EGFR Mutation is a Prognostic Factor in Lung Cancer Patients with Pleural Dissemination Detected During or After Surgery.

BACKGROUND: Primary lung tumors are sometimes resected when either pleural dissemination (PD) or malignant pleural effusion (MPE) exists. This study clarified the prognostic factors for non-small cell lung cancer (NSCLC) with either PD and MPE, or both, detected during or after surgery. PATIENTS AND METHODS: We examined patients with NSCLC from a multicenter database who had either PD, MPE, or both, detected during or after surgery between 2005 and 2015. Hazard ratios and 95% confidence intervals were estimated using the Cox proportional hazards model adjusted for potential confounding factors. RESULTS: Among 9463 registered patients, PD, MPE, or both, were found in 114 patients with NSCLC during or after surgery. Primary tumor resection and exploratory thoracotomy were performed in 65 and 49 patients, respectively. In univariate analysis, adenocarcinoma, clinically undetected lymph node metastasis (c-N0 or unknown), EGFR mutation, and combination of chemotherapy or tyrosine kinase inhibitors after surgery were better prognostic factors for overall survival (OS), whereas in the multivariate analysis, adenocarcinoma, clinically undetected lymph node metastasis, and EGFR mutation were favorable independent prognostic factors in OS. Additionally, limited to patients with EGFR mutation, patients with primary lung tumor resection showed a significantly better 5-year OS than those with exploratory thoracotomy (86.4 vs. 44.8%; p < 0.001). CONCLUSION: Our findings show that surgical resection of primary tumors could improve the prognosis of patients with PD, MPE, or both, detected during or after surgery when the tumors harbor an EGFR mutation.

Correlation between pleural tags on CT and visceral pleural invasion of peripheral lung cancer that does not appear touching the pleural surface.

OBJECTIVES: To evaluate the association between a sign and visceral pleural invasion (VPI) of peripheral non-small-cell lung cancer (NSCLC) that does not appear touching the pleural surface. METHODS: A total of 221 consecutive patients with NSCLC that did not appear touching the pleural surface, ≤ 3 cm in solid tumor diameter, and was surgically resected between January 2009 and December 2015 were included. We focused on the flat distortion of the tumor caused by an arch-shaped linear tag between the tumor and the pleura on CT and named it a bridge tag sign. We evaluated the associations between the clinicopathological features of the tumor, including the bridge tag sign, and VPI. We also evaluated the associations between histopathological findings and the bridge tag sign. The utility of the bridge tag sign in the diagnosis of VPI was statistically assessed. RESULTS: The bridge tag sign was observed in 48 (20.8%) patients. VPI was positive in 9 (4.1%) patients; among these, the bridge tag sign was positive in 8 patients. In multivariate analysis, a bridge tag sign was significantly associated with VPI. The bridge tag sign was associated with longer contact length of the pleura with the tumor and trapezoid type pleural retraction. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of the bridge tag sign in the diagnosis of VPI were 88.9%, 83.5%, 83.7%, 18.6%, and 99.4%, respectively. CONCLUSIONS: A bridge tag sign on CT might improve the accuracy of the prediction of VPI. KEY POINTS: • We present the bridge tag sign which is defined as a flat distortion of an NSCLC tumor by an arch-shaped linear tag between the tumor and chest wall or interlobar fissure. • The bridge tag sign was an independent predictive factor for visceral pleural invasion. • The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of the bridge tag sign in the diagnosis of visceral pleural invasion were 88.9%, 83.5%, 83.7%, 18.6%, and 99.4%, respectively.

[Effective Treatment of Secondary Spontaneous Pneumothorax due to Pulmonary Mycobacterium Avium Complex by Thoracoscopic Intra-fistula Filling with Suture Closure].

