[Synchronous Multiple Thymoma Suggested to be Multi-centric Origin:Report of a Case].

A 57 years-old man was referred to our hospital because of an abnormal shadow in the left hilum on a screening chest X-ray. His physical exam and laboratory data were not notable. Chest computed tomography (CT) showed two nodules one of which is cystic in the anterior mediastinum, and positron emission tomography with 18F-fluoro-2-deoxy-D-glucose showed relatively mild uptake in both tumors. We suspected mucosa associated lymphoid tissue (MALT) lymphoma or multiple thymomas, and performed thoracoscopic thymo-thymectomy. The operative findings showed two separated tumors in the thymus. Histopathological examination revealed that both tumors were type B1 thymomas of 35 mm and 40 mm in size. Since both tumors were encapsulated without continuity, multi-centric origin was suggested.

Impact of postoperative complications on outcomes of second surgery for second primary lung cancer.

PURPOSE: The best surgical approach for second primary lung cancer remains a subject of debate. The purpose of this study was to review the postoperative complications after second surgery for second primary lung cancer and to investigate the outcomes based on these complications. METHODS: The clinical data of 105 consecutive patients who underwent pulmonary resection for multiple primary lung cancers between January, 1996 and December, 2017, were reviewed according to the Martini-Melamed criteria. RESULTS: After the second surgery, low body mass index (BMI) (< 18.5 kg/m2) (P = 0.004) and high Charlson comorbidity index (CCI) (P = 0.002) were independent predictors of postoperative complications. Survival analysis revealed the 5-year overall survival rates of 74.5% and 61.4% for patients without postoperative complications and those with postoperative complications (P = 0.044), respectively, but the 5-year cancer-specific survival rates of 82.5% and 80.0% (P = 0.926), respectively. During this period, there were significantly more respiratory-related deaths of patients with complications than of those without complications (P = 0.011). CONCLUSION: Surgical intervention is feasible and potentially effective for second primary lung cancer but may not achieve positive perioperative and long-term outcomes for patients with a low BMI or a high CCI. Treatment options should be considered carefully for these patients.

The impact of emphysema on surgical outcomes of early-stage lung cancer: a retrospective study.

BACKGROUND: The presence of emphysema on computed tomography (CT) is associated with an increased frequency of lung cancer, but the postoperative outcomes of patients with pulmonary emphysema are not well known. The objective of this study was to investigate the association between the extent of emphysema and long-term outcomes, as well as mortality and postoperative complications, in early-stage lung cancer patients after pulmonary resection. METHODS: The clinical records of 566 consecutive lung cancer patients who underwent pulmonary resection in our department were retrospectively reviewed. Among these, the data sets of 364 pathological stage I patients were available. The associations between the extent of lung emphysema and long-term outcomes and postoperative complications were investigated. Emphysema was assessed on the basis of semiquantitative CT. Surgery-related complications of Grade ≥ II according to the Clavien-Dindo classification were included in this study. RESULTS: Emphysema was present in 63 patients. The overall survival and relapse-free survival of the non-emphysema and emphysema groups at 5 years were 89.0 and 61.3% (P < 0.001), respectively, and 81.0 and 51.7%, respectively (P < 0.001). On multivariate analysis, significant prognostic factors were emphysema, higher smoking index, and higher histologic grade (p < 0.05). Significant risk factors for poor recurrence-free survival were emphysema, higher smoking index, higher histologic grade, and presence of pleural invasion (P < 0.05). Regarding Grade ≥ II postoperative complications, pneumonia and supraventricular tachycardia were more frequent in the emphysema group than in the non-emphysema group (P = 0.003 and P = 0.021, respectively). CONCLUSION: The presence of emphysema affects the long-term outcomes and the development of postoperative complications in early-stage lung cancer patients.

[Thoracoscopic Left Upper Division Segmentectomy for Multiple Ground-glass Nodules Using Preoperative Virtual-assisted Lung Mapping].

