[Experience with High-grade Fetal Lung Adenocarcinoma;Report of a Case].

A 61-year-old woman, who was revealed to have a 11 mm pulmonary nodule in the right middle lobe by computed tomography, was diagnosed with adenocarcinoma using bronchoscopy. Fluorodeoxyglucose-positron emission tomography (FDG-PET) showed FDG accumulation in the tumor, with a maximum standardized uptake value( SUVmax) of 2.47. Therefore, she underwent thoracoscopic right middle lobectomy. Histopathological examination revealed invasive growth of cylindrical tumor cells with clear glycogen-filled cytoplasm and a relatively high-grade nuclear atypia in tubulopapillary structures; no morula was observed. Immunohistochemically, the membranes of the tumor cells were positively stained for ß-catenin, indicating high-grade fetal adenocarcinoma (pT1bN0M0, pathologic stageⅠA2). The postoperative course was uneventful, without recurrence 6 months after surgery.

[Postoperative Chylothorax Likely to be Successfully Treated by Lymphangiography;Report of a Case].

A 74-year-old man underwent right upper lobectomy and systemic lymph node dissection with video-assisted thoracoscopic surgery. Chylothorax occurred on postoperative day (POD) 1st. Under fasting management, the patient underwent pleurodesis on POD 5th and 7th, subcutaneous octreotide acetate injection on POD 6th, and lymphangiography on POD 9th. The amount of drainage decreased on POD 10th, and the drainage tube was removed on POD 12nd. Lymphangiography has been reported as one of effective procedures to treat postoperative chylothorax. The present case is also considered to be successfully treated by lymphangiography.

[Lung Adenocarcinoma with Pulmonary Aspergillosis Showing Cavity Disappearance;Report of a Case].

A 49-year-old man complaining of fever, chest pain, and hemosputum was examined at a local hospital. A chest computed tomography (CT) scan revealed a 35 mm mass shadow with cavity in the right upper lobe, but a transbronchial lung biopsy could not establish a complete diagnosis. After 1 month follow-up, the patient was referred to our hospital because the mass shadow wall remained thick despite the cavity shrinking. The mass shadow cavity disappeared 2 months after the 1st CT at our hospital. Video-assisted thoracic surgery was performed for both making diagnosis and treatment. The patient was diagnosed with non-small cell lung cancer with pulmonary aspergillosis during surgery, and a right upper lobectomy with systematic lymph node dissection was performed. Pathological examinations revealed that the tumor was a T3N0M0 stage II B adenocarcinoma with pulmonary aspergillosis. The patient was treated with adjuvant chemotherapy 4 months after surgery and is under follow-up.

[Intrapulmonary Solitary Fibrous Tumor;Report of a Case].

An abnormal lung shadow was detected in a 39-year-old woman at physical examination and she was followed-up carefully at a nearby hospital. After 5 years follow-up, the patient was referred to our hospital for further examination of the abnormal shadow. A chest computed tomography(CT) scan revealed a 12 mm well-circumscribed nodular shadow in the right lower lobe. A benign tumor such as a hamartoma was suspected preoperatively;video-assisted thoracic surgery was performed for both diagnosis and treatment. Partial resection of the right lower lobe was performed and the tumor was diagnosed as an intrapulmonary solitary fibrous tumor (SFT). No malignant features, such as nuclear atypia, necrosis, or mitotic activity, were identified. Careful observation will be necessary, because a few SFTs have a propensity to recur or metastasize. The post-operative course was uneventful and there has been no recurrence at 7 years after surgery.

[Can Pulmonary Rehabilitation during Preoperative Chemoradiotherapy for Non-small Cell Lung Cancer Improve the Respiratory Function?].

OBJECTIVE: Chemoradiotherapy for non-small cell lung cancer (NSCLC) can impair pulmonary function, particularly when it is followed by surgery. This study aimed to document the changes in respiratory function as a result of a perioperative intensive pulmonary rehabilitation program in patients with NSCLC who underwent induction chemoradiotherapy. METHODS: A total of 82 consecutive patients underwent pulmonary resection after undergoing induction chemoradiotherapy. A pulmonary rehabilitation program was started at the same time as the induction chemoradiotherapy. Standard respiratory function tests were performed before and after induction chemoradiotherapy. Treatment-related mortality and the incidence of postoperative respiratory complications were investigated. The Wilcoxon signed-rank test was used to analyze the differences in spirometric changes. RESULTS: All patients underwent a pulmonary rehabilitation program for an average of 10 weeks. Significant increases were observed in forced vital capacity (FVC) [+6.4%, p=.0096] and forced expiratory volume in 1 second( FEV(1))[ +10.4%, p<.0001]. Diffusing capacity of the lung for carbon monoxide decreased(-14.0%, p<.0001). Patients with respiratory impairment (FVC <80% predicted or FEV(1)/FVCp<70%) showed significant improvements in FVC( +13.9%, p=.0025) and FEV(1)( +22.5%, p<.0001). Significant increases were observed in FVC( +7.0%, p=.0042) and FEV(1)( +10.8%, p<.0001) in patients with a smoking history. There was no mortality, and postoperative respiratory morbidity was 6.1%.