Secondary spontaneous pneumothorax associated with pulmonary Mycobacterium avium complex (MAC) infection is often difficult to treat. Pneumothorax associated with pulmonary MAC is characterized by a large fistula with a cavity or bronchodilation, and pleural thickening due to pleurisy. Herein, we report two cases of pneumothorax with pulmonary MAC successfully treated by minimally invasive thoracoscopic intra-fistula filling with a suture closure method. At operation, after fully filling the fistula with a polyglycolic acid (PGA) sheet and fibrin glue, the fistula was sutured with covering the PGA sheet and fibrin glue. Postoperative course was uneventful and both patient could discharged from the hospital.

[Assessment of Fat-free Diet for Postoperative Chylothorax].

BACKGROUND: Chylothorax after lung cancer surgery is relatively rare but must be considered as a complication of thoracic surgery. METHOD: Between January 2012 and June 2017, 818 patients underwent lung cancer surgery at our hospital. Among them, 14 (1.7%) patients with chylothorax were retrospectively reviewed. Three patients were treated with oral intake cessation except water and total parental nutrition( TPN)[TPN group], 11 patients were treated with a fat-free diet( fat-free diet group). RESULTS: The drainage period was similar in both group [group TPN;13 (12~14) days and group fat-free diet;15.7 (6~42) days]. In the TPN group, 3 patients underwent pleurodesis and no patient needed surgical intervention. In the fat-free diet group, 5 patients improved only with diet management. Pleurodesis was necessary in 5 of which 3 underwent surgical intervention. CONCLUSIONS: A fat-free diet is useful in treating chylothorax after lung cancer surgery.

[Long Term Placement of Endobronchial Watanabe Spigot for Empyema with Bronchopleural Fistula].

A 63-years old man referred to our hospital complaining of fever and dyspnea. He had severe diabetes. Chest computed tomography revealed left empyema with bronchopleural fistula and right pneumonia. Chest drainage was performed, but his general condition was too bad to perform surgical treatment. We performed bronchial embolization with Endobronchial Watanabe Spigot (EWS) which successfully closed the bronchopleural fistula resulting in the cure of pneumonia. Even at 1 year after treatment, good condition is being kept under the placement of EWS.

[Air Bubble in the Left Ventricle due to Computed Tomography Guided Lung Needle Biopsy].

Computed tomography (CT) guided lung biopsy is a useful examination in diagnosing pulmonary diseases, but the complications such as pneumothorax or pulmonary hemorrhage can not be ignored. Among them, air embolization is a severe complication, although it is infrequently encountered. Forty two-year-old man admitted to our department for the examination of left lung tumor. CT guided lung biopsy was performed. After examination, the patient showed disturbance in cardiac function, which recovered in several minutes. Chest CT revealed air bubble in the left ventricle. After 2-hours head down position followed by bed rest, air bubble is confirmed to be dissappeared by CT.

Two autopsied gastric cancer cases of rare drug-induced pneumonia associated with nivolumab plus S-1 and oxaliplatin: a case report.

Background: Drug-induced pneumonia, especially immune-related adverse events, can sometimes be fatal, and it is crucial to seize the signs for early treatment. A clinical trial (ATTRACTION-4) reported no cases of grade 4 or 5 pneumonia or interstitial lung disease associated with nivolumab plus S-1 and oxaliplatin. However, we encountered two cases of fatal pneumonia induced by this regimen. Case Description: The two patients were in their 70s, male and diagnosed gastric cancer with peritoneal dissemination. The patient of case 1 underwent surgery and adjuvant chemotherapy nine years before. The patient of case 2 was diagnosed unresectable 6 months before and chemo naïve. Both patients received nivolumab plus S-1 and oxaliplatin for the dissemination. The onset of both cases occurred after the fifth dose of the regimen, and the responses to corticosteroids were transient and limited. Computed tomography showed bilateral consolidation and ground-glass opacities, seemingly similar to an organizing pneumonia pattern. Acute and organizing stages of diffuse alveolar damage were detected histopathologically. Despite showing notable antitumor effects, both patients had indications of interstitial pneumonitis before admission, such as elevation of C-reactive protein (CRP) and Krebs von den Lungen-6 (KL-6) levels and slight lung opacity or respiratory symptoms approximately 10 days before admission. Conclusions: Patients undergoing nivolumab plus S-1 and oxaliplatin should be closely followed up with imaging, evaluation of symptom including oxygen saturation, and serological marker analysis such as lactate dehydrogenase, CRP, and KL-6. Early detection of pneumonia leads to adequate cessation of chemotherapy and early treatment, and this can prevent severe adverse events.

