The effect of polyglycolic acid sheet in preventing postoperative recurrent pneumothorax: a prospective cohort study.

BACKGROUND: Primary spontaneous pneumothorax occasionally relapses, even after bullectomy; therefore, coverage of the bullectomy staple line for pleural reinforcement is common in Japan. However, the appropriate covering materials have not yet been determined. METHODS: This was a longitudinal prospective cohort study. Data were available for patients aged < 40 years with primary spontaneous pneumothorax who underwent their first thoracoscopic bullectomy between July 2015 and June 2021. We used oxidized regenerated cellulose (ORC) sheets from July 2015 to June 2018, and polyglycolic acid (PGA) sheets from July 2018 to June 2021. The postoperative recurrence-free survival rate was evaluated. The characteristics of the recurrent cases (radiographic, intraoperative, and pathological findings) were also evaluated. The extent of pleural adhesions was classified into the following three groups: none, medium, or extensive. RESULTS: A total of 187 patients were included in the study. There were 92 and 95 participants in the ORC and PGA sheet groups, respectively. The postoperative recurrence-free survival rates were significantly higher in the PGA sheet group than in the ORC sheet group (ORC group vs. PGA group, 82.9% vs. 95.4%, p = 0.031). In recurrent cases, there was a significant difference in terms of pleural adhesion (0.0% [12 of 12, none] vs. 100.0% [four of four, extensive], p < 0.001). CONCLUSIONS: Compared with ORC sheets, PGA sheets are an effective material for preventing early recurrence of primary spontaneous pneumothorax. Strong local pleural adhesions potentially contribute to decreasing recurrence.

Lymph node dissection in thymic carcinomas and neuroendocrine carcinomas.

OBJECTIVES: Although lymph node (LN) metastases are not uncommon in thymic carcinomas, preoperative LN evaluation, intraoperative lymph node dissection (LND) and postoperative outcomes remain unknown. The aim of this study was to elucidate the characteristics of and outcomes in patients with thymic carcinomas and thymic neuroendocrine carcinomas undergoing LND. METHODS: A retrospective chart review was performed using our multi-institutional database to identify patients who underwent resection and LND for thymic carcinoma or thymic neuroendocrine carcinoma between 1991 and 2018. An enlarged mediastinal LN was defined as having a short-axis diameter >1 cm. We assessed survival outcomes using the Kaplan-Meier analysis. RESULTS: N1-level LND was performed in 41 patients (54.6%), N2-level LND in 14 patients (18.7%) and both-level LND in 16 patients (21.3%). Pathological LN metastasis was detected in 20 patients (26.7%) among the 75 patients undergoing LND. There was a significant difference in the number of LN stations (P = 0.015) and metastasis factor (P = 0.0042) between pathologically LN-positive and pathologically LN-negative patients. The sensitivity of enlarged LNs on preoperative computed tomography was 18.2%. There was a tendency towards worse overall survival of pathologically N2-positive patients, although the difference was not statistically significant (P = 0.15). CONCLUSIONS: Preoperative CT appears to play a limited role in detecting pathological LN metastases. Our findings suggest that the significance of N1- and N2-level LND should be evaluated in prospective studies to optimize the postoperative management of patients with thymic carcinomas and neuroendocrine carcinomas.

Survival outcomes of resection for pulmonary malignancies including non-small cell lung cancer and pulmonary metastasis after esophagectomy for esophageal carcinoma.

OBJECTIVES: This study investigated survival outcomes of resection for pulmonary malignancies after esophagectomy for esophageal carcinoma, comparing non-small cell lung cancer and pulmonary metastases. METHODS: We retrospectively reviewed consecutive patients who underwent resection for pulmonary malignancies after esophagectomy for esophageal carcinoma between 2009 and 2018. The overall survival and relapse-free survival rate were assessed using Kaplan-Meier analysis. RESULTS: Eleven patients had non-small cell lung cancer and eight patients had pulmonary metastases from esophageal carcinoma. The 5-year overall survival rate was 92.9% in all patients with a median follow-up period of 50.4 (range: 9.1-130.2) months. While the 5-year overall survival rate was 100.0% in patients with non-small cell lung cancer, it was 85.7% in patients with pulmonary metastases from esophageal carcinoma. The 5-year relapse-free survival rate was 85.7% in patients with non-small cell lung cancer. CONCLUSIONS: Our data suggest that resection for pulmonary malignancies after esophagectomy for esophageal carcinoma is associated with favorable survival outcomes and should be considered in selected patients.

