Artificial Intelligence Recognition Model Using Liquid-Based Cytology Images to Discriminate Malignancy and Histological Types of Non-Small-Cell Lung Cancer.

INTRODUCTION: Artificial intelligence image recognition has applications in clinical practice. The purpose of this study was to develop an automated image classification model for lung cancer cytology using a deep learning convolutional neural network (DCNN). METHODS: Liquid-based cytology samples from 8 normal parenchymal (N), 22 adenocarcinoma (ADC), and 15 squamous cell carcinoma (SQCC) surgical specimens were prepared, and 45 Papanicolaou-stained slides were scanned using whole-slide imaging. The final dataset of 9,141 patches consisted of 2,737 N, 4,756 ADC, and 1,648 SQCC samples. Densenet-121 was used as the DCNN to classify N versus malignant (ADC+SQCC) and ADC versus SQCC images. AdamW optimizer and 5-fold cross-validation were used in the training. RESULTS: For malignancy prediction, the sensitivity, specificity, and accuracy were 0.97, 0.85, and 0.94, respectively, in the patch-level classification, and 0.92, 0.88, and 0.91, respectively, in the case-level classification. For SQCC prediction, the sensitivity, specificity, and accuracy were 0.86, 0.91, and 0.90, respectively, in the patch-level classification and 0.73, 0.82, and 0.78, respectively, in the case-level classification. CONCLUSION: The DCNN model performed excellently in predicting malignancy and histological types of lung cancer. This model may be useful for predicting cytopathological diagnosis in clinical situations by reinforcing training.

Modified open-thoracotomy-view approach in robotic-assisted thoracoscopic lung resection.

Robotic-assisted thoracoscopic surgery (RATS) is widely performed in thoracic surgery. The open-thoracotomy-view approach (OTVA) is one approach in RATS lung resection. OTVA is a good surgical approach that provides the same field of view as that with open thoracotomy and allows active participation of the assistant. However, the OTVA has certain limitations compared with other approaches, such as difficulty placing a robotic arm in the lower intercostal space, the assistant port is positioned further from the hilum, and CO2 insufflation is required. We have made some modifications to the OTVA by placing one of the robotic arms in the lower intercostal space, which enhances the operability for the surgeon without the need for CO2 insufflation. Additionally, by positioning the assistant port between the robotic arms, the assistant is closer to the hilum, and there is no requirement for a closed port owing to the absence of CO2 insufflation, resulting in improved performance by the assistant. Therefore, for the assistant to perform well, it is necessary to make modifications to the OTVA to widen the typically narrow space between the robotic arms. We performed lung resection using our modified 4-port 3-arm OTVA method in 20 patients from June 2022 to July 2023. Although we have not used our modified OTVA in a large number of cases, we have not observed critical issues to date. In this report, we introduce our modified OTVA as an option in RATS for lung resection.

Treatment Patterns and Postoperative Activities of Daily Living in Patients with Non-small Cell Lung Cancer: A Retrospective Study Using Nationwide Health Services Utilization Data in Japan.

BACKGROUND: The number of older patients with cancer has been increasing. This study aimed to determine the proportion of postoperative decline in activities of daily living (ADL), hospital mortality rate, home healthcare services use, and adjuvant chemotherapy treatment patterns of patients with early-stage non-small cell lung cancer (NSCLC) across age groups. METHODS: We analyzed health service utilization data of patients aged ≥ 40 years diagnosed with clinical stage I or II NSCLC in 2015 who underwent thoracoscopy or thoracotomy. The Barthel index was used to determine the proportions of patients aged 40-64, 65-74, ≥ 75 years who experienced a decline in the ADL of ≥ 10 points at postoperative discharge compared to the ADL at admission. RESULTS: Overall, 19,780 patients were analyzed. The proportion of patients with ADL decline slightly increased with increasing age: 1.1%, 1.6%, and 3.5% after thoracoscopic surgery, and 1.4%, 2.8%, and 4.8% after thoracotomy among those aged 40-64, 65-74, and ≥ 75 years, respectively. The hospital mortality rate and proportion of home healthcare services use was fewer than 10 cases, or < 2%. The unexpected readmission rate was slightly higher among those aged ≥ 75 years (3.7% for thoracoscopic surgery, 4.7% for thoracotomy) than among those aged 40-64 years (1.8% for thoracoscopic surgery, 2.5% for thoracotomy). CONCLUSION: The difference in the proportion of patients with ADL decline between those aged 40-64 and ≥ 75 years was approximately 3%. This study provides practical information for clinicians involved in the care of older patients who undergo thoracic surgery.