Prognostic impact of lymphovascular invasion compared with that of visceral pleural invasion in patients with pN0 non-small-cell lung cancer and a tumor diameter of 2 cm or smaller.

BACKGROUND: Both visceral pleural invasion (VPI) and lymphovascular invasion (LVI) have been shown to be adverse prognostic factors for early-stage non-small-cell lung cancer (NSCLC). Positive VPI upstages the T category of tumors ≤ 2 cm (T1a) to T2a, whereas LVI is not adapted as a descriptor for the Tumor, Node, Metastasis classification system. This study was conducted to evaluate the prognostic impacts of VPI and LVI in patients with pN0 NSCLC and a tumor diameter of ≤ 2 cm. METHODS: We reviewed records of a total of 142 patients with pN0 NSCLC and a tumor diameter of ≤ 2 cm, who underwent lobectomy with hilar and mediastinal lymph node dissection between January 2001 and December 2009. We conducted univariate and multivariate analyses to evaluate the impact of VPI, LVI, and other clinicopathologic factors on survival. RESULTS: Visceral pleural invasion and LVI were diagnosed as positive in 18 (12.7%) and 22 (15.5%) patients, respectively. Male sex, squamous cell carcinoma, positive VPI, and positive LVI were risk factors for overall survival. Squamous cell carcinoma, positive VPI, and positive LVI were risk factors for relapse-free survival. In multivariate analysis, squamous cell carcinoma and positive LVI were independent risk factors for overall survival, and positive LVI was an independent risk factor for relapse-free survival. CONCLUSIONS: Positive LVI was more important than VPI as a prognostic factor in patients with pN0 NSCLC and a tumor diameter of ≤ 2 cm. Adjuvant chemotherapy should be considered for such patients, to improve the treatment outcomes.

[Pulmonary abscess caused by fish bone].

We describe an extremely rare case of pulmonary abscess caused by fish bone which stabbed the lung from transesophageal route. A 60-year-old woman referred to our hospital complaining of fever. Three days before, she had swallowing pain while eating the bony parts of a fish. An examination on admission showed that C-reactive protein (CRP) is 9.70 mg/dl. Chest computed tomography (CT)revealed, 4 cm mass shadow in the right upper lobe and fish bone material in the mass shadow. Esophagography showed no abnormal findings. Right upper lobectomy was performed under the diagnosis of pulmonary abscess by fish bone. Post operative course was uneventful. The cause was suspected of migration of a fish bone into the right upper lobe via mediasinum and thoracic cavity from esophagus.

Surgical outcome of ipsilateral anatomical resection for lung cancer after pulmonary lobectomy.

OBJECTIVES: Ipsilateral reoperation after pulmonary lobectomy is often challenging because of adhesions from the previous operation. We retrospectively examined the surgical outcome and prognosis of ipsilateral anatomical resection for lung cancer after pulmonary lobectomy using a multicentre database. METHODS: We evaluated the perioperative outcomes and overall survival of 51 patients who underwent pulmonary lobectomy followed by ipsilateral anatomical resection for lung cancer between January 2012 and December 2018. In addition, patients with stage I non-small-cell lung cancer (NSCLC) were compared with 3411 patients with stage I lung cancer who underwent pulmonary resection without a prior ipsilateral lobectomy. RESULTS: Ipsilateral anatomical resections included 10 completion pneumonectomies, 19 pulmonary lobectomies and 22 pulmonary segmentectomies. Operative time was 312.2 ± 134.5 min, and intraoperative bleeding was 522.2 ± 797.5 ml. Intraoperative and postoperative complications occurred in 9 and 15 patients, respectively. However, the 5-year overall survival rate after anatomical resection followed by ipsilateral lobectomy was 83.5%. Furthermore, in patients with c-stage I NSCLC, anatomical resection followed by ipsilateral lobectomy was not associated with worse survival than anatomical resection without prior ipsilateral lobectomy. CONCLUSIONS: Anatomical resection following ipsilateral lobectomy is associated with a high frequency of intraoperative and postoperative complications. However, the 5-year overall survival in patients with c-stage I NSCLC who underwent ipsilateral anatomical resection after pulmonary lobectomy is comparable to that in patients who underwent anatomical resection without prior pulmonary lobectomy.