Clinicopathological significance of staple line coverage with an oxidized regenerated cellulose sheet after bullectomy for primary spontaneous pneumothorax.

BACKGROUND: Oxidized regenerated cellulose (ORC) sheet, in surgery of primary spontaneous pneumothorax, is used to reinforce the visceral pleura around the staple line coverage aiming to prevent a postoperative recurrence. We evaluated the effect of ORC on recurrence within 2 years after surgery. METHODS: A total of 201 patients aged < 40 years who underwent bullectomy for primary spontaneous pneumothorax at our institution were retrospectively reviewed. They were classified into an ORC sheet coverage group (ORC group, n = 100) and a non-coverage group (n-ORC group, n = 101). Two-year recurrence-free survival rates are assessed between the two groups with associated analysis of radiographical and operative findings. RESULTS: ORC had no effect on the recurrence rate. CT images and re-operative findings showed regenerated bullae in 19 and 14 patients, close to staple lines in 14 and 11 patients, respectively. White pleural thickening within the covered area was observed in all patients of the ORC group. Pathological findings also showed pleural thickening in eight patients and bulla regeneration under pleural thickening in six patients. CONCLUSIONS: Coverage with an ORC sheet after bullectomy did not prevent the regeneration of bullae and postoperative recurrence, regardless of exerting a reinforcement effect on the visceral pleura histologically.

Efficacy and safety of surgery for spontaneous pneumothorax in elderly patients.

OBJECTIVES: There is no clear consensus on the surgical indications for spontaneous pneumothorax in elderly patients. In this study, we aimed to assess the efficacy and safety of surgical treatment of spontaneous pneumothorax in patients aged ≥70 years. We also sought to identify the risk factors for postoperative prolonged air leaks and complications in such patients. METHODS: Data pertaining to 104 elderly patients who underwent surgery out of 206 patients (aged ≥70 years) who were diagnosed with spontaneous pneumothorax at our institution between 1994 and 2018 were retrospectively reviewed. The incidences of postoperative persistent air leaks (≥2 days) and postoperative complications (≥grade 3; Clavien-Dindo classification) were analysed for efficacy and safety assessment, respectively. RESULTS: Median postoperative air leaks continued for 0 days (range 0-25); 14.4% patients developed ≥grade 3 postoperative complications. On the basis of results of multivariable analysis, it was observed that a higher PaCO2 level was significantly associated with prolonged postoperative air leaks [odds ratio (OR) 1.08, 95% confidence interval (CI) 1.00-1.17; P = 0.047]. Poorer performance status was associated with a significantly increased risk of postoperative complications, as assessed by multivariable analysis (OR 6.13, 95% CI 1.38-27.3; P = 0.017). The recurrence rate was 4.8%; mortality rate of patients was 2.9%. Three-year survival rate after surgery was 73.8%. CONCLUSIONS: Surgical treatment of spontaneous pneumothorax may be effective and safe in selected elderly patients. Moreover, higher PaCO2 and poorer performance status were independent risk factors for postoperative persistent air leaks and complications, respectively.

Multifocal thymic cysts with cholesterol granuloma.

A 56-year-old female presented to our department with chest discomfort. Contrast-enhanced computed tomography (CT) revealed a cyst and nodule in the anterior mediastinum; positron emission tomography-CT showed an increased uptake in the nodule. Total thymectomy was performed to obtain a definitive diagnosis and treatment. A pathological diagnosis of multifocal thymic cysts with cholesterol granuloma was made. Microscopic examination revealed different-sized cysts scattered in the thymus. These cysts were filled with cholesterol clefts and manifested three different phase characters. The nodule comprised granuloma-containing cholesterol clefts. We report a rare case of a patient whose histopathology presented a series of cholesterol granuloma formations.

The synergistic role of ATP-dependent drug efflux pump and focal adhesion signaling pathways in vinorelbine resistance in lung cancer.