IgG4-related lung disease with recurrent pulmonary lesions during steroid therapy and difficulty in differentiating from malignancy: a case report.

BACKGROUND: Immunoglobulin G4-related disease (IgG4-RD) is characterized by the formation of inflammatory lesions with fibrosis and infiltration of IgG4-positive plasma cells and lymphocytes in various organs of the body. Since the first report of IgG4-related autoimmune pancreatitis, IgG4-RD affecting various organs has been reported; however, only a few reports of IgG4-related lung disease (IgG4-RLD) exist. In this report, we describe a case of IgG4-RLD that was difficult to differentiate from malignancy, and the usefulness of the surgical approach in determining the appropriate diagnosis and treatment plan. CASE PRESENTATION: A 61-year-old man was referred to our hospital after a chest radiograph revealed an abnormal chest shadow. At the time of his first visit, he had a slight fever and dyspnea on exertion. Chest computed tomography (CT) revealed a middle lobe hilar mass with irregular margins and swelling of the right hilar and mediastinal lymph nodes. These findings were not present on CT 1.5 years ago. 18F-fluorodeoxyglucose-positron emission tomography revealed a mass lesion with a maximum diameter of 5.5 cm, maximum standardized uptake value (SUVmax) of 11.0, and areas with high SUV in the hilar and mediastinal lymph nodes. We suspected lung cancer or malignant lymphoma and performed a thoracoscopic lung biopsy to confirm the diagnosis. Histopathological examination revealed no malignant findings, and IgG4-RLD was diagnosed. One month after treatment with prednisolone (PSL), the tumor had shrunk, but a CT scan during the third month of PSL treatment revealed multiple nodular shadows in both lungs. Considering the possibility of malignant complications and multiple lung metastases, we performed thoracoscopic partial lung resection of the new left lung nodules to determine the treatment strategy. Histopathological examination revealed no malignant findings in any of the lesions, and the patient was diagnosed with IgG4-RLD refractory to PSL monotherapy. CONCLUSIONS: IgG4-RLD refractory to PSL monotherapy showed changes from a solitary large mass (pseudotumor) to multiple nodules on chest CT. It was difficult to distinguish malignancy from IgG4-RLD based on imaging tests and blood samples alone, and the surgical approach was useful in determining the appropriate diagnosis and treatment plan.

Analysis of Risk Factors for Bronchopleural Fistula after Surgical Treatment of Lung Cancer.

PURPOSE: Bronchopleural fistula (BPF) is a potential serious complication of lobectomy or more radical surgery for non-small-cell lung cancer (NSCLC). We aimed to evaluate the risk factors for BPF. METHODS: The study cohort comprised 635 patients who had undergone lobectomy or more radical surgery for NSCLC from March 2005 to December 2017. We examined the following risk factors for BPF: surgical procedure, medical history, preoperative treatment, and surgical management. RESULTS: In all, 10 patients (1.6%) had developed postoperative BPFs. Univariate logistic regression analysis showed that surgical procedure, medical history (arteriosclerosis obliterans [ASO]), and bronchial stump reinforcement were significant risk factors. Multivariate analysis showed that only surgical procedure (right lower lobectomy, p = 0.011, odds ratio = 17.4; right middle lower lobectomy, p = 0.003, odds ratio = 59.4; right pneumonectomy, p <0.001, odds ratio = 166.0) was a significant risk factor. Multivariate analysis confined to the surgical procedure of lobectomy showed that right lower lobectomy (p = 0.011, odds ratio = 36.5) and diabetes (HbA1c ≥8.0) (p = 0.022, odds ratio = 31.7) were significant risk factors. CONCLUSION: When lobectomy or more radical surgery is performed for NSCLC, right lower lobectomy, middle lower lobectomy, and right pneumonectomy are significant risk factors for postoperative BPF. Thoracic surgeons should acquire the techniques of bronchoplasty and angioplasty to avoid such invasive procedures.

