Persistent Nodules Research Articles

Long-term follow-up of persistent pulmonary pure ground-glass nodules with deep learning-assisted nodule segmentation.

To investigate the natural history of persistent pulmonary pure ground-glass nodules (pGGNs) with deep learning-assisted nodule segmentation. Between January 2007 and October 2018, 110 pGGNs from 110 patients with 573 follow-up CT scans were included in this retrospective study. pGGN automatic segmentation was performed on initial and all follow-up CT scans using the Dr. Wise system based on convolution neural networks. Subsequently, pGGN diameter, density, volume, mass, volume doubling time (VDT), and mass doubling time (MDT) were calculated automatically. Enrolled pGGNs were categorized into growth, 52 (47.3%), and non-growth, 58 (52.7%), groups according to volume growth. Kaplan-Meier analyses with the log-rank test and Cox proportional hazards regression analysis were conducted to analyze the cumulative percentages of pGGN growth and identify risk factors for growth. The mean follow-up period of the enrolled pGGNs was 48.7 ± 23.8months. The median VDT of the 52 pGGNs having grown was 1448 (range, 339-8640) days, and their median MDT was 1332 (range, 290-38,912) days. The 12-month, 24.7-month, and 60.8-month cumulative percentages of pGGN growth were 10%, 25.5%, and 51.1%, respectively, and they significantly differed among the initial diameter, volume, and mass subgroups (all p < 0.001). The growth pattern of pGGNs may conform to the exponential model. Lobulated sign (p = 0.044), initial mean diameter (p < 0.001), volume (p = 0.003), and mass (p = 0.023) predicted pGGN growth. Persistent pGGNs showed an indolent course. Deep learning can assist in accurately elucidating the natural history of pGGNs. pGGNs with lobulated sign and larger initial diameter, volume, and mass are more likely to grow. • The pure ground-glass nodule (pGGN) segmentation accuracy of the Dr. Wise system based on convolution neural networks (CNNs) was 96.5% (573/594). • The median volume doubling time (VDT) of 52 pure ground-glass nodules (pGGNs) having grown was 1448days (range, 339-8640days), and their median mass doubling time (MDT) was 1332days (range, 290-38,912days). The mean time to growth in volume was 854 ± 675days (range, 116-2856days). • The 12-month, 24.7-month, and 60.8-month cumulative percentages of pGGN growth were 10%, 25.5%, and 51.1%, respectively, and they significantly differed among the initial diameter, volume, and mass subgroups (all p values < 0.001). The growth pattern of pure ground-glass nodules may conform to exponential model.

Quantitative CT Analysis for Predicting the Behavior of Part-Solid Nodules with Solid Components Less than 6 mm: Size, Density and Shape Descriptors

Persistent part-solid nodules (PSNs) with a solid component &lt;6 mm usually represent minimally invasive adenocarcinomas and are significantly less aggressive than PSNs with a solid component ≥6 mm. However, not all PSNs with a small solid component behave in the same way: some nodules exhibit an indolent course, whereas others exhibit more aggressive behavior. Thus, predicting the future behavior of this subtype of PSN remains a complex and fascinating diagnostic challenge. The main purpose of this study was to apply open-source software to investigate which quantitative computed tomography (CT) features may be useful for predicting the behavior of a select group of PSNs. We retrospectively selected 50 patients with a single PSN with a solid component &lt;6 mm and diameter &lt;15 mm. Computerized analysis was performed using ImageJ software for each PSN and various quantitative features were calculated from the baseline CT images. The area, perimeter, mean Feret diameter, linear mass density, circularity and solidity were significantly related to nodule growth (p ≤ 0.031). Therefore, quantitative CT analysis was helpful for predicting the future behavior of a select group of PSNs with a solid component &lt;6 mm and diameter &lt;15 mm.

Incidence and natural course of CT-detected pulmonary ground-glass nodules in Chinese women with breast cancer: a retrospective, single-center, long-term follow-up study in 4682 consecutive patients

