Morphological basis of the lung adenocarcinoma subtypes.

Lung adenocarcinoma (LUAD), which accounts for a large proportion of lung cancers, is divided into five major subtypes based on histologic characteristics. The clinical characteristics, prognosis, and responses to treatments vary among subtypes. Here, we demonstrate that the variations of cell-cell contact energy result in the LUAD subtype-specific morphogenesis. We reproduced the morphologies of the papillary LUAD subtypes with the cellular Potts Model (CPM). Simulations and experimental validations revealed modifications of cell-cell contact energy changed the morphology from a papillary-like structure to micropapillary or solid subtype-like structures. Remarkably, differential gene expression analysis revealed subtype-specific expressions of genes relating to cell adhesion. Knockdown experiments of the micropapillary upregulated ITGA11 gene resulted in the morphological changes of the spheroids produced from an LUAD cell line PC9. This work shows the consequences of gene mutations and gene expressions on patient prognosis through differences in tissue composing physical forces among LUAD subtypes.

Alveolar adenoma with a single cyst: A case report.

Alveolar adenoma is a rare and benign pulmonary tumor, which originates from type II pneumocytes and is often incidentally identified on radiographic images. Alveolar adenoma presents as a peripleural, solitary and cystic nodule in the lung and may mimic other types of lung tumors, thus rendering its differential diagnosis difficult. Alveolar adenoma is diagnosed based on histopathological and immunohistochemical analyses. The present study describes the case of a 50-year-old male patient with alveolar adenoma. He visited a local doctor ~3 years prior due to left chest pain. A chest computed tomography scan revealed a cystic lesion in segment 8 of the left lung. A nodular shadow appeared in the cyst and gradually increased in size; the patient was thus referred to the authors' hospital. The nodule was well-defined, solitary and solid; thus, lung cancer or aspergilloma were suspected. Thoracoscopic wedge resection was performed as diagnostic therapy. The frozen sections were non-diagnostic, and a pathological examination revealed an alveolar adenoma with no evidence of malignancy and a negative culture. The patient had a good post-operative course, with no sign of recurrence at the follow-up evaluation 46 months later. On the whole, alveolar adenoma is a rare, benign pulmonary tumor that is difficult to diagnose pre-operatively.

Expression of Preferentially Expressed Antigen in Melanoma, a Cancer/Testis Antigen, in Carcinoma In Situ of the Urinary Tract.

Carcinoma in situ (CIS) of the urinary tract comprises 1-3% of all urothelial malignancies and is often a precursor to muscle-invasive urothelial carcinoma (UC). This study aimed to examine the expression profiles of preferentially expressed antigen in melanoma (PRAME), a cancer/testis antigen, and assess its diagnostic and therapeutic applications in CIS, given that its expression in UC has been minimally studied and has not yet been analyzed in CIS. We selected consecutive patients with CIS who underwent biopsy and/or transurethral tumor resection at the Osaka Medical and Pharmaceutical University Hospital. Immunohistochemical staining for PRAME and p53 was performed. Overall, 53 patients with CIS (6 females and 47 males) were included. Notably, PRAME expression was observed in 23 of the 53 patients (43.4%), whereas it was absent in the non-neoplastic urothelial epithelium. Furthermore, no correlation was found between PRAME expression and aberrant p53 expression. Therefore, PRAME expression may serve as a useful marker for CIS of the urinary tract. Furthermore, PRAME may be a candidate for the novel therapeutic target for standard treatment-refractory CIS patients.

[Multiple Metastatic Lung Tumors in the Left Upper Lobe Complicated with Hypoplasia and Chronic Atelectasis of the Left Lower Lobe:Report of a Case].

An 80-year-old man with surgical history of colon cancer was referred to our department for surgical treatment for multiple metastatic lung tumors in the left upper lobe. The patient had been showing complete atelectasis of the left lower lung lobe one year prior to the consultation. Six months after wedge resections for the pulmonary metastases, the left lower lobe was re-expanded, showing bronchiectasis with rudimentary pulmonary artery branches. Further, the ventilation-perfusion scintigraphy showed decreased uptake in the left lower lobe. These findings indicated that the patient had the hypoplasia of the left lower lobe.

