[Surgical Treatment and Outcomes for Synchronous Multiple Lung Cancer].

OBJECTIVES: With the advent of high-resolution chest imaging systems and lung cancer screening programs, the number of patients diagnosed with multiple primary lung cancers is increasing. For the treatment of multiple lung cancers, a surgical procedure that preserves the lung function while ensuring curability is required. We herein report the surgical strategy and outcomes of synchronous multiple lung cancer. SUBJECTS: The subjects were 83 patients with synchronous multiple lung cancer who received surgical resection between January 2010 and March 2020. Cases within the same lobe were excluded, and only cases with two or more lobes involved were included in this study. RESULTS: The study enrolled 39 male and 44 female patients, and the mean age was 67.8 years old. Sixty-five patients had cancers within a unilateral lobe, and all had undergone surgery for one term. Eighteen patients had cancers in bilateral lobes, and 17 of them received secondary surgery for more advanced cancer. Bilobectomy was performed in 9 patients( 10.8%), consisting of 5 upper-middle lobectomies, 3 middle-lower lobectomies, and 1 right middle lobectomy with left lower lobectomy. Seventy-four patients (89.2%) underwent combination surgery with sublobar resection, such as segmentectomy and partial resection. Pneumonectomy was not performed in any patients. The histologic type was adenocarcinoma in 78 patients (94.0%), and 37 patients (47.4%) had adenocarcinoma in situ. Regarding the most advanced pathological stage, 57 patients( 68.7%) were stage≤Ⅰ, and 26( 31.3%) were stage≥Ⅱ. Postoperative complications were observed in 29 patients( 34.9%), and persistent pulmonary fistula of ≥7 days after the surgery was the most common, being observed in 16 patients. Operative death within 30 days after surgery occurred in 2 patients( 2.4%)[ due to pneumonia in 1 and cerebral infarction in 1]. None of the patients required home oxygen therapy after surgery. Recurrence occurred in 20 patients;14 of these had pathological stage ≥Ⅱ, 11 had lymph node metastases, and 2 had pleural dissemination. The recurrence patterns were metastasis to other organs, pleural dissemination, or lymph node metastasis;no local recurrence was observed. The mean recurrence-free survival was 32.4 months, and the five-year survival rate was 84.8%. On comparing outcomes according to the most advanced pathological stage, the five-year survival rate for stage ≤Ⅰdisease was 94.9%, and that for stage ≥Ⅱ disease was 61.7%, showing a significantly better prognosis for stage ≤Ⅰdisease (p<0.001). CONCLUSIONS: Selecting an appropriate operative procedure for synchronous multiple lung cancer renders the prognosis equivalent to that of single cancer. Surgical treatments, including sublobar resection, are thus deemed important.

Expression of vascular endothelial growth factor receptor in thymic epithelial tumors.

Thymic epithelial tumors (TETs) are rare and the major symptoms are not obvious until the tumor progresses to a relatively large size and compresses the surrounding organs. As its growth is aggressive and it metastasizes to distant organs, it is important to find novel effective therapies. Lenvatinib, a vascular endothelial growth factor receptor (VEGFR) inhibitor, is approved as a drug therapy for thymic carcinoma (TC); however, although it is a molecular targeted therapy, there are no obvious predictors of therapeutic efficacy. The present study aimed to assess the association between clinicopathological factors and the protein expression of VEGFR, which is associated with tumor aggressiveness and the efficacy of VEGFR inhibitors. The VEGFR-2 protein expression was evaluated in 144 patients with TETs who underwent surgical resection. The present study assessed whether the expression of VEGFR-2 protein was associated with TET classification and pathological stage, progression-free survival and overall survival (OS). A total of 94 cases (65.2%) were positive for VEGFR-2 protein. The expression of VEGFR-2 was higher in the more aggressive type B3 thymoma and TC (88.5%) than in types A, AB, B1 and B2 thymoma (60.2%). The 5-year OS rate for the overall population was 53.1%. The 5-year OS rates of patients with negative VEGFR-2 staining score values (66.5%) were significantly longer than in patients with positive VEGFR-2 staining score values (42.5%; P=0.000078). Furthermore, the pathological stage was the only factor significantly associated with OS in multivariate analysis. The results of the present study suggest the possibility that the indications for VEGF inhibitor therapy could be extended to type B3 thymoma.

Pathologically noninvasive cancer predictors and surgical procedure for peripheral lung cancer.