Clinical Features of Patients With Second Primary Lung Cancer After Head and Neck Cancer.

BACKGROUND: In survivors of head and neck cancer (HNC), second primary lung cancer (SPLC) often develop as a result of a common risk factor, that is, smoking. A multicenter experience was reviewed to evaluate how the history of a diagnosis of HNC affects the outcomes of patients undergoing pulmonary resection for SPLC. METHODS: A multicenter retrospective analysis of patients hospitalized between January 2012 and December 2018 was performed. From a cohort of 4521 patients undergoing therapeutic pulmonary resection for primary non-small cell lung cancer, 100 patients with a previous history of HNC (HNC group) were identified. These patients were compared with a control group consisting of 200 patients without an HNC history from the same cohort pair-matched with operating facility, age, sex, and pathologic stage of lung cancer. RESULTS: At the time of surgery for SPLC, the HNC group showed malnutrition with a lower prognostic nutritional index compared with the control group (P < .001). The HNC group was determined to have postoperative complications more frequently (P = .02). The 5-year overall survival rates in the HNC and control groups were 59.0% and 83.2%, respectively (P < .001). Statistically, HNC history, lower prognostic nutritional index, squamous cell lung cancer, and TNM stage were identified to be independently associated with poor survival. CONCLUSIONS: Patients with SPLC after primary HNC often present with malnutrition and are predisposed to postoperative complications and poor survival after pulmonary resection.

[Clinical assessment of granulocyte colony-stimulating factor producing lung cancer].

OBJECTIVE: The aim of this study was to reveal the clinicopathological feature of granulocyte colony-stimulating factor (G-CSF) producing lung cancer. METHOD: Nine cases of G-CSF producing lung cancer from July 2003 to July 2008 were retrospectively evaluated. RESULTS: All cases were male, 8 cases were poorly differentiated carcinoma. Average of leucocyte and serum G-CSF were 23,378/microl and 128.6 pg/ml respectively. Five cases had febrile symptom, average of serum C-reactive protein (CRP) was 13.37 mg/dl. Immunohistological examination showed positive staining for G-CSF in 6 cases. Serum interleukin-6 (IL-6) level was elevated in 3 cases. Clinical stages were IB in 2, IIB in 2, IIIA in 3 and IIIB in 2 patients. Chemotherapy was performed for patients with stage IIIB. Operation was performed for the other cases. Five cases were died within 12 months, whereas 4 cases are surviving for 6 to 16 months. CONCLUSION: Generally, the prognosis of G-CSF producing lung cancer seems to be poor, but in our institute there were 2 cases who lived over 1 year without disease. It is important to establish more effective adjuvant therapy for G-CSF producing tumor.

[Pericardial cyst that involved thoracic duct].

A 79-year-old man was admitted to our hospital because of swallowing disturbance. Chest X-ray and computed tomography (CT) scan revealed 7 x 6 cm cystic shadow in posterior mediastinum. We diagnosed that swallowing disturbance caused by pericardial cyst. Cysticotmy was performed. Three days after operation, chylothorax occurred. Conservative therapy was not effective, we performed re-operation 28 days later from the 1st operation. There was aperture of thoracic duct inside of cyst, and thoracic duct was ligated. After the 2nd operation, chylothorax was cured.

[Pulmonary hamartoma associated with lung cancer].