[Radiofrequency Ablation for Pulmonary Metastasis of Ovarian Cancer Caused Iatrogenic Pneumothorax, Leading to Empyema].

A female patient in her 40s who underwent surgery for recurrent right lung metastasis from resected ovarian cancer was referred to our department because of the right pneumothorax due to radiofrequency ablation for multiple lung metastases. Methicillin-resistant Staphylococcus epidermidis( MRSE) was detected from the tip of the drainage catheter indicated persistent pulmonary fistula with right empyema, and surgical treatment was performed. A white coat of the whole lung surface and air leakage were observed at radiofrequency ablation (RFA) treated lesion and partial resection of the right lung, debridement, and irrigation were performed. A pathological examination revealed residual viable ovarian cancer cells and pleural fistula.

A retrospective analysis of treatment selection and risk factors of treatment failure and recurrence in patients with spontaneous pneumothorax.

Background: Conservative observation with/without oxygen supplementation, aspiration, or tube drainage is selected as an initial treatment for spontaneous pneumothorax. In this study, we examined the efficacy of initial management for cessation of air leak and prevention of recurrence, with consideration of the degree of lung collapse. Methods: Spontaneous pneumothorax in patients who underwent initial management in our institute between January 2006 and December 2015 were included in this retrospective, single-institutional study. Multivariate analyses were conducted to identify risk factors related to the treatment failure after initial treatment and those related to ipsilateral recurrence after last treatment. Results: Of 668 episodes of 522 patients, 198 events were initially treated by observation, 22 by aspiration, and 448 by tube drainage. Successive outcome for cessation of air leak in initial treatment was achieved in 170 (85.9%), 18 (81.8%), and 289 (64.5%) events, respectively. In the multivariate analysis for predicting failure after first treatment, previous episode of ipsilateral pneumothorax [odds ratio (OR) 1.9; 95% confidence interval (CI): 1.3-2.9; P<0.01], high degree of lung collapse (OR 2.1; 95% CI: 1.1-4.2; P=0.032), and bulla formation (OR 2.6; 95% CI: 1.7-4.1; P<0.0001) were the significant risk factors for treatment failure. Recurrence of ipsilateral pneumothorax was observed in 126 (18.9%) cases: 18 of 153 cases (11.8%) in the observation group, 3 of 18 cases in the aspiration group (16.7%), 67 of 262 cases in the tube drainage group (25.6%), 15 of 63 cases in the pleurodesis group (23.8%), and 23 of 170 cases in the surgery group (13.5%). In the multivariate analysis for predicting recurrence, previous episode of ipsilateral pneumothorax was a significant risk factor [hazard ratio (HR) 1.8; 95% CI: 1.2-2.5; P<0.001]. Conclusions: Predictive factors for failure after initial treatment were recurrence of ipsilateral pneumothorax, high degree of lung collapse, and radiological evidence of bullae. The predictive factor for recurrence after the last treatment was the previous episode of ipsilateral pneumothorax. Observation was superior to tube drainage in success rate to cease air leak and recurrence rate, although this effect was not statistically significant.

Risk factors for postoperative cerebral infarction in Lung Cancer patients: a retrospective study.

