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BACKGROUND: Total pleural covering (TPC) is an innovative surgical procedure in which the entire visceral pleura is wrapped with sheets of oxidized regenerated cellulose (ORC) mesh under video-assisted thoracoscopic surgery. We have previously reported that TPC could successfully prevent pneumothorax recurrence in patients with lymphangioleiomyomatosis (LAM). However, the actual efficacy and preventive effect of TPC on pneumothorax recurrence remains unclear as many LAM patients already had pleural adhesion prior to TPC that was induced by thoracic surgery and/or pleurodesis. The purpose of this study is to evaluate the effects of TPC on pneumothorax recurrence and pulmonary function in LAM patients with no history of thoracic surgeries or pleurodesis. METHODS: We retrospectively reviewed medical charts of 52 patients (60 hemithoraces) who underwent TPC at our center, from January 2003 to September 2019, as a first surgical intervention for pneumothorax. RESULTS: Pneumothorax recurrence occurred in 12 patients [14 of 60 hemithoraces (23.3%)] during the observation period [27 months (14.7; 56.4) = median (lower; upper quartiles)]. The probability of recurrence-free hemithorax post TPC was 81.1% at 2.5 years and 64.1% at 5 years. TPC did not produce a significant decrease in either VC %predicted (pred) or FEV(1)/FVC. The pre- vs. post-TPC median (lower; upper quartiles) VC %pred was 85.7% (79.7; 98.0) vs. 87.2% (72.3; 95.6), P=0.535 and the FEV(1)/FVC was 84.6% (75.7; 89.6) vs. 83.0% (71.8; 87.0), P=0.667. Mechanistic/mammalian target of rapamycin (mTOR) inhibitors (mTORI) were subsequently initiated in 19 patients (36.5%) because of the progression of LAM. The postoperative FEV(1%)pred was significantly lower in patients who required mTORI than in those who did not [68.1% (57.3; 82.9) vs. 88.7% (84.6; 89.8), P=0.020]; the decline rate in FEV(1%)pred/year from pre to post TPC was significantly greater in LAM patients who required mTORI than in those who did not [−9.37% (−4.73; 12.9) vs. −1.94% (1.52; −4.50), P=0.029]. Postoperative complications were found in 25 of 52 hemithoraces (48.1%). CONCLUSIONS: TPC can prevent pneumothorax recurrence without causing ventilatory impairment or severe pleural symphysis in LAM patients. TPC is an effective treatment option for LAM-associated pneumothorax based on its efficacy and safety.

Primary spontaneous pneumothorax is relatively rarer in women than in men. In addition, women develop secondary spontaneous pneumothorax, such as lymphangioleiomyomatosis, which is rare and difficult to diagnose. Therefore, the clinical characteristics of primary spontaneous pneumothorax in women remain unknown presently. We compared the clinical characteristics of primary spontaneous pneumothorax between the two sexes at two pneumothorax centers. Between January 2015 and July 2019, we retrospectively evaluated 627 cases (106 women and 521 men) who underwent first video-assisted thoracoscopic surgery for primary spontaneous pneumothorax and extracted the medical backgrounds and postoperative recurrence between the sexes. Univariate and multivariate analysis was used to examine the effect of sexual specificity on postoperative recurrence. Among women and men with PSP, the mean ages were 27.8 ± 10.7 and 24.3 ± 10.0 years, respectively; their mean heights were 162.0 ± 5.9 and 173.3 ± 6.1 cm, respectively. These differences were statistically significant. Three women (2.8%) and 54 men (10.4%) developed postoperative recurrence, which showed significant difference on Kaplan–Meier analysis (p = 0.027). Univariate and multivariate analysis showed the factors; women (p = 0.045, hazard ratio: 0.289 [95% confidence interval 0.086–0.973]) and smoker (p = 0.035, hazard ratio: 0.269 [95% confidence interval 0.079–0.909]) had the preventing factor for postoperative recurrence, respectively. Women with PSP had lower postoperative recurrence rate than men. Although we could not reveal why women had lower postoperative recurrence rates than men in this study, the sexual difference such as hormonal cycle, development of body structure possibly affects the clinical characteristics of women with primary spontaneous pneumothorax.

When the presence of endometriotic lesions are not evident by hematoxylin and eosin staining, CD10 is used to highlight and confirm the presence of endometriotic stroma. However, CD10 is not specific only to the endometrial stroma but is also expressed in many other cells. Recently, interferon-inducible transmembrane protein 1 (IFITM1) was reported as a highly specific immunohistochemical marker of normal endometrial stroma and endometrial stromal neoplasm. In this study, we examined the expression of IFITM1 and CD10 in 18 cases of ovarian endometriosis and 44 cases of extragenital endometriosis. Among the 62 patients, 62 (100.0%) were positive for IFITM1 and 60 (96.8%) for CD10, and CD10 was negative in 2 cases that were positive for IFITM1. Additionally, we found that IFITM1 sensitivity was unaffected by the presence or absence of hormonal therapy. To the best of our knowledge, this represents the first demonstration of IFITM1 as a highly sensitive stromal marker of ovarian and extragenital endometriosis.

