Dynamic monitoring of pulmonary endometriosis based on HRCT

Dynamic monitoring of pulmonary endometriosis based on HRCT | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Dynamic monitoring of pulmonary endometriosis based on HRCT Yunlong Ni, Xia Feng, Yingying Zhou This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4540695/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Endometriosis (EMS) refers to the appearance, growth and infiltration of endometrial tissues (glands and stroma) in the uterine cavity covering the endometrium and other parts of the uterus, repeated bleeding, Rare pelvic and intraperitoneal endometriosis can invade various areas such as the pleura, lungs, groin, umbilical cord, diaphragm, sciatic nerve, external ear, scalp, etc.Thoracic endometriosis syndrome (TES) is a rare disorder characterized.It can be divided into pleural and pulmonary endometriosis (PEM)according to the site of the lesion.The pathogenesis of TES has not yet been clarified, and multiple hypotheses have been proposed to explain its pathogenesis and clinical manifestations.The abnormality of the immune system is one of the important factors that cause and promote the occurrence and development of EMS.We report a 32-year-old woman diagnosed at our hospital with PEM presented a clinical characteristic of intermittent cough and hemoptysis and a pathologic manifestation of a large amount of hemosiderin deposition and a small amount of fibrous tissue.The patient was treated with leuprolide combined with tibolone. The patient’s cough and hemoptysis improved significantly within a short period of time, and his lung lesions improved significantly.At the same time,he did not develop serious related complications.Our report suggests that Add-back therapy of the patient’s conditions is necessary in PEM patients with not accepted surgical treatment.Leuprolide combined with tibolone may be an induction therapy with safety and feasibility.However, more clinical trials are needed to validate the efficacy and safety of the therapeutic regimen. pulmonary endometriosis high-resolution computerized tomography leuprolide tibolone case report combination treatment Figures Figure 1 Figure 2 1. Introduction Endometriosis(EMS)refers to the presence of endometrial tissue (glands and stroma) in the uterine cavity,covering the endometrium,and outside the uterus.The appearance, growth,invasion,and repeated bleeding of ectopic endometrium can lead to pain, infertility, nodules or masses.Rare cases of endometriosis can affect various parts of the body.the clinical manifestations of ectopic endometriosis outside the pelvic cavity often accompany symptoms related to periodic changes in the affected area. Thoracic endometriosis syndrome(TES)with about 2% occurs in the chest, of which only 1/5 occurs in the lung parenchyma[ 1 ].Up to 80% of women with TES present with concomitant pelvic endometriosis[ 2 ].Pulmonary endometriosis (PEM) is a relatively rare disease, manifested as hemoptysis during menstruation intrapleural ectopic endometriosis can present with pneumothorax during menstruation.Abnormal expression and regulation of related genes, immune inflammatory response, and abnormal expression of sex hormone receptors are closely related to the occurrence of endometriosis[3].High-Resolution Computerized Tomography(HRCT) is important for the diagnosis of pulmonary endometriosis but it must be combined with clinical history[4].The diagnostic points include:Fertility female patients with menstrual cycle-related periodic hemoptysis;Hemoptysis usually occurs within a few days before and after menstruation;There has been dysmenorrhea, induced abortion in the past medical history;chest CT shows patchy high-density shadows in the lungs, with density Uniform, with clear boundaries,such as similar lung segments appearing in two menstrual periods internal changes, and no abnormal findings in the lung during the menstrual period or the cessation of hemoptysis can be confirmed.Most lesions of pulmonary endometriosis are located in the lung parenchyma and the role of pleural, bronchoscopy and hydrothorax cytology examination limit.The pathological findings of macrophages containing hemosiderin are considered compatible and even suggest endometriosis. As we reported below based on HRCT images,we observed the cyclic changes in pulmonary endometriosis closely related to the menstrual cycle.Combined with 3D bronchial tree CT imaging and biopsy pathology results,we confirmed the diagnosis of pulmonary endometriosis.and we observed the good safety and efficacy of leuprorelin combined with Add-back therapy(Tibolone)for the treatment of patients for long-term treatment patients with severe chest pain and hemoptysis. 2. Case presentation A 32-year-old woman during menstruation was admitted to the Hangzhou Third People's Hospital in Dec 2022 because of chest pain for 2 months,cough for 2 weeks.and hemoptysis for 3 days.3 months ago,the patient also during menstruation underwent HRCT examination due to intermittent cough, which showed a partially solid nodule in the upper lobe of the right lung(Figures 1A).After two weeks of anti-inflammatory treatment(Moxifloxacin 0.4g oral QD),CT reexamination showed that the lesions in the upper lobe of the right lung had almost completely absorbed(Figures 1B).She had no known medical history or recent illnesses.When admitted,She denied having a fever,night sweats,or weight loss.No work or occupational contact history, medication intake history,or recent travel history.She had one previous cesarean section with a healthy female infant two years ago.On initial examination in our critical care unit,The patient’s initial vital signs revealed a heart rate of 84 beats/min; BP, 120/79 mm Hg;respiratory rate,20 breaths/min.and oxygen saturation,97% at rest on room air.The patient was 154.5 cm (60.9 in) tall and weighed 48.4 kg (106.7 lb) (BMI, 20.3 