BACKGROUND: Postoperative cerebral infarction is a rare but serious complication after lung cancer surgery. We aimed to investigate the risk factors and evaluate the efficiency of our devised surgical procedure to prevent cerebral infarction. METHODS: We retrospectively examined 1,189 patients who underwent a single lobectomy for lung cancer at our institution. We identified the risk factors for cerebral infarction and investigated the preventive effects of performing resection of the pulmonary vein as the last step of the surgical procedure during left upper lobectomy. RESULTS: Among the 1,189 patients, we identified 5 male patients (0.4%) with postoperative cerebral infarction. All five underwent left-sided lobectomy including three upper and two lower lobectomies. Left-sided lobectomy, a lower forced expiratory volume in 1 s, and lower body mass index were associated with postoperative cerebral infarction (Ps < 0.05). The 274 patients who underwent left upper lobectomy were stratified by two procedures: lobectomy with resection of the pulmonary vein as the last step of the surgical procedure (n = 120) and the standard procedure (n = 154). The former procedure significantly shortened the length of the pulmonary vein stump when compared with the standard procedure (mean stump length: 15.1 vs. 18.6 mm, P < 0.01), and the shorter pulmonary vein might possibly prevent postoperative cerebral infarction (frequency: 0.8% vs. 1.3%, Odds ratio: 0.19, P = 0.31). CONCLUSIONS: Resecting the pulmonary vein as the last step during the left upper lobectomy enabled the length of the pulmonary stump to be significantly shorter, which may contribute to preventing cerebral infarction.

[Giant Bullae Misdiagnosed as Pneumothorax:Report of a Case].

A 46-year-old man was taken to a hospital by ambulance because of sudden onset of dyspnea, and was inserted chest drainage tube with a diagnosis of right-sided tension pneumothorax on chest X-ray. Since the chest drainage was not effective, he was transferred to our institute. Based on chest computed tomography (CT) findings, a diagnosis of giant bullae of the right lung was made, and surgical treatment was performed. Postoperatively, the improvement of respiratory function was confirmed.

The surgical Apgar score predicts postoperative complications and the survival in lung cancer patients.

PURPOSE: The surgical Apgar score (SAS)-calculated using the intraoperative variables estimated blood loss, lowest heart rate, and lowest mean systolic pressure-is associated with mortality in cancer surgery. We investigated the utility of the SAS in patients with lung cancer undergoing surgery. METHODS: We retrospectively analyzed the data of 691 patients who underwent surgery for primary lung cancer between 2015 and 2019 in a single institute and analyzed the impact of the SAS. RESULTS: Of the 691 patients, 138 (20%), 57 (8.2%), and 7 (1.0%) had postoperative complications of all grades, grades ≥ III, and grade V, respectively, according to the Clavien-Dindo classification. The C-index for postoperative complications of grades ≥ III was 0.605. A lower score (0-5 points) (odds ratio 3.09 against 8-10 points, P = 0.04) and a lower percentage of vital capacity (odds ratio 0.97, P = 0.04) were independent negative risk factors for major postoperative complications. Patients with a lower score (0-5 points) had poor 5-year overall and cancer-specific survival rates (60.1% and 72.3%, respectively; P < 0.05 for both). CONCLUSIONS: The surgical Apgar score predicted postoperative complications and the long-term survival. Surgeons may improve surgical results using the SAS.

Stagnating blood flow related to thrombus formation in pulmonary vein stump after left upper lobectomy.

OBJECTIVES: A thrombus can occur in the stump of the pulmonary vein after left upper lobectomy, potentially causing postoperative cerebral infarction. This study aimed to verify the hypothesis that stagnation of blood flow inside the pulmonary vein stump causes thrombus formation. METHODS: The three-dimensional geometry of the pulmonary vein stump after left upper lobectomy was recreated using contrast-enhanced computed tomography. Blood flow velocity and wall shear stress (WSS) inside the pulmonary vein stump were analysed using the computational fluid dynamics (CFD) method and compared between the two groups (those with or without thrombus). RESULTS: The volumes of average flow velocity per heartbeat < 10 mm/s, 3 mm/s, 1 mm/s (p-values 0.0096, 0.0016, 0.0014, respectively) and the volumes where flow velocity was always below the three cut-off values (p-values 0.019, 0.015, 0.017, respectively) were significantly larger in patients with a thrombus than in those without thrombus. The areas of average WSS per heartbeat < 0.1 Pa, 0.03 Pa, 0.01 Pa (p-values 0.0002, < 0.0001, 0.0002, respectively), and the areas where WSS was always below the three cut-off values (p-values 0.0088, 0.0041, 0.0014, respectively) were significantly larger in patients with thrombus than in those without thrombus. CONCLUSIONS: The area of blood flow stagnation in the stump calculated by CFD method was significantly larger in patients with than in those without thrombus. This result elucidates that stagnation of blood flow promotes thrombus formation in the pulmonary vein stump in patients who undergo left upper lobectomy.

