孤立性肺结节的临床诊断
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摘要
无论男性还是女性，肺癌都是最常见导致死亡的肺部疾病，每年大约有175000新发诊断病例，同时每年有157000死亡病例。据估计大约在人的一生中，每18个女人及12个男人之中就会有一例肺癌病例发生，死于肺癌的人数要超过后三位恶性疾病死亡数的总和，它们分别是乳腺癌、结肠癌、前列腺癌，而肺癌的最常见表现是影像学上小于3cm或普通胸片上大于3cm的孤立性肺肿块。
孤立性肺结节被定义为是一种圆形或是椭圆形高密度的直径小于3cm，且至少2/3被正常肺组织所包绕，同时需除外淋巴瘤、肺不张及肺炎的一种肺部疾病，但对于较大的病变一般不包括在这一定义之中，因为在许多情况下它们是恶性的。孤立性肺结节大约可见于2%的胸部影像学检查患者，关于孤立性肺结节的鉴别诊断非常广泛，许多病变最后被证实为是肉芽肿或是错构瘤，所以发现孤立性肺结节并明确它的性质是非常重要的，因为如果孤立性肺结节是恶性的，死亡率可以达到85%。及早发现小的孤立性肺结节可以减少由于肺部恶性病变导致的死亡，但孤立性肺结节为良性的话，那么不必要的手术不但使患者不能享受手术所带来的益处，反而使患者不得不忍受手术所带来的并发症。
虽然我们不能仅仅依据影像学特征来得出诊断结论，但是影像学检查常常在孤立性肺结节的诊断中能够发挥更大的作用，在这篇文章中我们将会把恶性孤立性肺结节的一些影像学特点进行归类和分析,为临床更好的诊断孤立性肺结节及减少误诊打下基础。
孤立性肺结节的影像学诊断和分析是临床的常见问题，临床诊断过程包括对患者临床病史的询问，以及对影像学上结节的大小、形态及能否获得结节组织学诊断依据来加以判断。最可靠的是影像学上特征性的良性表现，但是这些良性的表现常常在影像学检查中是不存在的，如果一旦怀疑为恶性病变则应早行病理学检查，我们的原则是不仅要努力发现小的恶性结节从而及时手术加以切除，同时还要避免对良性病变进行不必要的手术，随着临床上各种新技术的应用，对于孤立性肺结节的诊断手段和水平也在不断的提高。
本文通过对已经发表的四种临床上常用影像学诊断方法对肺部肿块诊断文章的meta分析，这四种检查方法分别是动态CT增强检查、动态磁共振增强检查、PET检查、单光子发射成像检查，同时评价了它们对于孤立性肺结节诊断的敏感性及特异性，为临床医师选择合适的影像学检查手段及降低费用提供依据。
在过去10年中，PET检查越来越多的被用于性质不确定肺结节的鉴别诊断，许多肺结节患者术前曾经行最近的PET检查或与CT的融合检查，PET的检查原理是通过判断肿块对18F去氧葡萄糖的摄取程度来判断肿块的良恶性，但是由于支气管肺癌及肉芽肿疾病对该物质均有较高的代谢活性，所以均可呈现阳性表现，我们通过对已明确性质的已被切除且经过病理学证实的肺部肿块的CT及PET影像学特点的回顾性研究为临床更好的将PET-CT用于孤立性肺结节的诊断打下基础。
目的：由于PET在二者中的阳性发生率均很高，PET不能够很好的鉴别支气管源肺恶性肿瘤和肉芽肿疾病,我们通过系统分析已被切除的经病理学证实的肺癌及肉芽肿疾病患者的PET及CT影像学特征为更好的鉴别PET阳性支气管肺癌及肉芽肿疾病打下基础。
方法：我们回顾性分析研究了2005年1月到2012年2月之间的93例手术切除患者，术后经过病理学证实的支气管肺癌及肉芽肿患者，同时对它们术前的CT及PET影像学特征进行回顾性分析。对每一个肿块在CT影像学上的表现，如结节及肿块的边缘特征、肿块大小、倍增时间、病变所在部位、肿块外形、内部特征、钙化特点、支气管充气征、空洞征及血管集束征等方面均进行了仔细的评估，同时得出对肿块的印象性诊断，然后对肿块的各影像学特征行多元logistic回归分析,同时也对在该段时间内术前关于支气管肺癌及肉芽肿性病变的PET检查数据做了分析。
结果：68%（65/96）的被切除肿块是癌性的，而32%（31/96）的肿块是肉芽肿性的。CT在65%(20/31)肉芽肿性疾病中呈良性表现，在5%(3/65)肺癌之中呈现良性表现（P<0.0001，阴性预测值[NPV]为87%[20/23],与肉芽肿性疾病明显相关的良性影像学特征是血管集束征、空洞症、不规则外形、无胸膜牵拉及实性密度改变。联合非毛刺样边缘、不规则外形及实性密度症对良性肿块的阴性预测值可达86%(12/14)。PET阳性率在癌性疾病中为86%(56/65)，肉芽肿性疾病中为97%(30/31)(p=0.11)，PET阳性率在两种疾病中均很高，但无统计学差异。在1995年到2009年期间切除的肿块中18%(2/14)是肉芽肿性疾病(p=0.066)，肉芽肿病变的切除率从18%增加到32%，增加了78%，但在该研究中未获显著差异(p=0.066)。
结论：CT影像学特征可以协助PET减少恶性肿块误诊的可能性，但也不能够完全避免，其中血管集束征、空洞症、不规则外形、无胸膜牵拉及实性密度改变对良性病变的阴性预测值最高,若联合非毛刺样边缘、不规则外形及实性密度征对良性肿块的阴性预测值可达86%(12/14)。
目的：该文目的在于评价各种影像学检查方法在单发肺部肿块中对恶性病变的诊断价值。同时创建一个根据各种诊断方法的临床数据所建立的线图及图表来帮助诊断恶性病变。