kg/m2).She had congestion of posterior pharyngeal wall,breath sounds in both lungs were clear, no rales or wheeze,and had normal cardiac, abdominal, neurological,and skin examinations.She had regular menses but associated with severe dysmenorrhea.WBC count was 6.6×109/L (normal, 3.5 to 10.5 109/L) with 62.7% neutrophils.Renal and hepatic functions were normal. C-reactive protein was 0.7 mg/L(normal, < 10 mg/L).Hemoglobin was 121g/L(normal, 120 to 160g/L).HIV serologic result was negative.Pneumococcal and Legionella urinary antigens were negative.and d-dimer was elevated(0.96 mg/mL(normal value, < 0.5 mg/dL).The T cell spot test for tuberculosis (T-SPOT.TB) was negative.Anti-HAV IgM and hepatitis C the early antibody IgM anti-HCV in serum were negative. Chest HRCT showed a nodular high density shadow in the upper lobe of the right lung,ground glass density shadow was observed around the lesion.(Figures 1C).Ceftriaxone (2g,qd, ivgtt) was given. After 5 weeks,The lesion in the upper lobe of the right lung was not absorbed.(Figures 1D).Three-dimensional(3D) reconstruction of the bronchial tree from contiguous scanning of thin-section CT further revealed the presence of a solid nodule in the right superior lobe,which is Partial connection with bronchi(Figures 2A,B).A flexible bronchoscopy with BAL revealed no new organisms,An extensive micro biologic workup of the BAL fluid for bacterial,viral,fungal,and mycobacterial pathogens was negative.CT-guided percutaneous transthoracic needle aspiration was recommended to further characterize the lesions(Figures 2C,D),histopathology of the lung showed a large amount of hemosiderin deposits with a small amount of fibrous tissue (Figures 2E).Based on the clinical history,radiographic findings,And pathologic examination of the examination of the puncture tissue,the diagnosis of pulmonary endometriosis(PEM) was established.She was given leuprorelin acetate 3.75 mg,with an additional suspension solvent of 2 ml, is administered for the first time on the third day of the menstrual cycle, with a subcutaneous injection at the upper arm.This was followed by one injection every four weeks for a total of three injections. 2.1 Outcome and follow-up Chest HRCT images showed radiographic improvement on repeat CT scan imaging at that 4 weeks follow-up appointment.(Figures 1E).Her symptoms was disappeared,with no coughing,hemoptysis,or chest pain.8 months later,She experienced mild chest pain, insomnia, and muscle ache during her menstrual period. The chest HRCT showed that the density of the lesion in the right upper lobe of the lung had slightly increased compared to before(Figures 1F).Testosterone derivatives therapy(Leuprorelin,3.75mg,sc) combined with add-back therapy(Tibolone,1.25mg,qd) was given.CT scans showed that the lesion in the upper lobe of the right lung still existed,but the density of the lesion decreased significantly 10 days later(Figures 1G).The chest imaging showed stable results after a month of CT reexamination(Figures 1H).She had no chest pain, and her sleep quality and muscle soreness had significantly improved.The clinical course of the patient is shown in Figure 3. 3. Discussion Endometriosis (EMS) refers to the appearance, growth and infiltration of endometrial tissues (glands and stroma) in the uterine cavity covering the endometrium and other parts of the uterus,repeated bleeding,and then causing pain, infertility and gynecological diseases such as nodules or masses.The pathogenesis of Thoracic endometriosis syndrome (TES) has not yet been clarified,Multiple hypotheses have been proposed to explain its pathogenesis and clinical manifestations.A possible explanation for the development of these lesions is given by the implantation theory of Sampson. during menstruation,vital endometrium is retrograde delay shed from the uterus through the fallopian tubes into the abdomen, where it adheres to the peritoneum and develops into vascularized endometriotic lesions.Other possible pathogenesis include the theory of body cavity epithelial metaplasia, vascular and lymphatic metastasis, and stem cell theory. It is generally acknowledged that an estimated 10% of all women during their reproductive years (from the onset of menstruation to menopause) are affected by endometriosis.This equates to 176 million women throughout the world, who have to deal with the symptoms of endometriosis during the prime years of their lives.Common locations of endometriosis Endometriosis lesions can be found anywhere in the pelvic cavity:on the ovaries the fallopian tubes on the pelvic side-wall (peritoneum) the uteros.Rare pelvic and intraperitoneal endometriosis can invade various areas such as the pleura,lungs,groin, umbilical cord,diaphragm,sciatic nerve, external ear, scalp, etc. TES is a rare disorder characterized by the presence of functional endometrial tissue within the chest cavity.It can be divided into pleural and pulmonary parenchymal endometriosis according to the site of the lesion. Up to 80% of women with TES present with concomitant pelvic endometriosis.In one observational study of Women with the diagnosis of endometriosis, defined as codes 617 (International Classification of Diseases,ninth revision,ICD–9) or N80 (ICD–10), were retrieved from the PAR.Obstetric outcome was assessed through linkage with the MBR.Out of 709 090 women,3110 were treated as inpatients with a first diagnosis of endometriosis after their first delivery. Women with a diagnosis of endometriosis before their first delivery were excluded.The Cox analyses yielded a hazard ratio of 1.8(95% CI 1.7–1.9) for endometriosis in women who had had aprevious caesarean section compared with women with vaginal deliveries only.The risk of endometriosis increased over time: one additional case of endometriosis was found for every 325 women undergoing caesarean section within 10 years.In addition to the recognised risk of scar