Background Increased use of thin-section computed tomography (CT) scans has revealed that small lung nodules, termed ground-glass nodules, are frequent in primary breast cancer patients and are associated with pre-invasive or invasive pulmonary adenocarcinomas. However, little is known of the incidence and fate of ground-glass nodules. Purpose To elucidate the incidence and natural course of CT-detected pulmonary ground-glass nodules in Chinese women with breast cancer. Material and Methods We retrospectively reviewed data from female breast cancer patients who underwent lung CT scans and who were followed for ≥3 months after the initial scan to identify the incidence of ground-glass nodules and any changes in them during the follow-up period. Results Between January 2008 and April 2018, 693 out of 4682 breast cancer patients (14.8%) had persistent lung ground-glass nodules as detected by CT scan. The median age was 52 years (interquartile range [IQR] = 45–62 years). Median nodule size was 4.9 mm in diameter on initial CT scan. Frequency of growth was 7.5% (52/693 patients). Median volume doubling time was 1092 days (IQR = 719–1808 days) for 39 growing in size nodules. Initial nodule size, nodule type, and follow-up period were independent predictors of nodule growth. Conclusion Most pulmonary ground-glass nodules in breast cancer patients were stable during long-term follow-up; most growing nodules had an indolent clinical course, suggesting that nodules should be monitored until growth is detected. This information is clinically relevant for accurate diagnosis of cancer stage and for appropriate treatment plans for patients with lung ground-glass nodules.

Persistent pulmonary subsolid nodules: How long should they be observed until clinically relevant growth occurs?

During the first two decades of 21 st century, there has been remarkable advance in the knowledge about lung cancer. One of the most important advances is persistent pulmonary subsolid nodules (SSNs) including pure ground-glass nodules (GGNs) and part-solid nodules (PSNs). Pulmonary SSNs, when persistent, have high probability of being pulmonary adenocarcinomas spectrum pathologically, and ironically show very indolent clinical courses over follow-ups (1-3). Many researchers investigated the natural history of persistent pulmonary SSNs, which included the frequency and pattern of interval growth, and the growth rate, to determine optimal management plan of patients with these nodules (4-8). However, uncertainty still remains on the natural course of persistent SSNs, especially with respect to the long-term consequences and ideal timing for surgical resection.

Quantitative features can predict further growth of persistent pure ground-glass nodule.

To evaluate whether quantitative features of persistent pure ground-glass nodules (PGGN) on the initial computed tomography (CT) scans can predict further nodule growth. This retrospective study included 59 patients with 101 PGGNs from 2011 to 2012, who received regular CT follow-up for lung nodule surveillance. Nineteen quantitative image features consisting of 8 volumetric and 11 histogram parameters were calculated to detect lung nodule growth. For the extraction of the quantitative features, semi-automatic GrowCut segmentation was implemented on chest CT images in 3D slicer platform. Univariate and multivariate analyses were performed to identify risk factors for nodule growth. With a median follow-up of 52 months, nodule growth was detected in 10 nodules by radiological assessment and in 16 nodules by quantitative features. In univariate analysis, 3D maximum diameter (MD), volume, mass, surface area, 90% percentile, and standard deviation value (SD) of PGGN on the initial CT scan were significantly different between stable nodules and nodules with further growth. In multivariate analysis, MD [hazard ratio (HR), 3.75; 95% confidence interval (CI), 2.14-6.55] and SD (HR, 2.06; 95% CI, 1.35-3.14) were independent predictors of further nodule growth. Also, the area under the curve was 0.896 (95% CI: 0.820-0.948) and 0.813 (95% CI: 0.723-0.883) for MD with a cut-off value of 10.2mm and SD of 50.0 Hounsfield Unit (HU). Besides, the growth rate was 55.6% (n=15) of PGGNs with MD >10.2 mm and SD >50.0 HU. Based on the initial CT scan, the quantitative features can predict PGGN growth more precisely. PGGN with MD >10.2 mm and SD >50.0 HU may require close follow-up or surgical intervention for the high incidence of growth.