Study Objective To identify the clinical presentation, diagnostic evaluation, operative or medical management, and postoperative recurrence of umbilical endometriosis. Design A retrospective national survey. Setting Obstetrics and Gynecology and Plastic Surgery Departments at a teaching hospital in Japan. Patients Patients with umbilical endometriosis or malignant transformation. Interventions A national survey was conducted to identify and evaluate cases of umbilical endometriosis or malignant transformation documented between 2006 and 2016. Measurements and Main Results The following were evaluated for each patient: age at diagnosis, body mass index, medical history, presence of extragenital endometriosis, surgical history, symptoms, imaging modalities, surgical therapy, hormonal therapy, follow-up period, postoperative recurrence, and time to recurrence. Ninety-six patients were identified with pathologically diagnosed benign umbilical endometriosis. The patients frequently had swelling (86.5%), pain (81.3%), or bleeding (44.8%) in the umbilicus. Sensitivity was 87.1% for physical examination, 76.5% for transabdominal ultrasonography, 75.6% for computed tomography, and 81.8% for magnetic resonance imaging. The cumulative recurrence rate was 1.34% at 6 months, 6.35% at 12 months, and 6.35% at 60 months after surgery. Importantly, there was no recurrence after wide resection including of the peritoneum (0 of 37 cases). The efficacy of dienogest (an oral progestin), gonadotropin-releasing hormone agonists, and oral contraceptives was 91.7%, 81.8%, and 57.1%, respectively. Finally, 2 cases of malignant transformation were identified. Conclusion There was a low recurrence rate following surgery, and hormonal treatment is an option, although the current findings suggest surgical therapy as the first choice of treatment for umbilical endometriosis.

The 7th Birt-Hogg-Dubé (BHD) International Symposium convened virtually in October 2021. The meeting attracted more than 200 participants internationally and highlighted recent findings in a variety of areas, including genetic insight and molecular understanding of BHD syndrome, structure and function of the tumor suppressor Folliculin (FLCN), therapeutic and clinical advances as well as patients’ experiences living with this malady.

Introduction Although three-port video-assisted thoracoscopic surgery (VATS) is the standard radical treatment for primary spontaneous pneumothorax (PSP), several issues need to be addressed as the postoperative recurrence rate remains relatively high. Although bullectomy is effective in preventing the postoperative recurrence of PSP, recurrent pneumothorax often occurs, requiring additional methods such as pleural covering with absorbable mesh sheets, surgical chemical pleurodesis, pleural abrasion, or pleurectomy. In addition, minimally invasive approaches that exceed three-port VATS are required according to the social demand. These approaches, such as uniportal VATS, reduced port surgery, and needlescopic surgery, have cosmetic merits, lower postoperative pain, and similar surgical results as three-port VATS. Areas covered We focused on conventional and novel treatments for PSP in this article. Expert opinion Effective methods that prevent postoperative recurrence and minimally invasive approaches will become popular in the near future.

Background Thoracic endometriosis-related pneumothorax is a secondary spontaneous pneumothorax caused by thoracic endometriosis. Diaphragmatic endometriosis is well-studied, but visceral and/or parietal pleural lesions are not. Although surgery is an effective treatment, postoperative recurrence rates are unsatisfactory probably due to inadequate understanding of underlying pathophysiology. We aimed to clarify the clinicopathological features of thoracic endometriosis. Methods In total, 160 patients who underwent thoracoscopic surgery from a single institution with histopathologically proven thoracic endometriosis from January 2015 to December 2019 were included. Clinicopathological characteristics and surgical outcomes were assessed retrospectively. Results The cohort median age was 41 (range 22–53) years. Pneumothorax was right-sided in 159 (99.4%) and left-sided in only 1 (0.6%) case. Visceral and parietal pleural lesions were diagnosed in 79 (49.4%) and 71 (44.4%) patients, respectively. In total, 104 visceral pleural lesions and 101 parietal pleural lesions were detected. The S4 region and the dorsal 6th intercostal space contained the largest number of visceral pleural (66 lesions) and parietal pleural lesions (25 lesions), respectively. Histopathological evaluation revealed endometriotic tissues, existing in the outer external elastic layer in all lesions, were localized or invaded deeply. The median follow-up period was 370 (range, 6–1824) days. The Kaplan-Meier method revealed that the 1- and 2-year postoperative recurrence rates were 13.8% and 19.3%, respectively. Conclusions Visceral pleural endometriotic lesions may be disseminated from the visceral pleural surface and infiltrate into the pleura. Intraoperatively, careful observation of the specific sites, such as the visceral pleura of S4 and the parietal pleura of 6th intercostal space, is important to reduce postoperative recurrence.

Lymphangioleiomyomatosis (LAM) is a rare pulmonary disease characterised by the proliferation of smooth muscle-like cells (LAM cells), and an abundance of lymphatic vessels in LAM lesions. Studies reported that vascular endothelial growth factor-D (VEGF-D) secreted by LAM cells contributes to LAM-associated lymphangiogenesis, however, the precise mechanisms of lymphangiogenesis and characteristics of lymphatic endothelial cells (LECs) in LAM lesions have not yet been elucidated. In this study, human primary-cultured LECs were obtained both from LAM-affected lung tissues (LAM-LECs) and normal lung tissues (control LECs) using fluorescence-activated cell sorting (FACS). We found that LAM-LECs had significantly higher ability of proliferation and migration compared to control LECs. VEGF-D significantly promoted migration of LECs but not proliferation of LECs in vitro. cDNA microarray and FACS analysis revealed the expression of vascular endothelial growth factor receptor (VEGFR)-3 and integrin α9 were elevated in LAM-LECs. Inhibition of VEGFR-3 suppressed proliferation and migration of LECs, and blockade of integrin α9 reduced VEGF-D-induced migration of LECs. Our data uncovered the distinct features of LAM-associated LECs, increased proliferation and migration, which may be due to higher expression of VEGFR-3 and integrin α9. Furthermore, we also found VEGF-D/VEGFR-3 and VEGF-D/ integrin α9 signaling play an important role in LAM-associated lymphangiogenesis.