Associated with an increase of small-sized lung cancer or metachronous second primary lung cancer, we have more opportunities to perform sublobar resection. Difficulties of identifying tumor location and appropriate surgical margin for small-sized ground-glass opacity (GGO) dominant lesions in thoracoscopic surgery is the big issue of sublobar resection. Virtual-assisted lung mapping (VAL-MAP) that makes markings on the lung surface through some peripheral bronchi by bronchoscopically projects intrapulmonary anatomy on the lung surface and literally draw a map. We report a case of thoracoscopic left upper division segmentectomy for multiple ground-glass nodules (GGNs) using preoperative VAL-MAP. A 65-year-old women who had undergone right upper lobectomy for primary lung cancer, and had multiple GGNs in the bilateral lungs was followed up as an outpatient. Eleven years after initial pulmonary resection, 2 lesions in the left upper division became bigger, and we decided to perform surgery for 4 GGNs in the left upper division including these 2 lesions. We preoperatively made bronchoscopic dye markings through B1+2c, B3a and B4a for in the left upper lobe. The 3 markings were intraoperatively identified. We decided the resection line based on the markings and performed thoracoscopic left upper division segmentectomy. The pathological diagnosis was minimally invasive adenocarcinoma, adenocarcinoma in situ and pneumonitis. Surgical margins were negative. VAL-MAP will assume an important role as an intraoperative navigation system for sublobar resection.

Clinical and Genetic Implications of Mutation Burden in Squamous Cell Carcinoma of the Lung.

BACKGROUND: Lung squamous cell carcinoma (LSCC) is a major histological subtype of lung cancer. In this study, we investigated genomic alterations in LSCC and evaluated the clinical implications of mutation burden (MB) in LSCC. METHODS: Genomic alterations were determined in Japanese patients with LSCC (N = 67) using next-generation sequencing of 415 known cancer genes. MB was defined as the number of non-synonymous mutations per 1 Mbp. Programmed death-ligand 1 (PD-L1) protein expression in cancer cells was evaluated by immunohistochemical analysis. RESULTS: TP53 gene mutations were the most common alteration (n = 51/67, 76.1%), followed by gene alterations in cyclin-dependent kinase inhibitor 2B (CDKN2B; 35.8%), CDKN2A (31.3%), phosphatase and tensin homolog (30.0%), and sex-determining region Y-box 2 (SOX2, 28.3%). Histological differentiation was significantly poorer in tumors with high MB (greater than or equal to the median MB) compared with that in tumors with low MB (less than the median MB; p = 0.0446). The high MB group had more tumors located in the upper or middle lobe than tumors located in the lower lobe (p = 0.0019). Moreover, cancers in the upper or middle lobes had significantly higher MB than cancers in the lower lobes (p = 0.0005), and tended to show higher PD-L1 protein expression (p = 0.0573). SOX2 and tyrosine kinase non-receptor 2 amplifications were associated with high MB (p = 0.0065 and p = 0.0010, respectively). CONCLUSIONS: The MB level differed according to the tumor location in LSCC, suggesting that the location of cancer development may influence the genomic background of the tumor.

Common driver mutations and smoking history affect tumor mutation burden in lung adenocarcinoma.

BACKGROUND: Recent progress in genomic analysis using next-generation sequencing technology has enabled the comprehensive detection of mutations and tumor mutation burden (TMB) in patients. A high TMB (TMB-H) tumor is defined as one with high somatic mutational rates, which correlates with clinical responses to certain treatments such as immunotherapies. We determined TMB in lung adenocarcinoma and clarified the characteristics of patients with TMB-H in relation to common driver mutations and smoking history. MATERIALS AND METHODS: Genomic aberrations and TMB were determined in Japanese patients with lung adenocarcinoma (n = 100) using next-generation sequencing of 415 known cancer genes. TMB-H was defined as > 20 mutations per megabase (Mb) of sequenced DNA. RESULTS: The median TMB was 13.5 (5-33) mutations/Mb. Ten of 100 (10%) patients showed TMB-H, and the others showed low TMB (TMB-L). Only two of 10 (20%) patients with TMB-H had one of the common driver mutations (ALK and ERBB2 mutation), whereas 57 of 90 (63%) patients with TMB-L had one of the driver mutations, including ALK, EGFR, ERBB2, ROS, RET, and MET (P < 0.05). Notably, no EGFR mutation was observed in patients with TMB-H. Eight of 10 (80%) patients with TMB-H had recent smoking history, whereas only 17 of 90 (19%) patients with TMB-L had recent smoking history (P < 0.001). CONCLUSIONS: We found that TMB-H is associated with smoking history, whereas TMB-L is associated with the common driver mutations in lung adenocarcinoma, which may impact treatment strategies for these patients.