The First 100 Cases of Epstein-Barr Virus-Positive Mucocutaneous Ulcers

In 2016, the World Health Organization provisionally classified Epstein-Barr virus (EBV)-positive mucocutaneous ulcer (EBVMCU) as a lymphoid neoplasm under the subcategory of mature B-cell neoplasms. Here we describe a 59-year-old Chinese woman with a long history of recurrent sinus and oropharyngeal infections and was diagnosed initially with EBVMCU and later, diffuse large B-cell lymphoma (DLBCL). She had sought medical attention after a particularly long bout of increased facial pressure and nasal obstruction. As a young adult she had undergone a tonsillectomy, adenoidectomy, and received innumerable treatments for bronchiectasis and recurrent sinopulmonary infections. A sinus computerized tomography (CT) scan showed mucosal thickening and swellings of the left frontal posterior sinus. A subsequent 18fludeoxyglucose (18FDG) positron emission tomography (PET)-CT scan showed a large hypermetabolic mass (standardized uptake value [SUV] 30.6) centered in the left half of the nasopharynx and sinus processes and extending across the mid-line. She underwent an endoscopic turbinate reduction with removal of a polypoid soft-tissue mass. Immunohistochemical studies indicated large atypical lymphoid cells that stained positively for CD20, CD30, EBER-1, MUM-1, OCT-2, and PAX-5 and variably for BCL-6, CD15, CD45, and CD79a. The Ki-67 proliferation index was 100% in the atypical cells. Tissue blocks were reviewed locally and at the National Institute of Health and were felt to be most consistent with EBVMCU. She received 4000 cGy involved-field external-beam radiation therapy over 20 fractions. At completion of treatment, no residual abnormalities were identified and no additional adjuvant therapy was pursued.Three years later she presented to medical attention with shortness of breath and a non-productive cough. A PET-CT scan showed whiteout of the left lung and intense 18FDG uptake in a left perihilar nodule (SUV of 18). Bronchoscopy revealed many reactive polypoid bronchial wall masses and a complete collapse of the lower left lobe due to an obstructing mass. The left lower lobe intraluminal mass biopsies however showed EBV-positive DLBCL of non-germinal center phenotype. She received six cycles of conventional R-CHOP therapy (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone) and 36 months later she remains cancer free but with persistent bronchial inflammatory nodules and recurrent infections.Using the key words “EBV mucocutaneous ulcers,” “EBV-associated lymphoproliferative disorders,” and “lymphoproliferative disorders,” we identified 100 cases of EBVMCU in the literature. EBVMCU is manifested as a well-circumscribed ulcer typically unifocal (90%) and of the oropharynx (58%), gastrointestinal (GI) tract (20%), and skin (20%). Immunohistochemical studies of the ulcers reveal monoclonal B-immunoblasts staining positively for CD20, CD30, EBER-1, MUM-1, OCT-2, and PAX-5 and staining variably for BCL-6, CD15, CD45, and CD79a. EBVMCU is most commonly associated with medication-induced (iatrogenic) immunosuppression (65%), advanced age-associated immunosenescence (27%), and primary (3%) and acquired (3%) immunodeficiencies. The median age for all EBVMCU cases is 68.5 (range, 16 -101) years. Of the 65 cases where medication-induced immunosuppression contributed to EBVMCU, 45 (69%) were in patients greater than 60 years-old. EBVMCU is a predominantly indolent disease reminiscent of post-transplant lymphoproliferative disorders in which conservative strategies are primarily employed with potential escalation to B-cell targeted therapy with or without cytotoxic chemotherapy, resection, and/or radiotherapy. Surveillance for EBVMCU should follow B-cell directed therapies and should be considered in the differential diagnosis in cases of suspected lymphoma relapse. Additionally, other LPDs, including lymphomas, should be monitored after resolution of EBVMCU. Due to overlap of the immunohistochemical profiles and risk factors associated with EBVMCU and other ulcerative LPDs of the oral and sinus cavities, nasopharynx, or GI tract, EBVMCU should be considered in the differential diagnosis to prevent under- or over-diagnosis and their associated potential repercussions. DisclosuresNo relevant conflicts of interest to declare.

A Decision Analysis of Follow-up and Treatment Algorithms for Nonsolid Pulmonary Nodules.

Purpose To evaluate management strategies and treatment options for patients with ground-glass nodules (GGNs) by using decision-analysis models. Materials and Methods A simulation was developed for 1 000 000 hypothetical patients with GGNs undergoing follow-up per the Lung Imaging Reporting and Data System (Lung-RADS) recommendations. The initial age range was 55-75 years (mean, 64 years). Nodules could grow and develop solid components over time. Clinically significant malignancy rates were calibrated to data from the National Lung Screening Trial. Annual versus 3-year-interval follow-up of Lung-RADS category 2 nodules was compared, and different treatment strategies were tested (stereotactic body radiation therapy, surgery, and no therapy). Results Overall, 2.3% (22 584 of 1 000 000) of nodules were clinically significant malignancies; 6.3% (62 559 of 1 000 000) of nodules were treated. Only 30% (18 668 of 62 559) of Lung-RADS category 4B or 4X nodules were clinically significant malignancies. The risk of clinically significant malignancy for persistent nonsolid nodules after baseline was higher than Lung-RADS estimates for categories 2 and 3 (3% vs <1% and 1%-2%, respectively). Overall survival (OS) at 10 years was 72% (527 827 of 737 306; 95% confidence interval [CI]: 71%, 72%) with annual follow-up and 71% (526 507 of 737 306; 95% CI: 71%, 72%) with 3-year-interval follow-up (P < .01). At 10 years, OS among patients whose nodules progressed to Lung-RADS category 4B or 4X was 80% after radiation therapy (49 945 of 62 559; 95% CI: 80%, 80%), 79% after surgery (49 139 of 62 559; 95% CI: 78%, 79%), and 74% after no therapy (46 512 of 62 559; 95% CI: 74%, 75%) (P < .01). Conclusion Simulation modeling suggests that the follow-up interval for evaluating ground-glass nodules can be increased from 1 year to 3 years with minimal change in outcomes. Stereotactic body radiation therapy demonstrated the best outcomes compared with lobectomy and with no therapy for nonsolid nodules. © RSNA, 2018 Online supplemental material is available for this article.