Birt–Hogg–Dubé syndrome (BHDS), an autosomal dominant inheritance disease caused by folliculin (FLCN) mutations, is associated with lung cysts and spontaneous pneumothorax. The possibility of FLCN haploinsufficiency in pleural mesothelial cells (PMCs) contributing to development of pneumothorax has not yet been clarified. Electron microscopy revealed exposed intercellular boundaries between PMCs on visceral pleura and decreased electron density around the adherens junctions in BHDS. To characterize cellular function of PMCs in BHDS patients (BHDS-PMCs), during surgery for pneumothorax, we established the flow cytometry-based methods of isolating high-purity PMCs from pleural lavage fluid. BHDS-PMCs showed impaired cell attachment and a significant decrease in proliferation and migration, but a significant increase in apoptosis compared with PMCs from primary spontaneous pneumothorax (PSP) patients (PSP-PMCs). Microarray analysis using isolated PMCs revealed a significant alteration in the expression of genes belonging to Gene Ontology terms “cell-cell adhesion junction” and “cell adhesion molecule binding”. Gene set enrichment analysis demonstrated that CDH1, encoding E-cadherin, was identified in the down-regulated leading edge of a plot in BHDS-PMCs. AMPK and LKB1 activation were significantly impaired in BHDS-PMCs compared with PSP-PMCs. Our findings indicate that FLCN haploinsufficiency may affect the E-cadherin-LKB1-AMPK axis and lead to abnormal cellular function in BHDS-PMCs.

Pleural disease is one of the presenting manifestations in some diffuse cystic lung diseases (DCLDs) and often becomes a key factor in diagnosing specific disorders. Various disorders belonging to DCLDs, lymphangioleiomyomatosis (LAM), Birt-Hogg-Dube syndrome (BHDS), and pulmonary Langerhans cell histiocytosis (PLCH) are frequently complicated by a spontaneous pneumothorax. Due to the diffuse nature of underlying pathogenic mechanisms involving visceral pleura, a pneumothorax in these three diseases recurs frequently if managed conservatively. In this context, the clinical practice guidelines for LAM recommend performing pleurodesis after an initial event of a spontaneous pneumothorax. However, alternative methods to manage a pneumothorax in DCLDs may be chosen, based on different value judgments and patient preferences. Another pleural disease recognized in DCLDs is chylous pleural effusion complicated by LAM. Chylothorax used to be managed by chemical or surgical pleurodesis, but due to its high effectiveness, sirolimus therapy is currently recommended to manage various lymphatic problems associated with LAM.

AIM We aimed to describe the clinical presentation, operative or medical management, and postoperative recurrence of bladder endometriosis (BE). METHODS We conducted a national survey to investigate BE cases from 2006 to 2016 in Japan. Histologically diagnosed cases were extracted and then investigated for the following factors: age at diagnosis, body mass index, symptoms, imaging modalities, surgical therapy, hormonal therapy, follow-up period, and postoperative recurrence. RESULTS Eighty-nine patients with pathologically benign BE were identified. Eighty patients underwent surgery, whereas nine did not. Moreover, 34 and 44 patients underwent transurethral resection (TUR) and partial cystectomy (PC), respectively. Cumulative recurrence rates were significantly higher with TUR than with PC (p

This study aimed to evaluate the recurrence rate after primary and secondary conservative treatments and to clarify the validity of current primary spontaneous pneumothorax management by comparing secondary conservative treatment and surgical outcomes. Data from 166 patients with primary spontaneous pneumothorax treated at a single site between September 2015 and March 2019 were retrospectively evaluated. Patient characteristics of those who received primary conservative therapy (n = 166) and secondary conservative therapy (n = 28) were summarized. The outcomes from patients who experienced recurrence (n = 64) were compared based on those who underwent surgery (n = 24) and those who underwent secondary conservative therapy (n = 28). The post-treatment day 60 recurrence rate was 27.1 and 49.5% cases in the primary and secondary treatment groups, respectively, which was significantly higher after secondary treatment than after primary treatment with conservative therapy (p = 0.032). The post-treatment one-year recurrence rate was 13.5 and 57.9% in patients who underwent surgery and secondary conservative treatment, respectively; secondary conservative treatment resulted in a significantly higher recurrence rate than surgery (p

Birt-Hogg-Dubé syndrome (BHDS) (OMIM #135150) is an autosomal dominant disease, characterized by fibrofolliculomas (FFs) of the skin, pulmonary cysts with/without pneumothorax, and renal tumors. The prevalence of skin manifestations reported for Japanese BHDS patients is lower (30%) compared with that of Western countries (75∼90%), which appear to be underestimated.To precisely examine the prevalence of skin lesions with dermoscopy and histopathology with reference to genetic analyses.We studied 31 patients (47.0±13.2years old, range 15-71) consisting of 26 unrelated families consecutively from May 2013 to June 2015 specifically for skin-colored papules on their faces and cervicothoracic regions. Patients initially suspected of BHDS from multiple pulmonary cysts that resulted in pneumothorax (30/31; 96.8%) received dermoscopic examinations and skin biopsies if applicable. The diagnosis of BHDS was established by folliculin (FLCN) genetic testing, and the results were compared to the histopathological findings of FFs or trichodiscomas (TDs).FLCN germline mutation was demonstrated in 25/26 (96.2%) unrelated families tested and 28/29 patients (96.6%) tested. Skin lesions were recognized in 26/31 patients (83.9%); skin biopsies were performed in 23 patients of whom FFs and/or TDs were histologically demonstrated in 17 (73.9%). Although our study population included patients whose skin manifestations were evaluated prior to or after FLCN genetic testing, skin lesions were clearly prevalent and recognizable irrespective of whether genetic testing was or wasn't done. When examined with dermoscopy, distinct FFs appeared as well-demarcated areas of pallor with central follicular openings in 13 of 15 FF-bearing patients (86.7%); however, those manifestations were not recognized for TD.Skin lesions appear to be more prevalent than previously reported (30% vs.73.9%) in Japanese BHDS patients. Dermoscopy is a useful diagnostic aid for finding FFs.

