Radiologically guided percutaneous core needle biopsy of the spleen: a reliable and safe diagnostic procedure for neoplastic and reactive conditions.

RATIONALE: Percutaneous core needle biopsy (CNB) of the spleen is rarely performed, due to concerns about its complications and low diagnostic yield. However, this procedure represents a potentially useful diagnostic tool, especially in patients with splenomegaly and no definitive diagnosis after a clinical and radiological work-up. METHODS AND RESULTS: We report the data on a cohort of 45 radiologically guided percutaneous core needle biopsies of the spleen from 44 patients performed at two centres. Platelet count and prothrombin time were within normal limits in all patients at the time of the procedure. The biopsy was ultrasound-guided in all cases except one, which was guided by computed tomography. An 18G needle was used in 82% of the cases, followed by 16G (10.2%) and 20G (7.8%) needles. The biopsy provided sufficient material for histological examination (including immunohistochemical studies) in 41 cases (91.1%). Haematological malignancies were most commonly diagnosed (52.3%); diffuse large B cell lymphoma (DLBCL) was the most frequent, followed by splenic marginal zone lymphoma (SMZL). For the most recent cases of DLBCL, the CNB provided sufficient material for fluorescence in-situ hybridisation to assess the status of MYC, BCL2 and BCL6. This allowed the identification of a case of high-grade B cell lymphoma with MYC and BCL2 rearrangement. Major complications were not reported; minor complications occurred in three cases (6.7%). CONCLUSIONS: Our data demonstrate that radiologically guided percutaneous CNB should be considered as a valid diagnostic tool, as it provides quick and reliable histological diagnoses avoiding the complications and risks of splenectomy.

Endobronchial ultrasound-guided transbronchial needle aspiration in patients with previously treated lung cancer.

PURPOSE: The sampling and accurate diagnosis of lymph nodes during the clinical history of lung cancer are essential for selecting the appropriate treatment strategies. This study aims to evaluate the feasibility of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in patients with previously treated lung cancer. METHODS: Patients who underwent EBUS-TBNA after treatment for lung cancer were retrospectively reviewed. We classified the patients into two groups; Group 1 (G1): Indicated to have a recurrence of new lesions after radical surgery or chemo/radiotherapy with a curative intent; and Group 2 (G2): Indicated to have residual tumor cells after undergoing primary treatment for chemo/radiotherapy or re-staging after induction therapy prior to surgery. RESULTS: Seventy previously treated lung cancer cases (G1, n = 52; G2, n = 18) were enrolled. Thirty-two cases (61.5%) had recurrent disease in G1, and 9 cases (50.0%) had nodal metastasis in G2. The diagnostic accuracy was 95.2% in G1 and 88.9% in G2. Twenty-four cases were examined for epidermal growth factor receptor (EGFR) mutations, and 9 (37.5%) cases had mutations, including two cases with a T790M mutation. Furthermore, in one case, a re-biopsy revealed that the initial adenocarcinoma had transformed into small cell lung cancer. CONCLUSION: Performing EBUS-TBNA during lung cancer treatment showed a high diagnostic yield. Samples obtained by EBUS-TBNA were helpful in determining when to perform repeat biomarker testing as well as for making pathological re-evaluations.

Molecular Nodal Staging Using miRNA Expression in Lung Cancer Patients by Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration.

BACKGROUND: The limited negative predictive value of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has often been discussed. OBJECTIVE: The aim of this study was to identify a highly sensitive molecular biomarker for lymph node staging by EBUS-TBNA. METHODS: Five microRNAs (miRNAs) (miR-200a, miR-200b, miR-200c, miR-141, and let-7e) were selected as biomarker candidates for the detection of nodal metastasis in a miRNA expression analysis. After having established a cutoff level of expression for each marker to differentiate malignant from benign lymph nodes among surgically dissected lymph nodes, the cutoff level was applied to snap-frozen EBUS-TBNA samples. Archived formalin-fixed paraffin- embedded (FFPE) samples rebiopsied by EBUS-TBNA after induction chemoradiotherapy were also analyzed. RESULTS: The expression of all candidate miRNAs was significantly higher in metastatic lymph nodes than in benign ones (p < 0.05) among the surgical samples. miR-200c showed the highest diagnostic yield, with a sensitivity of 95.4% and a specificity of 100%. When the cutoff value for miR-200c was applied to the snap-frozen EBUS-TBNA samples, the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were 97.4, 81.8, 95.0, 90.0, and 94.0%, respectively. For restaging FFPE EBUS- TBNA samples, the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were 100, 60.0, 80.0, 100, and 84.6%, respectively. Among the restaged samples, 4 malignant lymph nodes were false negative by EBUS-TBNA, but they were accurately identified by miR-200c. CONCLUSIONS: miR-200c can be used as a highly sensitive molecular staging biomarker that will enhance nodal staging of lung cancer.