Autologous Bone Marrow Mesenchymal Stem Cells Improve the Quality and Stability of Vascularized Flap Surgery of Irradiated Skin in Pigs.

Cutaneous radiation syndrome has severe long‐term health consequences. Because it causes an unpredictable course of inflammatory waves, conventional surgical treatment is ineffective and often leads to a fibronecrotic process. Data about the long‐term stability of healed wounds, with neither inflammation nor resumption of fibrosis, are lacking. In this study, we investigated the effect of injections of local autologous bone marrow‐derived mesenchymal stromal cells (BM‐MSCs), combined with plastic surgery for skin necrosis, in a large‐animal model. Three months after irradiation overexposure to the rump, minipigs were divided into three groups: one group treated by simple excision of the necrotic tissue, the second by vascularized‐flap surgery, and the third by vascularized‐flap surgery and local autologous BM‐MSC injections. Three additional injections of the BM‐MSCs were performed weekly for 3 weeks. The quality of cutaneous wound healing was examined 1 year post‐treatment. The necrotic tissue excision induced a pathologic scar characterized by myofibroblasts, excessive collagen‐1 deposits, and inadequate vascular density. The vascularized‐flap surgery alone was accompanied by inadequate production of extracellular matrix (ECM) proteins (decorin, fibronectin); the low col1/col3 ratio, associated with persistent inflammatory nodules, and the loss of vascularization both attested to continued immaturity of the ECM. BM‐MSC therapy combined with vascularized‐flap surgery provided mature wound healing characterized by a col1/col3 ratio and decorin and fibronectin expression that were all similar to that of nonirradiated skin, with no inflammation, and vascular stability. In this preclinical model, vascularized flap surgery successfully and lastingly remodeled irradiated skin only when combined with BM‐MSC therapy. Stem Cells Translational Medicine 2018:569–582

A Middle-Aged Female with Multiple Brownish Plaques and Nodules: A Case Report of Multiple Cutaneous Reticulohistiocytomas

Non-Langerhans-Cell histiocytosis spectrum of disorders includes multicentric reticulohistiocytosis (MR) and multiple cutaneous reticulohistiocytomas (MCR), which are very uncommon granulomatous conditions. In reticulohistiocytoma, the most common sites of involvement are extensor surfaces, particularly the hands and forearms and the classical lesions are characterised by firm brown or yellow papules, nodules and plaques. As MCR is a very rare granulomatous condition, we report here a middle-aged female a case of MCR and we highlight the significance of considering reticulohistiocytoma in the differential diagnoses of chronic and persistent brownish plaques or nodules on skin.

Visual discrimination of screen-detected persistent from transient subsolid nodules: An observer study.

PurposeTo evaluate whether, and to which extent, experienced radiologists are able to visually correctly differentiate transient from persistent subsolid nodules from a single CT examination alone and to determine CT morphological features to make this differentiation.Materials and methodsWe selected 86 transient and 135 persistent subsolid nodules from the National Lung Screening Trial (NLST) database. Four experienced radiologists visually assessed a predefined list of morphological features and gave a final judgment on a continuous scale (0–100). To assess observer performance, area under the receiver operating characteristic (ROC) curve was calculated. Statistical differences of morphological features between transient and persistent lesions were calculated using Chi-square. Inter-observer agreement of morphological features was evaluated by percentage agreement.ResultsForty-nine lesions were excluded by at least 2 observers, leaving 172 lesions for analysis. On average observers were able to differentiate transient from persistent subsolid nodules ≥ 10 mm with an area under the curve of 0.75 (95% CI 0.67–0.82). Nodule type, lesion margin, presence of a well-defined border, and pleural retraction showed significant differences between transient and persistent lesions in two observers. Average pair-wise percentage agreement for these features was 81%, 64%, 47% and 89% respectively. Agreement for other morphological features varied from 53% to 95%.ConclusionThe visual capacity of experienced radiologists to differentiate persistent and transient subsolid nodules is moderate in subsolid nodules larger than 10 mm. Performance of the visual assessment of CT morphology alone is not sufficient to generally abandon a short-term follow-up for subsolid nodules.