Background and objective Birt–Hogg–Dube syndrome (BHDS) is a rare hereditary disease that presents with multiple lung cysts and pneumothorax (PTX). Although some reports propose that findings from chest computed tomography enable one to distinguish BHDS from primary spontaneous pneumothorax (PSP), it is still unclear whether clinical features are useful for identifying patients with suspicion of BHDS from those with PTX. Methods We retrospectively reviewed the medical records of patients with PTX who underwent video-assisted thoracoscopic surgery at Nissan Tamagawa Hospital from January 2012 to December 2015. Results We identified a total of 1141 patients with PTX, including 54 with BHDS and 517 with PSP. Among them, logistic regression analysis segregated five features that were significantly associated with BHDS: familial history of PTX, past history of bilateral PTX, age at the first episode of PTX (≥25 years old (y.o.)), body mass index (≥18.5) and gender (female). We assigned scores of 3, 3, 2, 2 and 1 to the five features, respectively, to establish a system with a calculated score from 0 to 11. The cut-off value of a calculated score ≥ 4 yielded the highest sensitivity of 93% and specificity of 86%. Receiver operating characteristic (ROC) analysis showed the area under the curve reflecting an accuracy of this diagnostic test as 0.953. Conclusion BHDS has several clinical features distinct from PSP. Our scoring system consists of only five clinical variables that are easily evaluated and efficiently separate BHDS patients from those who have PTX without relying on an imaging study. Further prospective study is needed to confirm our findings.

Catamenial pneumothorax (CP) is generally caused by intraperitoneal air leaking from the uterus into the thoracic cavity via a defect in the endometrial tissue of the diaphragm and is usually detected in the right thorax. We report a case of left-sided CP caused by endometriosis in the visceral pleura and with no abnormal findings in the diaphragm. A 33-year-old female patient presented at the end of a course of low-dose contraceptive pills for pelvic endometriosis, with spontaneous pneumothorax in the left chest. Chest CT revealed a bulla in the left upper lung lobe. The patient underwent partial resection of the lung. Immunohistochemistry confirmed the presence of endometrial stromal tissue in the visceral pleura and confirmed this as the cause of pneumothorax since there were no observable abnormalities in the diaphragm. This case suggests that immunohistochemical examination of patients with spontaneous pneumothorax can detect alternative endometrial lesions.

Lymphangioleiomyomatosis (LAM) is a rare neoplastic disease entailing cystic destruction of the lungs and progressive respiratory failure. LAM lungs are histologically characterized by the proliferation of smooth muscle-like cells (LAM cells) and an abundance of lymphatic vessels. To elucidate the pathophysiological processes of LAM, cell-type-specific analyses are required. However, no method exists for isolating the individual types of cells in LAM lesions. Therefore, we established a fluorescence-activated cell sorting (FACS)-based method for the direct isolation of LAM cells and other various cellular components from LAM-affected lung tissue. We obtained LAM-affected lung tissue from resections or transplant recipients and prepared single-cell suspensions. FACS, immunohistochemical, and molecular analysis were used cooperatively to isolate HMB45-positive LAM cells with tuberous sclerosis complex ( TSC) 2 loss of heterozygosity (LOH). Using a combination of antibodies against an epithelial cell adhesion molecule (EpCAM) and podoplanin, we fractionated CD45-negative lung cells into three groups: lymphatic endothelial cells (LEC) (EpCAM−/podoplaninhi subset), alveolar type II cells (EpCAMhi/podoplanin− subset), and mesenchymal cells (EpCAM−/podoplanin−/low subset). During subsequent analysis of HMB45 expression, as a LAM-specific marker, we clearly identified LAM cells in the mesenchymal cell population. We then discovered that CD90+/CD34− cells in the mesenchymal cell population are not only positive for HBM45 but also had TSC2 LOH. These isolated cells were viable and subsequently amenable to cell culture. This method enables us to isolate LAM cells and other cellular components, including LAM-associated LEC, from LAM-affected lung tissues, providing new research opportunities in this field.

Birt-Hogg-Dubé syndrome (BHDS) is a rare hereditary disease that presents with multiple lung cysts and recurrent pneumothorax. These cysts occupy predominantly the lower-medial zone of the lung field adjacent to the interlobar fissure, and some of them abut peripheral pulmonary vessels. For the surgical management of pneumothorax with BHDS, the conventional approach of resecting all subpleural cysts and bullae is not feasible. Thus, after handling several bullae by using a stapler or performing ligation as a standardized treatment, we applied to a pleural covering technique to thicken the affected visceral pleura and then to prevent recurrence of pneumothorax. We herein report the successful application of a pleural covering technique via thoracoscopic surgery to treat the recurrent pneumothorax of a 30-year-old man with BHDS. This technique is promising for the management of intractable pneumothorax secondary to BHDS.

Background Birt-Hogg-Dubé syndrome (BHDS) is a recently recognized inherited multiple cystic lung disease causing recurrent pneumothoraces. Similarly to the lesions in patients with lymphangioleiomyomatosis (LAM), the pulmonary cysts are innumerable and widely dispersed and cannot all be removed. We recently described a total pleural covering (TPC) that covers the entire visceral pleura with oxidized regenerated cellulose (ORC) mesh. TPC successfully prevented the recurrence of pneumothorax in LAM patients. The purpose of this study was to evaluate the effect of an ORC pleural covering on pneumothorax recurrence in BHDS patients. Results This retrospective study enrolled a total of 81 pneumothorax patients with the diagnosis of BHDS who underwent 90 covering surgeries from January 2010 to August 2017 at Tamagawa Hospital. During the first half of the study period, a lower pleural covering (LPC) which covered the affected area with ORC mesh was mainly used to treat 38 pneumothoraces. During the second half of the study period, TPC was primarily performed for 52 pneumothoraces. All the thoracoscopic surgeries were successfully performed without serious complications (≥ Clavien-Dindo grade III). The median follow-up periods after LPC/TPC were 66/34 months, respectively. Pneumothorax recurrence rates after LPC at 2.5/5/7.5 years postoperatively were 5.4/12/42%, respectively; none of the patients who had underwent TPC developed postoperative pneumothorax recurrence (P = 0.032). Conclusions TPC might be an effective option for surgical treatment of intractable pneumothorax in patients with BHDS. Electronic supplementary material The online version of this article (10.1186/s13023-018-0790-x) contains supplementary material, which is available to authorized users.