Survival after repeated surgery for lung cancer with idiopathic pulmonary fibrosis: a retrospective study.

BACKGROUND: Patients with idiopathic pulmonary fibrosis (IPF) have a high risk of developing lung cancer, but few studies have investigated the long-term outcomes of repeated surgery in such patients. The purpose of this study was to evaluate the surgical outcomes of repeated lung cancer surgery in patients with IPF. METHODS: From January 2001 to December 2015, 108 lung cancer patients with IPF underwent pulmonary resection at two institutions; 13 of these patients underwent repeated surgery for lung cancer, and their data were reviewed. RESULTS: The initial procedures of the 13 patients were lobectomy in 8, segmentectomy in 2, and wedge resection in 3. The subsequent procedures were wedge resection in 10 and segmentectomy in 3. The clinical stage of the second tumor was stage IA in 12 and stage IB in 1. Postoperatively, 3 patients (23.1%) developed acute exacerbation (AE) of IPF and died. The rate of decrease in percent vital capacity was significantly higher in patients with AE than in those without AE (p = 0.011). The 3-year overall survival rate was 34.6%. The causes of death were cancer-related in 7, AE of IPF in 3, and metachronous lung cancer in 1. CONCLUSIONS: Despite limited resection, a high incidence of AE was identified. The early and long-term outcomes of repeated surgery in lung cancer patients with IPF were poor because of the high risk of AE of IPF and lung cancer recurrence. Long-term intensive surveillance will be required to determine whether surgical intervention is justified in patients with multiple primary lung cancers and IPF.

Characteristics and timing of recurrence during postoperative surveillance after curative resection for lung adenocarcinoma.

PURPOSE: To establish the most effective methods of postoperative surveillance to detect early recurrence of lung adenocarcinoma. METHODS: The subjects of this retrospective study were 485 patients with p-stage I-III lung adenocarcinoma, who underwent postoperative surveillance. We examined the sites and detection modes of recurrence and calculated the recurrence-free probabilities. Patients with stage I disease were divided into low- and high-risk recurrence groups using a risk score calculated by assigning points proportional to risk factor regression coefficients. RESULTS: Of the 112 patients with recurrence, 86 had intrathoracic recurrence. Routine computed tomography (CT) revealed recurrence in 60 patients. The recurrence-free probability curves showed that 95% of recurrences were identified within the first 4 years after resection in patients with stage II/III disease. In patients with stage I disease, the predictors of recurrence included male sex, positive pleural lavage cytology, moderate-to-poor differentiation, and visceral pleural invasion. Postoperative recurrences were detected throughout the follow-up period in the high-risk group. CONCLUSIONS: Routine chest CT plays an important role in the postoperative surveillance of lung adenocarcinoma. We recommend intensive follow-up during the early post-resection period for patients with advanced stage disease and long-term follow-up for high-risk patients with stage I disease.

[Fatal Respiratory Failure Developed during Chemotherapy for Diffuse Large B Cell Lymphoma that Occurred Late after Lung Transplantation].

