{"paper_id":"647c669b-76c1-4ce8-9743-9bb3ddf6fa5b","body_text":"Endometriosis is defined as the presence of endometrial tissue (stroma\nand functional glands) outside the uterine cavity. It is therefore a\nsituation when endometrial tissue is present in ectopic locations\ninstead of its eutopic site in the uterus, a condition first described\nby Maurer  et al .\n [1]  in 1958. It is found among women of reproductive\nage, with an incidence varying between 5% and 15%, as documented\nin the literature. [1 – 5]\nThe majority of ectopic sites are in the pelvic organs, with only\n8.9% - 12% reported as extrapelvic in location. [2 , 3]  While the thoracic\ncavity is one of the more common extrapelvic sites, [6 , 7]  a report\ndocumented gastrointestinal endometriosis as the most common site\n(32.3%). Another site is the urinary tract (5.9%), while together, the\nlungs, umbilicus, abdominal scars, liver, gall bladder, pancreas, breast\nand extremities constitute 61.8%. [2]  Endometriosis of the central\nnervous system and the heart has also been documented. [4]\nThoracic manifestation in endometriosis is varied, and collectively\nreferred to as thoracic endometriosis syndrome (TES). [3 , 5 , 6]  Various\ntheories have been propounded to explain this condition. [2 – 6]  The\ntheory of coelomic metaplasia is premised upon the common origin\nof endometrial and mesothelial cell from coelomic epithelium.\nAppropriate pathologic stimuli (probably refluxed menstrual blood)\nthen trigger metaplastic change. The retrograde menstruation or \nmigration theory postulates that diaphragmatic endometrial implants\nresult from shedding of eutopic endometrial tissue through the patent\nfallopian tube into the pelvis, and thence into the peritoneal fluid.\nThe physiologic hypothesis suggest that high circulating levels of\nprostaglandin F 2 \npresent during menstruation cause vasoconstriction\nand bronchospasm, which predisposes to alveolar rupture, hence\npneumothorax. The transgenital-transdiaphragmatic passage of air\ntheory explains how pneumothorax develops from air movement\nfrom the vagina through the fallopian tube into the peritoneum and\nthrough congenital or acquired diaphragmatic defects into the pleural\ncavity. Transgenital movement of air is aided by deficiency of mucus\nplug during menses. The concept of clockwise peritoneal circulation,\nstarting from the pelvis and upwards through the right paracolic\ngutter to the right hypochondrium, may facilitate the migration\ntheory. Lastly, microembolisation of endometrial cells into the lungs\nthrough venous or lymphatic circulation have been postulated in\nthe metastatic theory. Though none of these theories individually\ncompletely explains the TES phenomenon, there may be interplay\nbetween the various mechanisms.\nTES remains an uncommon condition, with the literature mostly\ndocumenting case reports or case series, and the manifestation\nis often varied. Furthermore, there is a paucity of reporting of this \ncondition from the African continent. We therefore constituted an\nendometriosis study group and present a report of this rare condition\nfrom North Central Nigeria.\n\nWe conducted a retrospective review of medical records of patients\ndiagnosed with endometriosis at the University of Ilorin Teaching\nHospital over a 3.5-year period (January 2014 - June 2017). All\npatients presented through either the obstetrics and gynaecology or\nthoracic and cardiovascular surgery department.\nIdentification of cases managed was from the databases of the\ndepartments as portals of entry, as well as the hospital medical records\ndatabase. The index of suspicion used in identifying possible TES\npatients included chest symptoms and signs related to the menstrual\ncycle, with or without a background diagnosis of pelvic endometriosis\nor chronic pelvic pain. The diagnostic approach included a history\nand physical examination at presentation, review of gynaecological\nhistory/gynaecologist review, management of emergency needs\nplus sample collection, other procedures and biopsy as required and\nnecessary supportive treatments.\nAlso documented were their demographic characteristics, mode of\npresentation and diagnosis, the treatment offered and their outcomes.\nData were collected and descriptive statistics presented using Excel\n(Microsoft, USA).