方法：研究中对CT、PET、MR及SPECT在诊断恶性肿块中的作用做了分析研究。我们对所有的已经发表的研究数据重新做了分析，同时对纳入研究的文献质量进行了评估。每一种诊断方法对单发性肺部肿块中恶性病变鉴别的阳性及阴性似然比均被再次仔细计算。238篇文献当中44篇文献被纳入到研究之中。
结果：各种诊断方法的阳性似然比分别为CT3.91(95%可信区间2.42,5.40), MRI4.57(3.03,6.1), PET5.44(3.56,7.32)及SPECT5.16(4.03,6.30)。阴性似然比为: CT0.10(0.03,0.16), MRI0.08(0.03,0.12), PET0.06(0.02,0.09)、SPECT0.06(0.04,0.08)。
结论：由于这四项诊断方法它们对于肺部肿块的诊断价值差异是非常小的。所以临床医师可以采用这四种诊断方法之中的任何一种用于对肺部肿块的诊断，但如果考虑到价格及技术的推广程度而言，SPECT似乎更应成为单发肺肿块诊断的首选方法。
No matter male or female, lung cancer is the most common lung disease leadingcause of death, there are about175,000new diagnosed cases every year, while157000deaths each year. It is estimated there will be a case of lung cancer occurred in18women and12men in one life, the number died of lung cancer is more than additionalthree malignant diseases, which are breast cancer, colon cancer, prostate cancer. themost common manifestation of lung cancer is imaging solitary pulmonary nodules lessthan3cm nodules or chest X-ray one larger than3cm.
The solitary pulmonary nodule is defined as a circular or oval-shaped high-density,diameter is less than3cm and at least2/3is surrounding by normal lung tissue,lymphoma atelectasis and pneumonia need excepted at the same time, but to a largerlesions are generally not included in this definition, because in most cases they aremalignant. Solitary pulmonary nodule is seen in about2%of patients chest imaging,their differential diagnosis often is difficult, many lesions be proved is granuloma orhamartoma finally, so find solitary pulmonary and make sure its nature is veryimportant, if the solitary pulmonary nodule is malignant, the mortality rate can reach85%. So early detection of small solitary pulmonary nodules can reduce the cause ofdeath due to malignant lung lesions, but if solitary pulmonary nodule is benign, thepatients is not only enjoy the benefits of surgery, but also endure unnecessary surgerycomplications.
Although we can not draw diagnostic conclusions on the basis of imaging featuressolely, but imaging checks are often play a greater role in the diagnosis of solitarypulmonary nodule, where we will give classification and analysis of imagingcharacteristics to malignant solitary pulmonary nodule.