Inhibition of Cell-surface Molecular GPR87 With GPR87-suppressing Adenoviral Vector Disturb Tumor Proliferation in Lung Cancer Cells.

BACKGROUND/AIM: GPR87 is a member of the cell surface molecular G protein-coupled receptors (GPCR) family and suggested to contribute to the viability of human tumor cells. Its tumor-specific expression and cell surface location make it a potential molecule for targeted therapy. In the present study, we aimed to examine the effect of silencing GPR87 expression and explore the possibility of establishing gene therapy against GPR87-overexpressing lung cancer. MATERIALS AND METHODS: Twenty malignant cell lines were investigated and GPR87-overexpressing H358 and PC9 lung cancer cells were subjected to inhibiting experiments. A short hairpin siRNA targeting the GPR87 gene was transformed into an adenoviral vector (Ad-shGPR87). Real-time RT-PCR and western blot analyses were performed to evaluate gene and protein expression. Tumors derived from human H358 cells were subcutaneously implanted in nude mice for in vivo experiments. RESULTS AND CONCLUSION: About 50% (10/20) malignant cells showed GPR87-overexpression, especially for lung cancer cells (70%, 7/10). Ad-shGPR87 effectively down-regulated the GPR87 expression, and significantly inhibited the cell proliferation in GPR87-overexpressing H358 and PC9 cells. Treatment with Ad-shGPR87 exerted a significant antitumor effect against the GPR87-expressing H358 xenografts. In addition, the gene expression of H3.3, a recently proved activator for GPR87 transcription, was positively correlated with GPR87 gene expression. Furthermore, a significant decrease of KRAS and c-Myc expression was observed in both cell lines after Ad-shGPR87 infection. In conclusion, GPR87 may play a critical role in cancer cell proliferation, and indicate its potential as a novel target for lung cancer treatment.

Characteristics of multiple nodules in a patient with pulmonary Langerhans cell histiocytosis: A case report.

BACKGROUND: The common computed tomography findings of pulmonary Langerhans cell histiocytosis (PLCH) are multiple cysts and micronodules predominantly in middle to upper lung lobes. Non-cystic nodules and large nodules are atypical findings of PLCH. CASE SUMMARY: The patient was a 48-year-old Japanese man with a smoking history (20 cigarettes/d, 28 years) and no symptoms. Multiple nodules existed in all lung lobes, predominantly in the right lower lobe. Some nodules seemed to be distributed randomly, and others were adjacent to bronchus. Most nodules were solid; some small ones were cystic. The largest nodule was 22 mm in diameter. Although metastatic lung tumors were suspected, thoracoscopic lung biopsy led to the diagnosis of PLCH. At 6 months after he quit smoking, all nodules had almost disappeared. We investigated the characteristics of nodules at diagnosis in detail. Of 349 nodules in total, 116 were in upper and 199 were in lower lobes. Ninety-six (27.5%) were cystic; the remaining 253 (72.5%) were non-cystic. The prevalence of cystic nodules was higher in upper lobes than in lower lobes (right upper 37.5% vs lower 18.2%, P = 0.0068; left upper 48.1% vs lower 24.4%, P = 0.0078). The average size (dia.) of cystic nodules was smaller than that of non-cystic nodules (5.03 mm vs 7.40 mm, respectively, P < 0.0001). CONCLUSION: Although multiple non-cystic nodules including large nodules (over 20 mm) are atypical, PLCH should be included in differential diagnoses. The presence of small cystic nodules predominantly in upper lobes and asymptomatic situation are also important for differential diagnoses to distinguish from metastatic cancers.

Intraoperative Computed Tomography Navigation During Thoracoscopic Segmentectomy for Small-sized Lung Tumors.

Performance of thoracoscopic pulmonary segmentectomy for primary lung cancer or pulmonary metastases has recently increased. In patients with emphysema, identification of the intersegmental line is often difficult. For nonpalpable lesions, securing a sufficient surgical margin is more likely to be uncertain. The purpose of this study was to evaluate the efficacy of intraoperative computed tomography (CT) scan during video-assisted thoracoscopic surgery (VATS) pulmonary segmentectomy. This study included 12 patients who underwent intraoperative CT-assisted VATS segmentectomy between January 2015 and August 2016. After dividing the corresponding vessels and bronchi, the intersegmental line was marked by clipping, and intraoperative CT scan was performed under bilateral lung ventilation. The intraoperative CT or 3-dimensional CT reconstruction images were used by the surgeons to confirm the correct anatomical segmental border and to secure a sufficient resection margin. In all patients, the location of the lesions to be resected, the intersegmental border, and the surgical margins could be confirmed while performing VATS segmentectomy. Complete resection was achieved in all patients. Although the pathologic margins tended to be shorter than the surgical margins on intraoperative CT images, there was a strong correlation between these 2 variables (r = 0.963, P < 0.0001). Intraoperative CT scan during VATS segmentectomy was useful for identifying the location of nonpalpable lesions, confirming anatomical intersegmental borders and securing the resection margins. Intraoperative CT navigation could enable a more definitive VATS segmentectomy for nonpalpable lesions.