endometrioma,an association between caesarean section and general pelvic endometriosis(9). The main symptom of patients with TES with chest pain linked with menstrual periods.It can occur in 90% of patients,and one-third of patients experienced difficulty breathing,as well as pneumothorax or hemothorax.Endometrial limited to the diaphragm can be accompanied by pain in the ipsilateral chest, shoulders, upper limbs, and neck.Patients with bronchial or pulmonary endometrial diseases typically experience hemoptysis.Catamenial hemoptysis happens when there is repetitive bleeding in one or both lungs. This often happens at the same time as menstruation, as hormonal changes cause the endometriosis patches to swell and bleed. It occurs in 5% of people with thoracic endometriosis.Symptoms can include:coughing up blood chest pain shortness of breath. The chest radiographic findings in PEM can assist in diagnosis,manifested as small pulmonary nodules with clear or unclear boundaries,or ground-glass exudates accompanied by bleeding.If checked during non menstrual periods,the chest CT results may be negative(10).For patients with menstrual hemoptysis,bronchial arteriography can also be used to diagnose pulmonary parenchymal endometriosis. Due to convenient and non-invasive detection technology,CT virtual bronchoscopy of bronchi is useful to attain the relationship between lesions and bronchi in recent years.In addition,thoracoscopy is increasingly being used for the diagnosis of intrathoracic anomalies.To improve the diagnostic rate.Thoracoscopy should be performed during the menstrual period. Diagnosis should exclude other lung diseases, especially tumors and tuberculosis.The serum CA125 level may increase.in patients with PEM(11). Only about one-third of patients with pulmonary endometriosis can obtain a clear histopathological diagnosis(12),mainly due to the repeated bleeding of the endometrium, which disrupts the typical pathological tissue structure and is difficult to detect.However,as long as evidence of bleeding such as hemosiderin containing cells or red blood cells is found in the alveoli, It could also be diagnosed as pulmonary endometriosis.with typical periodic clinical manifestations. In terms of treatment,for patients presenting with unstable conditions,the emergency treatment methods for hemothorax,pneumothorax,or hemoptysis should be followed first.For patients presenting with stable conditions, medication should be the main treatment.Since the discovery and synthesis of GnRH-a in 1971,many long-acting preparations and analogs of GnRH have been synthesized,which have shown efficacy in alleviating symptoms such as endometriosis pain and reducing the size of endometriosis masses,effectively delaying and inhibiting recurrence(13-17).Long term use of GnRH-a can alleviate symptoms of endometriosis, effectively delay and inhibit recurrence(18,19).Leuprorelin acetate is a commonly used therapeutic drug that can regulate hormones and alleviate clinical symptoms(20-22).However, long-term use of this class of drugs can cause a series of menopausal-like symptoms and bone loss due to decreased estrogen levels(23-25).The theoretical basis of the anti-addition therapy is the "estrogen threshold theory" proposed by Barbieri et al.which controls estrogen levels within a relatively low range (theoretical threshold is 110-146 pmol/L),with little effect on bone metabolism, but at the same time can inhibit the growth of ectopic endometrium,with significant efficacy.The long-term application of GnRH-a combined with Add-back therapy(ABT) is an effective treatment for EMS,but there are still differences in the formulation and application dose(26,27). Von et al.applied tibolone to patients, and the results showed that perimenopause symptoms were significantly alleviated,and problems caused by abnormal vasomotor activity were greatly improved, and it could effectively alleviate the emotions of medication users.It can be used in the transition period of menopause, and as a common supplement for medication,it can be widely applied in late menopause(28,29).Zupi et al.reported that Tibolone can effectively alleviate or eliminate menopausal-like symptoms(30). When medication treatment fails or the patient cannot tolerate it,Surgical intervention should be considered.For patients with fertility requirements with PEM, it is recommended to try to get pregnant actively.In general, it is recommended to use GnRH for 3-6 months to observe the therapeutic effect.If the treatment is effective, other medications such as oral contraceptives, progesterone,danazol can be continued for maintenance treatment to achieve the effect of inhibiting ectopic endometrium.The recurrence rate of pneumothorax and hemothorax after discontinuation of medication is still higher than 50%. Symptom relief and disappearance of imaging lesions can be continued with maintenance treatment with drugs such as combined oral contraceptive(COC) and Dexamethasone.Pregnancy is recommended for those with fertility requirements.There is a possibility of recurrence after discontinuing the medication. Surgical treatment may be necessary for those who fail drug treatment,The combination of postoperative endocrine therapy can reduce the recurrence rate(31-33). The development and popularization of video assisted thoracoscopy (VATS) greatly reduce surgical trauma,and can clearly display and comprehensively explore thoracic lesions, thereby improving the positive rate of thoracic biopsy, making treatment more thorough, and reducing postoperative recurrence rate(34).Therefore, surgical treatment in TES,especially in patients with menstrual pneumothorax and hemothorax, is increasingly valued.During VATS surgery,the entire thoracic cavity, including the viscera, parietal pleura, and diaphragm, should be thoroughly explored, and all visible endometrial lesions should be removed to achieve radical treatment and