Endoscopic approach to pulmonary diseases: Clinical utility of medical thoracoscopy in diagnosis of pleural diseases

Thoracoscopy is useful for diagnosis of a number of lung diseases. We report our recent experience of medical thoracoscopy performed under local anesthesia in 142 cases. Of 124 patients with pleural effusion, 46 had pleuritis carcinomatosa, 11 had pleuritis tuberculosa, and 10 had malignant mesothelioma. We evaluated the utility of thoracoscopic observation and pleural biopsy in these three diseases. Almost of patients with malignant pleural effusion initially undiagnosed by the cytology of pleural effusion were diagnosed by thoracoscopy. Especially in malignant mesothelioma, thoracoscopy allowed accurate diagnosis. No serious complication was observed. Since medical thoracoscopy under local anesthesia is a rapid, easy, safe, and well-tolerated procedure with an excellent diagnostic yield, it is recommended as a diagnostic procedure for cases with pleural effusion.     

Differential Diagnosis of Tuberculous and Malignant Pleural Effusions: What is the Role of Adenosine Deaminase?

The objective of this study was to evaluate the utility of invasive and noninvasive diagnostic procedures in tuberculous pleurisy (TPE) in an area with intermediate incidence of tuberculosis. The aim was to determine the cutoff value for adenosine deaminase (ADA) and the sensitivity and specificity of ADA and evaluate pleural fluid cytology and pleural biopsy in the differential diagnosis of malignant and tuberculous pleurisy. The study included 121 patients. TPE was confirmed in 54 patients and malignant effusion in 67 patients. Criteria used for TPE diagnosis were positive cultures of effusion or biopsy specimen, tuberculous granulomas, or positive sputum cultures without other explanation for pleural effusion. Malignancy was diagnosed by either cytology or biopsy. The cutoff value of ADA in TPE was 49 U/L, sensitivity was 89.2%, specificity was 70.4%, positive predictive value (PPV) was 84.4%, and negative predictive value (NPV) was 78.4%. ADA activity below 16 U/L suggests that TPE is highly unlikely with sensitivity=38.5%, specificity=100%, PPV=100%, and NPV=57.4%. ADA effusion/serum ratio reached a cutoff in TPE of 1.7 (sensitivity=84.6%, specificity=72.2%, PPV=81.4%, NPV=71.4%). Sensitivity, specificity, PPV, and NPV of cytology evaluation for TPE are 72.2%, 70.1%, 66.1%, and 75.8%, respectively. Pleuroscopy-guided pleural biopsy had sensitivity=66.7%, specificity=100%, PPV=100%, and NPV=78.8%. In 27.8% of TPE cases, pleural fluid cultures were positive. There is no doubt that pleuroscopy-guided biopsy is of great value for TPE diagnosis; however, sensitivity and specificity of noninvasive tests, especially ADA, can help to distinguish between TB and malignancy.     

Adenosine deaminase 2 in the diagnosis of tuberculous pleuritis

PURPOSE: We examined the usefulness of adenosine deaminase 2 (ADA2) in the diagnosis of tuberculous pleuritis. SUBJECTS: A hundred cases, 78 male and 22 female, with pleural effusion were examined. With regard to pleural effusion, 18 cases were transudate and 82 cases (9 tuberculous pleuritis, 27 lung cancer, 8 mesothelioma, 5 malignant diseases except lung cancer and mesothelioma, 5 benign asbestos pleurisy, 10 empyema, 10 parapneumonic effusion, one SLE, one parasitic infection, and 6 undetermined etiology) were exudates. The last 6 cases with unknown origin were excluded in this study. RESULTS: Pleural adenosine deaminase (ADA) was 90.4 +/- 22.4 U/l (mean +/- SD) and pleural ADA2 was 80.4 +/- 21.9 U/l in tuberculous pleuritis, both were significantly higher than those in non-tuberculous exudates (p < 0.001). In the diagnosis of tuberculous pleuritis, pleural ADA showed 100% sensitivity and 88% specificity, whereas pleural ADA2 showed 100% sensitivity and 91% specificity. CONCLUSION: Pleural ADA2 is useful in the diagnosis of tuberculous pleuritis, which has similar sensitivity and a little better specificity compared with pleural ADA.     