The vinorelbine (VRB) plus cisplatin regimen is widely used to treat non-small cell lung cancer (NSCLC), but its cure rate is poor. Drug resistance is the primary driver of chemotherapeutic failure, and the causes of resistance remain unclear. By focusing on the focal adhesion (FA) pathway, we have highlighted a signaling pathway that promotes VRB resistance in lung cancer cells. First, we established VRB-resistant (VR) lung cancer cells (NCI-H1299 and A549) and examined its transcriptional changes, protein expressions, and activations. We treated VR cells by Src Family Kinase (SFK) inhibitors or gene silencing and examined cell viabilities. ATP-binding Cassette Sub-family B Member 1 (ABCB1) was highly expressed in VR cells. A pathway analysis and western blot analysis revealed the high expression of integrins ß1 and ß3 and the activation of FA pathway components, including Src family kinase (SFK) and AKT, in VR cells. SFK involvement in VRB resistance was confirmed by the recovery of VRB sensitivity in FYN knockdown A549 VR cells. Saracatinib, a dual inhibitor of SFK and ABCB1, had a synergistic effect with VRB in VR cells. In conclusion, ABCB1 is the primary cause of VRB resistance. Additionally, the FA pathway, particularly integrin, and SFK, are promising targets for VRB-resistant lung cancer. Further studies are needed to identify clinically applicable target drugs and biomarkers that will improve disease prognoses and predict therapeutic efficacies.

Hypoxia-inducible factor 1 promotes chemoresistance of lung cancer by inducing carbonic anhydrase IX expression.

Lung cancer treatment is difficult owing to chemoresistance. Hypoxia-inducible factor 1 (HIF-1) and HIF-1-induced glycolysis are correlated with chemoresistance; however, this is not evident in lung cancer. We investigated the effect of HIF-1α and carbonic anhydrase IX (CAIX), a transmembrane protein neutralizing intracellular acidosis, on chemoresistance and prognosis of lung cancer patients after induction chemoradiotherapy. Associations of HIF-1α, glucose transporter 1 (GLUT1), and CAIX with chemoresistance of lung cancer were investigated using A549 lung cancer cells under normoxia or hypoxia in vitro. HIF-1α-induced reprogramming of glucose metabolic pathway in A549 cells and the effects of HIF-1 and CAIX on the cytotoxicity of vinorelbine were investigated. Immunohistochemical analyses were performed to determine HIF-1α, GLUT1, and CAIX expression levels in cancer specimens from lung cancer patients after induction chemoradiotherapy. Hypoxia induced HIF-1α expression in A549 cells. Moreover, hypoxia induced GLUT1 and CAIX expression in A549 cells in a HIF-1-dependent manner. Glucose metabolic pathway was shifted from oxidative phosphorylation to glycolysis by inducing HIF-1α in A549 cells. HIF-1 and CAIX induced chemoresistance under hypoxia, and their inhibition restored the chemosensitivity of A549 cells. The expression levels of HIF-1α, GLUT1, and CAIX were associated with poor overall survival of lung cancer patients after induction chemoradiotherapy. HIF-1 and CAIX affected the chemosensitivity of A549 cells and prognosis of lung cancer patients. Therefore, inhibition of HIF-1 and CAIX might improve prognosis of lung cancer patients after induction chemoradiotherapy. Further analysis might be helpful in developing therapies for lung cancer.

Is volumetric 3-dimensional computed tomography useful to predict histological tumour invasiveness? Analysis of 211 lesions of cT1N0M0 lung adenocarcinoma.

OBJECTIVES: The purpose of this study was to use Hounsfield unit (HU) thresholds of computed tomography (CT) images to predict pathological lymph node metastasis and tumour invasiveness of cT1N0M0 lung adenocarcinoma on 3D evaluations. METHODS: Preoperative CT images of 211 lesions of surgically resected cT1N0M0 lung adenocarcinoma were retrospectively examined. The tumour size was calculated in 1D, 2D and 3D views. Tumours with -300 HU and over were defined as 'solid tumours', and those between -800 and -301 HU were defined as 'ground glass opacity tumours'. Tumours with -800 HU and over were assumed to be the whole tumour entity. The proportion of 'solid tumour' within the whole tumour entity was also calculated as the 'solid tumour ratio'. These were compared with pathological information. RESULTS: Solid tumour size and ratio were positively correlated with microscopic invasion to pleura, vessels and lymphatics in all dimensional evaluations. Pathological lymph node metastases were also well predicted by solid tumour size and ratio in all dimensional evaluations. The P-values for the receiver operating characteristic (ROC) curves of 1D, 1D ×2, 2D and 3D evaluations were: solid tumour size P = 0.013, 0.014 and 0.032; and solid tumour ratio 0.016, 0.0032 and <0.0001. In comparisons of 1D, 2D and 3D evaluations, 'solid tumour size' of the area under the curve (AUC) of ROC to detect pathological lymph node metastases was not significant. However, strikingly, the 3D solid tumour ratio was found to be significantly more accurate for the prediction of pathological lymph node metastases than the 1D and 2D solid tumour ratios on ROC evaluation (AUC: 1D 0.736, 2D 0.803 and 3D 0.882; P-values for the AUC comparisons were P = 0.013 for 3D versus 1D and P = 0.022 for 3D versus 2D). The correlations of subtypes of adenocarcinoma and the 3D solid tumour ratio were also investigated. Subtypes of adenocarcinoma were well correlated with the 3D solid tumour ratio. CONCLUSIONS: Preoperative 3D CT using threshold values of -800 and -300 HU was useful for predicting pathological lymph node metastases and tumour invasiveness of cT1N0M0 lung adenocarcinoma.