Cytological characteristics of histological types of lung cancer by cytomorphometric and flow cytometric analyses using liquid-based cytology materials.

BACKGROUND: Distinguishing the histological types of lung cancer is essential for determining treatment strategies in clinical practice. In this study, cytomorphological characteristics and proliferative activities were compared among histological types of lung cancer by cytomorphometric and flow cytometric analyses using liquid-based cytology (LBC) samples. METHODS: Scraped LBC samples from 73 surgically resected specimens were collected between August 2018 and November 2019. Papanicolaou-stained and paired Ki-67-stained slides were used for cytomorphometric analyses. Another sample for each case was analyzed using a flow cytometric system (LC-1000). The cell proliferation index (CPIx) was calculated to evaluate proliferative activity. RESULTS: In total, 73 cases, including cases of adenocarcinoma (n = 53), squamous cell carcinoma (n = 14), small cell carcinoma (n = 1), large cell neuroendocrine carcinoma (NEC; n = 3), and pleomorphic carcinoma (n = 2) were evaluated. Small cell carcinoma and large cell NEC were categorized into a single group, NEC. The adenocarcinoma group tended to have a larger nuclear area and longer perimeter than other histological types. The NEC group had a considerably higher Ki-67 labeling index and significantly higher CPIx than other histological types (p = .030). A significant positive correlation was observed between the Ki-67 labeling index and CPIx for all cases (r = 0.362, p = .002). CONCLUSION: The Ki-67 labeling index and flow cytometric analyses focus on proliferative activity for the distinction of histological types of lung cancer, thereby guiding clinical decision-making.

An innovative oral management procedure to reduce postoperative complications.

Background: Numerous studies have shown that improving oral hygiene contributes to a reduction in the risk of postoperative complications in patients with head and neck cancer, cardiac disease, and esophageal cancer. However, the beneficial standard for oral management procedures during the perioperative period has not yet been established. Therefore, our aim was to determine whether or not their innovative oral management intervention contributed to a reduction in postoperative complications in lung cancer. Methods: We performed a retrospective analysis of medical records of patients who underwent lung cancer surgery with lobectomy and pneumonectomy at Kyorin University Hospital. Patients were divided into 2 groups: a perioperative oral management intervention group that underwent lung cancer surgery from April 2016 to March 2018 (n = 164), and a control group without oral management that underwent surgery from April 2014 to March 2016 (n = 199). In particular, our oral management procedure emphasized oral mucosa stimulation to induce saliva discharge as in gum chewing, rather than simply using teeth brushing to reduce oral microbiome. Therefore, our oral management procedure is different from traditional oral care. Results: This study demonstrated that our oral management practice was associated with a decline in the occurrence of postoperative pneumonia (odds ratio, 0.184; 95% CI, 0.042-0.571; P = .009), postoperative hospital stay duration (ß coefficient, -4.272; 95% CI, -6.390 to -2.155; P < .001) and Clavian-Dindo classification grade II or above (odds ratio, 0.503; 95% CI, 0.298-0.835; P = .009). Conclusions: We propose an innovative new strategy using their unique oral management procedure to reduce postoperative complications resulting from pulmonary resection.

Bilateral recurrent laryngeal nerve paralysis diagnosed using dynamic digital radiography during the COVID-19 pandemic.

Dynamic digital radiography (DDR) is a motion-detecting technique with high temporal resolution. Flexible laryngoscopy is a common modality for the observation of the larynx; however, it generates aerosol. DDR is an easy and less risky screening test for the diagnosis of recurrent laryngeal nerve paralysis during the COVID-19 pandemic.

Cytomorphometric and flow cytometric analyses using liquid-based cytology materials in subtypes of lung adenocarcinoma.

