PSP exist. Furthermore, TERP is virtually \nindistinguishable from PSP based on the findings of imaging tests such as chest X -ray \nand computed tomography ( CT), because the amount of ectopic endometrial tissue \nimplanted within the respiratory system is too small for detection by such examinations  \n[5]. A preferable scenario is that TERP is suspected before surgery, because the \napproaches for therapy as well as the recurrence rate [12, 13] are quite different between \nTERP and PSP. \nAs previously describe d, the clinical features of TERP are right -sided \npneumothorax and a history of pelvic endometriosis  [5]. In contrast, patients with PSP \ntend to be tall  [14] and usually have a smoking history  [15, 16]. However, few reports \n\n \ndirectly compare the clinical fea tures of TERP and PSP nor do they clarify the \nsignificance of each clinical variable.  The aim of this study is  to clarify the clinical \nfeatures of TERP as compared with PSP.   \n \nMETHODS \nStudy population \nThe clinical and histopathological files of all female  patients who underwent \nvideo-assisted thoracoscopic surgery (V A TS) in the Pneumothorax Research Center \nduring the six -year period from January 2005 to December 2010 were retrospectively \nreviewed. The patients who were histopathologically diagnosed as havi ng TERP or PSP \nwere included in this study. According to Alifano et al., we made a diagnosis of TERP \nwhen the existence of endometrial stroma or the endometrial glands in the resected \ndiaphragm and/or lung tissue was confirmed immunohistochemically by the presence of \nstrong nuclear staining for either estrogen or progesterone receptors [11]. The diagnosis \nof PSP was made when 1) pneumothorax occurred in otherwise healthy individuals with \nnormal or essentially normal underlying lungs on CT images of the ches t, and 2) blebs \nand/or bullae were histologically confirmed in the resected lung specimen.  In patients \nwith PSP, we were unable to collect information from medical records on the \nrelationship between the occurrence of pneumothorax and menstrual cycle. \n\n \nFor patients with TERP and PSP,  we compared the ages, pneumothorax side, height, \nbody weight, smoking habits, history of pelvic endometriosis, number of pneumothorax \nepisodes before surgery, duration of follow -up after surgery and postoperative \nrecurrence rate . We assigned the scores to each clinical variables found to be an \nindependent predictor for the diagnosis of TERP, weighted according to the \nbeta-coefficients from the multivariate logistic model  [17]. We calculated a total score \nfor each patient and anal yzed the performance characteristics of the score for the \ndiagnosis of TERP. The study was approved by the institutional review board of Nissan \nTamagawa Hospital (approval number 12-012).  \n \nStatistical analysis \nThe quantitative data are presented as means ± SD. The differences between \nthe patients with TERP and PSP were analyzed using the Chi -square test for categorical \nvariables and student’s t-test for quantitative variables. A multiple logistic regression \nanalysis was used to assess the role of several v ariables as predictive factors for TERP. \nThe contribution of each potential predictive facto r was denoted by an odds ratio and \nthe associated 95% confidence interval (CI). A receiver operating characteristic (ROC) \ncurve was used to analyze the probability of TERP diagnosis in dependence on the \ncalculated score. A value of p < 0.05 was considered to be significant. A statistical \n\n \nsoftware package (JMP, version 10.0.2; SAS Institute; Cary, NC, USA) was used for the \nstatistical analysis. \n \nRESULTS \nA total of 562  female patients with spontaneous pneumothorax was admitted \nfor treatment during the six -year study period. Of these, 393 patients underwent V A TS \nfor pneumothorax. Ninety -two (23.4%) of the 393 patients were diagnosed as having \nTERP and 33.6% (132/393) as having PSP. Thirty (32.6%) of the 92 patients with TERP \nhad catamenial pneumothorax with the remainder (62/92, 67.4%) classified as \nnon-catamenial.   \nCharacteristics of the study population are summarized in Table 1. The patients \nwith TERP showed significa ntly distinct features differing from those in the patients \nwith PSP. The TERP group were older, shorter  and usually had right -sided \npneumothorax plus pelvic endometriosis but little or no history of smoking. Many \npreoperative pneumothorax episodes were no ted. One exception was a patient with \nTERP whose pneumothorax was left -sided. The postoperative recurrence of \npneumothorax was more frequently noted in patients with TERP. \nTo find the predictive factors for TERP, we performed multivariable analysis \n(Table 2). The right-sided pneumothorax showed the greatest odds ratio among the other \n\n \npredictive factors, followed by history of pelvic endometriosis, age ≥ 31 years old, no \nsmoking history, the number of preoperative pneumothorax episodes ≥ 4, and height ≤ \n159 cm in that order. \nNext, we assigned a score to each predictive factor to establish discriminant \nanalysis between TERP and PSP. We excluded two factors, height and the number of \npreoperative pneumothorax episodes, from the discriminant analysis, since these  are \nlikely to be greatly influenced by race and the medical treatment available for \npneumothorax; additionally, these two factors interfered with generalizing the outcome. \nAccordingly, we adopted the four factors to which scores of 3 to 6 were assigned th en \nestablished a system with calculated scores from 0 to 18 (Table 2). These scores were \ntested at different cut -off values. The cut -off values of a calculated score ≧12 yielded \nthe highest positive predictive value (86.0% with 95% CI of 81.5% - 90.5%) for TERP \nand negative predictive value (95.2% with 95% CI of 92.3% - 98.0%) for PSP (Table 3). \nThe ROC curve reflects the accuracy of the diagnostic test: area under the curve was \n0.9665 (Figure 1).  \n \nDISCUSSION \nWe found that TERP had distinct clinical featur es as compared with those of \nPSP, enabling us to establish a simple scoring system to distinguish TERP from PSP. We \n\n \ndemonstrated that this system had a satisfactorily high positive predictive value for \nTERP as well as a negative one for PS P. The scoring sy stem utilize s four clinical \nvariables identified here that are easily obtainable by history taking and physical \nexamination: the side of pneumothorax, history of pelvic endometriosis, patient age, and \nsmoking history. These clinical variables have been rep orted in the literature to be \nassociated with TERP or PSP  [5, 14 – 16]. Although a concrete diagnosis of TERP is \nrequired for histologic examination of the diaphragm or the lung tissue, the scoring \nsystem developed here seems to be suitable for suspecting TERP, thereby reducing the \noversight of TERP in female patients with pneumothorax.  \nCatamenial pneumothorax has been reported to occur on the right side in \nalmost all such cases [5], and only two case reports of left catamenial pneumothorax  [9, \n18] and two case reports of bilateral catamenial pneumothorax  [19, 20] exist. However, \nthose reports lacked information about the histopathological diagnosis of thoracic \nendometriosis. This study thus provides the first description of a left -sided TERP based \non a histopathological diagnosis. PSP has no documented laterality so far [2]. Therefore, \nthe presence of left pneumothorax in females has a high diagnostic value for PSP.  \nEvaluating the past history of pelvic endometriosis is valuable for diagnosing \nTERP in female patients with pneumothorax. In this study, 58.7% (54/92) of the patients \nwith TERP had a history of pelvic endometriosis. The percentage of patients with pelvic \n\n \nendometriosis among those with catamenial pneumothorax varies broadly and is \nreported to be 18 to 84% [4, 21]. In the majority of patients with thoracic endometriosis, \nthe condition is believed to have spread from pelvic endometriosis  [5]. Therefore, the \nvariations in published results are likely due to the different methods used to diagnose \npelvic endometriosis. A definitive diagnosis of pelvic endometriosis requires diagnostic \nlaparoscopy, and results from that procedure indicate that the prevalence of pelvic \nendometriosis among patients of reproductive age is 5 to 10%  [22]. In the present study, \n2.3% (3/132) of the patients with PSP had a history of pelvic endometriosis.  \nPrevious analyses of catamenial pneumothorax calculated a mean age within \nthe 30s with a range in such patients from 15 to 54 years  [5]. However, patients with \nPSP are often in their early 20s but rarely beyond the age of 40 years [2]. The mean age \nof patients with TERP examined here was about 10 years older than that of patients with \nPSP. Therefore, it is important to consider the patient’s age when diagnosing TERP in \nfemale patients with pneumothorax.  \n Habitual smoking has been associated with a risk of developing PSP  [15, 16]; \nadditionally, patients with PSP tended to be taller than control patients in a previous \nstudy [14]. Elsewhere, TERP did not correlate with either the patients’ height or habitual \nsmoking [5]. The results of our study are consistent with these findings.  \nThis study has several limitations. First, our subjects were located at the \n\n \nPneumothorax Research Center, which is specialized for the treatment of pneum othorax \nand where many patients with intractable pneumothorax are referred. Accordingly, \nclinical features for TERP and PSP may be biased. Second, we included only the \npatients with PSP whose diagnoses were confirmed histologically. Since we usually \nresect lung tissue only when large and/or multiple bullae are apparent during surgery, \nthe patients with PSP in our study may represent a biased population that is not \nrepresentative for PSP. Third, we could not have evaluated the significance of the onset \nof pneumothorax during a menstrual cycle as a factor in differentiating TERP from PSP, \nbecause no information about the relationship of pneumothorax onset and menstrual \nperiod was obtainable for the patient with PSP. Finally, because this was a retrospective \ncohort study, a prospective study to validate our scoring system is needed.  \nIn conclusion, we have established a scoring system for the diagnosis of TERP \nthat is based on the assignment of weighted values to easily include four clinical \nvariables. This syst em has a highly positive predictive value for TERP as well as a \nnegative predictive value for PSP. This logical scheme provides a useful tool for \npredicting TERP in the care of female patients with pneumothorax. \n \nConflicts of interest \nNone of the authors has any conflicts of interest with regard to this study.  \n\n \nAcknowledgment \nWe thank Ms. Phyllis Minick for her excellent proofreading of English writing. \n\n \n \nReferences.  \n1) Noppen M, De Keukeleire T (2005) Pneumothorax. Respiration 76: 121-127. \n2) Baumann MH, S trange C, Heffner JE, et al (2001) Management of spontaneous \npneumothorax: an American College of Chest Physicia ns Delphi consensus statement. \nChest 119: 590-602. \n3) Alifano M, Roth T, Mamilleri Broet S C, Schussler O, Magdeleinat P, Regnard JF \n(2003) Catamenial pneumothorax; a prospective study. Chest 124: 1004-1008. \n4) Joseph J, Sahn SA (1996) Thoracic endometriosis syndrome: new observation from \nan analysis of 110 cases. Am J Med 100: 164-170. \n5) Alifano M, Trisolini R, Cancellieri A, Regnard JF (2006) Thoracic endometriosis: \ncurrent knowledge. Ann Thorac Surg 81: 761-769. \n6) Korom S, Canyurt H, Missbach A, et al (2004)  Catamenial pneumothorax revisited: \nclinical approach and systematic review of the literature. J Thorac Cardiovasc Surg 128: \n502-508. \n7) Ch annabasavaiah AD, Joseph JV  (2010) Thoracic endometriosis: revisiting the \nassociation between clinical presentation and thoracic pathology based on thoracoscopic \nfindings in 110 patients. Medicine (Baltimore) 89: 183-188. \n8) Maure r CR, Schaal JA, Mendez FL  (1958) Chronic recurring spontaneous \npneumothorax due to endometriosis of the diaphragm. JAMA 168: 2013-2014.  \n\n \n9) Rossi NP, Goplerud CP (1974) Recurrent catamenial pnenumothorax. Arch Surg 109: \n173-176.  \n10) Lillington GA, Mitchell SP, Wood GA (1972)  Catamenial pneumothorax. JAMA  \n219: 1328-1332. \n11) Alifano M, Jablonski C, Kadiri H, et al  (2007) Catamenial and noncatamenial, \nendometriosis-related or nonendometriosis -related pneumothorax referred for surgery. \nAm J Respir Crit Care Med 176: 1048-1053. \n12) Hooper C, Maskell N  (2011) British Thoracic Society national pleural procedures \naudit 2010. Thorax 66: 636-637.  \n13) Tschopp JM, Rami -Porta R, Noppen M, Astoul P  (2006) Management of \nspontaneous pneumothorax: state of the art. Eur Respir J 28: 637-650.  \n14)Sadikot RT, Greene T, Meadows K, Armond AG  (1997) Recurrence of primary \npneumothorax. Thorax 52: 805-809.  \n15)Bense L, Eklund G , Odont D  (1987) Smoking and the increased risk of contacting \npneumothorax. Chest 92: 1009-1012.  \n16)Withers JN, Fishiback ME, Kiehl PV , Hannon JL (1964) Spontaneous pneumothorax. \nAm J Surg 108: 772-776.  \n17) Pinto LM, Dheda K, Theron G , et al  (2013) Development of a simple reliable \nradiographic scoring system to aid the diagnosis of pulmonary tuberculosis. PLoS One \n\n \n8: e54235.  \n18) Lee CY , Diloreto PC, Beaudoin J (1974) Catamenial pneumothorax. Obstet Gynecol \n44: 407-411. \n19) Laws HL, Fox LS, Y ounger B (1977) Bilateral catamenial pneumothorax. Arch Surg \n112: 627-628.  \n20) Wilhelm JL, Scommegna A  (1977) Catamenial pneumothorax: bilateral occurrence \nwhile on suppressive therapy. Obstet Gynecol 50: 227-231.  \n21) Tripp HF, Obney JA  (1999) Consideration of anatomic defects in the etiology of \ncatamenial pneumothorax. J Thorac Cardiovasc Surg 117: 632-633. \n22) Chatman DL, Ward AB  (1982) Endometriosis in adolescents. J Reprod Med 27 : \n156-160. \n \n \n \n \n \n\n \n \nFigure legends \nFigure 1. ROC curve for the prediction of TERP using the calculated score.  \nNote that the score of 12 gives 93.5% of sensitivity and 89.4% of specificity. \nThe method for calculating the score appears in the footnote of Table 2.  \n \n \n\n                                                       \n \nTable 1. Characteristics of study population. \n \n \nPatients with  \nTERP \n(n = 92) \nPatients with \n PSP \n(n = 132) \np value \nAge (years old) (range) 38.6 ± 5.7 (24 - 50) 27.7 ± 9.8 (14 - 67) < 0.01 \nSide of pneumothorax \nRight \nLeft \n \n91 (98.9%) \n1 (1.1%) \n \n56 (42.4%) \n76 (57.6%) \n< 0.01 \nHeight (cm) 159.0 ± 4.9 160.9 ± 5.9 < 0.05 \nWeight (kg) 49.1 ± 5.7 47.6 ± 6.1 0.074 \nSmoking habit \nCurrent/former smoker \nNon-smoker \n \n6 (6.5%) \n86 (93.5%) \n \n41 (31.1%) \n91 (68.9%) \n \n< 0.01 \nHistory of pelvic endometriosis 54 (58.7%) 3 (2.3%) < 0.01 \nThe number of preoperative pneumothorax episodes 8.1 ± 3.2 2.8 ± 1.6 < 0.01 \nPostoperative follow-up period (months) 36.2 ± 22.3 12.0 ± 11.8 < 0.01 \nThe number of patient with postoperative recurrence 36 (39.1%) 23 (17.4%) < 0.01 \n\n                                                       \n \nTable 2. Factors predicting TERP.  \n \n* If each risk factor does not exist, the score “0” is given in the following equation: \nCalculated score = Right pneumothorax (score 6 or 0) + History of pelvic endometriosis (score 5 or 0) + Age ≥ 31 years old (score 4 or 0) + \nNo history of smoking (score 3 or 0).  \nNA, not adopted \n \nRisk factors Odds ratio 95% CI p value Score \nAssigned* \nRight pneumothorax 440.3 15.0 - 12943.4 < 0.01 6 \nHistory of pelvic endometriosis 115.1 10.2 - 1306.2 < 0.01 5 \nAge ≥ 31 year 78.0 12.1 - 502.1 < 0.01 4 \nNo history of smoking 13.4 3.0 - 61.0 < 0.01 3 \nThe number of preoperative pneumothorax episodes ≥ 4 5.8 1.4 - 23.6 < 0.05 NA \nHeight ≤ 159 cm 4.1 1.2 - 14.2 < 0.05 NA \n\n                                                       \n \nTable 3. Diagnostic significance of calculated score to differentiate between TERP and PSP. \n \nNumbers in parentheses indicate 95% CI.  \n \n Sensitivity Specificity Positive predictive value Negative predictive value \nCalculated score ≥ 12 0.935 \n(0.902 - 0.967) \n0.894 \n(0.854 - 0.934) \n0.860 \n(0.815 - 0.905) \n0.952 \n(0.923 - 0.980) \n\n                                                       \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \nLung vol. 192 No. 4 \n平成 26 年 8 月 1 日 公表済","source_license":"public-domain-us","license_restricted":false}