Intraoperative computed tomography after tumor marking with metal clips for non-palpable lung tumors.

BACKGROUND: Locating small, non-palpable lung tumors during video-assisted thoracoscopic surgery (VATS) is difficult. In this paper, we report a simple method to identify such tumors during VATS, using intraoperative computed tomography (IO-CT). METHODS: From 2015 to 2017, we performed IO-CT scans for patients who preoperatively seemed to have non-palpable lung tumors. We initially tried to locate these tumors by finger palpation through the thoracoscopic ports. IO-CT scans were performed after marking tumors with metal clips. However, difficult-to-palpate tumors were marked by initially locating the intercostal muscle from preoperative CT. Metal clips were applied just under the intercostal muscle, and IO-CT scans were performed. After locating the tumor in relationship to the marking clips, patients would undergo wedge resections during VATS, using surgical staplers. RESULTS: We used this procedure on 21 tumors in 18 patients, including 9 non-palpable tumors and 12 palpable tumors (mean tumor size: 7.3 mm; mean distance from pleura: 6.8 mm). All tumors were identified intraoperatively, and all patients successfully underwent wedge resections during VATS, with no intra-postoperative complications. CONCLUSION: IO-CT scans after tumor marking with metal clips during VATS can accurately locate non-palpable small sized lung tumors. IO-CT scans should be indicated for tumors that are preoperatively considered to be non-palpable.

Customized Adjuvant Chemotherapy Based on Biomarker Examination May Improve Survival of Patients Completely Resected for Non-small-cell Lung Cancer.

AIM: Adjuvant platinum-based chemotherapy is recommended for patients with completely resected stage II (N1) or III (N2) non-small cell lung cancer (NSCLC). However, the optimal chemotherapy regimen is difficult to predict for individual patients. Our previous prospective study on individualized treatment according to biomarker status, such as excision repair cross-complementing 1 (ERCC1), class III ß-tubulin (tubulin), thymidylate synthase (TYMS) and ribonucleotide reductase M1 (RRM1), achieved encouraging results in patients with advanced NSCLC. The present study further examined the effect of biomarker-based adjuvant chemotherapy in patients with completely resected NSCLC. PATIENTS AND METHODS: Between January 2006 and December 2014, 66 patients with localized (stage I-IIIA) NSCLC who underwent R0 operation received 2-4 cycles of platinum doublet adjuvant chemotherapy: Platinum plus docetaxel, platinum plus pemetrexed for adenocarcinoma, and platinum plus tegafur/gimeracil/oteracil combination (TS-1) for squamous cell carcinoma (SCC) were selected according to the registered protocol at each period. Immunohistochemistry was used to evaluate the biomarkers: ERCC1 status for platinum, tubulin for docetaxel, and TYMS for pemetrexed and TS-1. A matched chemotherapy regimen meant that platinum plus docetaxel was administered in patients negative for ERCC1 and negative for tubulin, platinum plus pemetrexed in patients with adenocarcinoma positive for tubulin, negative for ERCC1 and negative for TYMS, and platinum plus TS-1 in those with SCC positive for tubulin, negative for ERCC1 and negative for TYMS. RESULTS: The 5-year survival rate was 77.5% considering all 66 patients, and 85.7%, 71.8%, and 78.8% for those with p-stage I, II, and III, respectively. Patients who received a matched chemotherapy regimen (n=13; platinum plus docetaxel in eight, platinum plus pemetrexed in five) had significantly better 5-year survival than patients with unmatched biomarker status (n=53) (100% vs. 71.0%, p=0.0011). CONCLUSION: Customized adjuvant chemotherapy based on biomarker examination significantly improved the survival of patients with NSCLC, regardless of p-stage.

Potent effect of adenoviral vector expressing short hairpin RNA targeting ribonucleotide reductase large subunit M1 on cell viability and chemotherapeutic sensitivity to gemcitabine in non-small cell lung cancer cells.