We report here a case of fatal respiratory failure developed during chemotherapy for diffuse large B cell lymphoma that occurred late after lung transplantation. 25-year- old man underwent lung transplantation from brain death donor for respiratory failure due to interstitial pneumonia at the age of 16 years old. Two years after transplantation, his respiratory function decreased gradually. Chronic lung allograft dysfunction including bronchiolitis obliterans( BOS) and restrictive allograft syndrome was suspected and immunosuppression was enhanced. Nine years after transplantation, he had abdominal pain and physical examination suggested intestinal obstruction. Small intestine endoscopy revealed an ulcer at jejunum and diffuse large B cell lymphoma( DLBCL) was finally diagnosed by biopsy. Chemotherapy was planned for lymphoma, but respiratory failure progressed just before chemotherapy. Chest computed tomography showed infiltrative shadow in right lung, so we suspected presence of lymphoma and chemotherapy was carried out. After chemotherapy, abnormal shadow in the right lung disappeared. Although chemotherapy was effective, respiratory failure progressed and he died. Pathological examination from autopsy showed mixture of BOS, diffuse alveolar damage, invasion of aspergillus and acute fibrinoid organizing pneumonia but no residual DLBCL was found in the lung.

[Simultaneous pulmonary resection and endovascular repair for patients with coexisting primary lung cancer and aneurysm].

The surgical strategy for coexisting lung cancer and aneurysm is controversial owing to the risk of aneurysm rupture during the perioperative period of pulmonary resection. We performed simultaneous pulmonary resection and endovascular repair in 2 patients with coexisting lung cancer and aneurysm. Case 1:A 74-year-old man presented at our hospital with cT2aN0M0 lung cancer and a 5.0 cm abdominal aortic aneurysm. Because computed tomography indicated the possibility of advanced lung cancer, we decided to perform simultaneous surgery for lung cancer and the aneurysm. Under general anesthesia, endovascular aneurysm repair was performed before right lower lobectomy with lymphadenectomy. The postoperative course was uneventful, and the patient was discharged on postoperative day 12. Case 2:A 72-year-old man presented at our hospital with cT2aN1M0 lung cancer, a 5.0 cm left internal iliac artery aneurysm, and right renal cell carcinoma( RCC). Because the lung cancer was advanced and the patients needed following surgical treatment for RCC, we decided to perform simultaneous surgery for lung cancer and the aneurysm. Under general anesthesia, endovascular aneurysm repair was performed before right upper lobectomy with lymphadenectomy. The postoperative course was uneventful, and the patient was discharged on postoperative day 11.

[Detection of the communication site by dye injection method at the surgery for pleuroperitoneal communication].

A 65-year-old male with end stage renal failure due to IgA nephritis commenced continuous ambulatory peritoneal dialysis (CAPD). Three weeks after initiation of CAPD, right hydrothorax developed. Then, we strongly assumed pleuroperitoneal communication( PPC) although the pleural effusion did not show high concentration of glucose. He underwent thoracoscopic surgery for PPC. On the inner, central tendons part of the diaphragm, there were a few blebs. One hour after 3 l of peritoneal dialysis solution containing 15 ml indigocarmine was instilled into the abdomen through a CAPD catheter, the blebs were tense and colored blue by the dye solution. The blebs were directly sutured and diaphragm was covered by polyglycolic acid sheet and fibrin glue all over. Since then, he resumed CAPD, without recurrence of hydrothorax. Then we investigated the treatment outcome of video-assisted thoracic surgery (VATS) for PPC in Japan. The outcome was poorer in cases in which communication was not detected intraoperatively. These patients should be given sufficient consideration for surgical procedure.

Significance of preoperative evaluation of modified advanced lung cancer inflammation index for patients with resectable non-small cell lung cancer.