Imaging diagnosis and analysis about solitary pulmonary nodule is a commonclinical problem, the clinical diagnostic process include the patient's clinical history and imaging nodule size、shape and availability of nodular histological diagnosis. The mostreliable imaging characteristics is benign performance，But they are usually have notexist. Once malignant lesions is suspected highly，we should give a pathologically examat once, our principle is not only to give a timely surgery for identified small malignantnodules, but also to avoid unnecessary surgery for benign lesions, with the clinicalapplication of new technologies, diagnostic tools and level to solitary pulmonary noduleare constantly improved.
For select the appropriate imaging checks and reduce the cost of treatment，wehave a meta analysis to published articles of four commonly used imaging diagnosticchecks, they are dynamic enhanced CT, dynamic magnetic resonance, PET, singlephoton emission tomography examination.
In the past, the PET check be used for the differential diagnosis to uncertainpulmonary nodule more and more, many patients of pulmonary nodule havepreoperative PET or PET-CT fusion check, which benign or malignant nodules isjudged by18F-FDG uptake in PET checks, but in lung cancer and granulomatousdisease usually have same high metabolic activity, which show same positiveperformance, for avoid misdiagnosis and use PET-CT in clinical better, we have aretrospective study to PET-CT imaging performance.
Abstract: PET distinguish between bronchogenic carcinoma and granuloma isdifficult，But positive results may lead operation. We carefully evaluated the CT andPET appearance of resected carcinomas and granulomas to show CT and PET imagingfeatures that could be used to distinguish between disease of bronchogenic carcinomaand granuloma.
Objective: We retrospectively identified93consecutive patients between January2005and February2012who had operation of a pulmonary nodule pathologicallydiagnosed as bronchogenic carcinoma or granuloma and preoperative feature with CTand PET. Each nodule was evaluated on CT for size, doubling time, location, margin,shape, internal characteristics, calcification, clustering, air bronchograms, and cavitation.A diagnostic result was got. Bivariate and logistic regression analyses were finished.Pre-PET data about the proportion of operated granulomas and carcinomas betweenJanuary2005and December2009were reviewed.
Methods: Sixty-eight percent (65/96) of nodules were carcinomas and32%(31/96)were granulomas. The CT appearance was benign in65%(20/31) of granulomas and5%(3/65) of carcinomas (p <0.0001; negative predictive value [NPV] is87%[20/23]).Specific CT appearance obviously correlation with granuloma were clustering,cavitation, irregular shape, no pleural tags, and solid attenuation. Granulomasrepresented (9/50) of resected masses in1995and2009(p=0.066). Rate ofPET-positive in carcinomas is86%(56/65) and97%(30/31) in granuloma，There is notstatistical differences (p=0.11)。Rate of resected granuloma is increased from18%to32%，All increases is78%。But there is not statistical differences in this study(p=0.066)。
Results: CT appearance reduce but cannot avoid the possibility that a nodule ofPET positive is malignant. Among of CT imaging appearance，The most valuable todistinguish is clustering, cavitation, irregular shape, no pleural tags, and solidattenuation，The combination of nonspiculated margin, irregular shape, and solid attenuation had an NPV of86%(12/14).
Objective: The aim of this article was to assess the clinical effects of diagnostictests for evaluating malignancy within a solitary pulmonary nodule (SPN), and toestablish a nomogram or table using clinical data and noninvasive radiology (positive)test results to estimate post-test probability of malignancy.
Methods: Studies that examined computed tomography (CT), magnetic resonanceimaging (MRI), positron emission tomography (PET) and single photon emissioncomputed tomography (SPECT) for the evaluation of SPN. Two investorsindependently abstracted data and evaluated study quality. Study-specific and overallpositive likelihood ratios (LRs) for each diagnostic test confirming a diagnosis ofmalignancy and negative LR for each diagnostic test excluding a diagnosis ofmalignancy within an SPN were calculated.
Result: Forty-four of238articles were included. Positive LRs for diagnostic testswere: CT3.91(95%confidence interval2.42,5.40), MRI4.57(3.03,6.1), PET5.44(3.56,7.32) and SPECT5.16(4.03,6.30). Negative LRs were: CT0.10(0.03,0.16),MRI0.08(0.03,0.12), PET0.06(0.02,0.09) and SPECT0.06(0.04,0.08).