The pulmonary surgical Apgar score for lung cancer surgery predicts postoperative complications and long-term survival.

OBJECTIVES: The surgical Apgar score, calculated using 3 intraoperative variables (blood loss, lowest mean arterial pressure and lowest heart rate), is associated with mortality in cancer surgery. The original score has less applicability in lung cancer surgery; therefore, we innovated the modified pulmonary surgical Apgar score with additional intraoperative oxygen saturation representing pulmonary parenchymal damage and cardiopulmonary dynamics. METHODS: We retrospectively analysed the data of 691 patients who underwent surgery for primary lung cancer between 2015 and 2019 at a single institute. We analysed the utility of the pulmonary surgical Apgar score compared with the original surgical Apgar score. RESULTS: Postoperative complications were observed in 57 (8.2%) and 7 (1.0%) of the 691 patients who were stratified as grade ≥III and V, respectively, according to the Clavien-Dindo classification. We compared the fitness of the score in predicting postoperative complications; the calculated c-index (0.622) was slightly higher than the original c-index (0.604; P = 0.398). Patients were categorized into 3 groups based on their scores as follows: 0-6 points (n = 59), 7-9 points (n = 420) and 10-12 points (n = 212). Univariable and multivariable analyses demonstrated that a lower score was an independent negative risk factor for postoperative complications (odds ratio 3.53; P = 0.02). Patients with lower scores had a considerably poor 5-year overall survival (64.6%) (P = 0.07). CONCLUSIONS: The pulmonary surgical Apgar score predicts postoperative complications and long-term survival in patients with lung cancer undergoing surgery and may be utilized for postoperative management.

Symptom severity trajectories and distresses in patients undergoing video-assisted thoracoscopic lung resection from surgery to the first post-discharge clinic visit.

This study aimed to characterize patients' symptom severity trajectories and distresses from video-assisted thoracoscopic lung resection to the first post-discharge clinic visit. Seventy-five patients undergoing thoracoscopic lung resection for diagnosed or suspected pulmonary malignancy prospectively recorded daily symptom severity on a 0-10 numeric scale using the MD Anderson Symptom Inventory until the first post-discharge clinic visit. The causes of postoperative distresses were surveyed, and symptom severity trajectories were analyzed using joinpoint regression. A rebound was defined as a statistically significant positive slope after a statistically significant negative slope. Symptom recovery was defined as symptom severity of ≤3 in two contiguous measurements. The accuracy of pain severity on days 1-5 for predicting pain recovery was determined using area under the receiver operating characteristic curves. We applied Cox proportional hazards models for multivariate analyses of the potential predictors of early pain recovery. The median age was 70 years, and females accounted for 48%. The median interval from surgery to the first post-discharge clinic visit was 20 days. Trajectories of several core symptoms including pain showed a rebound from day 3 or 4. Specifically, pain severity in patients with unrecovered pain had been higher than those with recovered pain since day 4. Pain severity on day 4 showed the highest area under the curve of 0.723 for predicting pain recovery (P = 0.001). Multivariate analysis identified pain severity of ≤1 on day 4 as an independent predictor of early pain recovery (hazard ratio, 2.86; P = 0.0027). Duration of symptom was the leading cause of postoperative distress. Several core symptoms after thoracoscopic lung resection showed a rebound in the trajectory. Specifically, a rebound in pain trajectory may be associated with unrecovered pain; pain severity on day 4 may predict early pain recovery. Further clarification of symptom severity trajectories is essential for patient-centered care.

Bronchogenic cyst with atypical imaging findings and repeated ruptures in a short period of time: A case report.