A case of CD56 positive T-cell lymphoma originating from mediastinal lymph nodes]

The patient, a 63-year-old man was admitted to our hospital with complaints of high-grade fever and left chest pain. The chest X-ray film taken on admission showed the presence of pleural effusion. The chest CT scan revealed left mediastinal enlargement. Examination of the pleural effusion showed a high concentration of adenosine deaminase (ADA) and the cytological examination showed no malignancy. We diagnosed pleuritis tuberculosa. His general condition worsened in spite of anti-tuberculosis therapy and soluble interleukin-2 receptor (sIL-2R) was elevated. The video-assisted thoracoscopic biopsy was negative. Soon after that the lymph nodes from the left supraclavicular region to the mediastinum became swollen. The diagnosis of peripheral T-cell lymphoma, unspecified (WHO classification) with CD56 expression, was established based on the results of lymph node biopsy and pleural effusion cytology. He was treated with cyclophosphamide/doxorubicin/vincristine/prednisolone (CHOP) chemotherapy. Since two courses of chemotherapy were not effective we changed to carboplatin/ifosfamide/ etoposide/dexamethasone (DeVIC) chemotherapy. His condition improved and a complete response was obtained. In conclusion, the presence of a high level of ADA in the pleural effusion and resistance to anti-tuberculosis therapy should suggest a malignant lymphoma.     

腺苷脱氨酶在胸腔积液鉴别诊断中的作用

目的探讨腺苷脱氨酶(ADA)在胸腔积液鉴别诊断的价值。方法用G iusti比色法测定187例胸腔积液中胸水ADA水平。结果以ADA≥45U/L为阳性界值,阳性率结核性胸膜炎占80%(48/60例);漏出液占11.6%(5/43例);恶性肿瘤占19.7%(12/61例);肺炎、脓胸占28.6%(4/14例);经t检验结核性胸膜炎与非结核性胸腔积液ADA≥45U/L水平时有显著差异(P<0.01)。结论ADA在结核性胸腔积液中有应用价值,但需与PPD试验、结核中毒症状、血沉增快等因素综合考虑。     

A case of natural killer cell lymphoma with high adenosine deaminase level in pleural effusion]

A 61-year-old man was admitted to our hospital with cough, breathlessness, anorexia and chest pain. Chest radiograph showed right pleural effusion and also a chest CT scan showed right pleural effusion with thickening of the right visceral pleura, pericardial effusion and a liver tumor. The pleural effusion was slightly bloody and exudative. The adenosine deaminase (ADA) level in the pleural effusion was elevated. Because the cytological examintion of the pleural effusion showed no malignancy, we diagnosed pleuritis tuberculosa. The serum-soluble interleukin-2 receptor level was also elevated. His general condition worsened in spite of the chemotherapy with antibiotics and antituberculous drugs. We finally diagnosed the case as natural killer (NK) cell lymphoma from CT-guided needle biopsy just before death, and necropsy. In this case, the high level of ADA in the pleural effusion suggested lymphoma.     

胸水和血清ADA、TB-Ab-IgG联合检测对结核性胸膜炎的诊断探讨

目的 探讨胸水/血清腺苷脱氨酶(ADA)、结核抗体(TB-Ab-IgG)联合检测对结核性胸膜炎的诊断价值.方法 采用斑点金免疫渗滤试验(DIGFA)和酶连续监测法对234例胸腔积液进行胸水/血清ADA和TB-Ab-IgG检测结果进行分析.结果 结核性胸膜炎患者174例其胸水、血清中TB-Ab-IgG的阳性率分别为62.0%和70.1%,特异性分别为93.1%(56/60)和86.6%(52/60).ADA活性在结核性和癌性胸腔积液中分别为(59.58±29.85)U/L和(15.31±7.36)U/L(P<0.01).以P-ADA>40 U/L做为诊断结核的临界值,其敏感性为79.3%,特异性为86.4%;以P-ADA/S-ADA>1为临界值,其敏感性为97.7%,特异性为95.5%.结论 胸水和血清ADA、TB-Ab-IgG联合检测在结核性胸膜炎与非结核性胸膜炎上具有诊断与鉴别诊断价值.     