Conclusion: Differences in performance for all tests were negligible; Hence, theclinician may confidently use any of the four tests presented in further evaluating anSPN. Given the less cost and prevalence of the technology, SPECT seems to be the firstchoice for additional testing in SPN evaluation.
孤立性肺结节被定义为是一种圆形或是椭圆形高密度的直径小于3cm，且至少2/3被正常肺组织所包绕，同时需除外淋巴瘤、肺不张及肺炎的一种肺部疾病，但对于较大的病变一般不包括在这一定义之中，因为在许多情况下它们是恶性的。孤立性肺结节大约可见于2%的胸部影像学检查患者，关于孤立性肺结节的鉴别诊断非常广泛，许多病变最后被证实为是肉芽肿或是错构瘤，所以发现孤立性肺结节并明确它的性质是非常重要的，因为如果孤立性肺结节是恶性的，死亡率可以达到85%。及早发现小的孤立性肺结节可以减少由于肺部恶性病变导致的死亡，但孤立性肺结节为良性的话，那么不必要的手术不但使患者不能享受手术所带来的益处，反而使患者不得不忍受手术所带来的并发症。
虽然我们不能仅仅依据影像学特征来得出诊断结论，但是影像学检查常常在孤立性肺结节的诊断中能够发挥更大的作用，在这篇文章中我们将会把恶性孤立性肺结节的一些影像学特点进行归类和分析,为临床更好的诊断孤立性肺结节及减少误诊打下基础。
孤立性肺结节的影像学诊断和分析是临床的常见问题，临床诊断过程包括对患者临床病史的询问，以及对影像学上结节的大小、形态及能否获得结节组织学诊断依据来加以判断。最可靠的是影像学上特征性的良性表现，但是这些良性的表现常常在影像学检查中是不存在的，如果一旦怀疑为恶性病变则应早行病理学检查，我们的原则是不仅要努力发现小的恶性结节从而及时手术加以切除，同时还要避免对良性病变进行不必要的手术，随着临床上各种新技术的应用，对于孤立性肺结节的诊断手段和水平也在不断的提高。
本文通过对已经发表的四种临床上常用影像学诊断方法对肺部肿块诊断文章的meta分析，这四种检查方法分别是动态CT增强检查、动态磁共振增强检查、PET检查、单光子发射成像检查，同时评价了它们对于孤立性肺结节诊断的敏感性及特异性，为临床医师选择合适的影像学检查手段及降低费用提供依据。
在过去10年中，PET检查越来越多的被用于性质不确定肺结节的鉴别诊断，许多肺结节患者术前曾经行最近的PET检查或与CT的融合检查，PET的检查原理是通过判断肿块对18F去氧葡萄糖的摄取程度来判断肿块的良恶性，但是由于支气管肺癌及肉芽肿疾病对该物质均有较高的代谢活性，所以均可呈现阳性表现，我们通过对已明确性质的已被切除且经过病理学证实的肺部肿块的CT及PET影像学特点的回顾性研究为临床更好的将PET-CT用于孤立性肺结节的诊断打下基础。
目的：由于PET在二者中的阳性发生率均很高，PET不能够很好的鉴别支气管源肺恶性肿瘤和肉芽肿疾病,我们通过系统分析已被切除的经病理学证实的肺癌及肉芽肿疾病患者的PET及CT影像学特征为更好的鉴别PET阳性支气管肺癌及肉芽肿疾病打下基础。
方法：我们回顾性分析研究了2005年1月到2012年2月之间的93例手术切除患者，术后经过病理学证实的支气管肺癌及肉芽肿患者，同时对它们术前的CT及PET影像学特征进行回顾性分析。对每一个肿块在CT影像学上的表现，如结节及肿块的边缘特征、肿块大小、倍增时间、病变所在部位、肿块外形、内部特征、钙化特点、支气管充气征、空洞征及血管集束征等方面均进行了仔细的评估，同时得出对肿块的印象性诊断，然后对肿块的各影像学特征行多元logistic回归分析,同时也对在该段时间内术前关于支气管肺癌及肉芽肿性病变的PET检查数据做了分析。
结果：68%（65/96）的被切除肿块是癌性的，而32%（31/96）的肿块是肉芽肿性的。CT在65%(20/31)肉芽肿性疾病中呈良性表现，在5%(3/65)肺癌之中呈现良性表现（P<0.0001，阴性预测值[NPV]为87%[20/23],与肉芽肿性疾病明显相关的良性影像学特征是血管集束征、空洞症、不规则外形、无胸膜牵拉及实性密度改变。联合非毛刺样边缘、不规则外形及实性密度症对良性肿块的阴性预测值可达86%(12/14)。PET阳性率在癌性疾病中为86%(56/65)，肉芽肿性疾病中为97%(30/31)(p=0.11)，PET阳性率在两种疾病中均很高，但无统计学差异。在1995年到2009年期间切除的肿块中18%(2/14)是肉芽肿性疾病(p=0.066)，肉芽肿病变的切除率从18%增加到32%，增加了78%，但在该研究中未获显著差异(p=0.066)。
结论：CT影像学特征可以协助PET减少恶性肿块误诊的可能性，但也不能够完全避免，其中血管集束征、空洞症、不规则外形、无胸膜牵拉及实性密度改变对良性病变的阴性预测值最高,若联合非毛刺样边缘、不规则外形及实性密度征对良性肿块的阴性预测值可达86%(12/14)。
目的：该文目的在于评价各种影像学检查方法在单发肺部肿块中对恶性病变的诊断价值。同时创建一个根据各种诊断方法的临床数据所建立的线图及图表来帮助诊断恶性病变。