BACKGROUND: The histological classifications of invasive lung adenocarcinoma subtypes are considered to predict patient prognosis after surgical treatment. The objectives of this study were to evaluate cytomorphological characteristics and proliferative activities among the histological predominant patterns by performing cytomorphometric and flow cytometric analyses using liquid-based cytology materials. METHODS: Cytological samples fixed by liquid-based cytology preservatives from 53 surgically-resected lung adenocarcinoma specimens were obtained between August 2018 and November 2019. The Papanicolaou-stained and paired Ki-67-stained slides were analyzed for calculating nuclear morphology (nuclear area, nuclear perimeter and nuclear circularity) and Ki-67 labeling index using software. The cell proliferation index (CPIx) was calculated and cellular information including cell cycle stage of tumor cells was obtained by flow cytometry. RESULTS: The 53 cases included papillary (n = 29), acinar (n = 8), lepidic (n = 5), and solid (n = 4) subtypes, and invasive mucinous adenocarcinoma (n = 7) were also included. In the lepidic pattern, nuclear area (79.6 ± 28.8 µm2 ) and perimeter (34.1 ± 6.1 µm) were relatively larger and longer than those of the other predominant patterns. The Ki-67 labeling index of the solid pattern (27.9 ± 12.5%) was highest compared with those of other predominant patterns. There were statistically significant differences in the lepidic versus solid patterns and the papillary versus solid patterns (p = .013 and p = .039, respectively). The calculated mean CPIx of the lepidic and the acinar patterns were approximately two-fold higher than those of the other predominant patterns. CONCLUSION: By revealing the differences of cytomorphological characteristics, these methodologies might be used for diagnosing cytopathological materials using digital cytopathology.

Optimal Preservations of Cytological Materials Using Liquid-Based Cytology Fixatives for Next-Generation Sequencing Analysis.

INTRODUCTION: Molecular targeted therapies have been established for various diseases, including cancers, and there is an increasing need for molecular testing on cytology specimens. The aim of this study was to determine the optimal preservation methods of liquid-based cytology (LBC) materials for molecular testing. METHODS: Cytological samples from 35 surgical resected non-small cell lung carcinoma specimens were obtained between June 2016 and June 2021. The samples were fixed in CytoRich™ red Preservative and stored at 4°C. One week later, three tubes were prepared from each specimen sample and divided into the following groups: the SurePath™ group (continued storage at 4°C), Frozen (Fr) group (stored at -80°C after centrifugation), and LBC-Cell Block (LBC-CB) group (generation of paraffin-embedded CB and storage at 4°C). Samples from 5 patients were used for the time course analysis, and we performed evaluations on these samples at 1, 3, 6, 12, 24, and 36 months. The concentrations and purities of extracted DNA and RNA were measured. The double-stranded DNA (dsDNA) and RNA concentrations were also measured by a fluorometer. The DNA and RNA integrities were quantified by the DNA and RNA integrity number. RESULTS: Evaluation of samples was performed at baseline and the six timepoints. In the LBC-CB group, DNA and dsDNA concentrations were higher rather than those in the other groups. The RNA concentration of the LBC-CB group was relatively high compared with those of the other groups at the 36-month timepoint. The Fr group maintained higher DNA quality compared with the other groups over 3 years. The LBC-CB group maintained a higher RNA quality than the other groups until 24 months. CONCLUSION: LBC-CB preparation is an effective method to maintain DNA/RNA quality and quantity in long-duration preservation for eventual molecular testing. Therefore, LBC-CB may have applications on preanalytical stage for molecular genomic testing such as next-generation sequencing.

Clinical impact of perioperative atrial fibrillation on long-term recurrence of malignancy.

Perioperative complications have been reported to be associated with a lower incidence of cancer-free survival. Perioperative atrial fibrillation (POAF) is one of occasionally observed complications in patients with malignancies who undergo noncardiac surgeries. However, the long-term clinical impact of POAF on those with malignancies have remained unknown. This was a prospective, single-center, observational study. Patients who underwent noncardiac surgeries for definitive malignancies between 2014 and 2017 were included. The primary and secondary endpoints were 3-year recurrence of malignancies and cancer death, respectively. The present study included consecutive 752 patients (mean age, 68 ± 11 years; males, 62%), and POAF was observed in 77 patients. The follow-up duration was 1037 (interquartile range, 699-1408) days. The 3-year recurrence of malignancies was observed in 239 (32%) patients (POAF, 32 [42%]; non-POAF, 207 [31%]) and 3-year mortality was 130 patients (17%). Cardiac, noncardiac, and cancer deaths were observed in 4 (0.5%), 126 (17%), and 111 (15%) patients, respectively. Multivariate Cox regression analysis demonstrated that POAF was associated with 3-year recurrence of malignancies (hazard ratio [HR], 1.70; 95% confidence interval [CI], 1.15-2.52). Landmark analysis demonstrated that POAF tended to be correlated with the incidence of 3-year cancer death (HR, 1.79; 95% CI, 0.96-3.31). In conclusion, POAF is associated with the subsequent recurrence of malignancies. The association of arrhythmia with cancer death may be revealed under longer follow-up durations.Clinical Trial Registration: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000018270 . UMIN ID: UMIN000016146.