prevent recurrence. Based on our review of the available literature, this is the first case reported in the literature in which observed imaging dynamic changes of PEM using HECT.Our case report suggests that leuprolide acetate combined with tibolone may be on efficacy treatment effects and quality of life in patients with pulmonary endometriosis.However, more clinical studies are needed to confirm the therapeutic effect of GnRH Therapy combined with Add-back therapy in PEM. Abbreviations EMS,Endometriosis;PEM, Pulmonary endometriosis; TES, Thoracic endometriosis syndrome;HRCT, High-Resolution Computerized Tomography; LA,Leuprolide acetate;GnRH-a,Gonadotrophin-releasing hormone agonist;ABT, Add-back therapy. Declarations Data availability statement The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation. Ethics statement The studies involving humans were approved by the ethics review committee of Hangzhou Third People's Hospital.The studies were conducte din accordance with the locallegislation and institutional requirements.Written informed consent for participation was not required from the participants or the participants’legal guardians/next of kin in accordance with the national legislation and institutional requirements. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article. Author contributions HL: Conceptualization, Formal analysis, Methodology, Writing– original draft, Writing – review & editing. XCZ: Funding acquisition, Supervision, Writing – review & editing. XF: Data curation, Writing – review & editing. YYZ: Data curation, Writing –review & editing. YLN: Conceptualization, Supervision, Writing –review & editing. Funding The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article. Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Publisher’s note All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. References Alifano M, Trisolini R, Cancellieri A, Regnard JF. Thoracic endometriosis: current knowledge. Ann Thorac Surg 2006 Feb;81(2):761-9.doi:10.1016/j.athoracsur.2005.07.044 Bougie O, Yap MI, Sikora L, Flaxman T, Singh S. 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Fertil Steril. 2004 Nov;82(5):1303-8. doi: 10.1016/j.fertnstert.2004.03.062 Olive DL, Pritts EA. Treatment of endometriosis. N Engl J Med. 2001 Jul 26;345(4):266-75. doi: 10.1056/NEJM200107263450407 Joseph J, Reed CE, Sahn SA. Thoracic endometriosis. Recurrence following hysterectomy with bilateral salpingo-oophorectomy and successful treatment with talc pleurodesis. Chest. 1994 Dec;106(6):1894-6. doi: 10.1378/chest.106.6.1894 Nezhat C, Main J, Paka C, Nezhat A, Beygui RE. Multidisciplinary treatment for thoracic and abdominopelvic endometriosis. JSLS. 2014 Jul-Sep;18(3):e2014.00312. doi: 10.4293/JSLS.2014.00312. PMID: 25392636 Ciriaco P, Muriana P, Lembo R, Carretta A, Negri G. Treatment of Thoracic Endometriosis Syndrome: A Meta-Analysis and Review. Ann Thorac Surg. 2022 Jan;113(1):324-336. doi: 10.1016/j.athoracsur.2020.09.064 Additional Declarations No competing interests reported. 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Introduction","content":"\u003cp\u003eEndometriosis(EMS)refers to the presence of endometrial tissue (glands and stroma) in the uterine cavity,covering the endometrium,and outside the uterus.The appearance, growth,invasion,and repeated bleeding of ectopic endometrium can lead to pain, infertility, nodules or masses.Rare cases of endometriosis can affect various parts of the body.the clinical manifestations of ectopic endometriosis outside the pelvic cavity often accompany symptoms related to periodic changes in the affected area. Thoracic endometriosis syndrome(TES)with about 2% occurs in the chest, of which only 1/5 occurs in the lung parenchyma[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].Up to 80% of women with TES present with concomitant pelvic endometriosis[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].Pulmonary endometriosis (PEM) is a relatively rare disease, manifested as hemoptysis during menstruation intrapleural ectopic endometriosis can present with pneumothorax during menstruation.Abnormal expression and regulation of related genes, immune inflammatory response, and abnormal expression of sex hormone receptors are closely related to the occurrence of endometriosis[3].High-Resolution Computerized Tomography(HRCT) is important for the diagnosis of pulmonary endometriosis but it must be combined with clinical history[4].The diagnostic points include:Fertility female patients with menstrual cycle-related periodic hemoptysis;Hemoptysis usually occurs within a few days before and after menstruation;There has been dysmenorrhea, induced abortion in the past medical history;chest CT shows patchy high-density shadows in the lungs, with density Uniform, with clear boundaries,such as similar lung segments appearing in two menstrual periods internal changes, and no abnormal findings in the lung during the menstrual period or the cessation of hemoptysis can be confirmed.Most lesions of pulmonary endometriosis are located in the lung parenchyma and the role of pleural, bronchoscopy and hydrothorax cytology examination limit.The pathological findings of macrophages containing hemosiderin are considered compatible and even suggest endometriosis.\u003c/p\u003e \u003cp\u003eAs we reported below based on HRCT images,we observed the cyclic changes in pulmonary endometriosis closely related to the menstrual cycle.Combined with 3D bronchial tree CT imaging and biopsy pathology results,we confirmed the diagnosis of pulmonary endometriosis.and we observed the good safety and efficacy of leuprorelin combined with Add-back therapy(Tibolone)for the treatment of patients for long-term treatment patients with severe chest pain and hemoptysis.