Concordant pattern of radiologic, morphologic, and genomic changes during compensatory lung growth.

BACKGROUND: Although compensatory lung growth (CLG) after lung resection has been reported in various mammalian species, it has generally been thought that the lung cannot regenerate in adult humans. We recently developed a method for evaluating lung weight using a radiologic analysis and demonstrated that the lung was heavier than expected in adult humans after pulmonary resection. In this study, we serially evaluated the morphologic, radiologic, and genomic status during CLG in pneumonectomized mice. METHODS: The serial changes in morphology and gene expression of the remnant right lung after left pneumonectomy were examined in adult male mice. The alveolar density was determined by the mean linear intercept, and the weight was estimated using the Hounsfield value and volumetric data from micro-computed tomography. The parameters were obtained on days 3, 7, and 30 after left pneumonectomy or thoracotomy only (sham control). RESULTS: After left pneumonectomy, the right lung became significantly progressively larger in volume and weight on postoperative days 3, 7, and 30 in comparison to the sham controls (P < 0.01). The estimated weight also significantly increased in association with the real volume on postoperative days 3, 7, and 30 (P < 0.01). The cardiac lobe markedly increased in size. During the observation period, the alveolar density was always lower in the pneumonectomized mice than in controls. A microarray analysis revealed that multiple genes related to proliferation (but not specific alveolar development) were initially upregulated until postoperative day 7 and then returned to normal after 1 mo. The morphologic and genomic changes were more evident in the cardiac lobe than in the upper lobe during the observation period. CONCLUSIONS: The morphologic, radiologic, and genomic changes during CLG were related to each other in pneumonectomized mice. The present study revealed an association between the radiologically estimated weight and other parameters, indicating a marked CLG reaction of the cardiac lobe.

Bronchial Embolization with an Endobronchial Watanabe Spigot for Broncho-Gastric Tube Fistula.

Anastomotic failure of a gastric tube inserted for reconstruction following esophagectomy, which is relatively rare, causes pleural infection and persistent pleural irritation, leading to communication with the pulmonary parenchyma. Although several interventions have been reported to treat such broncho-gastric tube fistulas, refractory cases remain. We herein report the successful treatment by endoscopic bronchial occlusion with an endobronchial Watanabe spigot in 2 patients who suffered from the above complication.

Mini grasping basket forceps for endobronchial foreign body removal in pediatric patients.

BACKGROUND: Appropriate device selection is crucial for endobronchial foreign body removal using a bronchoscope. In pediatric patients, bronchoscopy requires the use of a thin device due to the narrow access to the airway, limiting the range of useful endobronchial devices. We herein review our experience in endobronchial foreign body removal with a focus on the type of bronchoscope and the instruments used in comparison with the literature, and investigate the utility of mini grasping basket forceps (FG-55D, Olympus® ; and Zero Tip™ , Airway Retrieval Basket, Boston Scientific). METHODS: Between April 2008 and April 2016, foreign bodies were removed from the airway of 12 pediatric patients by bronchoscopy. These cases are reviewed in this study. The clinical presentation, location and characteristics of the foreign bodies, and the type of bronchoscope and instruments used were analyzed. RESULTS: A consecutive series of 12 pediatric patients was retrospectively reviewed, and the therapeutic characteristics investigated. Nuts were the most frequently observed foreign body. Seven of the 12 pediatric patients required an ultrathin bronchoscope (diameter, 2.8 mm) for foreign body removal. Only one patient required a rigid scope in addition to flexible bronchoscopy. The most frequently used instrument was a mini grasping basket forceps (n = 7; 58%), which was used with a 1.2 mm instrument channel (n = 4; 33%). CONCLUSIONS: The use of a mini grasping basket forceps in combination with an ultrathin flexible bronchoscope was useful for removing smooth, soft materials such as a nuts or beans in pediatric cases.