Der tuberkulöse Pleuraerguss

Approximately one third of the world’s population is infected with Mycobacterium tuberculosis and among communicable diseases tuberculosis is the second leading cause of death. The most common type of tuberculosis is pulmonary tuberculosis. Among the extrapulmonary manifestations, tuberculous pleuritis ranks second only after lymphatic tuberculosis. Tuberculous pleuritis is most commonly a disease with acute onset which is self-limiting in the majority of cases. A large proportion of patients though develop some form of active tuberculosis after a latency period. Therefore the correct diagnosis and the initiation of treatment are of the utmost importance. The easiest way to establish the diagnosis of tuberculous pleuritis is to demonstrate an elevated ADA (adenosine deaminase) in a lymphocytic effusion. Should pleural fluid analysis be nondiagnostic, the diagnosis of tuberculous pleuritis can be established with percutaneous closed needle biopsy in over 80% of cases. All patients with an undiagnosed pleural effusion after closed needle biopsy require thoracoscopy with selected biopsies taken under direct vision. The diagnostic yield of thoracoscopy is close to 100% in tuberculous pleuritis.     

胸膜活检对原因不明的渗出性胸腔积液的诊断价值

目的观察胸膜活检术在渗出性胸腔积液诊断中的价值。方法对146例渗出性胸腔积液患者行胸膜活检，同时取胸水及痰送检抗酸杆菌及癌细胞。结果146例胸膜活检第一次活检成功率71．9％，特异性病理诊断92例，病理诊断阳性率63％。恶性胸腔积液胸膜活检阳性率58％，胸水细胞学检查阳性率22％，痰找癌细胞阳性率16％。结核性胸腔积液胸膜活检阳性率66．6％，痰找抗酸杆菌阳性率5．2％。结论胸膜活检是一项安全、简单、有效的胸膜疾病的重要的内科确诊手段。     

Simultaneous measurements of adenosine deaminase activity and tuberculostearic acid in pleural effusions for the diagnosis of tuberculous pleuritis.

Adenosine deaminase (ADA) activity and tuberculostearic acid (TSA) levels in pleural effusions were measured in 18 patients with active tuberculous pleuritis, 16 patients suspected of having tuberculous pleuritis, 14 patients with carcinomatous pleuritis, and 19 patients suffering from pleuritis of non-malignant and non-tuberculous etiology. In the patients with active tuberculous pleuritis, ADA was elevated in 56% and TSA was positive in 78%. In 83% of these patients, either ADA was elevated or TSA was positive. ADA was elevated together with a positive TSA in 50%. In contrast, TSA was positive in only 6% and ADA was elevated in 24% of the patients with non-tuberculous pleuritis, and none of these patients showed the combination of an elevation of ADA and a positive TSA. These results suggest that simultaneous measurements of both ADA and TSA in pleural effusions are useful for the diagnosis of tuberculous pleuritis.     