方法：研究中对CT、PET、MR及SPECT在诊断恶性肿块中的作用做了分析研究。我们对所有的已经发表的研究数据重新做了分析，同时对纳入研究的文献质量进行了评估。每一种诊断方法对单发性肺部肿块中恶性病变鉴别的阳性及阴性似然比均被再次仔细计算。238篇文献当中44篇文献被纳入到研究之中。
结果：各种诊断方法的阳性似然比分别为CT3.91(95%可信区间2.42,5.40), MRI4.57(3.03,6.1), PET5.44(3.56,7.32)及SPECT5.16(4.03,6.30)。阴性似然比为: CT0.10(0.03,0.16), MRI0.08(0.03,0.12), PET0.06(0.02,0.09)、SPECT0.06(0.04,0.08)。
结论：由于这四项诊断方法它们对于肺部肿块的诊断价值差异是非常小的。所以临床医师可以采用这四种诊断方法之中的任何一种用于对肺部肿块的诊断，但如果考虑到价格及技术的推广程度而言，SPECT似乎更应成为单发肺肿块诊断的首选方法。
No matter male or female, lung cancer is the most common lung disease leadingcause of death, there are about175,000new diagnosed cases every year, while157000deaths each year. It is estimated there will be a case of lung cancer occurred in18women and12men in one life, the number died of lung cancer is more than additionalthree malignant diseases, which are breast cancer, colon cancer, prostate cancer. themost common manifestation of lung cancer is imaging solitary pulmonary nodules lessthan3cm nodules or chest X-ray one larger than3cm.
The solitary pulmonary nodule is defined as a circular or oval-shaped high-density,diameter is less than3cm and at least2/3is surrounding by normal lung tissue,lymphoma atelectasis and pneumonia need excepted at the same time, but to a largerlesions are generally not included in this definition, because in most cases they aremalignant. Solitary pulmonary nodule is seen in about2%of patients chest imaging,their differential diagnosis often is difficult, many lesions be proved is granuloma orhamartoma finally, so find solitary pulmonary and make sure its nature is veryimportant, if the solitary pulmonary nodule is malignant, the mortality rate can reach85%. So early detection of small solitary pulmonary nodules can reduce the cause ofdeath due to malignant lung lesions, but if solitary pulmonary nodule is benign, thepatients is not only enjoy the benefits of surgery, but also endure unnecessary surgerycomplications.
Although we can not draw diagnostic conclusions on the basis of imaging featuressolely, but imaging checks are often play a greater role in the diagnosis of solitarypulmonary nodule, where we will give classification and analysis of imagingcharacteristics to malignant solitary pulmonary nodule.