Does segmentectomy really preserve the pulmonary function better than lobectomy for patients with early-stage lung cancer?

PURPOSE: Recently, segmentectomy has been considered as an alternative to lobectomy in early peripheral non-small lung cancer (NSCLC); however, controversy has remained regarding the long-term functional advantage after segmentectomy. The aim of this study was to analyze the postoperative lung function after segmentectomy and lobectomy for non-small cell lung cancer. METHODS: Patients with p-T1aN0M0 NSCLC who had undergone segmentectomy (n = 37) or lobectomy (n = 33) were retrospectively analyzed. The ratios of postoperative to preoperative forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were defined as the recovery rates. The radiological lung volume and weight were evaluated before and more than 6 months after surgery, and the postoperative values were compared with the predicted values that were calculated from the preoperative values, subtracting the resected lobes or segments. RESULTS: The clinical characteristics, including the preoperative lung function showed no significant differences between the groups. No statistical differences were recognized in the trend lines for recovery ratios of FVC and FEV1.0 (P = 0.96 and P = 0.33). The recovery ratios for radiologic lung volume and weight showed no significant differences (P = 0.46 and P = 0.22). The postoperative lung volume and weight were almost the same as the predicted values after segmentectomy, whereas those after lobectomy were significantly higher than the predicted values. CONCLUSIONS: No functional advantage for segmentectomy was observed during long-term follow-up, possibly due to compensatory lung growth after lobectomy.

[The History and Development of Experimental Rodent Models of Chronic Lung Allograft Dysfunction after Lung Transplantation].

Chronic lung allograft dysfunction (CLAD) is a critical impediment to the long-term survival after lung transplantation. A rat orthotopic lung transplantation model was developed in the early 1970s, and using this model, our laboratory has shown that the immunopathogenesis of CLAD involves both allogeneic immunity and autoimmunity. However, further investigation of CLAD is limited by the scarcity of transgenic and knockout strains. The model most widely used to study CLAD, the mouse model of heterotopic tracheal transplantation, has some incomplete pathophysiologic features of CLAD, which limits the utility of this model. Unlike other solid organ transplants, vascularized and aerated murine lung transplantation has only recently been developed. We have also reported that minor, but not major, histocompatibility antigens mismatch induced the development of CLAD in murine orthotopic lung transplants and that CLAD development was interleukin-17-dependent. This mini-review underscores the history and development of rodent models of CLAD after lung transplant, including the findings from our previous studies. In addition, the future direction of rodent models is also discussed.

Logistic regression model for diagnosis of transition zone prostate cancer on multi-parametric MRI.

OBJECTIVES: We aimed to develop logistic regression (LR) models for classifying prostate cancer within the transition zone on multi-parametric magnetic resonance imaging (mp-MRI). METHODS: One hundred and fifty-five patients (training cohort, 70 patients; temporal validation cohort, 85 patients) underwent mp-MRI and transperineal-template-prostate-mapping (TPM) biopsy. Positive cores were classified by cancer definitions: (1) any-cancer; (2) definition-1 [≥Gleason 4 + 3 or ≥ 6 mm cancer core length (CCL)] [high risk significant]; and (3) definition-2 (≥Gleason 3 + 4 or ≥ 4 mm CCL) cancer [intermediate-high risk significant]. For each, logistic-regression mp-MRI models were derived from the training cohort and validated internally and with the temporal cohort. Sensitivity/specificity and the area under the receiver operating characteristic (ROC-AUC) curve were calculated. LR model performance was compared to radiologists' performance. RESULTS: Twenty-eight of 70 patients from the training cohort, and 25/85 patients from the temporal validation cohort had significant cancer on TPM. The ROC-AUC of the LR model for classification of cancer was 0.73/0.67 at internal/temporal validation. The radiologist A/B ROC-AUC was 0.65/0.74 (temporal cohort). For patients scored by radiologists as Prostate Imaging Reporting and Data System (Pi-RADS) score 3, sensitivity/specificity of radiologist A 'best guess' and LR model was 0.14/0.54 and 0.71/0.61, respectively; and radiologist B 'best guess' and LR model was 0.40/0.34 and 0.50/0.76, respectively. CONCLUSIONS: LR models can improve classification of Pi-RADS score 3 lesions similar to experienced radiologists. KEY POINTS: • MRI helps find prostate cancer in the anterior of the gland • Logistic regression models based on mp-MRI can classify prostate cancer • Computers can help confirm cancer in areas doctors are uncertain about.