BACKGROUND: In this retrospective study, based on recent studies reporting the superiority of sublobar resection to lobectomy for peripheral small size non-small cell lung cancer (NSCLC), we investigated the optimal pathological factors for predicting noninvasive cancer and the selection of operative procedure. METHODS: Patients with peripheral NSCLC of ≤2 cm who underwent surgery at our hospital between January 2010 and June 2020 were included in this study. We evaluated the relationship between pathologically noninvasive cancer and predictive factors according to the area under the curve (AUC) and accuracy, and the cutoff value was set to investigate indications for sublobar resection. RESULTS: The comparison of the AUCs revealed that the maximum standardized uptake value and consolidation to tumor (C/T) volume ratio were better predictors than the C/T ratio. Among the three factors, the C/T volume ratio showed the best accuracy. The patients were divided into two groups (low and high) using the cutoff value of the C/T volume ratio and compared according to the surgical procedure (lobectomy vs. segmentectomy). In the low-group, there was no significant difference in the prognosis. In the high-group, the 5-year recurrence-free survival rate of the patients who received lobectomy was 87.8%, while that of patients who received segmentectomy was 75.8% (p = 0.08). CONCLUSIONS: The C/T volume ratio was the best preoperative pathologically noninvasive predictive factor. Sublobar resection should be performed with caution in cases with significant solid components on three-dimensional images.

Preoperative detection of pleural adhesions using dynamic chest radiography: prospective analysis.

Background: To plan a surgical approach and predict the operative time or bleeding volume, it is important to determine the presence of pleural adhesions before surgery. Dynamic chest radiography (DCR) is a new modality that can dynamically capture X-rays, and we assessed the utility of DCR for detecting pleural adhesions preoperatively. Methods: The subjects of this study were those who underwent DCR before surgery from January 2020 to May 2022. The preoperative evaluation was performed by three imaging analysis modes, and pleural adhesion was defined as the that spreading to more than 20% of the thoracic cavity and/or taking more than 5 minutes to dissect. Results: Of the 120 total patients, DCR was performed properly for 119 (99.2%). Accurate preoperative evaluations of pleural adhesions were confirmed in 101 patients (84.9%), with a sensitivity of 64.5%, specificity of 91.0%, positive predictive value of 74.1%, and negative predictive value of 88.0%. Conclusions: DCR was very easy to perform in all preoperative patients with all manner of thoracic disease. We demonstrated the utility of DCR, showing its high specificity and negative predictive value. DCR has the potential to become a common preoperative examination for detecting pleural adhesions with further improvements in software programs.

Impact of ground glass opacity in a three-dimensional analysis for pathological findings and prognosis in stage IA pure solid lung cancer.

Background: We investigated whether a three-dimensional (3D) analysis could correct the discrepancy between conventional computed tomography findings and pathological findings and contribute to prognostic stratification in early pure solid lung cancer. Methods: A total of 370 patients with two-dimensional (2D) pure solid, clinical stage IA non-small cell lung cancer (NSCLC) who underwent complete resection at our hospital between January 2010 and March 2021 were included in the present study. We classified the patients into the 3D solid group and the 3D ground glass opacity (GGO) group according to the consolidation volume/tumor volume ratio (C/T volume ratio) measured using a Synapse Vincent 3D analysis workstation, and compared the pathological findings and prognosis between the two groups. Results: There were 142 (38.4%) patients in the 3D GGO group. Lepidic lesions were significantly more frequent in the 3D GGO group (27.6% vs. 59.2%, P<0.001). Lymphatic invasion, vascular invasion and lymph node metastasis were significantly more frequent in the 3D solid group (52.2% vs. 27.5%, P<0.001; 67.5% vs. 43.0%, P<0.001; 22.3% vs. 11.2%, P=0.04). A Cox proportional hazards multivariate analysis for overall survival (OS) and recurrence-free survival (RFS) showed that 3D solid was an independent poor prognostic factor [hazard ratio (HR): 1.981, P=0.02; HR: 1.815, P=0.02]. Kaplan-Meier curves for 5-year OS (74.1% vs. 87.8%, P<0.001) and 5-year RFS (65.6% vs. 84.9%, P<0.001) showed significant differences between the two groups. Conclusions: The C/T volume ratio determined by a 3D analysis detects GGO and reflects the pathological findings, and further prognostic stratification is possible in early 2D pure solid lung cancer.

Bronchiolar adenoma/ciliated muconodular papillary tumor mixed with adenocarcinoma in situ in the same tumor.

Bronchiolar adenoma (BA)/ciliated muconodular papillary tumor (CMPT) is defined as a benign tumor composed of epithelial and basal cells. Recently, some cases with driver mutations or malignant transformation have been observed. Thus, whether BA/CMPT is benign or malignant remains controversial. We herein report an extremely rare case of a 68-year-old woman with a CMPT accompanied by adenocarcinoma in situ (AIS). BA/CMPT existed inside the AIS. The BA/CMPT component did not show any driver mutations; however, the AIS component had an EGFR driver mutation in exon 19. The accumulation of cases and further studies are needed to discuss the malignant potential of BA/CMPT.