白介素27和腺苷脱氢酶单独及联合检测对结核性胸膜炎诊断价值

目的 探讨白介素27((interleukin-27,IL-27)和腺苷脱氨酶(adenosine deaminase,ADA)单独检测及两者联合检测结果对结核性胸膜炎和恶性肿瘤所致胸腔积液的鉴别诊断价值。方法 选取2017年12月1日至2018年7月29日福建省福州肺科医院收治的胸腔积液患者101例,通过闭式胸膜活检、内科胸腔镜检查获得病理学证据或者痰/胸腔积液分枝杆菌培养阳性及菌种鉴定结果。根据诊断结果分为结核性胸膜炎患者61例(结核组);恶性肿瘤所致胸腔积液患者40例(恶性组),其中肺黏膜相关淋巴瘤1例,恶性胸膜间皮瘤1例,肺黏液表皮样癌1例,非霍奇金淋巴瘤1例,小细胞肺癌3例,肺腺癌33例。采用酶联免疫吸附法检测两组患者胸腔积液中的IL-27和ADA的含量并进行统计学分析。应用受试者工作曲线(ROC)确定IL-27和ADA检测结果对鉴别结核性胸膜炎与恶性肿瘤所致胸腔积液的最佳临界值,并进一步分析IL-27与ADA联合检测(串联试验、并联试验)对于诊断结核性胸膜炎的价值。结果 结核组患者胸腔积液中检测到的IL-27和ADA浓度分别为[409.48(229.04,954.97)]ng/L和(45.88±14.33)U/L,明显高于恶性组[分别为115.74(77.72,161.97)ng/L和10.50(7.00,15.00)U/L],差异均有统计学意义(Z=3.139,P<0.01;t=4.006,P<0.01)。绘制ROC曲线确定IL-27鉴别结核性胸腔积液与恶性胸腔积液诊断的最佳临界值为176.31ng/L,敏感度和特异度分别为85.25% (52/61)和82.50% (33/40);ADA鉴别结核性胸腔积液与恶性胸腔积液诊断的最佳临界值为28U/L,敏感度和特异度分别为93.44% (57/61)和87.50% (35/40)。串联试验方法联合检测,特异度(95.00%,38/40)较单独检测IL-27(82.50%,33/40)及单独检测ADA(87.50%,35/40)均明显升高,并有较好的敏感度(81.97%,50/61);并联试验方法联合检测,敏感度(96.72%,59/61)较单独检测IL-27(85.25%,52/61)及单独检测ADA(93.44%,57/61)均明显升高,但特异度较低(75.00%,30/40)。结论 胸腔积液中IL-27和ADA对结核性胸膜炎的诊断均有较高价值;IL-27和ADA串联试验有助于结核性和恶性肿瘤所致胸腔积液的鉴别诊断。     

Subpleural mononuclear cell infiltration. Significance in the differential diagnosis of pleuritis showing nonspecific histologic findings

To determine if patients who had lymphocyte-rich pleural effusion and a pleural biopsy without any specific findings could be histopathologically differentiated between those with tuberculous and nontuberculous pleuritis, we histologically re-evaluated the pleural biopsies of all patients whose pleural effusion was predominant with lymphocytes and contained no malignant cells. A total of 40 patients with a nonspecific histologic findings of pleural biopsy specimen were categorized based on their ultimate diagnosis as having tuberculous (n = 15), carcinomatous (n = 10) or nontuberculous, benign pleuritis (n = 15). The pleural biopsy specimen of patients with nontuberculous, benign pleuritis frequently showed a band-like infiltration of mononuclear cells in the subpleural adipose tissue with minimal pleural inflammatory infiltrate (10 out of 15 patients), while the same finding was infrequent in those with tuberculous pleuritis (0 out of 15, p = 0.0001) and pleuritis associated with carcinoma (three out of 10, p = 0.082). Based on these results, the presence of band-like infiltration of mononuclear cells in the subpleural adipose tissue with minimal pleural inflammatory infiltrate in pleural biopsy specimens of patients with lymphocyte-rich pleural effusion suggests that the pleuritis is nontuberculous in its nature.     

Level of antibodies against mycobacterial glycolipid in the effusion for diagnosis of tuberculous pleural effusion

BACKGROUND: Diagnosing tuberculous pleural effusion (pTB) is often difficult because the culturing of tubercle bacilli results in a negative test in the majority of cases. Serological tests for the detection of antibodies to tuberculous glycolipid (TBGL) and lipoarabinomannan (LAM) have been introduced for the diagnosis of pulmonary tuberculosis. We examined the levels of these antibodies, adenosine deaminase (ADA) and interferon-gamma (IFN-gamma) in the pleural effusion and compared their diagnostic values in pTB. METHODS: We studied 65 patients with pleural effusion. Of those, 19 patients were diagnosed as having pTB according to our broad case definition. The etiologies in the other 46 patients were malignant effusion, transdative effusion and miscellaneous diseases. Determiner TBGL antibody (D-TBGL-Ab) and MycoDot were used for the detection of anti-LAM and anti-TBGL antibodies, respectively, in the pleural effusion. RESULTS: The sensitivity of ADA was 78.9% (15/19) and the specificity 97.8% (45/46). The sensitivity of IFN-gamma was 84.2% (16/19) and the specificity 93.5% (43/46). The sensitivities of D-TBGL-Ab and MycoDot were both 52.6% (10/19) and their specificities were 95.7% (44/46) and 97.8% (45/46), respectively. When DTBGL-Ab (cutoff point: 2.0 U/ml) and ADA activity (cutoff point: 57 IU/l) were combined, the sensitivity was 94.7% (18/19) and the specificity 93.5% (43/46). CONCLUSIONS: In the diagnosis of pTB, D-TBGL-Ab and MycoDot each have low sensitivity but high specificity. When D-TBGL-Ab is used in combination with ADA, the sensitivity and specificity are both >90%. We conclude that D-TBGL-Ab and ADA in combination are useful in the diagnosis of pTB.     