Nodular scabies: a persistent nodular eruption

Nodular scabies is a hypersensitivity reaction to scabietic infestation characterized by persistent pruritic nodules that can remain even after treatment of the initial infestation. We present a demonstrative case of an infant who presented with nodular scabies.

Increased histopathological yield for granulomatosis with polyangiitis based on nasal endoscopy of suspected active lesions.

To present the results of an endoscopic and histopathologic evaluation of suspected nasal active granulomatosis with polyangiits (GPA) lesions, describe them as seen by the ENT specialist, and propose a guide for tissue sampling of the nasal cavity to improve the yield of confirmatory histology. Randomly selected patients seen from December 1997-October 2007 had a thorough endoscopic nasal evaluation, preceded by careful cleansing of the nasal cavity. Endoscopic lesions were described; sensitivities, specificities, and predictive values of the composites of endoscopic and histological activity were determined. Six lesions, some not previously described in detail, were observed: white submucosal nodules, mucosal swelling, polypoid nodules, vascular submucosal dilatations, bloody submucosal patches, and ulcers. Of these, polypoid nodules (PPV 100%), persistent white submucosal nodules (PPV 81%), and bloody submucosal patches (PPV 93%) had the better diagnostic performance with confirmed histological diagnosis. Careful nasal cavity preparation, observation, and description of the nasal mucosa can guide tissue sampling documenting active GPA. This can lead to a better histological yield when definitive proof of the disease is needed.

Semiquantative Visual Assessment of Sub-solid Pulmonary Nodules \u22663\u2009cm in Differentiation of Lung Adenocarcinoma Spectrum

We aimed to analyze CT features of persistent subsolid nodules (SSN) ≦3 cm diagnosed pathologically as adenocarcinoma spectrum to investigate whether parameters enable distinction between invasive pulmonary adenocarcinomas (IPAs) and pre-invasive lesions. A total of 129 patients with 141 SSNs confirmed with surgically pathologic proof were retrospectively reviewed. Of 141 SSNs, there were 57 pure ground-glass nodules (GGNs), 22 heterogeneous GGNs, and 62 part-solid nodules. SSN subclassification showed a significant linear trend with invasive degree of the adenocarcinoma spectrum (pure GGNs 7%; heterogeneous GGNs 36.4%; part-solid nodules 85.5%, P for trend <0.0001). For IPA detection in 141 SSNs, a solid part of ≧3 mm was the most specificity (sensitivity, 76.9%; specificity, 94.7%), followed by air-bronchogram sign (sensitivity, 53.8%; specificity, 89.5%), SSN subclassification (sensitivity, 81.5%; specificity, 88.2%), and a lesion size ≧12 mm (sensitivity, 84.6%; specificity, 76.3%). For IPA detection in 79 pure or heterogeneous GGNs, the heterogeneous GGN sign was the most useful finding, with most specificity (sensitivity, 66.7%; specificity, 79.1%), followed by CT attenuation (HU) of ≧−493 (sensitivity, 75%; specificity, 74.6%) and a lesion size ≧10 mm (sensitivity, 83.3%; specificity, 70.1%). In conclusion, this simple combined visual and semiquantitative analysis of CT features helps distinguish IPAs from pre-invasive lesions.

The impact of chemotherapy on persistent ground-glass nodules in patients with lung adenocarcinoma