Background and objective A major pathogenic factor for catamenial pneumothorax is thoracic endometriosis. However, thoracic endometriosis-related pneumothorax (TERP) can develop as either catamenial or non-catamenial pneumothorax (CP). Therefore, the aim of this study was to elucidate the clinical differences between catamenial and non-catamenial TERP. Methods The clinical and pathological data in female patients who underwent video-assisted thoracoscopic surgery at the Pneumothorax Research Center during an 8-year period were retrospectively reviewed. This study included 150 female patients with surgico-pathologically confirmed TERP. The subjects were divided into two groups, those having all of the pneumothorax episodes in the catamenial period (CP group) and those who did not (non-CP group). We compared the clinical characteristics and surgico-pathological findings between these two groups. Results Of the 150 TERP patients, 55 (36.7%) were classified in the CP group, and 95 (63.3%) in the non-CP group. In regard to the locations of endometriosis, all TERP patients had diaphragmatic endometriosis, while pleural implantation was recognized in 34 of the 55 (61.8%) patients in the CP group and 42 of the 95 (44.2%) patients in the non-CP group (P

The aim was to characterize the computed tomographic (CT) findings from Japanese patients with lymphangioleiomyomatosis (LAM).CT scans of the chest, abdomen, and pelvis from 124 patients with sporadic LAM (S-LAM, mean age, 37.4 years) and 14 patients with tuberous sclerosis complex (TSC)-LAM (mean age, 35.6 years) were analyzed.Pulmonary nodules (18.8%) and hepatic angiomyolipoma (AML, 24.3%) were more common in our patients than those in previous reports. Compared with TSC-LAM, S-LAM group had a higher frequency of pulmonary nodules (28.6% vs 32.3%, P0.01) and lower frequencies of air-space consolidation (21.4% vs 2.4%, P0.01), pneumothorax (28.6% vs 8.1%, P=0.02), pulmonary hilar lymphadenopathy (14.3% vs 0.8%, P0.01), renal AML (85.7% vs 17.4%, P0.01), hepatic AML (71.4% vs 17.4%, P0.01), and retrocrural lymphadenopathy (14.3% vs 1.4%, P=0.04). Axial lymphatic abnormalities (i.e., thoracic duct dilatation, lymphadenopathy, and lymphangioleiomyoma) were most common in the pelvis and tended to decrease in incidence with increased distance from the pelvis.The incidence of some CT findings in Japanese patients differed from those in previous reports. Axial lymphatic abnormalities noted here suggest that the origin of LAM cells may be the pelvis.

Birt-Hogg-Dubé syndrome (BHDS) is a rare hereditary disease that presents with multiple lung cysts and pneumothorax (PTX). Although some reports propose that findings from chest computed tomography enable one to distinguish BHDS from primary spontaneous pneumothorax (PSP), it is still unclear whether clinical features are useful for identifying patients with suspicion of BHDS from those with PTX.We retrospectively reviewed the medical records of patients with PTX who underwent video-assisted thoracoscopic surgery at Nissan Tamagawa Hospital from January 2012 to December 2015.We identified a total of 1141 patients with PTX, including 54 with BHDS and 517 with PSP. Among them, logistic regression analysis segregated five features that were significantly associated with BHDS: familial history of PTX, past history of bilateral PTX, age at the first episode of PTX (≥25 years old (y.o.)), body mass index (≥18.5) and gender (female). We assigned scores of 3, 3, 2, 2 and 1 to the five features, respectively, to establish a system with a calculated score from 0 to 11. The cut-off value of a calculated score ≥ 4 yielded the highest sensitivity of 93% and specificity of 86%. Receiver operating characteristic (ROC) analysis showed the area under the curve reflecting an accuracy of this diagnostic test as 0.953.BHDS has several clinical features distinct from PSP. Our scoring system consists of only five clinical variables that are easily evaluated and efficiently separate BHDS patients from those who have PTX without relying on an imaging study. Further prospective study is needed to confirm our findings.

We consider the longest common subsequence (LCS) problem with the restriction that the common subsequence is required to consist of at least k length substrings. First, we show an O(mn) time algorithm for the problem which gives a better worst-case running time than existing algorithms, where m and n are lengths of the input strings. Furthermore, we mainly consider the LCS in at least k length order-isomorphic substrings problem. We show that the problem can also be solved in O(mn) worst-case time by an easy-to-implement algorithm.

Aims To characterize the pathological features of pulmonary cysts, and to elucidate the possible mechanism of cyst formation in the lungs of patients with Birt–Hogg–Dube syndrome (BHDS), a tumour suppressor gene syndrome, using histological and morphometric analyses. Methods and results We evaluated 229 lung cysts from 50 patients with BHDS and 117 from 34 patients with primary spontaneous pneumothorax (PSP) for their number, size, location and absence or presence of inflammation. The BHDS cysts abutted on interlobular septa (88.2%) and had intracystic septa (13.6%) or protruding venules (39.5%) without cell proliferation or inflammation. The frequencies of these histological characteristics differed significantly from those seen in the lungs of patients with PSP (P