\n\nWe documented a total of 21 patients presenting with endometriosis,\nrepresenting 1.27% of all gynaecological admissions during the study\nperiod. Of these, 8 patients (38.1%) presented with TES. This represented\n1.2% of admissions for thoracic disorders during the study period. The\ncharacteristics of these patients are presented in  Table 1 . Twelve patients\n(57.1%) had extrapelvic presentation, of whom the TES 8 comprised\n66.7%; the others were 2 gastrointestinal (GIT) (25%) and 2 umbilical\n(16.7%) cases (2 patients had combined TES and GIT presentation). All\npatients had had multiple episodes of symptomatology for TES before\npresentation and diagnosis at our facility.\nTES  = thoracic endometriosis syndrome;  Rt  = right\nCCP  = catamenial chest pain;  CPE  = catamenial pleural effusion\nCPT  = catamenial pneumothorax;  CSE  = catamenial surgical emphysema\nCHp  = catamenial haemoptysis;  VATS  = video-assisted thoracoscopic surgery\nCTTD  = closed thoracostomy tube drainage;  GIT  = gastrointestinal tract\nThe age range for TES was 14 - 38 years (median 31, mean 28.7\n(standard deviation (SD) 8.63), and 87.5% were nulliparous. The most\ncommon variety of TES among the patients was catamenial pleural \neffusion (CPE) in six (75%) patients; three (37.5%) had catamenial\nchest pain (CCP), two (25%) each presented with catamenial\npneumothorax (CPT) and catamenial haemoptysis (CHp) while one\n(12.5%) had catamenial surgical emphysema (CSE). In addition, four\n(50%) of the patients had multiple thoracic manifestations, while\nright-sided TES occurred in seven (87.5%). The patient with CSE\nhad bilateral diffuse thoracic, nuchal and facial surgical emphysema.\nSeven patients (87.5%) had concomitant extrathoracic manifestation,\nall involving the pelvis, of whom two (28.6%) had an additional\nGIT manifestation; thus 25% of all patients with TES had GIT\nmanifestation  (Table 1) .\nTable 2  shows that diagnosis was based on strong clinical grounds\nin all patients, establishing catamenial relationship to presentation.\nIn three (37.5%) patients who had a chest tube  in situ  prior to onset\nof menstruation, the effluent increased in volume and became\nhaemorrhagic with menstruation. Histological confirmation was\nobtained in four (50%) cases, while serum CA-125 was performed in\nthree patients, with elevated results found in two of them.\nClosed thoracostomy tube drainage (CTTD) plus chemical\npleurodesis was the most frequent intervention technique, accounting\nfor 62.5% (five patients), while diagnostic video-assisted thoracoscopic\nsurgery (VATS) was performed on two (25%) patients. Another\ntwo (25%) had thoracotomy with parietal pleurectomy after failed\nchemical pleurodesis.  Fig. 1  shows endometriotic nodules on the\ndiaphragm at thoracotomy of patient 5 on the list, while  Fig. 2  shows\nthe photomicrograph of the histology of the same patient.\nEndometriotic nodules on the diaphragm.\nPhotomicrograph of histology on endometrioma (haematoxylin\nand eosin staining, magnification ×400) showing a dilated endometrial\ngland surrounded by endometrial stroma, including mononuclear\ninflammatory cells (mostly macrophages).\nHowever, \ntwo patients were managed non-operatively. In addition, two patients\nhad recurrent pleural effusion during subsequent menstruation\nfollowing an initial successful treatment. Both were counselled\nfor thoracotomy for parietal pleurectomy, but one opted for repeat\nchemical pleurodesis, while the other chose expectant management.\nNo mortality was recorded, and patients were transferred to the\ngynaecology service for hormonal therapy, apart from two patients\nwho had had hormonal treatment prior to presentation with thoracic\nmanifestations.\n\nTES refers to a constellation of manifestations resulting from\ngrowth of endometrial-like glands and stroma in the lungs, on\nthe pleural surfaces or in the airway. [3 , 5 - 7 , 9 , 10]  It is an uncommon\ncondition, documented in the literature mostly in case reports and\ncase series. [5 - 7 , 9 - 12]  An analysis of 110 case reports/series published\nin English was conducted by Joseph and Sahn in 1996, [13]  and\nChannabasavaiah and Joseph, [4]  in 2010, conducted a similar\nreview with the same number of patients, covering a 6.5-year\nperiod. Haga  et al ., [14]  in Tokyo, Japan, reported 84 cases of CPT \nwhile evaluating 570 cases of spontaneous pneumothorax in\nwomen.Over a 7-year period, Hwang  et al .\n [2]  documented 15 cases\nat a single centre in Seoul, Korea. Forty cases were reported by\nDvorakovskaya  et al .\n [15]  from St Petersburg Hospital, but the\nduration of collation was not stated. Reports from Africa are even\nrarer: there is a report of 3 cases by Ekpe  et al .\n [16]  from South\nSouth Nigeria, and a case report each from Ghana [17]  and Uganda.\n [18]  There is one review article each from Nigeria and Zimbabwe.\n [3 , 19]  TES is a rare but important extrapelvic manifestation of\nendometriosis. We therefore document these eight cases of TES\nseen over 3.5 years at a tertiary hospital in North Central Nigeria.