To evaluate the response of persistent ground glass nodules (GGNs) in patients with lung adenocarcinoma treated with platinum-based chemotherapy on computed tomography (CT). We retrospectively studied patients with GGNs that met the following criteria: (I) GGNs found in patients with lung adenocarcinoma, which persist for more than 3 months; (II) patients treated with platinum-based (cisplatin or carboplatin) chemotherapy for at least 2 cycles; (III) ground glass proportion ¡Ý50%. For each patient, if more than two CTs satisfied the inclusion criteria, then the baseline and last CTs were used for analysis, defined as CT1 and CT2. A total of 91 persistent pulmonary GGNs in 51 patients fulfilled the inclusion criteria. We defined growth as a nodule ¡Ý2 mm increase in diameter or showing up a solid portion. GGN response to therapy was assessed and compared with the baseline CT. Differences in CT findings were analyzed using a paired t-test and Pearson ¦Ö2 test. Between 2010 and 2015, 25 of the 51 (49%) were male and 26 of the 51 (51%) were female. The average age at time of detection of a GGN was 63.8 (range, 36-84) years. Mean follow-up duration was 24.1¡À17.9 months. During the follow-up periods, on a per-nodule basis, 94.5% of GGNs (n=86) remained unchanged in size. Only 5.5% GGNs (n=5) in 5 patients increased in size. The nodules CT feature in each lung adenocarcinoma clinical stage show no difference. No significant difference was found in the size, attenuation, volume, and mass of GGN between baseline and post-treatment measurements, regardless of the type of chemotherapy (P>0.05). The clinical course of GGNs in patients with lung adenocarcinoma is predominantly indolent, and platinum-based chemotherapy may have no effect on the growth of persistent GGNs.

Persistent pruritic subcutaneous nodules and hypopigmentation in a young boy.

Persistent pruritic subcutaneous nodules and hypopigmentation in a young boy.

High-resolution Computed Tomography Features Distinguishing Benign and Malignant Lesions Manifesting as Persistent Solitary Subsolid Nodules

IntroductionWe retrospectively investigated the high-resolution computed tomography features that distinguish benign lesions (BLs) from malignant lesions (MLs) appearing as persistent solitary subsolid nodules (SSNs). Materials and MethodsIn 2015, the data from patients treated in our department with persistent solitary SSNs 5 to 30 mm in size were analyzed retrospectively. The demographic data and HRCT findings were analyzed and compared between those with BLs and MLs. ResultsOf the 1934 SSNs, 94 were BLs and 1840 were MLs. One half of the MLs (920 SSNs) were randomly selected and analyzed. The BLs were classified into 2 subgroups: 28 pure ground-glass nodules (pGGNs) and 66 part-solid nodules (PSNs). After matching in each group, 56 pGGNs and 132 PSNs in the ML group were selected. In the pGGN subgroup, multivariate analysis found that a well-defined border (odds ratio [OR], 4.320; 95% confidence interval [CI], 1.534-12.168; P = .006; area under the curve, 0.705; 95% CI, 0.583-0.828; P = .002) and a higher average CT value (OR, 1.007; 95% CI, 1.001-1.013; P = .026; area under the curve, 0.715; 95% CI, 0.599-0.831; P = .001) favored the diagnosis of malignancy. In the PSN subgroup, multivariate analysis revealed that a larger size (OR, 1.084; 95% CI, 1.015-1.158; P = .016), a well-defined border (OR, 3.447; 95% CI, 1.675-7.094; P = .001), and a spiculated margin (OR, 2.735; 95% CI, 1.359-5.504; P = .005) favored the diagnosis of malignancy. ConclusionIn pGGNs, a well-defined lesion border and a larger average CT value can be valuable discriminators to distinguish between MLs and BLs. In PSNs, a larger size, well-defined border, and spiculated margin had greater predictive value for malignancy.

Surgical Treatment of Small Pulmonary Nodules Under Video-assisted Thoracoscopy (A Report of 129 Cases)