Molecular characterization of chronic obstructive pulmonary disease-related non-small cell lung cancer through aberrant methylation and alterations of EGFR signaling.

BACKGROUND: The aim of this study was to evaluate the molecular influence of chronic obstructive pulmonary diseases (COPD) on the pathogenesis of non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: The methylation profiles of 12 genes, and the epidermal growth factor receptor (EGFR) and KRAS mutations were determined for samples from 229 NSCLC patients. In addition, protein expression of EGFR and HER2 in 116 NSCLCs was analyzed based on the presence or absence of COPD. RESULTS: IL-12Rbeta2 and Wif-1 methylation and HER2 overexpression were more frequent events in the COPD group. Eighty nonmalignant lung tissues had no correlation with any molecular changes between the COPD and the non-COPD group. EGFR mutation was significantly higher in the non-COPD group, while EGFR expression was inversely correlated with %FEV1.0. In the COPD group, unmethylated SPARC and sFRP-2 genes or a negative CpG island methylator phenotype (CIMP) was a negative prognostic factor, while methylation of p16(INK4A) and WNT antagonist genes was a negative prognostic factor in the non-COPD group. CONCLUSIONS: Novel characteristics of COPD-related NSCLC were identified by examination of methylation profiles and alterations of EGFR signaling. In consideration of the high sensitivity to smoking in patients with COPD, NSCLC with COPD might be a distinct population of smoke-related NSCLC, the genetic profile of which is quite different from non-COPD NSCLC.

Risk factors of postoperative recurrence of primary spontaneous pneumothorax.

BACKGROUND: Spontaneous pneumothorax is common in relatively young, healthy patients. The risk factors for postoperative recurrence after correction are not fully understood. METHODS: We retrospectively reviewed the records of patients who underwent surgery for spontaneous pneumothorax between January 2006 and October 2017. We assessed the possible factors causing postoperative recurrence using univariate and multivariate analyses. We then used the inverse probability of treatment-weighted method to correct for confounding factors. RESULTS: Postoperative recurrence was observed in 41 of 233 patients (17.6%). A significant association with recurrence was noted for primary spontaneous pneumothorax (PSP), never smokers, thoracoscopic surgery, patients younger than 30 years, operative time less than 100 minutes, and surgery by a resident surgeon. Patients younger than 30 years of age had a 5-year recurrence-free probability of 46.3%. On multivariate analysis, patients younger than 30 years was an independent risk factor for recurrence. The confounding factors for recurrence of PSP included patients younger than 30 years, surgery by a resident surgeon, and thoracoscopic surgery. After adjusting for confounders, patients younger than 30 years was the only factor associated with recurrence (P=0.015). Patients who underwent bulla ligation with pleural reinforcement using an absorbable polyglycolic acid (PGA) sheet had a 4% recurrence rate and a 5-year recurrence-free probability of 90.0%. CONCLUSIONS: Patients younger than 30 years of age is a significant factor for postoperative recurrence in patients with PSP. Surgeons may attempt to prevent postoperative recurrence by devising the operative method and pleural reinforcement methods.

Differential gene analysis during the development of obliterative bronchiolitis in a murine orthotopic lung transplantation model: A comprehensive transcriptome-based analysis.

BACKGROUND: Obliterative bronchiolitis (OB) is a known issue during minor histocompatibility antigen (mHA) disparity during lung transplantation. This study evaluated gene expression in a murine orthotropic lung transplantation model using microarray analysis. METHODS: Left lungs from C57BL/10(H-2b) donor mice were transplanted into mHA-mismatched C57BL/6(H-2b) recipient mice. Three groups (OB, non-OB, and sham controls) were confirmed pathologically and analyzed. Gene expression changes in the lung grafts were determined by microarray and immunohistochemical staining, and genes were verified by quantitative PCR in the lungs and mediastinal lymph nodes (LNs). RESULTS: A total of 1343 genes were upregulated in the OB lungs compared to the sham group. Significant upregulation was observed for genes related to innate, e.g. Tlr2 and CCL3 and adaptive immunity, e.g. H2-ab1 and Il-21. Positive labeling for MHC class II antigen was observed in the bronchial epithelium of OB accompanied with B cells. We found increased Tlr2, Ccl3, H2-ab1, Il-21, Ighg3, Ifng, and Pdcd1 mRNA expression in the OB lung, and increased Il-21, Ighg3, and Pdcd1 expression in the OB LNs. CONCLUSIONS: Adaptive and innate immune reactions were involved in OB after lung transplantation, and genetic examination of related genes could be used for detection of OB.