In cases of extragenital endometriosis or microscopic endometriosis lesions, pathological diagnosis can be challenging because endometriotic stroma and glands represent only a minor component of fibrotic endometriotic lesions. For better accuracy of diagnosis, the development of a sensitive and specific epithelial marker is beneficial. Previous studies showed that PAX8 is a highly sensitive and specific marker for primary and metastatic Mullerian epithelial tumors. Therefore, we sought to examine whether PAX8 is a highly sensitive marker for glands in extragenital endometriosis. Eight and 47 samples of ovarian endometrioma and extragenital endometriosis, respectively, were evaluated in this study. We calculated the percentage of samples positively immunostained for PAX8, CD10, estrogen receptor (ER), and progesterone receptor (PR). PAX8 was positive for endometriotic epithelial cells in 95.7% (45/47) of extragenital endometrioses and in 100% (8/8) of ovarian endometrioses. CD10 was positive for endometriotic stromal cells in 97.9% (46/47) of extragenital endometrioses. PAX8 was strongly positive for glands, even in a CD10-negative case. The expression of PAX8, CD10, and PR was not affected by preoperative hormonal therapy, and the positive rate of ER staining was significantly reduced by preoperative hormonal therapy. In conclusion, PAX8 is a highly sensitive epithelial marker for extragenital endometriosis. This specific expression was maintained under hormonal therapy. It is noteworthy that extragenital endometriosis maintains the expression of this lineage marker, although it occurs at various sites, and its cause and mechanism of development might be different. PAX8 nuclear expression can be useful in detecting extragenital endometriosis in clinical practice.

Re-expansion pulmonary edema is an uncommon condition that occurs when a collapsed lung is expanded. The aim of the present study was to investigate the incidence and risk factors associated with re-expansion pulmonary edema which may occur as a complication when carrying out treatment for spontaneous pneumothorax. A total of 462 patients with spontaneous pneumothorax treated with chest tube drainage in inpatient settings at the Nissan Tamagawa Hospital during the 6-year period between January 2007 and December 2012 were retrospectively evaluated. The data were analyzed to identify any clinical differences between the patients with and without re-expansion pulmonary edema. Re-expansion pulmonary edema occurred on 30 (6.5 %) of the 462 patients. The duration of lung collapse in the patients with re-expansion pulmonary edema was longer than that observed in the patients without re-expansion pulmonary edema. (7.7 ± 9.1 and 2.4 ± 4.6 days). This difference was statistically significant (P

Background Lymphangioleiomyomatosis (LAM) is a rare disease caused by dysregulated activation of the mammalian target of rapamycin (mTOR). Sirolimus, an inhibitor of mTOR, has been reported to decrease the size of angiomyolipomas and stabilize pulmonary function in patients with LAM. However, the optimal dose for the treatment of LAM remains unclear. Methods We conducted a retrospective, observational study of 15 patients with LAM who underwent sirolimus therapy for more than 6 months. The efficacy was evaluated by reviewing the patients' clinical courses, pulmonary function and chest radiologic findings before and after the initiation of sirolimus treatment. Results All patients had blood trough levels of sirolimus lower than 5ng/mL. Sirolimus treatment improved the annual rates of change in FVC and FEV 1 in the 9 patients who were free from chylous effusion (FVC, −101.0 vs. +190.0mL/y, p =0.046 and FEV 1 , −115.4 vs. +127.8mL/y, p =0.015). The remaining 7 patients had chylous effusion at the start of sirolimus treatment; the chylothorax resolved completely within 1−5 months of treatment in 6 of these cases. These results resembled those of previous studies in which blood trough levels of sirolimus ranged from 5 to 15ng/mL. Conclusions Low-dose sirolimus (trough level, 5ng/mL or less) performed as well as the higher doses used previously for improving pulmonary function and decreasing chylous effusion in patients with LAM.

PURPOSE Primary spontaneous pneumothorax is believed to result from blebs, or from other abnormalities of the pleural surface. There is no consensus as to whether a change in weather conditions can precipitate spontaneous pneumothorax. The aim of the present study was to investigate the influence of weather conditions on the onset of primary spontaneous pneumothorax. METHODS The case histories of 1051 inpatients with primary spontaneous pneumothorax treated at Nissan Tamagawa Hospital between January 2006 and December 2011 were analyzed retrospectively. Data on weather conditions were collected daily throughout the 6-year period. The data were analyzed to determine differences in weather conditions between days on which primary spontaneous pneumothorax occurred and those on which it did not. RESULTS Primary spontaneous pneumothorax occurred on 819 (37.3%) of 2191 study days. On days before and the day of primary spontaneous pneumothorax onset, the difference in mean atmospheric pressure was 0.6 hPa lower than on days in which no primary spontaneous pneumothorax occurred. This difference was statistically significant (P = 0.015). There was no statistical difference in mean, maximum, and minimum temperature, hours of sunshine, amount of precipitation, and mean and minimum humidity between days with and those without primary spontaneous pneumothorax. CONCLUSION This largest study of the literature showed decreased atmospheric pressure might play an important role in the occurrence of primary spontaneous pneumothorax.

A 34-year-old male with frequent recurrence of right pneumothorax was admitted to our hospital. He was a current smoker and outwardly male without genital aplasia. He was diagnosed as tuberous sclerosis complex (TSC) at 2 year-old and underwent transcatheter arterial embolization for right renal hemorrhage due to renal tumor 2 years ago. Chest Computed Tomography showed that he had multiple tiny round cystic lesions with thin wall in both lungs. The recurrent pneumothorax was expected to be associated with TSC-Lymphangioleiomyomatosis (LAM). Video-assisted thoracic surgery was successfully performed. The operative and histological findings revealed that the bullae were classified into two groups; emphysematous bullae and bullae due to LAM. His postoperative course was uneventful. TSC-LAM is extremely rare, but in some cases the clinical recognition might be escaped due to subtle findings of bullae in early LAM, resulting in diagnosis as spontaneous pneumothorax.