Bronchogenic cysts are the most common primary cysts of the mediastinum. Although most are asymptomatic, some bronchogenic cysts cause symptoms such as chest pain and dyspnea. Here, we report a case of bronchogenic cyst that ruptured twice in a short period of time in a patient who presented with sudden back pain. The lesion was apparent on computed tomography (CT) as a mass lesion with heterogeneous and high attenuation in the posterior mediastinal region. CT-guided puncture performed for diagnostic purposes revealed the contents as bloody fluid. The patient suffered chest pain approximately 3 months after the first presentation, and re-growth and re-rupture of the mass was suspected. The lesion was surgically resected and pathologically diagnosed as a bronchogenic cyst. Spontaneous rupture is a very rare complication of bronchogenic cyst, usually into the trachea, pleural cavity, or pericardial cavity. However, there are no reports of multiple ruptures. This case highlights the importance of recognizing the atypical imaging findings of bronchogenic cyst and the rare complication of rupture.

SMARCA4-deficient undifferentiated tumor that responded to chemotherapy in combination with immune checkpoint inhibitors: A case report.

Thoracic SMARCA4-deficient undifferentiated tumors are a new type of neoplasm that commonly occur in the mediastinum, progress rapidly, and show a poorer prognosis. We report a case of thoracic SMARCA4-deficient undifferentiated tumor in the right thoracic cavity in a patient with a history of heavy smoking and presenting with respiratory distress and hemoptysis. Imaging showed pleural effusion and thickening. A diagnostic right pleural biopsy yielded multiple white nodules and pale bloody pleural effusion accumulated in the right thoracic cavity. Histopathologically, the tumor cells were large, some exhibited rhabdoid cytology, and they were surrounded by an infiltration of inflammatory cells. These tumor cells were negative for SMARCA4, p40, NUT, and claudin-4, leading to establishing a diagnosis of thoracic SMARCA4-deficient undifferentiated malignancy. We treated the patient with atezolizumab, carboplatin, and nab-paclitaxel. The patient achieved stable disease at 7 months during this study. Although there is no standard treatment of this disease, our reported treatment may contribute to improved prognosis, requiring further research.

Results of emergency salvage lung resection after chemo- and/or radiotherapy among patients with lung cancer.

OBJECTIVES: This study aimed to elucidate the outcomes of emergency salvage surgery following life-threatening events (serious haemorrhage and/or infections) among patients with lung cancer who had undergone chemo- and/or radiotherapy. MATERIALS AND METHODS: We analysed the data of patient from 2015 to 2020, retrospectively. The clinical characteristics, including preoperative treatment, perioperative outcomes and survival time, were analysed. RESULTS: Of the 862 patients who underwent primary lung cancer surgeries, 10 (1.2%) underwent emergency surgeries. The preoperative clinical characteristics were: median age, 63.7 years [interquartile range (IQR) 55-70.5]; sex (male/female), 9/1; clinical staging before initial treatment (I/II/III/IV), 1/1/3/5; initial treatment (chemoradiotherapy/chemotherapy/proton beam therapy), 5/4/1; and indications for emergency surgery (lung abscess/lung abscess with haemoptysis/haemoptysis/empyema), 5/3/1/1. The selected procedures and results were as follows: lobectomy/bilobectomy/pneumonectomy, 8/1/1 (all open thoracotomies); median operation time, 191.0 min (IQR 151-279); median blood loss, 1071.5 ml (IQR 540-1691.5); postoperative severe complications, 3 (30%); hospital mortality, none; median postoperative hospital stay, 37 days (12-125); control of infection and/or haemoptysis, all the cases; final outcome (alive/dead), 3/7 (all the cancer deaths); median postoperative survival, 9.4 months (IQR 4.3-20.4); and median survival from initial treatment, 19.4 months (IQR 8.0-66.9). CONCLUSIONS: Emergency salvage lung resection is a technically challenging procedure; however, the results were feasible and acceptable when the surgical indication, procedure and optimal timing were considered carefully by a multidisciplinary team. Although the aim was palliation, some patients who received additional chemotherapy afterwards and, thus, had additional survival time.

Solitary pulmonary metastasis after meningioma surgery of the head: a case report.