Prostaglandin E2 receptor 2 overexpression in squamous cell carcinoma of the lung correlates with p16INK4A methylation and an unfavorable prognosis.

Several studies have described p16INK4A and prostaglandin E2 (PGE2) co-alterations in various solid tumors, including non-small cell lung cancer (NSCLC). In this study, we examined the correlation between PGE2 receptor 2 (EP2) expression and p16INK4A methylation in NSCLC, and the association with clinicopathological features and prognostic significance. We retrospectively reviewed 88 NSCLC patients who underwent resection from July 1993 to May 1997. The tumors included 43 adenocarcinomas, 39 squamous cell carcinomas, and 6 large cell carcinomas. EP2 expression was determined by immunostaining, and p16INK4A methylation was analyzed by methylation specific PCR. EP2 was overexpressed in 44% of NSCLC patients, 61% of adenocarcinoma cases, 28% of squamous cell carcinoma cases, and 33% of large cell carcinoma cases. EP2 expression positively correlated with lymph node metastasis (P=0.034), especially in patients with squamous cell carcinoma (P<0.009). Methylation of p16INK4A was detected in 34% of NSCLC patients, 23% of adenocarcinoma cases, 44% of squamous cell carcinoma cases, and 50% of large cell carcinoma cases. In patients with squamous cell carcinoma, EP2 overexpression correlated with poor prognosis with a relative risk of 2.4 (confidence interval 2.1-51.8, P<0.003), and positively correlated with p16INK4A methylation (P<0.024). Adenocarcinoma patients with p16INK4A methylation had poor prognosis with a relative risk of 2.4 (confidence interval 1.8-69.7, P<0.009), but this was not correlated with EP2 expression. In conclusion, EP2 overexpression was common in NSCLCs, especially in adenocarcinomas. Synchronous alteration of p16INK4A and EP2 may accelerate progression of squamous cell carcinomas. These two alterations may differentially affect pathogenesis among subtypes of NSCLC.

The probability of nodal metastasis in novel T-factor: the applicability of sublobar resection.

BACKGROUND: Recently sublobar resection is often indicated for small-sized peripheral lung cancer according to size or the consolidation/tumor ratio on CT; however, the T-factor classification drastically changed in the 8th version. We investigated the relationship between a novel clinical T-factor classification, which includes other clinical information and the pathologic N-factor, to evaluate the applicability of the novel T-factor classification to sublobar resection. METHODS: From January 2013 to October 2017, 545 patients with cTis or cT1 lung cancer underwent surgery. Patients with non-peripheral type, induction treatment, cN≥1, cM1, and those without nodal dissection, preoperative evaluation by thin-sliced CT or FDG-PET were excluded. Finally, 325 patients were eligible for inclusion. All clinical parameters were prospectively collected and retrospectively analyzed. The 8th edition of TNM classification was utilized. RESULTS: Nodal metastasis was detected in 38 (11.7%) patients. Among cTis/1mi/1a/1b/1c patients (n=10/11/51/146/107), pN1 and pN2 were observed in 0/0/2/9/10 and 0/0/1/8/8, respectively. cT1b/c patients showed a significantly higher rate of nodal metastasis (P=0.024). Among 253 cT1b/c patients, solid-type tumors (n=177) were more frequently associated with nodal metastasis. A ROC curve analysis revealed that SUVmax 1.9 was the cutoff value (AUC=0.827) for the presence of nodal metastasis. Using the 2 parameters of solid-type or SUVmax ≥1.9, we could successfully exclude patients with nodal metastasis, for whom sublobar resection is not indicated. CONCLUSIONS: In terms of nodal metastasis, sublobar resection can be applicable for all cTis/1mi tumors; patients with cT1a/b/c tumors with mixed GGO and low SUVmax are candidates for sublobar resection.