Imaging diagnosis and analysis about solitary pulmonary nodule is a commonclinical problem, the clinical diagnostic process include the patient's clinical history and imaging nodule size、shape and availability of nodular histological diagnosis. The mostreliable imaging characteristics is benign performance，But they are usually have notexist. Once malignant lesions is suspected highly，we should give a pathologically examat once, our principle is not only to give a timely surgery for identified small malignantnodules, but also to avoid unnecessary surgery for benign lesions, with the clinicalapplication of new technologies, diagnostic tools and level to solitary pulmonary noduleare constantly improved.
For select the appropriate imaging checks and reduce the cost of treatment，wehave a meta analysis to published articles of four commonly used imaging diagnosticchecks, they are dynamic enhanced CT, dynamic magnetic resonance, PET, singlephoton emission tomography examination.
In the past, the PET check be used for the differential diagnosis to uncertainpulmonary nodule more and more, many patients of pulmonary nodule havepreoperative PET or PET-CT fusion check, which benign or malignant nodules isjudged by18F-FDG uptake in PET checks, but in lung cancer and granulomatousdisease usually have same high metabolic activity, which show same positiveperformance, for avoid misdiagnosis and use PET-CT in clinical better, we have aretrospective study to PET-CT imaging performance.
Abstract: PET distinguish between bronchogenic carcinoma and granuloma isdifficult，But positive results may lead operation. We carefully evaluated the CT andPET appearance of resected carcinomas and granulomas to show CT and PET imagingfeatures that could be used to distinguish between disease of bronchogenic carcinomaand granuloma.
Objective: We retrospectively identified93consecutive patients between January2005and February2012who had operation of a pulmonary nodule pathologicallydiagnosed as bronchogenic carcinoma or granuloma and preoperative feature with CTand PET. Each nodule was evaluated on CT for size, doubling time, location, margin,shape, internal characteristics, calcification, clustering, air bronchograms, and cavitation.A diagnostic result was got. Bivariate and logistic regression analyses were finished.Pre-PET data about the proportion of operated granulomas and carcinomas betweenJanuary2005and December2009were reviewed.
Methods: Sixty-eight percent (65/96) of nodules were carcinomas and32%(31/96)were granulomas. The CT appearance was benign in65%(20/31) of granulomas and5%(3/65) of carcinomas (p <0.0001; negative predictive value [NPV] is87%[20/23]).Specific CT appearance obviously correlation with granuloma were clustering,cavitation, irregular shape, no pleural tags, and solid attenuation. Granulomasrepresented (9/50) of resected masses in1995and2009(p=0.066). Rate ofPET-positive in carcinomas is86%(56/65) and97%(30/31) in granuloma，There is notstatistical differences (p=0.11)。Rate of resected granuloma is increased from18%to32%，All increases is78%。But there is not statistical differences in this study(p=0.066)。
Results: CT appearance reduce but cannot avoid the possibility that a nodule ofPET positive is malignant. Among of CT imaging appearance，The most valuable todistinguish is clustering, cavitation, irregular shape, no pleural tags, and solidattenuation，The combination of nonspiculated margin, irregular shape, and solid attenuation had an NPV of86%(12/14).
Objective: The aim of this article was to assess the clinical effects of diagnostictests for evaluating malignancy within a solitary pulmonary nodule (SPN), and toestablish a nomogram or table using clinical data and noninvasive radiology (positive)test results to estimate post-test probability of malignancy.
Methods: Studies that examined computed tomography (CT), magnetic resonanceimaging (MRI), positron emission tomography (PET) and single photon emissioncomputed tomography (SPECT) for the evaluation of SPN. Two investorsindependently abstracted data and evaluated study quality. Study-specific and overallpositive likelihood ratios (LRs) for each diagnostic test confirming a diagnosis ofmalignancy and negative LR for each diagnostic test excluding a diagnosis ofmalignancy within an SPN were calculated.
Result: Forty-four of238articles were included. Positive LRs for diagnostic testswere: CT3.91(95%confidence interval2.42,5.40), MRI4.57(3.03,6.1), PET5.44(3.56,7.32) and SPECT5.16(4.03,6.30). Negative LRs were: CT0.10(0.03,0.16),MRI0.08(0.03,0.12), PET0.06(0.02,0.09) and SPECT0.06(0.04,0.08).
Conclusion: Differences in performance for all tests were negligible; Hence, theclinician may confidently use any of the four tests presented in further evaluating anSPN. Given the less cost and prevalence of the technology, SPECT seems to be the firstchoice for additional testing in SPN evaluation.
引文
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