Background Spontaneous pneumothorax is a major and frequently recurrent complication of lymphangioleiomyomatosis (LAM). Despite the customary use of pleurodesis to manage pnenumothorax, the recurrence rate remains high, and accompanying pleural adhesions cause serious bleeding during subsequent lung transplantation. Therefore, we have developed a technique of total pleural covering (TPC) for LAM to wrap the entire visceral pleura with sheets of oxidized regenerated cellulose (ORC) mesh, thereby reinforcing the affected visceral pleura and preventing recurrence. Methods Since January 2003, TPC has been applied during video-assisted thoracoscopic surgery for the treatment of LAM. The medical records of LAM patients who had TPC since that time and until August 2014 are reviewed. Results TPC was performed in 43 LAM patients (54 hemithoraces), 11 of whom required TPC bilaterally. Pneumothorax recurred in 14 hemithoraces (25.9%) from 11 patients (25.6%) after TPC. Kaplan-Meier estimates of recurrence-free hemithorax were 80.8% at 2.5 years, 71.7% at 5 years, 71.7% at 7.5 years, and 61.4% at 9 years. The recurrence-free probability was significantly better when 10 or more sheets of ORC mesh were utilized for TPC (P = 0.0018). TPC significantly reduced the frequency of pneumothorax: 0.544 ± 0.606 episode/month (mean ± SD) before TPC vs. 0.008 ± 0.019 after TPC (P

Background BirteHoggeDubesyndrome (BHDS) is an inherited autosomal genodermatosis characterised by fibrofolliculomas of the skin, renal tumours and multiple lung cysts. Genetic studies have disclosed that the clinical picture as well as responsible germline FLCN mutations are diverse. Objectives BHDS may be caused by a germline deletion which cannot be detected by a conventional genetic approach. Real-time quantitative polymerase chain reaction (qPCR) may be able to identify such a mutation and thus provide us with a more accurate clinical picture of BHDS. Methods This study analysed 36 patients with multiple lung cysts of undetermined causes. Denaturing high performance liquid chromatography (DHPLC) was applied for mutation screening. If no abnormality was detected by DHPLC, the amount of each FLCN exon in genome was quantified by qPCR. Results An FLCN germline mutation was found in 23 (63.9%) of the 36 patients by DHPLC and direct sequencing (13 unique small nucleotide alterations which included 11 novel mutations). A large genomic deletion was identified in two of the remaining 13 patients by qPCR (one patient with exon 14 deletion and one patient with a deletion encompassing exons 9 to 14). Mutations including genomic deletions were most frequently identified in the 3 9 -end of the FLCN gene including exons 12 and 13 (13/25¼52.0%). The BHDS patients whose multiple cysts prompted the diagnosis in this study showed a very low incidence of skin and renal involvement. Conclusions BHDS is due to large deletions as well as small nucleotide alterations. Racial differences may occur between Japanese and patients of European decent in terms of FLCN mutations and clinical manifestations.

Lymphangioleiomyomatosis (LAM) is a rare neoplastic disease in which abnormal smooth muscle-like cells (LAM cells) proliferate in the lungs and along the axial lymphatic systems, including the lymph nodes and thoracic ducts. LAM cells are transformed due to loss-of-function type mutations of either the TSC1 or TSC2 tumor suppressor genes. The pathological features include the proliferation of benign-looking LAM cells and the existence of abundant lymphatic vessels that are associated with clinical conditions such as chyle leakage. LAM cells produce potent lymphangiogenic growth factors (VEGF-C and VEGF-D) and the lymphatic vessel density within LAM lesions correlates with the histologic severity of LAM. The serum VEGF-D level increases in LAM, especially in patients with lymphatic involvement. LAM cell clusters (LCCs), which are postulated pathologically to be generated by lymphangiogenesis-mediated fragmentation and subsequent shedding into the lymphatic circulation, are observed in both chylous effusion and LAM-associated lymphatics within LAM tissue specimens. The identification of LCCs in chylous effusion together with the characteristic clinical manifestations can therefore be an alternative for a lung biopsy if LAM patients are complicated with chylous effusion.LAM appears to be a disease involving a dysfunction of the lymphatic system and a fascinating model of tumor dissemination that is exclusively lymphangitic. LAM-associated lymphangiogenesis that mediates the shedding of LCCs seems to play a central role in the dissemination of LAM cells and progression in LAM and it may also be a potential therapeutic target as well as the dysregulated mTOR signaling pathway.

Objective: Birt-Hogg-Dube syndrome (BHDS) includes multiple lung cysts with recurrent pneumothoraces. It is unable to technically remove all diffused lung cysts for preventing recurrent pneumothorax by VATS. Since multiple lung cysts of BHDS are especially at mediastinal side, basal area, and interlobular space, Those areas fail in chemical pleurodesis. They are not adhesive because of cardiac movements and respiratory movements. We developed an innovative thoracoscopic surgical technique to cover visceral pleura with regenerated oxidized cellulose meshes(ROC) in order to reinforce the visceral pleura. It was named the lower pleural covering technique (LPC). The purpose of this study is to evaluate the clinical outcome of patients who underwent the lower pleural covering technique. Methods: From January 2010 to September 2014, the covering surgery by VATS was performed for 58 pneumothoraces in 53 patients genetically diagnosed as BHDS. The medical records of 53 patients were retrospectively reviewed. Results: There were 27 women and 26 men (mean age: 41 year-olds, range: 19-68) and the surgical sides were right 33/ left 25. All the covering procedures were performed with 10 ± 2.6 (range: 5 - 18) sheets of ROC mesh (10.2 x 20.3 cm) in 120 ± 38 (range: 59 - 215) minutes. LPC was successfully performed without Clavien-Dindo grade 3-4 postoperative complications. The median follow-up period after the surgery was 14 (range: 0.4 -52) months, and recurrence-free rate at one / two / three / four years after LPC were 0 / 4.0 / 8.8 / 8.8 %, respectively. Conclusions: The lower pleural covering is the innovative and effective surgery for recurrent pneumothorax in BHDS with diffused lung cysts.