腺苷脱氨酶及IL-22对结核性胸膜炎诊断价值的探究

目的探讨胸腔积液中腺苷脱氨酶(ADA)和白细胞介素22(IL-22)检测对结核性胸膜炎(TPE)的诊断价值.方法对2015年10月至2017年8月在河北大学附属医院呼吸内科住院的108例胸腔积液患者的临床资料进行分析,最终有104例患者经内科胸腔镜确诊,其中TPE患者38例,恶性胸腔积液患者40例,类肺炎性胸腔积液患者26例;对胸腔积液中ADA和IL-22水平进行统计分析.结果(1)108例患者经胸腔镜直视下取病理活检的诊断率为96.3%(104/108).(2)TPE组中ADA和IL-22水平均显著高于恶性胸腔积液组和类肺炎性胸腔积液组,差异均有统计学意义(P值均<0.05);胸腔积液中ADA和IL-22诊断TPE的敏感度和特异度分别为92.1%和87.9%,78.9%和90.9%.(3)受试者工作特征曲线结果显示,胸腔积液ADA和IL-22诊断TPE的曲线下面积分别为0.904和0.914,最佳诊断阈值分别为34.4 U/L和44.28 ng/L.(4)两者平行试验的敏感度和特异度分别为98.3%、79.9%,敏感度较单独检测提高;系列试验的敏感度和特异度分别为72.2%、98.9%,特异度较单独检测提高.结论(1)内科胸腔镜是一项操作简便、创伤小、并发症少的操作方法,可作为TPE的早期诊断与鉴别诊断;(2)胸腔积液ADA和IL-22水平对诊断TPE具有一定价值,可作为临床辅助诊断TPE的实验室指标;(3)ADA和IL-22联合检测可提高TPE的诊断率.     

IgG4-related pleural disease diagnosed by a re-evaluation of chronic bilateral pleuritis in a patient who experienced occasional acute left bacterial pleuritis

A 78-year-old man with cryptogenic chronic bilateral lymphoplasmacytic pleuritis, diagnosed based on left parietal pleural biopsy specimens obtained by pleuroscopy, developed acute left bacterial pleuritis. The left pleural effusion was neutrophil dominant, however, the right pleural effusion showed lymphoplasmacytic infiltration. Laboratory examinations revealed that his serum IgG4 concentration was increased, with a higher level of IgG4 in the right pleural effusion. Re-evaluation of the previous biopsy specimens using an immunostaining method revealed numerous IgG4-positive plasma cell infiltrations with IgG4-positive/IgG-positive plasma cells at 85.4%. Accordingly, the new diagnosis of this patient was considered to be chronic bilateral IgG4-related pleuritis.     