OBJECTIVES: Body composition and systemic inflammation/nutrition have been identified as important clinical factors in cancer patients. The modified advanced lung cancer inflammation index (mALI), which combines body composition and systemic inflammation/nutrition, is defined as appendicular skeletal muscle index × serum albumin/neutrophil-lymphocyte ratio. This retrospective study aimed to investigate associations between preoperative mALI and surgical outcomes in non-small cell lung cancer (NSCLC) patients. METHODS: We examined 665 patients with resectable stage I-III NSCLC who underwent pulmonary resection. Patients were divided into low-mALI (n = 168) and high-mALI (n = 497) based on the lower quartile. Kaplan-Meier curves and Cox regression analysis were used to assess the prognostic value of mALI. We then performed 1:1 propensity score matching (PSM) for high- and low-mALI to further investigate impacts on survival. RESULTS: Overall survival (OS) and recurrence-free survival (RFS) were both significantly poorer in the low-mALI group than in the high-mALI group (58.2% vs. 79.6%, P < 0.001; 48.8% vs. 66.7%, P < 0.001, respectively). Multivariate analysis revealed low-mALI as an independent predictor of OS (hazard ratio [HR], 2.116; 95% confidence interval (CI) 1.458-3.070; P < 0.001) and RFS (HR, 1.634; 95% CI 1.210-2.207; P = 0.001). After PSM, low-mALI remained as an independent predictor of OS (HR, 2.446; 95% CI 1.263-4.738; P = 0.008) and RFS (HR 1.835; 95% CI 1.074-3.137; P = 0.026). CONCLUSION: Preoperative mALI appears to offer an independent predictor of poor surgical outcomes as a simple, routinely available, and inexpensive biomarker in patients with resectable NSCLC.

Significance of preoperative evaluation of skeletal muscle index and immune-nutritional status for patients with early-stage non-small cell lung cancer.

OBJECTIVES: Sarcopenia involves several mechanisms, including age-related changes, nutritional deficiencies, and inflammation, and is associated with unfavorable clinical outcomes. However, the significance of skeletal muscle index (SMI) and immune-nutritional status for patients with early-stage non-small cell lung cancer (NSCLC) remains unclear. This retrospective study was performed to investigate associations between preoperative SMI based on computed tomography (CT) at the L1 level and immune-nutritional status, and whether these factors correlated with surgical outcomes. METHODS: We retrospectively investigated 386 patients with stage I-II NSCLC who underwent curative anatomical pulmonary resection. SMI was assessed on CT at the L1 level and patients were divided into low-SMI (n = 97) and high-SMI (n = 289) groups. We examined the significance of SMI for postoperative outcomes and evaluated correlations between SMI and clinical characteristics, including immune-nutritional status. RESULTS: Low SMI was significantly associated with body mass index and geriatric nutritional risk index. Five-year overall survival rate was significantly lower in the low-SMI group (66.0%) than in the high-SMI group (82.2%, P = 0.004). Multivariate analysis revealed SMI (hazard ratio [HR] 1.850; 95% confidence interval [CI] 1.091-3.135; P = 0.022) and prognostic nutritional index (PNI) (HR 2.031; 95% CI 1.231-3.352; P = 0.006) as independent predictors of overall survival. Low SMI correlated significantly with postoperative complications (P = 0.024). CONCLUSIONS: Low preoperative SMI based on CT at the L1 level appears associated with poor prognosis and postoperative complications among patients with early-stage NSCLC. PNI is also an independent prognostic factor for surgical outcomes.

Maximum Standardized Uptake Value on Positron Emission Tomography is Associated With More Advanced Disease and High-risk Features in Lung Adenocarcinoma.

18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) has been widely used for preoperative staging of lung adenocarcinomas. The aim of this study was to determine whether a high maximum standardized uptake value (SUVmax) could correlate with pathological characteristics in those patients. We retrospectively reviewed patients with clinical stage 0-IA lung adenocarcinoma who underwent preoperative 18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography followed by curative anatomical resection. To identify more advanced disease and high-risk features, representing visceral pleural involvement, pulmonary metastasis, lymph node involvement, and lymphovascular involvement in resected surgical specimens, univariate and multivariate logistic regression analyses were performed. The optimal cutoff point for the SUVmax was determined by receiver operating characteristic analysis. In 2 groups divided according to the cutoff point, the disease-free survivals were calculated and compared using the Kaplan-Meier method and the log-rank test. More advanced disease and high-risk features were identified in 55 (18.9%) of the 291 patients. SUVmax was significantly correlated with more advanced disease and high-risk features, as did the consolidation/tumor ratio on computed tomography. Only 2 (1.2%) of the 169 patients with a SUVmax <3.20 showed more advanced disease and high-risk features, compared with 43.4% of patients with a SUVmax ≥3.20. The disease-free survival was significantly higher in patients with a SUVmax <3.20 than in those with a SUVmax ≥3.20 (P = 0.002). A high SUVmax correlates with more advanced disease and high-risk features in patients with clinical stage 0-IA lung adenocarcinoma. The SUVmax should be considered when deciding treatment strategy in early-stage lung adenocarcinoma.