\u003c/p\u003e"},{"header":"2. Case presentation","content":"\u003cp\u003eA 32-year-old woman during menstruation was admitted to the Hangzhou Third People\u0026apos;s Hospital in Dec 2022 because of chest pain for 2 months,cough for 2 weeks.and hemoptysis for 3 days.3 months ago,the patient also during menstruation underwent HRCT examination due to intermittent cough, which showed a partially solid nodule in the upper lobe of the right lung(Figures 1A).After two weeks of anti-inflammatory treatment(Moxifloxacin 0.4g oral QD),CT reexamination showed that the lesions in the upper lobe of the right lung had almost completely absorbed(Figures 1B).She had no known medical history or recent illnesses.When admitted,She denied having a fever,night sweats,or weight loss.No work or occupational contact history, medication intake history,or recent travel history.She had one previous cesarean section with a healthy female infant two years ago.On initial examination in our critical care unit,The patient\u0026rsquo;s initial vital signs revealed a heart rate of 84 beats/min; BP, 120/79 mm Hg;respiratory rate,20 breaths/min.and oxygen saturation,97% at rest on room air.The patient was 154.5 cm (60.9 in) tall and weighed 48.4 kg (106.7 lb) (BMI, 20.3 kg/m2).She had congestion of posterior pharyngeal wall,breath sounds in both lungs were clear, no rales or wheeze,and had normal cardiac, abdominal, neurological,and skin examinations.She had regular menses but associated with severe dysmenorrhea.WBC count was 6.6\u0026times;109/L (normal, 3.5 to 10.5 109/L) with 62.7% neutrophils.Renal and hepatic functions were normal. C-reactive protein was 0.7 mg/L(normal, \u0026lt; 10 mg/L).Hemoglobin was 121g/L(normal, 120 to 160g/L).HIV serologic result was negative.Pneumococcal and Legionella urinary antigens were negative.and d-dimer was elevated(0.96 mg/mL(normal value, \u0026lt; 0.5 mg/dL).The T cell spot test for tuberculosis (T-SPOT.TB) was negative.Anti-HAV IgM and hepatitis C the early antibody IgM anti-HCV in serum were negative.\u003c/p\u003e\n\u003cp\u003eChest HRCT showed a nodular high density shadow in the upper lobe of the right lung,ground glass density shadow was observed around the lesion.(Figures 1C).Ceftriaxone (2g,qd, ivgtt) was given. After 5 weeks,The lesion in the upper lobe of the right lung was not absorbed.(Figures 1D).Three-dimensional(3D) reconstruction of the bronchial tree from contiguous scanning of thin-section CT further revealed the presence of a solid nodule in the right superior lobe,which is Partial connection with bronchi(Figures 2A,B).A flexible bronchoscopy with BAL revealed no new organisms,An extensive micro biologic workup of \u0026nbsp;the BAL fluid for bacterial,viral,fungal,and mycobacterial pathogens was negative.CT-guided percutaneous transthoracic needle aspiration was recommended to further characterize the lesions(Figures 2C,D),histopathology of the lung showed a large amount of hemosiderin deposits with a small amount of fibrous tissue (Figures 2E).Based on the clinical history,radiographic findings,And pathologic examination of the examination of the puncture tissue,the diagnosis of pulmonary endometriosis(PEM) was established.She was given leuprorelin acetate 3.75 mg,with an additional suspension solvent of 2 ml, is administered for the first time on the third day of the menstrual cycle, with a subcutaneous injection at the upper arm.This was followed by one injection every four weeks for a total of three injections.\u003c/p\u003e\n\u003cp\u003e2.1 Outcome and follow-up\u003c/p\u003e\n\u003cp\u003eChest HRCT images showed radiographic improvement on repeat CT scan imaging at that 4 weeks follow-up appointment.(Figures 1E).Her symptoms was disappeared,with no coughing,hemoptysis,or chest pain.8 months later,She experienced mild chest pain, insomnia, and muscle ache during her menstrual period. \u0026nbsp;The chest HRCT showed that the density of the lesion in the right upper lobe of the lung had slightly increased compared to before(Figures 1F).Testosterone derivatives therapy(Leuprorelin,3.75mg,sc) combined with add-back therapy(Tibolone,1.25mg,qd) was given.CT scans showed that the lesion in the upper lobe of the right lung still existed,but the density of the lesion decreased significantly 10 days later(Figures 1G).The chest imaging showed stable results after a month of CT reexamination(Figures 1H).She had no chest pain, and her sleep quality and muscle soreness had significantly improved.The clinical course of the patient is shown in Figure 3.\u003c/p\u003e"},{"header":"3. Discussion","content":"\u003cp\u003eEndometriosis (EMS) refers to the appearance, growth and infiltration of endometrial tissues (glands and stroma) in the uterine cavity covering the endometrium and other parts of the uterus,repeated bleeding,and then causing pain, infertility and gynecological diseases such as nodules or masses.The pathogenesis of Thoracic endometriosis syndrome (TES) has not yet been clarified,Multiple hypotheses have been proposed to explain its pathogenesis and clinical manifestations.A possible explanation for the development of these lesions is given by the implantation theory of Sampson. during menstruation,vital endometrium is retrograde delay shed from the uterus through the fallopian tubes into the abdomen, where it adheres to the peritoneum and develops into vascularized endometriotic lesions.Other possible pathogenesis include the theory of body cavity epithelial metaplasia, vascular and lymphatic metastasis, and stem cell theory.\u003c/p\u003e\n\u003cp\u003eIt is generally acknowledged that an estimated 10% of all women during their reproductive years (from the onset of menstruation to menopause) are affected by endometriosis.This equates to 176 million women throughout the world, who have to deal with the symptoms of endometriosis during the prime years of their lives.Common locations of endometriosis Endometriosis lesions can be found anywhere in the pelvic cavity:on the ovaries the fallopian tubes on the pelvic side-wall (peritoneum) the uteros.Rare pelvic and intraperitoneal endometriosis can invade various areas such as the pleura,lungs,groin, umbilical cord,diaphragm,sciatic nerve, external ear, scalp, etc.