Pulmonary hamartoma is most common benign tumor of the lung and is not recognised as having a character of malignant transformation. So, longtime radiological observation is not uncommon for patients with diagnosis of pulmonary hamartoma from computed tomography (CT) finding. Although pulmonary hamartoma does not transform to malignancy, high frequency of coexistence hamartoma and lung cancer has been reported. We experienced 14 cases of resected pulmonary hamartoma, and 3 of them had lung cancer, showing that 21.4% of pulmonary hamartoma coexisted with lung cancer. Patients with pulmonary hamartoma should undergo sufficient evaluations for malignancy.

Development of a new tissue-engineered sheet for reconstruction of the stomach.

We have developed tissue-engineered digestive tracts composed of collagen scaffold and an inner silicon sheet and successfully used it to repair defects in parts of the esophagus, stomach, and small intestine. However, some improvements were demanded for clinical usage because the silicon sheet presented technical difficulties for suturing and endoscopic removal. New tissue-engineered sheet (New-sheet) was composed of a single-piece and reinforced collagen scaffold with biodegradable copolymer. One beagle dog was used to evaluate whether New-sheet could withstand suturing in comparison with native digestive tracts using a tensile tester. Seven beagle dogs had a 5-cm circular defect created in the stomach. New-sheet soaked with autologous peripheral blood or bone marrow aspirate was sutured to the gastric wall. Endoscopic, histological, and immunohistochemical assessment was performed to evaluate regeneration of the stomach up to 16 weeks. Tensile strength testing showed that the mucosal side of New-sheet had strength almost equivalent to the mucosa of the esophagus (P = 0.61). Endoscopically, regeneration of the mucosa started from the circumference after 4 weeks, but a small linear ulcer was still evident at 16 weeks. The regenerated stomach shrank by 60-80% of its original size and histologically showed villous mucosa and underlying dense connective tissue. Immunohistochemically, the regenerated area expressed alpha-smooth-muscle actin but was negative for basic calponin, irrespective of the source of soaked blood. New-sheet shows sufficient strength for suturing, no dehiscence, and better biocompatibility for clinical use, although further examination will be necessary to create a functional digestive tract.

Influence of intersegmental plane size and segment division methods on preserved lung volume and function after pulmonary segmentectomy.

OBJECTIVES: We previously reported that the use of a stapler to divide intersegmental planes did not decrease preserved pulmonary volume or function relative to electrocautery. However, preservation of pulmonary volume or function can be compromised when a stapler is used with larger intersegmental planes. Here, we assessed the correlations between preserved lung volume and pulmonary function after segmentectomy and the size of the intersegmental planes, based on the division method. METHODS: Intersegmental plane sizes in 56 patients were semi-automatically calculated using image analysis software on computed tomography images. The ratios of the remnant segment and ipsilateral lung volumes to their preoperative values (R-seg and R-ips) and the ratio of the postoperative pulmonary function relative to the predicted value were calculated based on three-dimensional volumetry. Correlations between preserved lung volume and pulmonary function and the intersegmental plane sizes were analyzed according to the division method. RESULTS: Intersegmental planes were divided by either electrocautery or with a stapler (EC/Mixed) in 21 patients and by stapler alone (ST) in 35 patients. There was no difference in the average size of the intersegmental planes between the two groups. The intersegmental plane size negatively correlated with R-seg in the ST group. CONCLUSIONS: Using the stapler method, as the size of the intersegmental planes increased, the preserved remnant segmental volume decreased; however, relation between the plane size and preserved pulmonary function was unclear. These findings indicate that stapler use is acceptable even for large intersegmental planes.