The primary care in terms of emergency for pneumothorax is chest drainage in almost cases. The following cases of pneumothorax and the complications need something of surgery and treatments. Pneumothorax with subcutaneous emphysema often needs small skin incisions around the drainage tube. Tension pneumothorax often needs urgent chest drainage. Pneumothorax with intractable air leakage often needs interventional treatments like endobroncheal occlusion (EBO) or thoracographic fibrin glue sealing method (TGF) as well as urgent thoracoscopic surgery. Pneumothorax with acute empyema also often needs urgent thoracoscopic surgery within 2 weeks if chest drainage or drug therapy are unsuccessful. It will probably become chronic empyema of thorax after then. Pneumothorax with bleeding needs urgent thoracoscopic surgery in case of continuous bleeding over 200 ml/2 hours. In any cases of emergency for pneumothorax, respiratory physicians should collaborate with respiratory surgeons at the 1st stage because it is important to timely judge conversion of surgical treatments from medical treatments.

A major pathogenic factor for catamenial pneumothorax is thoracic endometriosis. However, thoracic endometriosis-related pneumothorax (TERP) can develop as either catamenial or non-catamenial pneumothorax (CP). Therefore, the aim of this study was to elucidate the clinical differences between catamenial and non-catamenial TERP.The clinical and pathological data in female patients who underwent video-assisted thoracoscopic surgery at the Pneumothorax Research Center during an 8-year period were retrospectively reviewed. This study included 150 female patients with surgico-pathologically confirmed TERP. The subjects were divided into two groups, those having all of the pneumothorax episodes in the catamenial period (CP group) and those who did not (non-CP group). We compared the clinical characteristics and surgico-pathological findings between these two groups.Of the 150 TERP patients, 55 (36.7%) were classified in the CP group, and 95 (63.3%) in the non-CP group. In regard to the locations of endometriosis, all TERP patients had diaphragmatic endometriosis, while pleural implantation was recognized in 34 of the 55 (61.8%) patients in the CP group and 42 of the 95 (44.2%) patients in the non-CP group (P 0.05).A significant difference in the proportion of patients with pleural endometriosis was observed between catamenial and non-catamenial TERP. The ectopic sites of the endometriosis may be responsible for the timing of the pneumothorax episodes.

Thoracic endometriosis-related pneumothorax (TERP) is a secondary condition specific for females, but in a clinical setting, TERP often is difficult to distinguish from primary spontaneous pneumothorax (PSP) based on a relationship between the dates of pneumothorax and menstruation. The purpose of this study was to clarify the clinical features of TERP compared with PSP. We retrospectively reviewed the clinical and histopathological files of female patients with pneumothorax who underwent video-assisted thoracoscopic surgery in the Pneumothorax Research Center during the 6-year period from January 2005 to December 2010. We analyzed the clinical differences between TERP and PSP. The study included a total of 393 female patients with spontaneous pneumothorax, of whom 92 (23.4 %) were diagnosed as having TERP and 33.6 % (132/393) as having PSP. We identified four factors (right-sided pneumothorax, history of pelvic endometriosis, age ≥31 years, and no smoking history) that were statistically significant for predicting TERP and assigned 6, 5, 4, and 3 points, respectively, to establish a scoring system with a calculated score from 0 to 18. The cutoff values of a calculated score ≥12 yielded the highest positive predictive value (86 %; 95 % confidence interval (CI) 81.5–90.5 %) for TERP and negative predictive value (95.2 %; 95 % CI 92.3–98 %) for PSP. TERP has several distinct clinical features from PSP. Our scoring system consists of only four clinical variables that are easily obtainable and enables us to suspect TERP in female patients with pneumothorax.

Modern thoracoscopy with a video-assisted system clearly demonstrates the pleural cavity, and its application under local anesthesia is useful in diagnosing pleural diseases. However, its influence on the cardiorespiratory system is not well understood. The aim of the current study was to evaluate this problem by performing cardiorespiratory monitoring during thoracoscopy in 66 patients with focal bullous lung disease. Duration of thoracoscopy was 12.3 ± 5.1 minutes (mean ± standard deviation). After establishing open pneumothorax with a thoracoscope inserted into the pleural cavity, the average respiratory rate increased (29.7 ± 24.6%; p Abstract: Journal of Bronchology7:215-220, 2000. Abstract: HR, heart rate; RR, respiratory rate; SpO2, oxygen saturation; BP, blood pressure; syst, systolic; diast, diastolic; avg, average; % Δ, percent change; min, minimum

Objective Prolonged air leaks in patients with spontaneous pneumothorax are not infrequent. The aim of this study was to assess the duration of air leaks and define the clinical variables associated with the therapeutic success of chest tube drainage for spontaneous pneumothorax. Methods A total of 441 patients with spontaneous pneumothorax treated with chest tube drainage between 2008 and 2012 were retrospectively evaluated. The clinical differences between the patients successfully treated with drainage and those who required more invasive procedures were analyzed. Results Invasive procedures, such as video-assisted thoracic surgery (n=121), fibrin glue administration through a chest tube (n=8) and pleurodesis with OK-432 (n=21), were performed in 34% (150/441) of the patients. The treatment rate of chest drainage alone was higher in the patients with initial pneumothorax (72%; 124/170) than in those with recurrent pneumothorax (62%; 167/271) (p=0.015). In addition, this rate was higher in the patients with moderate lung collapse (70%; 167/237) than in those with severe lung collapse (61%; 124/204) (p=0.032). Conclusion Patients with recurrent pneumothorax or severe lung collapse associated with prolonged air leakage are more likely to receive invasive procedures.