ADA在结核性胸腔积液中诊断意义

目的比较结核性胸水ADA和非结核性胸水ADA活性差异和诊断阳性率，并观察不同年龄组结核性胸水中ADA活性水平和诊断的阳性率。方法对80例结核性胸水患者和48例的非结核性胸水ADA进行分析，并以60岁为界限分为两组，进行组间ADA活性和诊断结核阳性率比较。结果结核性胸水患者中ADA活性高于非结核性胸水患者的ADA，并且ADA诊断结核性胸膜炎的阳性率高于后者。另外，结核性胸水ADA在不同年龄组间无显著性差异。结论：胸水中ADA的检测对结核性胸水的临床诊断有较大帮助。     

What is the significance of non‐specific pleuritis? A trick question

Non‐specific pleuritis (NSP) is defined as fibrinous or inflammatory pleuritis which cannot be attributed to a specific benign or malignant etiology. It can be diagnosed in biopsies in up to 30% of cases of exudative pleuritis after thoracoscopy, with a mean of 19.2%. In 66 out of 469 (14.2%) patients in combined series, a malignant pleural disease (mostly mesothelioma) was found during a follow‐up of at least 21 months. Most likely, a follow‐up time of 12 months is sufficient, although the current routine is a follow‐up of 2 years. Because of a benign course in 85% of patients with NSP, a repeated invasive procedure after thoracoscopy is only indicated in a limited group of patients. The most important indications for a repeated pleural biopsy are persistent chest pain, recurrent pleural effusion, radiologic findings suggestive for malignant pleural disease.     

内科胸腔镜在不明原因胸腔积液诊断中的应用

目的 分析内科胸腔镜在不明原因胸腔积液诊断中的价值及其安全性.方法 对我院呼吸内科及重症医学科2010年4月至2013年4月收治的92例不明原因胸腔积液患者行内科胸腔镜检查,观察胸膜病变,直视下病变处多部位活检并行病理检查.结果 92例胸腔积液患者确诊84例,诊断阳性率为91.3％,其中恶性胸腔积液48例,结核性胸腔积液29例,非特异性炎症4例,化脓性胸膜炎2例,结节病1例,病因不明8例,术后疼痛11例,发热3例,出血1例.结论 内科胸腔镜检查有助于进一步明确不明原因胸腔积液的病因,且患者耐受性好、安全、有效,值得临床推广应用.     

Usefulness of pleural effusion antinuclear antibodies in the diagnosis of lupus pleuritis

We performed this study to determine sensitivity and specificity of pleural effusion antinuclear antibodies (ANA) at a titer of ≥1?:?160, and the ratio of pleural effusion to serum ANA of ≥1, to distinguish between pleural fluid from lupus pleuritis and other causes. A prospective study of 54 patients with pleural effusion (12 lupus pleuritis, seven parapneumonic effusion, 26 malignancy-associated pleural effusions, nine transudative effusions) was performed. ANA at a titer of ≥1?:?160 were found in 11 of 12 lupus pleuritis samples, and in four of 42 pleural effusions from non-systemic lupus erythematosus (SLE) patients. The pleural effusion ANA at a titer of ≥1?:?160 gave a sensitivity of 91.67% for lupus pleuritis, with a specificity of 83.33% when compared with all other pleural effusions, 90.91% when compared with exudative effusion (parapneumonic effusion and malignancy-associated effusion) and 55.56% when compared with the transudative pleural effusion group. Using the ratio of pleural effusion to serum ANA of ≥1, the sensitivity and the specificity decreased to 75.00% and 78.57%, respectively. This study provides further evidence that the pleural effusion ANA at a titer of ≥1?:?160 is a sensitive and specific diagnostic biomarker for lupus pleuritis in patients with lupus. However, pleural effusion ANA can occasionally be found in other conditions.     

闭式胸膜刷检术对恶性胸腔积液的诊断价值

目的评价闭式胸膜刷检术对恶性胸腔积液的诊断价值。方法临床疑诊的48例恶性胸腔积液行胸膜刷检、胸膜活检和胸水细胞学检查,比较各种方法和组合对肿瘤细胞的阳性率。结果43例确诊为恶性胸腔积液,胸膜刷检阳性率为62.8%,胸水细胞学检查阳性率为55.8%,胸膜活检阳性率为37.2%,以胸膜刷检最高,明显高于胸膜活检(P<0.05),但与胸水细胞学检查比较无显著性差异(P>0.05)。联合胸膜活检和胸膜刷检,阳性率提高为76.7%,3种方法联合应用阳性率为83.7%。结论胸膜刷检是一种简单、安全、有效的检查手段,对诊断恶性胸腔积液有较大的应用价值。