Notably small bronchial carcinoid accompanied by peripheral squamous cell carcinoma.

Our report presents the smallest bronchial carcinoid thus far associated with peripheral squamous cell carcinoma. A 79-year-old Japanese man presented with an abnormal shadow on chest radiography. Chest computed tomography revealed an ill-defined nodule at the left S9a area without lymph node involvement. At the time of bronchoscopy, a nodule of ~1 mm in diameter with a smooth surface was observed at the orifice of the left B8. Left lower lobectomy was performed. Pathologically, the S9a tumour was keratinizing squamous cell carcinoma with surgical stage IA3, and the left B8 tumour was a typical bronchial carcinoid. The patient was alive without recurrence 2 years after the surgery. Cases of combined carcinoid and lung cancer are rare. It may be possible to identify bronchial carcinoids early by careful observation of the bronchi during bronchoscopy for peripheral neoplastic lesions.

STAT3 activation in thymic epithelial tumors: correlation with cyclin D1, JAK3, and clinical behavior.

OBJECTIVES: Thymic epithelial tumors are the most common adult mediastinal tumors; however, their growth mechanism remains relatively unknown. Among the JAK/STAT pathway-related proteins, which control various intracellular events, STAT3 is deeply involved in cell proliferation. Constitutive activation of STAT3 and the resulting overexpression of cyclin D1 have been confirmed in various tumors, but have not been thoroughly investigated in thymic epithelial tumors. In this study, we immunohistochemically examined STAT3 activation, cyclin D1 expression, and JAK3 activation in thymic epithelial tumors and statistically analyzed their correlation with clinicopathological features. METHODS: Formalin-fixed paraffin-embedded specimens of 94 thymic epithelial tumors surgically resected at Kyorin University Hospital between 2005 and 2018 were included in this study. pSTAT3, cyclin D1, and pJAK3 were immunohistochemically examined, and the correlation with histology, Masaoka stage, and survival time was statistically analyzed. RESULTS: Cyclin D1 was found to be significantly overexpressed in the STAT3-activated group. This phenomenon was associated with histology and Masaoka stage. JAK3 was also activated in thymic epithelial tumors; however, JAK3 and STAT3 activation were not always correlated. Using survival time analysis, the STAT3-activated group, cyclin D1-expressed group, and JAK3-activated group had significantly lower progression-free survival times than those for both the non-activated and non-expressed groups. CONCLUSIONS: STAT3 activation may promote cyclin D1 overexpression in thymic epithelial tumors, and intracellular signaling pathways other than JAK3 may be involved in STAT3 activation. STAT3 activation, cyclin D1 overexpression, and JAK3 activation are biomarker candidates that indicate clinically poor prognosis.

Solitary fibrous tumour of the pleura arising in a pulmonary cavity.

Solitary fibrous tumour of the pleura (SFTP) arising in a cavity is extremely rare. A 66-year-old Japanese male presented with an abnormal shadow on his chest X-ray. Chest computed tomography showed a cavity of approximately 18 mm in diameter between the upper and lower lobes that contained a solid nodule within. Under the thoracoscope, the peduncle cystic tumour was removed with sufficient surgical margin. Macroscopically, a tumour of about 15 mm in diameter arose in the cystic cavity. Immunohistochemical stains were positive for CD34, bcl-2, and signal transduction and activator of transcription 6 (STAT6) but negative for smooth muscle actin (SMA), desmin, and epithelial membrane antigen (EMA), and a diagnosis of SFTP was made. The patient remains well without recurrence or any complications at two and a half years after the operation. SFTP should be considered when a tumour arises in a cavity existing in an interlobar space. It is important to determine whether the tumour is pedunculated or sessile during surgery and to perform the appropriate surgical procedure.

Subtyping and EGFR mutation testing from blocks of cytological materials, based on liquid-based cytology for lung cancer at bronchoscopic examinations.