Role of fluorodeoxyglucose-positron emission tomography in predicting the pathological response and prognosis after neoadjuvant chemoradiotherapy for locally advanced non-small-cell lung cancer.

OBJECTIVES: The present study compared the utility of fluorodeoxyglucose-positron emission tomography (FDG-PET) and computed tomography (CT) for predicting the pathological response and prognosis following neoadjuvant therapy for locally advanced non-small-cell lung cancer (NSCLC). METHODS: This retrospective analysis included 72 patients in whom adjacent structures showed involvement and/or cN2 NSCLC who received induction chemoradiotherapy (ICRT) and subsequent surgery at our hospital from 2008 to 2019. FDG-PET and CT were performed in all patients before and after ICRT using the same scanner with similar techniques. We calculated the reduction in the maximum standardized uptake value in FDG-PET (ΔSUVmax) and tumour size on CT (ΔCT-size) before and after ICRT and investigated the relationship between the pathological response and prognosis. RESULTS: The disease response was classified as a major pathological response in 43 patients, and a minor response in 29 patients. ΔSUVmax 60% and ΔCT-size 30% were identified as the optimal cut-off values for predicting a major pathological response. ΔSUVmax was superior to ΔCT-size in terms of sensitivity, specificity, positive predictive value and negative predictive value. Furthermore, ΔSUVmax was superior to ΔCT-size for predicting the prognosis. CONCLUSIONS: Based on the results of the present study, FDG-PET appeared to have greater utility than CT in predicting the pathological response following ICRT and the postoperative prognosis in patients with locally advanced NSCLC.

Treatment of secondary pneumothorax with interstitial lung disease: the surgical indications at the start of treatment is important.

Background: Secondary pneumothorax with interstitial lung disease (ILD) is often difficult to treat in comparison to primary pneumothorax. The purpose of this study was to analyze the actual management and outcome, and to find the most effective treatment. Methods: Among 180 patients with pneumothorax caused by ILD, who were managed between January 2000 and April 2021, 129 patients were included. Fifty-one patients with observation only were excluded. In the present study, a patient was considered to be cured if their chest tube could be removed. Results: The managements included chest tube drainage alone (n=41), pleurodesis (n=67), bronchoscopic treatment (n=14), and surgery (include overlapping cases) (n=25). The mean number of pleurodesis treatments was 2.4 (range, 1-9), and the most frequently used agent was blood-patch. All patients who received bronchoscopic treatment underwent bronchial occlusion with silicon spigots. The surgical procedures included bullectomy (n=20), lung cyst ligation (n=3), pleural covering with oxidized cellulose sheet (n=1), and spraying of fibrin glue alone (n=1). One hundred patients (77.5%) were curatively treated, 27 patients (20.9%) died, and 2 patients were transferred without chest tube removal. Among 25 patients who received surgery [including 6 patients with performance status (PS) ≥2], 24 patients (96.0%) were cured, and 1 patient died due to an acute exacerbation of ILD after surgery. The univariate analysis revealed that PS ≥2 and >3 pleurodesis treatments were significant non-curative factors, while steroid treatment before the development of pneumothorax was not. Conclusions: The outcomes of surgery for pneumothorax in patients with ILD were good, and it is desirable to consider the surgical indications.

Mediastinal hemangioma mimicking an invasive tumor growth: A case report.

INTRODUCTION AND IMPORTANCE: Mediastinal hemangiomas are a rare entity frequently developing in the anterior mediastinum. They may exhibit an infiltrating appearance into the surrounding tissue, and extensive surgery is often required despite its benign nature. We report a case of a mediastinal hemangioma mimicking an invasive tumor growth requiring a combined resection of the lung and diaphragm. CASE PRESENTATION: An asymptomatic 73 year-old-man presented with a 50 mm-sized mass on his chest radiography. A combined resection of the mediastinal mass with the part of the lower lobe of left lung and diaphragm not necessitating a patch repair was performed. The pathological findings were compatible with a diagnosis of a mediastinal hemangioma. Only fibrous adhesions were observed between the tumor and resected lung and diaphragm without any histological invasion. CLINICAL DISCUSSION: While imaging examinations play a key role in determining a preoperative diagnosis, mediastinal hemangiomas may pose a diagnostic challenge mainly due to its rarity. With a clinical suspicion of a hemangioma during the diagnostic work up, a dynamic CT might be helpful. CONCLUSIONS: In mediastinal hemangiomas, a preoperative diagnosis is essential in order to avoid extensive surgery. A hemangioma should be raised as a differential diagnosis for anterior mediastinal tumors, especially in cases with an infiltrative appearance that suggests the necessity for a combined resection of the surrounding organs.

Surgical treatment for synchronous multiple primary lung cancer: Is it possible to achieve both curability and preservation of the pulmonary function?