The combination of endobronchial elastography and sonographic findings during endobronchial ultrasound-guided transbronchial needle aspiration for predicting nodal metastasis.

BACKGROUND: During endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), the sonographic findings of B-mode imaging, as well as endobronchial elastography, can be obtained noninvasively and used for the prediction of nodal metastasis. METHODS: Patients with lung cancer or suspected lung cancer who underwent EBUS-TBNA were recorded prospectively and reviewed retrospectively. Both the B-mode sonographic and elastographic findings were independently evaluated for each lymph node. The sonographic features were classified according to previously published criteria. If oval shape, indistinct margins, homogenous echogenicity, and the absence of coagulation necrosis sign were all observed by B-mode imaging, then the lymph node was judged to be benign by sonographic imaging. In addition, if the stiffer area comprised more than 31% of the entire lymph node area, then the lymph node was judged to be malignant by elastography. We compared the results of these imaging-based predictions with the pathological diagnoses. RESULTS: The prevalence of nodal metastasis was 78/228 (34.2%). B-mode sonography predicted 95.8% of benign lymph nodes, and elastography predicted 72.1% of malignant lymph nodes. By combining the two modalities, 59 of 71 (83.1%) lymph nodes judged as malignant by both analyses were pathologically proven to be malignant, and 101 of 105 (96.2%) lymph nodes judged as benign by both analyses were pathologically proven to be benign. CONCLUSION: The combination of elastography and sonographic findings showed good sensitivity and a high negative predictive value, which may facilitate selecting the most suspicious lymph nodes for biopsy. KEY POINTS: Significant findings of the study. The combination of endobronchial elastography and sonography resulted in a higher diagnostic yield than either modality alone for predicting benign and malignant lymph nodes in patients with lung cancer. WHAT THIS STUDY ADDS: The combination of endobronchial elastography and sonography will help clinicians identify the most suspicious lymph nodes for puncturing during EBUS-TBNA, which may improve the efficiency of EBUS-TBNA.

Intracardiac Tumors With Extracardiac Extension Diagnosed by Endoscopic Ultrasound With Bronchoscope-Guided Fine-Needle Aspiration.

Obtaining biopsy specimens for pathologic diagnosis of primary cardiac tumors is challenging because of their anatomic location and the risk of tumor embolization. Due to the difficulty of histologic diagnosis and limited treatment strategies, it is not uncommon for patients to be treated based on radiologic findings alone. However, a firm pathologic diagnosis may permit more appropriate treatment selection, especially for those with primary cardiac lymphoma. Endoscopic ultrasound with bronchoscope-guided fine-needle aspiration is a minimally invasive modality for sampling mediastinal lymph nodes and mediastinal lesions adjacent to the esophagus. In this case report we present 2 patients with cardiac tumors that were successfully and safely diagnosed by endoscopic ultrasound with bronchoscope-guided fine-needle aspiration.

A Repeated Biopsy by EBUS-TBNA Contributed to the Selection of an Appropriate Therapeutic Regimen for a Lung Cancer Patient.

Since the development of third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors for lung cancer treatment, the need for a rebiopsy has increased. To select an appropriate therapeutic regimen, the genetic alterations in cancerous tissue should be determined. A rebiopsy plays an important role in the treatment of patients with diseases that are refractory to the previous generation of EGFR tyrosine kinase inhibitors. Cell-free DNA-based exploration is useful for determining the cause of treatment resistance in cases in which a rebiopsy is difficult; however, this method cannot detect histologic changes (a mechanism of resistance), which may lead to the selection of nonoptimum therapeutic agents. We herein report a case in which EGFR mutation-positive (exon 19 deletion) lung cancer was successfully treated with an appropriate chemotherapeutic regimen after disease progression. The regimen was selected based on the precise evaluation of a rebiopsy specimen, which determined the histologic type and detected a gene mutation.

Aberrant methylation of CXCL12 in non-small cell lung cancer is associated with an unfavorable prognosis.