\nManifestations constituting TES include CCP, CPT, CHt/CPE,\ncatamenial haemoptysis (CHp), pulmonary nodules and CPM. [2 – 8] \nThese presentations result from the presence of endometrial tissue on\nthe pleural surfaces (CCP, CPT, CPE, CPM), in the lung parenchyma\n(pulmonary nodule) or the airway (CHp). Pleural involvement is\nmore common, accounting for about 83% of TES, while parenchymal\nand airway involvement account for 17%, [9]  and our study found a\nsimilar distribution. An even rarer occurrence of endometriosis on\nthe thoracic aorta has been reported. [20]\nThe term catamenial is derived from the Greek word  Katamenios ,\nwhich means ‘monthly occurrence’. Thus development of these\nmanifestations in a temporal relationship to menstruation is vital to\nclinical diagnosis. The expected interval reported between symptoms\nand menstruation varies, but a 72-hour period before onset and after\ncessation of menstruation is considered acceptable. [13]\nOur study reflects a higher presentation of extrapelvic lesions,\nof 57% (12 of 21 patients with endometriosis), compared with the\n8.9% - 12% documented in the literature. [2 , 3]  The higher incidence of\nTES (66.7%) in extrapelvic sites has been reported in some studies; [5 , 6] \nhowever, contrary to reports of GIT dominance by others, [2]  in our\nstudy this constituted only 25%.\nThe mean age of occurrence of TES in our patients was 28.7 years (SD\n8.63); this is younger than the ~35 years reported in the literature. [2 - 4 , 8 , 10 , 13 , 21] \nThe presentation of CHp in one of our youngest patients (19 years) may\nsupport the postulate that this manifests at a relatively younger age than\nother forms of manifestation. [4]\nAn interesting finding from this study is the predominance of CPE,\naccounting for 75% of cases, while CCP was second, with 37.5%.\nWe also identified a rare occurrence of CSE without associated\npneumothorax. Most reports present either CPT (up to 73%) [3 – 7]  or\nCCP (80% - 90%) [3 , 7 , 21]  as the most common manifestation of TES. In a\nreview of 15 cases by Hwang  et al ., [2]  CHt accounted for 53%, while the\nremaining 47% were CPT cases. The 87.5% predominance on the right\nside in this study is consistent with previous reports of the vast majority\nof TES (above 85%) occurring in the right hemithorax. [2 , 3 , 5 , 6 , 10 , 13 , 21]  This\npredilection has been attributed to clockwise peritoneal circulation by\nsome authors. [5]\nMultisite involvement in extragenital endometriosis is rare.\nHowever, TES is often associated with pelvic endometriosis with an\nincidence varying from 18% to 84%. [2 , 6 , 13 , 21 , 22]  In this study, 87.5% had\nconcomitant TES and pelvic endometriosis. Studies have suggested\nthat pelvic endometriosis usually occurs about 5 years earlier than\nonset of thoracic manifestation. [13]\nOf the six patients who wished to become pregnant, only one had\nchildren, with the remaining 83.3% being infertile. The association \nbetween endometriosis and infertility has been well documented,\nwith 30% - 50% of patients with endometriosis estimated to be\ninfertile, while about 20% - 50% of infertile women are said to have\nendometriosis. [23 , 24]  The presence of endometrioma in the pelvis, with\nresultant adhesions, has been coined the ‘pelvic factor’. The distortion\nthat arises causes tubo-ovarian dis-co-ordination, and affects tube\npatency. [23 , 24]  Other possible mechanisms include endocrine and\novulatory abnormalities, altered peritoneal function and altered\nendometrial hormonal and cell-mediated function. [24]\nDiagnostic criteria in the establishment of thoracic endometriosis\ninclude clinical and histological factors, and the use of a biomarker.\nThe establishment of cyclical symptoms in temporal relationship\nwith menstruation, as seen in all patients in this study, is pivotal to\ndiagnosis. [6 , 16 , 21]  However, a confirmatory diagnosis is established\nwhen endometrial stroma and glands are identified histologically, as\nwas seen in 50% of our patients. [2 , 6]  Obtaining tissue for histological\ndiagnosis may not always be feasible, and pleural fluid or bronchial\nlavage cytology is often negative. The identification of endometriotic\nlesions by VATS or bronchoscopy may be easier during menstruation.