BACKGROUND: Liquid-based cytology (LBC) allows immunohistochemistry (IHC), fluorescence in situ hybridization, and molecular testing to be performed in fixed cell materials. We examined the feasibility of subtyping and EGFR mutation testing of bronchoscopic samples from patients with lung cancer using cell blocks (CB) based on LBC fixation (LBC-CB). METHODS: We included 35 consecutive patients with peripheral lung nodules who underwent endobronchial ultrasonography with a guide sheath in our hospital. Thirty of these patients were diagnosed with lung cancer by obtaining cytological samples. Cytological subtyping was performed with IHC using LBC-CB, and the Cobas EGFR Mutation Test ver. 2 was performed using extracted genomic DNA from the LBC-CB, formalin-fixed paraffin-embedded (FFPE) tissue, and matched plasma. RESULTS: Of the 30 cases, 25 were classified cytomorphologically as adenocarcinoma (ADC, n = 17) and squamous-cell carcinoma (SQCC, n = 8). The remaining five cases were classified by IHC as favor ADC (n = 3) and favor SQCC (n = 2) according to the WHO criteria. In the final ADC group (n = 20), EGFR mutations on the LBC-CB were identified in eight cases (40%; 1 exon 19 deletion, 6 L858R, and 1 L861Q). Mutations in FFPE samples were identified in seven cases (35%) at the same site in each case. Plasma EGFR mutations were identified in four cases (20%) at the same site. The CB detection rate was higher than for FFPE and plasma. CONCLUSION: LBC-CB is suitable for subtyping and EGFR mutation testing in lung cancers.

An enlarged azygos vein traversing an azygos lobe reveals a connection between the inferior vena cava and azygos vein.

We report a rare case where the inferior vena cava connected to the azygos vein, a diagnosis triggered by observation of an enlarged azygos vein traversing an azygos fissure. A 16-year-old male patient presented with an abnormal shadow on chest X-ray. Chest computed tomography showed an enlarged azygos vein connecting to the inferior vena cava, with no other connection to the atrium. There were no associated malformations. The patient remains alive and has been asymptomatic for the past two years. If the flow through the connection was to be interrupted during the course of thoracic or abdominal surgery, this would invariably prove to be fatal. In addition, this abnormality prevents direct access to the atrium on attempting interventional radiology via the inferior vena cava, for example, during ablation. When an azygos lobe is identified on a chest X-ray, a prominent solid structure traversing it may represent an engorged azygos vein with an anomalous course.

A rare post-lobectomy complication of right-to-left shunt via foramen ovale.

BACKGROUND: Various complications can cause hypoxemia after pulmonary resection for lung cancer, but intracardiac shunt that becomes symptomatic and causes severe hypoxemia postoperatively is very rare. We report a case that presented platypnea-orthodeoxia syndrome (POS) due to right-to-left shunt via patent foramen ovale (PFO). CASE: A 71-year-old man with a lung cancer in the left upper lobe was referred to our hospital. Left upper lobectomy was performed. Dyspnea developed postoperatively, which was worsened by sitting or standing and relieved in a recumbent position. Contrast transesophageal echocardiogram (TEE) and right intracardiac catheterization revealed a right-to-left shunt via PFO. Open-heart closure of PFO was performed and the patient was free from POS. CONCLUSIONS: Postoperative intracardiac shunt via PFO can cause severe hypoxemia after lung resection. POS suggests the possibility of intracardiac shunt and careful observation is needed.

Perioperative Atrial Fibrillation in Noncardiac Surgeries for Malignancies and One-Year Recurrence.

BACKGROUND: Perioperative atrial fibrillation (POAF) in noncardiac surgeries is common. However, it is unclear whether such atrial fibrillation (AF) recurs in the long term. METHODS: This study was a prospective, single-center, observational study that included patients who underwent noncardiac surgeries for malignancies. Patients were followed up for 1 year to evaluate the incidence of AF, ischemic stroke, and mortality. An event-triggered recorder was used in patients with POAF. The incidences were compared according to the presence of POAF. RESULTS: Of 752 consecutive patients, 77 (10.2%) developed POAF and wore an event recorder for 19 (12-30) days. AF and ischemic stroke at 1 year were observed in 24 patients (31.1%) and 2 patients (2.6%) with POAF and 4 patients (0.6%) and 3 patients (0.4%) without POAF, respectively. Of the 24 patients with POAF and AF recurrence, 22 (92%) were asymptomatic. Anticoagulation was prescribed in 67 patients (87%) with POAF. Multivariate Cox regression analysis demonstrated that a higher AF recurrence rate in patients with POAF was associated with hypertension (hazard ratio, 2.79; 95% confidence interval, 1.06-7.38) and serum creatinine level (hazard ratio for 20 µmol/L increase, 2.32; 95% confidence interval, 1.16-4.62). CONCLUSIONS: AF recurs in approximately 30% of patients with POAF with malignancy in the subsequent year; most recurrences are asymptomatic.