背景与目的影像技术的发展导致肺部微小结节尤其是肺磨玻璃结节（ground-glass opacity, GGO）检出逐年增多，但术前定性困难。本研究探讨肺部微小结节的临床诊断及微创手术治疗的必要性和可行性、病理诊断，微创切除及淋巴结切除的手术方式。方法对2013年12月-2016年11月接受电视胸腔镜手术（video-assisted thoracic surgery, VATS）治疗并有明确病理诊断的共129例患者的临床资料回顾性分析。所有患者术前行薄层计算机断层扫描（computed tomography, CT）扫描，其中21个微小结节术前行CT引导下Hook-wire定位，并根据病理性质及患者身体状况采用不同手术方式。结果共129个微小结节，实性结节（solid pulmonary nodule, SPN）37个，恶性比例是24.3%（9/37），术后病理结果为：肺原发性鳞状细胞癌3个，浸润性腺癌（invasive adenocarcioma, IA）3个，转移癌2个，小细胞肺癌（small cell lung cancer, SCLC）1个，错构瘤16个，其他炎症等良性病变12个；49个混合性GGO（mixed ground-glass opacity, mGGO）的恶性比例是63.3%（31/49），术后病理结果为：IA 19个，微浸润腺癌（micro invasive adenocarcioma, MIA）6个，原位腺癌（adenocarcioma in situ, AIS）4个，非典型性腺瘤样增生（atipical adenomatous hyperplasia, AAH）1个，SCLC 1个，炎症等良性病变18个；43个纯GGO（pure ground-glass opacity, pGGO）的恶性比例是86.0%（37/43），术后病理结果为：AIS 19个，MIA 6个，IA 6个，AAH 6个，炎症等良性病变6个；GGO总的恶性比例是73.9%（68/92）。52个良性病变均采用VATS肺楔形切除；原发性非小细胞肺癌（non-small cell lung cancer, NSCLC）共73例，VATS肺叶切除和淋巴结清扫33例，VATS肺楔形切除和选择性淋巴结切除6例，VATS肺段切除和选择性淋巴结切除6例，VATS肺楔形切除28例；2个转移癌和2个SCLC，采用VATS肺楔形切除术。另有6例患者术中冰冻病理存在误差，其中2例选择二次手术行肺叶切除和淋巴结清扫。45例有淋巴结病理结果NSCLC只有两例以SPN为表现的IA出现纵隔淋巴结转移，其余均未出现淋巴结转移。术后随访1个月-35个月，平均（15.1±10.2）个月，无复发及转移。结论肺部微小结节尤其是GGO，是恶性病灶的概率大，应积极外科处理；围手术期应与患者及家属充分告知冰冻病理结果存在误差可能性，避免医疗纠纷。

MA01.06 Long-Term Follow-Up of Small Pulmonary Ground-Glass Nodules Stable for 3 Years: Proper Follow-Up Period and Risk Factors for Subsequent Growth

It is uncertain how long persistent and stable ground-glass nodules (GGNs) should be followed although a minimum of 3 years is suggested. Here, we aimed to evaluate the proportion of GGNs showing subsequent growth after initial 3 years among GGNs that had been stable during the initial 3 years, and to determine clinical and radiologic factors associated with subsequent growth. We retrospectively analyzed patients who underwent further computed tomography after the initial 3-year follow-up period showing a persistent and stable GGN (at least 5-year follow-up from initial CT). Between May 2003 and June 2015, 453 GGNs (438 pure GGNs and 15 part-solid GGNs) were found in 218 patients. Of the 218 patients, 14 patients had 15 GGNs showing subsequent growth after the initial 3 years during the median follow-up period of 6.4 years. For the person-based analysis, frequency of subsequent growth of GGNs that had been stable during initial 3 years was 6.7% (14/218). For the nodule-based analysis, the frequency was 3.3% (15/453). In a multivariate analysis, age ≥ 65 years (odds ratio [OR], 5.51; p = 0.012), history of lung cancer (OR, 6.44; p = 0.006), initial size ≥ 8 mm (OR, 5.74; p = 0.008), presence of a solid component (OR, 16.58; p = 0.009), and an air bronchogram (OR, 5.83; p = 0.015) were independent risk factors for subsequent GGN growth.Between May 2003 and June 2015, 453 GGNs (438 pure GGNs and 15 part-solid GGNs) were found in 218 patients. Of the 218 patients, 14 patients had 15 GGNs showing subsequent growth after the initial 3 years during the median follow-up period of 6.4 years. For the person-based analysis, frequency of subsequent growth of GGNs that had been stable during initial 3 years was 6.7% (14/218). For the nodule-based analysis, the frequency was 3.3% (15/453). In a multivariate analysis, age ≥ 65 years (odds ratio [OR], 5.51; p = 0.012), history of lung cancer (OR, 6.44; p = 0.006), initial size ≥ 8 mm (OR, 5.74; p = 0.008), presence of a solid component (OR, 16.58; p = 0.009), and an air bronchogram (OR, 5.83; p = 0.015) were independent risk factors for subsequent GGN growth. For the individuals with GGNs having risk factors described above, the longer follow-up period is required to confirm subsequent GGN growth.