\u003c/p\u003e\n\u003cp\u003eTES is a rare disorder characterized by the presence of functional endometrial tissue within the chest cavity.It can be divided into pleural and pulmonary parenchymal endometriosis according to the site of the lesion. Up to 80% of women with TES present with concomitant pelvic endometriosis.In one observational study of Women with the diagnosis of endometriosis, defined as codes 617 (International Classification of Diseases,ninth revision,ICD\u0026ndash;9) or N80 (ICD\u0026ndash;10), were retrieved from the PAR.Obstetric outcome was assessed through linkage with the MBR.Out of 709 090 women,3110 were treated as inpatients with a first diagnosis of endometriosis after their first delivery. Women with a diagnosis of endometriosis before their first delivery were excluded.The Cox analyses yielded a hazard ratio of 1.8(95% CI 1.7\u0026ndash;1.9) for endometriosis in women who had had aprevious caesarean section compared with women with vaginal deliveries only.The risk of endometriosis increased over time: one additional case of endometriosis was found for every 325 women undergoing caesarean section within 10 years.In addition to the recognised risk of scar endometrioma,an association between caesarean section and general pelvic endometriosis(9).\u003c/p\u003e\n\u003cp\u003eThe main symptom of patients with TES with chest pain linked with menstrual periods.It can occur in 90% of patients,and one-third of patients experienced difficulty breathing,as well as pneumothorax or hemothorax.Endometrial limited to the diaphragm can be accompanied by pain in the ipsilateral chest, shoulders, upper limbs, and neck.Patients with bronchial or pulmonary endometrial diseases typically experience hemoptysis.Catamenial hemoptysis happens when there is repetitive bleeding in one or both lungs. This often happens at the same time as menstruation, as hormonal changes cause the endometriosis patches to swell and bleed. It occurs in 5% of people with thoracic endometriosis.Symptoms can include:coughing up blood chest pain shortness of breath.\u003c/p\u003e\n\u003cp\u003eThe chest radiographic findings in PEM can assist in diagnosis,manifested as small pulmonary nodules with clear or unclear boundaries,or ground-glass exudates accompanied by bleeding.If checked during non menstrual periods,the chest CT results may be negative(10).For patients with menstrual hemoptysis,bronchial arteriography can also be used to diagnose pulmonary parenchymal endometriosis. Due to convenient and non-invasive detection technology,CT virtual bronchoscopy of bronchi is useful to attain the relationship between lesions and bronchi in recent years.In addition,thoracoscopy is increasingly being used for the diagnosis of intrathoracic anomalies.To improve the diagnostic rate.Thoracoscopy should be performed during the menstrual period. Diagnosis should exclude other lung diseases, especially tumors and tuberculosis.The serum CA125 level may increase.in patients with PEM(11).\u003c/p\u003e\n\u003cp\u003eOnly about one-third of patients with pulmonary endometriosis can obtain a clear histopathological diagnosis(12),mainly due to the repeated bleeding of the endometrium, which disrupts the typical pathological tissue structure and is difficult to detect.However,as long as evidence of bleeding such as hemosiderin containing cells or red blood cells is found in the alveoli, It could also be diagnosed as pulmonary endometriosis.with typical periodic clinical manifestations.\u003c/p\u003e\n\u003cp\u003eIn terms of treatment,for patients presenting with unstable conditions,the emergency treatment methods for hemothorax,pneumothorax,or hemoptysis should be followed first.For patients presenting with stable conditions, medication should be the main treatment.Since the discovery and synthesis of GnRH-a in 1971,many long-acting preparations and analogs of GnRH have been synthesized,which have shown efficacy in alleviating symptoms such as endometriosis pain and reducing the size of endometriosis masses,effectively delaying and inhibiting recurrence(13-17).Long term use of GnRH-a can alleviate symptoms of endometriosis, effectively delay and inhibit recurrence(18,19).Leuprorelin acetate is a commonly used therapeutic drug that can regulate hormones and alleviate clinical symptoms(20-22).However, long-term use of this class of drugs can cause a series of menopausal-like symptoms and bone loss due to decreased estrogen levels(23-25).The theoretical basis of the anti-addition therapy is the \u0026quot;estrogen threshold theory\u0026quot; proposed by Barbieri et al.which controls estrogen levels within a relatively low range (theoretical threshold is 110-146 pmol/L),with little effect on bone metabolism, but at the same time can inhibit the growth of ectopic endometrium,with significant efficacy.The long-term application of GnRH-a combined with Add-back therapy(ABT) is an effective treatment for EMS,but there are still differences in the formulation and application dose(26,27). Von et al.applied tibolone to patients, and the results showed that perimenopause symptoms were significantly alleviated,and problems caused by abnormal vasomotor activity were greatly improved, and it could effectively alleviate the emotions of medication users.It can be used in the transition period of menopause, and as a common supplement for medication,it can be widely applied in late menopause(28,29).Zupi et al.reported that Tibolone can effectively alleviate or eliminate menopausal-like symptoms(30).