BACKGROUND: Ribonucleotide reductase large subunit (RRM1) is the main enzyme responsible for synthesis of the deoxyribonucleotides used during DNA synthesis. It is also a cellular target for gemcitabine (GEM). Overexpression of RRM1 is reportedly associated with resistance to GEM and the poor prognosis for many types of malignant tumours. Aim of the present study is to establish gene therapy against RRM1-overexpressing tumours. METHOD: An adenoviral vector that encoded a short hairpin siRNA targeting the RRM1 gene (Ad-shRRM1) was constructed. Two RRM1-overexpressing non-small cell lung cancer (NSCLC) lines, MAC10 and RERF-LC-MA, were used. Finally, a human tumour xenograft model in nude mice was prepared by subcutaneously implanting tumours derived from RERF-LC-MA cells. RESULTS: Ad-shRRM1 effectively downregulated RRM1 mRNA and protein in both types of NSCLC cells and significantly reduced the percentage of viable cells as detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay (p<0.005). Caspase 3/7 analysis revealed that transfection with Ad-RRM1 increased the percentage of apoptotic cells in culture containing either type of RRM1-overexpressing cell (p<0.001). Treatment with Ad-shRRM1 exerted a potent antitumour effect against the RRM1-overexpressing RERF-LC-MA xenografts (p<0.05). Furthermore, Ad-shRRM1-mediated inhibition of RRM1 specifically increased sensitivity to gemcitabine of each type of RRM1-overexpressing tumour cell. Combination treatment with Ad-shRRM1 and GEM exerted significantly greater inhibition on cell proliferation than Ad-shRRM1 or GEM treatment alone. CONCLUSION: RRM1 appeared to be a promising target for gene therapy, and Ad-shRRM1 had strong antitumour effects, specifically anti-proliferative and pro-apoptotic effects, against NSCLC cells that overexpressed RRM1. Combination therapy with Ad-shRRM1 and GEM may become a new treatment option for patients with NSCLC.

Overexpression of G protein-coupled receptor 87 correlates with poorer tumor differentiation and higher tumor proliferation in non-small-cell lung cancer.

G protein-coupled receptor 87 (GPR87) is a newly deorphanized member of the transmembrane G protein-coupled receptor family. Recently, GPR87 was suggested to contribute to the viability of human tumor cells and overexpression of GPR87 mRNA was detected in a number of malignant tumors, including lung cancer. We performed a retrospective study of GPR87 expression in association with clinical characteristics and biological markers in non-small-cell lung cancer (NSCLC). We investigated a total of 123 patients with NSCLC who underwent surgery between 1999 and 2004 (58 adenocarcinomas, 53 squamous cell carcinomas and 12 others). Immunohistochemistry was used to evaluate the intratumoral expression of GPR87 and the Ki-67 proliferation index. The TUNEL method was also used to investigate tumor apoptosis. A total of 63 tumors (51.2%) were found to be GPR87-positive. These tumors were more frequently encountered among squamous cell carcinomas rather than among adenocarcinomas (62.3 vs. 43.1%, respectively; P=0.044) and were significantly more frequently poorly and moderately differentiated rather than well differentiated (P=0.029). Moreover, the Ki-67 index was significantly higher in GPR87-positive compared to GPR87-negative tumors (57.0 vs. 40.0%, respectively; P=0.002). The overall survival was significantly worse for patients with GPR87-positive compared to those with GPR87-negative tumors (P=0.029). The Cox regression analyses also demonstrated that the GPR87 status was a significant prognostic factor for NSCLC patients [hazard ratio=2.053; P=0.018). The present study demonstrated that in NSCLC, the overexpression of GPR87 is significantly associated with poorer differentiation and higher proliferation. During the progression of NSCLC, GPR87 overexpression may be associated with the acquisition of a more aggressive phenotype and, therefore, is a potentially useful target for prognostication and treatment.

Thoracoscopic surgical treatment for pleuroperitoneal communication.

Hydrothorax as a result of pleuroperitoneal communication (PPC) is an uncommon but a well-known complication of continuous ambulatory peritoneal dialysis (CAPD). In this paper, we present a 60-year old man with diabetic renal failure who underwent CAPD. Two weeks after starting CAPD, chest radiographs showed a right-sided hydrothorax. Radioscintigraphy was performed and PPC was diagnosed. Eight days after the diagnosis, thoracoscopic surgery was performed. The leakage points were closed by direct suturing with absorbable polyglycolic acid felt and fibrin glue. The patient resumed CAPD 2 weeks later, and there was no recurrence of the right hydrothorax. Video-assisted thoracic surgery with direct suturing represents a feasible method for treating PPC with confirmed fistulae.