Incidence and complications of perioperative atrial fibrillation after non-cardiac surgery for malignancy.

BACKGROUND: Perioperative atrial fibrillation (POAF) is one of the common arrhythmias in the setting of non-cardiac surgeries for malignancy. As POAF may cause subsequent adverse events, it is important to confirm its characteristics and risk factors. MATERIALS AND METHODS: The prospective cohort study of surveillance for perioperative atrial fibrillation recurrence (PREDICT AF RECURRENCE) is an ongoing prospective, single-center, observational study that aims to illustrate the clinical impact of POAF in major non-cardiac surgery for malignancy. Patients who planned to undergo non-cardiac surgery for definitive/suspected malignancy were registered. Those with a history of AF and atrial flutter were excluded. Any 30-day complications included acute myocardial infarction, congestive heart failure, bleeding, thrombosis, any infection, and acute kidney injury. The primary endpoint was an incidence of POAF. RESULTS: The present study included 799 patients (age, 68 ± 11; male, 62%). Of these, 80 patients (10.0%) developed POAF. Notably, 66 patients (83%) had no symptoms. Any 30-day complications occurred in 180 patients (23%) (with POAF: 34 (43%); without POAF: 146 (20%); p < 0.001). POAF in 17 patients (50%) was preceded by the development of complications. No patient developed cardiogenic shock and/or acute heart failure. The association between 30-day complications and POAF development were analyzed using the multivariate adjusted model (odds ratio: 2.84; 95% confidence interval: 1.74-4.62; p < 0.001). CONCLUSION: Ten percent of patients who underwent non-cardiac surgery for malignancy developed POAF, which was strongly associated with perioperative complications. As a majority were asymptomatic, careful observation using electrocardiography monitoring is important to avoid oversights. CLINICAL TRIAL REGISTRATION: UMIN ID: UMIN000016146.

Genotyping and cytomorphological subtyping of lung adenocarcinoma based on liquid-based cytology.

BACKGROUND: Liquid-based cytology (LBC) samples allow immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and molecular testing of nucleic acids to be performed in the remaining fixed cells. The current study aimed to examine the relationship between gene mutational status and cytomorphological features in primary lung adenocarcinoma (ADC) using LBC materials. METHODS: Forty consecutive patients with primary lung ADC underwent surgical resection in our hospital. Cytological material was obtained by scraping the cut-surface of the lesion, and samples were fixed and stored as LBC materials using CytoRich Red. Epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations, anaplastic lymphoma kinase (ALK), and c-ros oncogene 1 (ROS1) gene rearrangements were detected, and cytomorphological studies were performed. RESULTS: Twenty cases (50%) were positive for EGFR mutation and four (10%) were positive for KRAS mutation. ALK gene rearrangement was identified in one case (2.5%) by IHC and FISH, and ROS1 gene rearrangement was identified in one case (2.5%) by IHC and real-time polymerase chain reaction. The KRAS-positive group included higher proportions of cases with an inflammatory background (100%), predominantly papillary architecture (75%), and papillary-type ADC pattern (75%) compared with the EGFR-positive group and the other group, which included ALK and ROS1 gene rearrangements. CONCLUSIONS: LBC material is suitable for use in molecular testing. Differences in major gene aberrations detected by this method might predict specific cytomorphological features.

A severe combined immunodeficiency disease mouse model of human adenocarcinoma with lepidic-predominant growth.

Severe combined immunodeficiency disease (SCID) mice with human lepidic adenocarcinoma were established by the intrabronchial implantation of fresh surgically resected specimens. Human pulmonary adenocarcinoma tissue from 16 different cases was transplanted into SCID mice, and SCID mouse tumors were established from four of these cases (25%). Among the four tumors, the tumor cells of two SCID mice showed replacement lepidic growth of mouse alveolar structures accompanied by multiple intrapulmonary lesions. Human lung carcinoma cell lines showing lepidic growth are rare and the xenograft models using the SCID mouse model developed in the current study will be useful for analyzing the growth and/or progression patterns and clinical behavior of lepidic adenocarcinoma, the major histological subtype of human carcinoma of the lung.