\u003c/p\u003e\n\u003cp\u003eWhen medication treatment fails or the patient cannot tolerate it,Surgical intervention should be considered.For patients with fertility requirements with PEM, it is recommended to try to get pregnant actively.In general, it is recommended to use GnRH for 3-6 months to observe the therapeutic effect.If the treatment is effective, other medications such as oral contraceptives, progesterone,danazol can be continued for maintenance treatment to achieve the effect of inhibiting ectopic endometrium.The recurrence rate of pneumothorax and hemothorax after discontinuation of medication is still higher than 50%. Symptom relief and disappearance of imaging lesions can be continued with maintenance treatment with drugs such as combined oral contraceptive(COC) and Dexamethasone.Pregnancy is recommended for those with fertility requirements.There is a possibility of recurrence after discontinuing the medication. Surgical treatment may be necessary for those who fail drug treatment,The combination of postoperative endocrine therapy can reduce the recurrence rate(31-33).\u003c/p\u003e\n\u003cp\u003eThe development and popularization of video assisted thoracoscopy (VATS) greatly reduce surgical trauma,and can clearly display and comprehensively explore thoracic lesions, thereby improving the positive rate of thoracic biopsy, making treatment more thorough, and reducing postoperative recurrence rate(34).Therefore, surgical treatment in TES,especially in patients with menstrual pneumothorax and hemothorax, is increasingly valued.During VATS surgery,the entire thoracic cavity, including the viscera, parietal pleura, and diaphragm, should be thoroughly explored, and all visible endometrial lesions should be removed to achieve radical treatment and prevent recurrence.\u003cbr\u003e\u0026nbsp; \u0026nbsp;Based on our review of the available literature, this is the first case reported in the literature in which observed imaging dynamic changes of PEM using HECT.Our case report suggests that leuprolide acetate combined with tibolone may be on efficacy \u0026nbsp;treatment effects and quality of life in patients with pulmonary endometriosis.However, more clinical studies are needed to confirm the therapeutic effect of GnRH Therapy combined with Add-back therapy in PEM.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eEMS,Endometriosis;PEM, Pulmonary endometriosis; TES, Thoracic endometriosis syndrome;HRCT, High-Resolution Computerized Tomography; LA,Leuprolide acetate;GnRH-a,Gonadotrophin-releasing hormone agonist;ABT, Add-back therapy.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eData availability statement\u003c/p\u003e\n\u003cp\u003eThe raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.\u003c/p\u003e\n\u003cp\u003eEthics statement\u003c/p\u003e\n\u003cp\u003eThe studies involving humans were approved by the ethics review committee of Hangzhou Third People\u0026apos;s Hospital.The studies were conducte din accordance with the locallegislation and institutional requirements.Written informed consent for participation was not required from the participants or the participants\u0026rsquo;legal guardians/next of kin in accordance with the national legislation and institutional requirements. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.\u003c/p\u003e\n\u003cp\u003eAuthor contributions\u003c/p\u003e\n\u003cp\u003eHL: Conceptualization, Formal analysis, Methodology, Writing\u0026ndash; original draft, Writing \u0026ndash; review \u0026amp; editing. XCZ: Funding acquisition, Supervision, Writing \u0026ndash; review \u0026amp; editing. XF: Data curation, Writing \u0026ndash; review \u0026amp; editing. YYZ: Data curation, Writing \u0026ndash;review \u0026amp; editing. YLN: Conceptualization, Supervision, Writing \u0026ndash;review \u0026amp; editing.\u003c/p\u003e\n\u003cp\u003eFunding\u003c/p\u003e\n\u003cp\u003eThe author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.\u003c/p\u003e\n\u003cp\u003eConflict of interest\u003c/p\u003e\n\u003cp\u003eThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.\u003c/p\u003e\n\u003cp\u003ePublisher\u0026rsquo;s note\u003c/p\u003e\n\u003cp\u003eAll claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAlifano M, Trisolini R, Cancellieri A, Regnard JF. Thoracic endometriosis: current knowledge. Ann Thorac Surg 2006 Feb;81(2):761-9.doi:10.1016/j.athoracsur.2005.07.044\u003c/li\u003e\n\u003cli\u003eBougie O, Yap MI, Sikora L, Flaxman T, Singh S. Influence of race/ethnicity on prevalence and presentation of endometriosis: a systematic review and meta-analysis. BJOG 2019 Aug;126(9):1104-1115.doi:10.1111/1471-0528.15692\u003c/li\u003e\n\u003cli\u003eSoo Hyun Ahn, Kasra Khalaj, Steven L Young, Bruce A Lessey, Madhuri Koti, Chandrakant Tayade.Immune-inflammation gene signatures in endometriosis patients.Fertil Steril,2016 106(6): 1420-1431.doi：10.1016/j.fertnstert.2016.07.005\u003c/li\u003e\n\u003cli\u003eRousset P, Rousset-Jablonski C, Alifano M, Mansuet-Lupo A, Buy JN, Revel MP. Thoracic endometriosis syndrome: CT and MRI features. Clin Radiol. 2014 Mar;69(3):323-30. doi: 10.1016/j.crad.2013.10.014\u003c/li\u003e\n\u003cli\u003eBrown J, Pan A, Hart RJ. Gonadotrophin-releasing hormone analogues for pain associated with endometriosis. Cochrane Database Syst Rev. 2010 Dec 8;2010(12):CD008475. doi: 10.1002/14651858.CD008475.pub2\u003c/li\u003e\n\u003cli\u003eJee BC, Lee JY, Suh CS, Kim SH, Choi YM, Moon SY. Impact of GnRH agonist treatment on recurrence of ovarian endometriomas after conservative laparoscopic surgery. Fertil Steril. 2009 Jan;91(1):40-5. doi: 10.1016/j.fertnstert.2007.11.027\u003c/li\u003e\n\u003cli\u003eDolapcioglu K, Dogruer G, Ozsoy S, Ergun Y, Ciftci S, Soylu Karapinar O, Aslan E. Theranekron for treatment of endometriosis in a rat model compared with medroxyprogesterone acetate and leuprolide acetate. Eur J Obstet Gynecol Reprod Biol. 2013 Sep;170(1):206-10. doi: 10.1016/j.ejogrb.2013.05.026\u003c/li\u003e\n\u003cli\u003eChen J, Gao H, Li Q, Cong J, Wu J, Pu D,et al. Efficacy and safety of remifemin on peri-menopausal symptoms induced by post-operative GnRH-a therapy for endometriosis: a randomized study versus tibolone. Med Sci Monit. 