Droplet digital PCR as a novel system for the detection of microRNA­34b/c methylation in circulating DNA in malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is a rare malignancy arising from the pleura that is difficult to diagnose, contributing to its dismal prognosis. Previously, we reported that the degree of microRNA (miR)­34b/c methylation in circulating DNA is associated with the development of MPM. Herein, we present a newly developed droplet digital PCR (ddPCR)­based assay for the detection of miR­34b/c methylation in circulating DNA in patients with MPM. We originally prepared two probes within a short amplicon of 60 bp, designing one from the positive strand and the other from the complementary strand. The two probes functioned cooperatively, and our established assay detected DNA methylation accurately in the preliminary validation. We subsequently verified this assay using clinical samples. Serum samples from 35 cases of MPM, 29 cases of pleural plaque and 10 healthy volunteers were collected from 3 different institutions and used in this study. We divided the samples into 2 groups (group A, n=33; group B, n=41). A receiver­operating characteristic curve analysis using the samples in group A determined the optimal cut­off value for the diagnosis of MPM, with a sensitivity of 76.9% and a specificity of 90%. On the other hand, the use of the same criterion yielded a sensitivity of 59.1% and a specificity of 100% in group B, and corresponding values of 65.7 and 94.9% for the entire cohort, indicating a moderate sensitivity and a high specificity. In addition, when the analysis was focused on stage II or more advanced MPM, the sensitivity improved to 81.8%, suggesting the possibility that the methylated allele frequency in MPM may be associated with the stage of disease progression. On the whole, the findings of this study indicate that miR­34b/c methylation in circulating DNA is a promising biomarker for the prediction of disease progression in patients with MPM.

The impact of coexisting lung diseases on outcomes in patients with pathological Stage I non-small-cell lung cancer.

OBJECTIVES: Cigarette smoking is a well-known cause of interstitial lung disease (ILD), pulmonary emphysema and lung cancer. Coexisting pulmonary disease can affect prognosis in patients with lung cancer. The aim of this study was to determine the influence of pulmonary disease on outcomes in patients with a smoking history who had undergone surgery for pathological Stage I non-small-cell lung cancer. METHODS: Medical records of 257 patients with a smoking history who underwent surgery for pathological Stage I non-small-cell lung cancer between June 2009 and December 2014 were reviewed. Coexisting ILDs were evaluated using high-resolution computed tomography. The degree of pulmonary emphysema was determined using image analysis software according to the Goddard classification. The impact of clinicopathological factors on outcome was evaluated. RESULTS: Among the 257 patients, ILDs were detected via high-resolution computed tomography in 60 (23.3%) patients; of these, usual interstitial pneumonia (UIP) patterns and non-UIP patterns were seen in 25 (9.7%) and 35 (13.6%) patients, respectively. The degree of pulmonary emphysema was classified as none, mild and moderate and included 50 (19.5%), 162 (63.0%) and 45 (17.5%) patients, respectively. The 5-year overall survival, cancer-specific survival and relapse-free survival were 80.7%, 88.0% and 74.9%, respectively, during a median follow-up period of 50.5 months. In multivariate analysis, the presence of a UIP pattern was shown to be an independent risk factor for poor outcome. CONCLUSIONS: The presence of a UIP-pattern ILD on high-resolution computed tomography images was shown to be a risk factor for poor outcome in patients with a smoking history who had undergone surgery for pathological Stage I non-small-cell lung cancer.

Air bronchogram in pleomorphic carcinoma of the lung is associated with favorable prognosis.

BACKGROUND: Pleomorphic carcinoma (PC) of the lung is a rare histological type of lung carcinoma. The association between computed tomography (CT) findings and histology with outcome remains unclear. We examined the relationships between CT features and histopathologic findings, and evaluated the impact of CT features and other clinicopathologic factors on survival. METHODS: Thirty-five consecutive patients with PC of the lung who underwent surgery between October 2010 and December 2015 were enrolled in this study. The 35 tumors were classified with or without air bronchogram in the tumors, and with or without intratumoral ground glass opacity (GGO) on CT. RESULTS: Air bronchogram and GGO were detected in 12 (34.3%) and 5 (14.3%) tumors, respectively. Multivariate analysis revealed that air bronchogram was significantly associated with the presence of adenocarcinoma components with lepidic growth patterns (P = 0.005), and predominance of adenocarcinomas (P = 0.026). GGO was significantly associated with the presence of adenocarcinoma component with lepidic growth pattern (P = 0.010). Air bronchogram was an independent favorable prognostic factor for overall survival, whereas GGO did not have a significant effect on survival. CONCLUSION: Air bronchogram observed in PCs of the lung is strongly related with histological components of the tumor and favorable outcome.