BACKGROUND: Meningioma is the most common type of benign primary brain tumor that is rarely associated with distant metastasis. No established treatment strategy for metastatic meningiomas exists to date. Herein, we report a case of solitary pulmonary metastasis of meningioma detected 2 years after neurosurgical resection of the primary tumor. CASE PRESENTATION: A 75-year-old male patient underwent neurosurgical resection of a convexity meningioma (World Health Organization grade II atypical meningioma), followed by postoperative radiotherapy for the residual tumor. Two postoperative years later, a solitary 10-mm pulmonary nodule in the left lower lung lobe was detected on chest computed tomography. The patient underwent video-assisted thoracoscopic left lower lobectomy for suspected pulmonary metastasis of meningioma. The pathological diagnosis was solitary pulmonary metastasis of meningioma. No sign of further recurrence was noted at 8 months postoperatively. CONCLUSIONS: We present a rare and unique surgical case of solitary pulmonary metastasis of meningioma. Further investigation is necessary to establish the standardized treatment strategy for metastatic meningiomas.

Preoperative renal dysfunction and long-term survival after surgery for non-small cell lung cancer.

OBJECTIVE: To investigate the association of preoperative renal dysfunction and long-term outcomes following lung cancer surgery. METHODS: Using the Japanese Lung Cancer Registry data, we retrospectively examined 16,377 patients who underwent surgery for non-small cell lung cancer during 2010. Patients' renal function status was categorized as follows: serum creatinine <1.5 mg/dL (control, n = 16,169), serum creatinine ≥1.5 mg/dL with no dialysis (nondialysis-dependent chronic kidney disease, n = 113), and dialysis-dependent end-stage renal disease (n = 95). The association of patients' characteristics with overall survival was evaluated using multivariate Cox proportional hazard model. RESULTS: The 5-year overall survival rates in patients with dialysis-dependent end-stage renal disease and with nondialysis-dependent chronic kidney disease were significantly worse than that in the control group (52.9% and 57.5% vs 78.0%; P < .001 for both comparisons), but were comparable to the reported 5-year overall survival rates in the natural history of end-stage renal disease (∼60%) and moderate to severe chronic kidney disease (∼50%). Cancer causes not related to lung cancer accounted for 62.2% of deaths in dialysis-dependent end-stage renal disease, which was more frequent than that in the control group (P = .002). Dialysis-dependent end-stage renal disease and nondialysis-dependent chronic kidney disease were independent risk factors for overall survival after lung cancer surgery (hazard ratio, 2.05 [P < .001] and hazard ratio, 2.04 [P = .001], respectively). CONCLUSIONS: Preoperative renal dysfunction may be adversely associated with overall survival after lung cancer surgery. Our findings could aid patients to set proper expectation of the risks and benefits about surgery for lung cancer.

Right Epipericardial Fat Necrosis After Thymectomy.

A 62-year-old male patient underwent median sternotomy and thymectomy for thymoma (World Health Organization classification type B1+B3, Masaoka classification stage II). A 10-month follow-up postoperative computed tomography showed a 22-mm nodule in the anterior mediastinal lipid tissue just above the right diaphragm. The patient was followed for 8 years, and the nodule's capsule eventually became calcified. Considering the possibility of postoperative recurrence of thymoma, we excised the nodule. The pathologic diagnosis was epipericardial fat necrosis. In some cases, fat necrosis is difficult to distinguish from malignancy by imaging only; surgical resection has diagnostic significance and should be considered.

[Pulmonary Nontuberculous Mycobacteriosis Difficult to Differentiate from Local Recurrence of the Metastatic Lung Tumor of the Uterine Cervix Cancer at the Staple-line:Report of a Case].

A 70-year-old woman underwent right S6 segmentectomy and left S6 partial resection for lung metastasis of uterine cervix cancer. Although she received adjuvant chemotherapy, chest computed tomography revealed a new pulmonary nodule on the staple stump of the right lung. We diagnosed the tumor as local recurrence at the stump and planned to continue chemotherapy. However, the size of the tumor increased, and we performed right middle and lower lobectomy. Based on the pathological and bacteriological examinations, an epithelioid cell granuloma infected by Mycobacterium avium was established.