BACKGROUND: With the advent of high-resolution chest imaging, the number of patients diagnosed with multiple primary lung cancers is increasing. For the treatment of multiple lung cancers, a surgical procedure that preserves pulmonary function while ensuring curability is required. METHODS: The study population included 85 patients with synchronous multiple primary lung cancer who received surgical resection between January 2010 and September 2020. Patients with synchronous lung cancer within the same lobe were excluded, and only patients with ≥2 involved lobes were included. The postoperative pulmonary function was examined at 3-6 months after the surgery. RESULTS: Sixty-seven patients had cancers within the ipsilateral lobe, and 18 patients had cancers in bilateral lobes. Seventy-six patients (89.4%) underwent combination surgery with limited resection (e.g., segmentectomy and wedge resection). The preoperative pulmonary functions (mean VC/%VC, mean FEV1 /%FEV1 , and mean %DLCO) were 3.06 L/100.2%, 2.23 L/96.1%, and 117.2%, respectively, and the postoperative pulmonary functions were 2.45 L/81.4%, 1.87 L/81.2%, and 102.6%. In each parameter, the predicted reductions of pulmonary function were almost the same as the predicted values. The 5-year survival rate was 85.0%. The 5-year survival rate according to the most advanced pathological stage was 94.9% for stage I disease, and 62.6% for stage ≥II, which was a significant difference (p < 0.001). CONCLUSIONS: Surgical treatment including limited resection, especially segmentectomy and wedge resection, for synchronous multiple primary lung cancer can preserve pulmonary function while ensuring curability.

Feasibility and prognostic benefit of induction chemoradiotherapy followed by surgery in patients with locally advanced non-small cell lung cancer.

BACKGROUND: The optimal treatment for patients with resectable non-small cell lung cancer (NSCLC) involving adjacent organs (T3 or T4) and/or cN2 remains unclear. We investigated whether or not induction chemoradiotherapy (ICRT) followed by surgery improves the survival. METHODS: We retrospectively analyzed 84 patients with NSCLC involving the adjacent organs and/or cN2 who underwent ICRT followed by surgery at our hospital from 2006 to 2018. Presurgical treatment consisted of 2 courses of platinum-doublet and concurrent radiotherapy (40-50 Gy) to the tumor and involved field. RESULTS: All 84 patients completed ICRT. One patient died after completion of ICRT due to bacterial pneumonia. Radiological responses to ICRT were a complete response (CR), n=1; partial response (PR), n=48; stable disease (SD), n=32; and progressive disease (PD), n=2 (overall response rate: 58.3%). Eighty-one patients underwent radical surgery. The procedures included lobectomy, n=66; bilobectomy, n=7; pneumonectomy, n=6; and segmentectomy, n=2 (including 49 extended resections). Seventy-three patients (90%) underwent complete resection. The postoperative morbidity rate was 30%. The 30- and 90-day mortality rates were 1.2% and 2.4%, respectively. A pathological CR (Ef3) and major response (Ef2) were achieved in 17 (21.0%) and 38 (46.9%) patients, respectively; a minor response (Ef1) was observed in 26 (32%). The 5-year overall survival (OS) and recurrence-free survival (RFS) rates were 58.0% and 45.6%, respectively. The median survival time was 73.2 months. Based on the response to ICRT, patients with radiological CR or PR showed better 5-year OS than those with SD (63.7% vs. 40.0%, P=0.020). Patients with Ef3 or Ef2 demonstrated a much better 5-year OS than those with Ef1 (65.0% vs. 24.4%, P=0.005). CONCLUSIONS: ICRT followed by surgery for patients with NSCLC involving the adjacent organs and/or cN2 was feasible and improved the survival. A CR/PR or Ef2/Ef3 after ICRT led to a better prognosis.

Solitary fibrous tumor of the pleura with marked cystic degeneration: a case report.

BACKGROUND: Solitary fibrous tumor of the pleura (SFTP) is a mesenchymal tumor, and computed tomography typically shows SFTPs as well-defined lobulated masses. We herein report a case of SFTP with cystic degeneration of the entire tumor. CASE PRESENTATION: The patient was a 67-year-old Japanese man who was referred to our hospital for an abnormal shadow on a chest X-ray. Computed tomography showed a 9-cm cystic tumor in the lower left lobe, with small nodules aggregated in the cyst. Pulmonary aspergillosis was suspected, and left basal segmentectomy was performed. A pedunculated cystic tumor was connected to the pleura with a stalk, and white polypoidal masses were found within the cystic tumor. Microscopy revealed uniform fibroblastic spindle cell proliferation and marked cystic degeneration, the cyst walls were formed of the same tumor cells. Immunohistochemical staining revealed that the tumor cells were positive for CD34, CD99, and BCL2. Based on these findings, the tumor was diagnosed as SFTP with cystic degeneration. CONCLUSION: We experienced an extremely rare case of atypical SFTP with cystic degeneration.