Chemokines play an important role in the pathogenesis of non-small cell lung cancer (NSCLC). However, aberrant methylation of CXCL12 has not been examined in NSCLC. CXCL12 mRNA expression and methylation were examined in 17 NSCLC cell lines by RT-PCR and methylation-specific PCR (MSP). MSP was performed on 236 tumor specimens from NSCLC patients who received curative intent surgery. CXCL12 and CXCR4 protein expression was examined in 90 of the 236 NSCLC specimens by immunohistochemistry. Down-regulation of CXCL12 expression was found in 10 of 17 (59%) NSCLC cell lines compared with normal bronchial cells. Treatment of 8 expression-negative cell lines with a demethylating agent restored expression in all cases. Twelve cell lines (71%) showed aberrant methylation, and good concordance between methylation and expression was present. Aberrant methylation occurred in 85 out of 236 (36%) primary NSCLCs in a tumor-specific manner. In multivariate analysis, CXCL12 methylation correlated strongly and independently with prognosis both in all patients with NSCLCs and in those with stage I NSCLCs (hazard ratio=1.68, P=0.015 and hazard ratio=3.58, P=0.017). Secreted protein CXCL12 and its receptor CXCR4 were abundant in NSCLC cells (72 out of 90, 80%; 57 out of 90, 63%) and correlated with the progression of NSCLCs. In conclusion, epigenetic silencing of CXCL12 is a frequent event in NSCLCs, and could be an independent and powerful prognostic marker in patients with NSCLCs and those with stage I disease. Analysis for CXCL12 may provide novel opportunities for prognosis and therapy of resected NSCLCs.

Bronchoscopic assessment of bronchial anastomosis by visualizing local circulation status-index of hemoglobin (IHb) imaging.

BACKGROUND: Healing of airway anastomosis is largely affected by local circulation. Index of hemoglobin (IHb) imaging is a color enhancement technique that clarifies local circulation in the gastrointestinal endoscopic field. In this study, we investigated the relationship between bronchoscopic assessment of bronchial anastomosis using IHb mode and occurrence of anastomosis-related complications. METHODS: IHb was calculated by logarithmic transformation for each pixel of the electronic endoscopic images and expressed by colors of red, green, and blue. The distribution of each color area was automatically calculated by the summation of pixels. A preliminary experiment spraying vasodilator on swine was performed to confirm the relationship between bronchial mucosal circulation and the IHb image. Forty consecutive patients who underwent bronchoplasty were divided into retrospective training and prospective validation cohorts, and anastomosis-related complications and IHb images were analyzed. RESULTS: The IHb images immediately and accurately reflected the mucosal changes in the animal experiment. Among 25 cases in the retrospective training cohort, 6 cases experienced complications, with significantly lower red and higher blue values in IHb observed (P=0.03 and P=0.01, respectively). A receiver operating characteristic (ROC) curve for IHb red and blue distributions revealed the thresholds to differentiate cases with complications as 89.2 and 109.0, respectively. An analysis of the prospective validation cohort revealed that IHb blue on POD 7 was a potentially reliable predictor of complications, with 60.0% sensitivity and 90.0% specificity. CONCLUSIONS: IHb mode of bronchoscopy may be useful for assessing the local circulatory condition of bronchoplasty, which can predict anastomosis-related morbidity.

Sclerosing pneumocytoma diagnosed by preoperative endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA).

BACKGROUND: Sclerosing pneumocytoma is a rare lung tumor that is usually recognized as a solitary nodule in the lung. Surgical removal is recommended; however, its clinical diagnosis is still an issue because it is difficult to differentiate from lung adenocarcinomas using a tiny sample obtained from biopsy. CASE PRESENTATION: We report a case of pulmonary sclerosing pneumocytoma located in the upper lobe of the right lung of a 34-year-old woman, which was diagnosed before surgery by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). A 3-cm irregular mass was detected by chest X-ray without any symptoms. She was referred to our hospital after being followed for 10 years in her previous clinic. During this follow-up period, the tumor had grown to 5 cm. We performed the EBUS-TBNA for the diagnosis. The histological findings obtained by EBUS-TBNA consisted of alveolar type 2-like cells that were positive for napsin A and round cells that were positive for vimentin. Based on these immunostaining results, we successfully diagnosed sclerosing pneumocytoma before surgery. Right upper lobectomy was performed, and the pathological diagnosis of the surgical specimen was also confirmed as sclerosing pneumocytoma. CONCLUSIONS: We herein report a case of sclerosing pneumocytoma, which was clinically diagnosed by EBUS-TBNA and resected surgically.