Association between epithelial-mesenchymal transition and cancer stemness and their effect on the prognosis of lung adenocarcinoma.

The epithelial-mesenchymal transition (EMT) and cancer stemness (CS) are reported to be pivotal phenomena involved in metastasis, recurrence, and drug-resistance in lung cancer; however, their effects on tumor malignancy in clinical settings are not completely understood. The mutual association between these factors also remains elusive and are worthy of investigation. The purpose of this study was to elucidate the association between EMT and CS, and their effect on the prognosis of patients with lung adenocarcinoma. A total of 239 lung adenocarcinoma specimens were collected from patients who had undergone surgery at Kyoto University Hospital from January 2001 to December 2007. Both EMT (E-cadherin,vimentin) and CS (CD133, CD44, aldehyde dehydrogenase) markers were analyzed through immunostaining of tumor specimens. The association between EMT and CS as well as the patients' clinical information was integrated and statistically analyzed. The molecular expression of E-cadherin, vimentin, and CD133 were significantly correlated with prognosis (P = 0.003, P = 0.005, and P < 0.001). A negative correlation was found between E-cadherin and vimentin expression (P < 0.001), whereas, a positive correlation was found between vimentin and CD133 expression (P = 0.020). CD133 was a stronger prognostic factor than an EMT marker. Elevated CD133 expression is the signature marker of EMT and CS association in lung adenocarcinoma. EMT and CS are associated in lung adenocarcinoma. Importantly, CD133 is suggested to be the key factor that links EMT and CS, thereby exacerbating tumor progression.

Retrospective case series analysing the clinical data and treatment options of patients with a tubercular abscess of the chest wall.

The tubercular abscess of the chest wall remains one of the differential diagnoses of a chest wall tumour, and the management strategy is controversial. We reviewed the medical records of 22 patients treated at our institution. Two patients were managed by antitubercular medications alone; eight patients were managed by medication and open drainage. Five patients underwent open drainage with subsequent radical surgery at a constant interval of time, and the mean duration between open drainage and radical surgery was 9.8 weeks (range, 3-12). Seven patients underwent radical surgery without prior open drainage. Five patients required rib resections, and curettage of infected pleural peel was necessary in 5 patients. Antitubercular drugs were administered basically for more than 6 months regardless of surgical management, including for more than 1 month prior to radical surgery. Postoperative empyema was seen in 1 patient after radical surgery. The mean follow-up duration was 32.8 months (range, 3-100), and there was no recurrence. Complete resection of the tubercular abscess with sufficient antitubercular therapy resulted in a satisfactory outcome. Antitubercular therapy with or without open drainage can be a viable choice.

Atypical carcinoid of thymus associated with multiple endocrine neoplasia syndrome type 1.

Thymic carcinoid associated with multiple endocrine neoplasia syndrome type 1 (MEN-1) is a rare tumor. We report a case of MEN-1-related thymic carcinoid. The patient reported herein had already been diagnosed with MEN-1 and was found to have a mediastinal mass. She underwent thymectomy with partial resection of the left innominate vein and lung. Histological examination revealed atypical carcinoid with infiltration. MEN-1 gene mutation was detected by employing the direct nucleotide sequencing method. Postoperative 2-fluoro-2-deoxyglucose positron emission tomography showed probable multiple metastases in the vertebrae and myocardium. However, she has been alive and asymptomatic for 2 years postoperatively. MEN-1-related thymic carcinoid is often insidious with a poor prognosis. We suggest chest computed tomography scan or magnetic resonance imaging for MEN-1 patients and serological or genetic screening for patients with thymic carcinoid to screen for MEN-1.