Ptgr1 expression is regulated by NRF2 in rat hepatocarcinogenesis and promotes cell proliferation and resistance to oxidative stress

Prostaglandin reductase-1 (Ptgr1) is an alkenal/one oxidoreductase that is involved in the catabolism of eicosanoids and lipid peroxidation such as 4-hydroxynonenal (4-HNE). Recently, we reported that Ptgr1 is overexpressed in human clinical and experimentally induced samples of hepatocellular carcinoma (HCC). However, how the expression of this gene is regulated and its role in carcinogenesis are not yet known. Here, we studied parameters associated with antioxidant responses and the mechanisms underlying the induction of Ptgr1 expression by the activation of Nuclear Factor (erythroid-derived-2)-like-2 (NRF2). For these experiments, we used two protocols of induced hepatocarcinogenesis in rats. Furthermore, we determined the effect of PTGR1 on cell proliferation and resistance to oxidative stress in cell cultures of the epithelial liver cell line, C9. Ptgr1 was overexpressed during the early phase in altered hepatocyte foci, and this high level of expression was maintained in persistent nodules until tumors developed. Ptgr1 expression was regulated by NRF2, which bound to an antioxidant response element at −653bp in the rat Ptgr1 gene. The activation of NRF2 induced the activation of an antioxidant response that included effects on proteins such as glutamate-cysteine ligase, catalytic subunit, NAD(P)H dehydrogenase quinone-1 (NQO1) and glutathione-S-transferase-P (GSTP1). These effects may have produced a reduced status that was associated with a high proliferation rate in experimental tumors. Indeed, when Ptgr1 was stably expressed, we observed a reduction in the time required for proliferation and a protective effect against hydrogen peroxide- and 4-HNE-induced cell death. These data were consistent with data showing colocalization between PTGR1 and 4-HNE protein adducts in liver nodules. These findings suggest that Ptgr1 and antioxidant responses act as a metabolic adaptation and could contribute to proliferation and cell-death evasion in liver tumor cells. Furthermore, these data indicate that Ptgr1 could be used to design early diagnostic tools or targeted therapies for HCC.

Refractory Isoniazid-Resistant Miliary TB or Something More?

SESSION TITLE: Fellow Case Report Poster - Chest Infections II SESSION TYPE: Affiliate Case Report Poster PRESENTED ON: Tuesday, October 25, 2016 at 01:30 PM - 02:30 PM INTRODUCTION: Miliary nodular pattern is defined by diffuse and symmetrically distributed micronodules (<3mm) within the lungs, and often pedagogically associated with hematogenously disseminated tuberculosis (TB). However, the differential is broader. CASE PRESENTATION: 57-year-old Chinese man, former smoker, with chronic HBV, history of incompletely treated pulmonary TB in 1996 presented with progressive dry cough, dyspnea, weight loss, fevers, chills, and night sweats. Chest x-ray showed bilateral diffuse nodularity, and sputum culture grew Mycobacterium tuberculosis. He was started on IRPE for miliary TB. Course was complicated by asymptomatic liver transaminitis requiring treatment discontinuation after 3 weeks. IRE/Levofloxacin were substituted. He was admitted to the hospital for worsening dyspnea and cough with concern for possible resistance. The original sputum culture revealed INH resistance but susceptibility to other first line agents, and he was discharged on RPE/Moxifloxacin. He was readmitted for medication noncompliance and new hypoxia. CT chest showed persistent diffuse pulmonary nodules, biapical scarring and emphysema. Liver biopsy showed concern for drug-induced versus autoimmune hepatitis, and he was started on prednisone and tenofovir, as well as a liver-sparing regimen of amikacin, ethambutol and moxifloxacin. He continued to worsen. Open lung biopsy of two different lobes revealed lung adenocarcinoma in both surgical specimens. DISCUSSION: The differential diagnosis of miliary pattern on chest imaging includes TB, metastatic disease, fungal infections, sarcoidosis, and pneumoconioses. Unlike miliary TB (micronodules ranging from 1 to 3mm), miliary metastatic lesions may have variable sizes (up to 1cm). Although this case had a number of reasons to anchor on a diagnosis of miliary TB, it is important to keep a broader differential for miliary pattern, and re-think the diagnosis when patients are not improving on appropriate therapy. CONCLUSIONS: We report a case of advanced stage lung adenocarcinoma appearing in a miliary nodular pattern in the setting of concurrent tuberculosis. Patients with diffuse miliary nodules, especially for those whose symptoms do not improve after tuberculosis treatment, should be evaluated for other diagnoses, such as cancer. Reference #1: Oikonomou, A et al. Mimics in chest disease: interstitial opacities. Insights Imaging. 2013;4:9-27. DISCLOSURE: The following authors have nothing to disclose: Kathleen Doo, Deepak Pradhan No Product/Research Disclosure Information