\nBronchoscopy performed within 2 days of onset of menses may improve\nlocalisation, especially in patients with CHp. [3 , 5]  The appearances\nof lesions on radiological imaging techniques are nonspecific. [2 , 5 , 10] \nFocal areas of consolidation, ill-defined opacities or bullous disease\non the lung, or hypo-attenuated areas on the diaphragm seen on\nchest computed tomography scans are not pathognomonic, and the\nsensitivity on magnetic resonant imaging may be superior. [2 , 3 , 5 , 10]  The\nbiomarker serum CA-125 is now used to improve the diagnosis of\nendometriosis. However, an elevated serum or pleural fluid level is\nnonspecific, as it is associated with any process causing irritation\nof mesothelial cells. [3 , 10]  We have only recently included this in the\ninvestigation protocol for our patients, and two of the three who had\nthe test showed an elevated level.\nTwo patients from our study did not require surgical intervention.\nCSE in patient 7 resolved on intranasal oxygen supplementation\nwhile she was nursed in semi-Fowler’s position. CPT in patient 8\nwas mild and allowed for reabsorption. Of the remaining 6 patients,\nCTTD was the initial line of treatment in order to relieve raised\nintrapleural pressure. Two patients (1 and 3) had diagnostic VATS,\nbut since our centre is not equipped for therapeutic VATS, parietal\npleurectomy could not be conducted. Patient 2 did not achieve lung\nre-expansion for chemical pleurodesis and declined thoracotomy for\nparietal pleurectomy. She had a modified ambulatory home drainage\nsystem instituted. The other five patients all had chemical pleurodesis;\nin one (20%) this was successful at first application, another one (20%)\nat second application, and two (40%) failed and proceeded to have\nthoracotomy and parietal pleurectomy. One patient with recurrence\ndeclined further intervention. Our observation that chemical\npleurodesis alone has a poor success rate in patients with CPE is\nsupported by the literature. [9 , 10 , 16]  This is expected, as continuous\nactivity from cyclical proliferation of endometrial implants, and\nalso migration through patent diaphragmatic defects, predisposes to\nrecurrence.\nWe recorded no mortality, however, and patients were referred to\nthe gynaecologist for hormonal therapy and further management.\nDespite individual case requirements, we propose a systematic\napproach to the management of TES, by a multidisciplinary team, \nconsisting of a gynaecologist, cardiothoracic surgeon, pulmonologist,\nhistopathologist, radiologist and anaesthesiologist. [3 , 11]  A high index of\nsuspicion is needed on clinical assessment and radiologic evaluation.\nInitial supportive oxygen, observation and rest are instituted for small\ncollections. Patients in respiratory distress need immediate relief by\neither thoracocentesis or tube thoracostomy, with fluid specimens\nobtained for microscopy, Ziehl Neelsen stain, chemistry, cytology\nand CA-125 assay. When available, VATS should be employed\nearly. This is currently the gold standard, as both diagnosis and\ntreatment (including resection of implants, closure of diaphragmatic\nfenestrations and pleurectomy with abrasive pleurodesis) can\nbe effected with the attendant benefit of minimal access. [3 , 5 , 11 , 21] \nCombined VATS and video-assisted laparoscopy is recommended\nby some researchers  [10]  Conventional thoracotomy should be utilised\nwhere VATS is unavailable, in cases of recurrence after VATS or\nfailure of the minimally invasive technique. Hormone therapy using\ngonadotrophin-releasing hormone analogue is recommended in the\nimmediate postoperative period and for 6 - 12 months afterwards. [2 , 6 , 10]\nTwo limitations of this study are its retrospective nature, and the\nsmall sample size. We have therefore constituted an endometriosis\nstudy group to collate prospectively collected data for future\npresentation.\n\nTES remains an uncommon condition despite being the most\ncommon extrapelvic manifestation of endometriosis. Its association\nwith pelvic presentation is further strengthened by this study. There is\nsome variability in the modes of manifestation of TES. Recurrent chest\nsymptoms in a woman of childbearing age with a history of infertility\nshould raise a high index of suspicion. Despite most literature\nreporting CPT as the most common TES manifestation, we found\nCPE to account for the majority of cases in our study. We also present\na rare manifestation of CSE. Being a developing country with paucity\nof facilities, the utilisation of VATS as a treatment option is limited\nin Nigeria. Chemical pleurodesis and conventional thoracotomy with\nparietal pleurectomy are therefore the most common intervention\nmodes. However, we found that chemical pleurodesis was generally\nunsuccessful in patients with TES; therefore, performing thoracotomy\nwithout attempting chemical pleurodesis may be a more beneficial in\nabsence of VATS.","source_license":"CC0","license_restricted":false}