2014 Oct 16;20:1950-7. doi: 10.12659/MSM.891353\u003c/li\u003e\n\u003cli\u003eAndolf E, Thorsell M, K?ll\u0026eacute;n K. Caesarean section and risk for endometriosis: a prospective cohort study of Swedish registries. BJOG. 2013 Aug;120(9):1061-5. doi: 10.1111/1471-0528.12236\u003c/li\u003e\n\u003cli\u003eHuang H, Li C, Zarogoulidis P, Darwiche K, Machairiotis N, Yang L,et al. Endometriosis of the lung: report of a case and literature review. Eur J Med Res. 2013 May 1;18(1):13. doi: 10.1186/2047-783X-18-13\u003c/li\u003e\n\u003cli\u003eBagan P, Berna P, Assouad J, Hupertan V, Le Pimpec Barthes F, Riquet M. Value of cancer antigen 125 for diagnosis of pleural endometriosis in females with recurrent pneumothorax. Eur Respir J. 2008 Jan;31(1):140-2. doi: 10.1183/09031936.00094206\u003c/li\u003e\n\u003cli\u003eWood DJ, Krishnan K, Stocks P, Morgan E, Ward MJ. Catamenial haemoptysis: a rare cause. Thorax. 1993 Oct;48(10):1048-9. doi: 10.1136/thx.48.10.1048\u003c/li\u003e\n\u003cli\u003eBrown J, Pan A, Hart RJ. Gonadotrophin-releasing hormone analogues for pain associated with endometriosis. Cochrane Database Syst Rev. 2010 Dec 8;2010(12):CD008475. doi: 10.1002/14651858.CD008475.pub2\u003c/li\u003e\n\u003cli\u003eDonnez J, Nisolle M, Gillerot S, Anaf V, Clerckx-Braun F, Casanas-Roux F. Ovarian endometrial cysts: the role of gonadotropin-releasing hormone agonist and/or drainage. Fertil Steril. 1994 Jul;62(1):63-6. doi: 10.1016/s0015-0282(16)56816-2\u003c/li\u003e\n\u003cli\u003ePetta CA, Ferriani RA, Abrao MS, Hassan D, Rosa E Silva JC, Podgaec S,et al. Randomized clinical trial of a levonorgestrel-releasing intrauterine system and a depot GnRH analogue for the treatment of chronic pelvic pain in women with endometriosis. Hum Reprod. 2005 Jul;20(7):1993-8. doi: 10.1093/humrep/deh869\u003c/li\u003e\n\u003cli\u003eCheng MH, Yu BK, Chang SP, Wang PH. A randomized, parallel, comparative study of the efficacy and safety of nafarelin versus danazol in the treatment of endometriosis in Taiwan. J Chin Med Assoc. 2005 Jul;68(7):307-14. doi: 10.1016/S1726-4901(09)70166-2\u003c/li\u003e\n\u003cli\u003eStrowitzki T, Marr J, Gerlinger C, Faustmann T, Seitz C. Detailed analysis of a randomized, multicenter, comparative trial of dienogest versus leuprolide acetate in endometriosis. Int J Gynaecol Obstet. 2012 Jun;117(3):228-33. doi: 10.1016/j.ijgo.2012.01.009\u003c/li\u003e\n\u003cli\u003eAgarwal SK, Annamarie D, Drosman SR, Laurence U, Foster WG, Pike MC, et al. (2015). Treatment of endometriosis with the gnrha deslorelin and add-back estradiol and supplementary testosterone.BioMed Research International,2015,12:1-9.doi:10.1155/2015/934164\u003c/li\u003e\n\u003cli\u003eRock JA, Truglia JA, Caplan RJ. Zoladex (goserelin acetate implant) in the treatment of endometriosis: a randomized comparison with danazol. The Zoladex Endometriosis Study Group. Obstet Gynecol. 1993 Aug;82(2):198-205. doi:10.1017/S0021875800021514.\u003c/li\u003e\n\u003cli\u003eBarbieri RL. 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Ann Thorac Surg. 2022 Jan;113(1):324-336. doi: 10.1016/j.athoracsur.2020.09.064\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"pulmonary endometriosis,high-resolution computerized tomography, leuprolide,tibolone,case report, combination treatment","lastPublishedDoi":"10.21203/rs.3.rs-4540695/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4540695/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eEndometriosis (EMS) refers to the appearance, growth and infiltration of endometrial tissues (glands and stroma) in the uterine cavity covering the endometrium and other parts of the uterus, repeated bleeding, Rare pelvic and intraperitoneal endometriosis can invade various areas such as the pleura, lungs, groin, umbilical cord, diaphragm, sciatic nerve, external ear, scalp, etc.Thoracic endometriosis syndrome (TES) is a rare disorder characterized.It can be divided into pleural and pulmonary endometriosis (PEM)according to the site of the lesion.The pathogenesis of TES has not yet been clarified, and multiple hypotheses have been proposed to explain its pathogenesis and clinical manifestations.The abnormality of the immune system is one of the important factors that cause and promote the occurrence and development of EMS.We report a 32-year-old woman diagnosed at our hospital with PEM presented a clinical characteristic of intermittent cough and hemoptysis and a pathologic manifestation of a large amount of hemosiderin deposition and a small amount of fibrous tissue.The patient was treated with leuprolide combined with tibolone. The patient’s cough and hemoptysis improved significantly within a short period of time, and his lung lesions improved significantly.At the same time,he did not develop serious related complications.Our report suggests that Add-back therapy of the patient’s conditions is necessary in PEM patients with not accepted surgical treatment.Leuprolide combined with tibolone may be an induction therapy with safety and feasibility.However, more clinical trials are needed to validate the efficacy and safety of the therapeutic regimen.\u003c/p\u003e","manuscriptTitle":"Dynamic monitoring of pulmonary endometriosis based on HRCT","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-06-26 18:58:47","doi":"10.21203/rs.3.rs-4540695/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"0f49daca-85d6-49fb-b0b6-93b85a3b032a","owner":[],"postedDate":"June 26th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-06-11T23:53:23+00:00","versionOfRecord":[],"versionCreatedAt":"2024-06-26 18:58:47","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4540695","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4540695","identity":"rs-4540695","version":["v1"]},"buildId":"2u56kwukJI3zHK-uzyFNs","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}