Surgical outcomes of ipsilateral metachronous second primary lung cancer.

OBJECTIVES: The optimal surgical approach for metachronous second primary lung cancer (MSPLC), especially ipsilateral MSPLC, remains unclear. This study aimed to review postoperative complications and examine surgical outcomes based on the extent of resection after surgery for ipsilateral MSPLC. METHODS: Clinical data from 61 consecutive patients who underwent pulmonary resection for ipsilateral MSPLC according to the Martini-Melamed criteria between January 2005 and December 2017 in 3 institutes were retrospectively reviewed. RESULTS: Postoperative complications were identified in 12 patients (19.7%). Regarding the combination of initial and second surgery, intraoperative bleeding was significantly greater in patients with anatomic-anatomic resection than in others (P < 0.001). Operation time was significantly longer in patients with anatomic-anatomic resection than in others (P < 0.001). However, postoperative complications showed no significant differences based on the combination of surgeries. Five-year overall survival rates in patients with anatomic resection and wedge resection after second surgery were 75.8% and 75.8%, respectively (P = 0.738), and 5-year recurrence-free survival rates were 54.2% and 67.6%, respectively (P = 0.368). Cox multivariate analysis identified ever-smoker status (P = 0.029), poor performance status (P = 0.011) and tumour size >20 mm (P = 0.001) as independent predictors of poor overall survival, while ever-smoker status (P = 0.040) and tumour size >20 mm (P = 0.007) were considered independent predictors of poor recurrence-free survival. CONCLUSIONS: Regarding postoperative and long-term outcomes for patients with ipsilateral MSPLC, surgical intervention is safe and offers good long-term survival. Wedge resection is an acceptable provided tumours ≤2 cm and ground-glass opacity-predominant as a second surgery for early-stage ipsilateral MSPLC.

Mutational signatures in squamous cell carcinoma of the lung.

BACKGROUND: Tumor mutational burden (TMB) has been identified as one of the predictors for the response to anti-programmed cell death-1 (anti-PD-1) antibody therapy and reported to correlate with smoking history in lung adenocarcinoma. However, in squamous cell carcinoma of the lung, the association between TMB and clinicopathological background factors, such as smoking history, has not been reported, including in our previous study. The mutational signature is a tool to identify the mutagens that are contributing to the mutational spectrum of a tumor by investigating the pattern of DNA changes. Here, we analyzed the mutational signature in lung squamous cell carcinoma to identify mutagens affecting the TMB. METHODS: Seven representative mutational signatures including signature 7 (SI7) [ultraviolet (UV)-related], SI4 (smoking), SI6/15 [mismatch repair (MMR)], SI2/13 [apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC)], and SI5 (clock-like) were analyzed in Japanese patients with lung squamous cell carcinoma (n=67) using data generated by next-generation sequencing consisting of a 415-gene panel. The relationships between signatures and clinico-pathological data including TMB and programmed death-ligand 1 (PD-L1) expression were analyzed. RESULTS: Although the reconstructed mutational counts were small with targeted sequencing (median: 30.1, range: 13.3-98.7), the distributions of signatures were comparable among samples, with 56 cases containing more than four signatures. The smoking-related SI4 was found in 45 cases and was significantly related with pack-year index (PYI) (P=0.026). The reconstructed mutation counts were highly correlated with SI4 (r=0.51, P<0.0001), whereas the correlation was weak with SI6/15 (MMR-related) and SI2/13 (APOBEC-related). There was no mutational signature related with PD-L1 expression. Some patients exhibited unique signatures; the patient with the highest mutational counts had a MMR signature, and another patient with a prominent UV signature had occupational exposure to UV, as he was employed as a neon sign engineer. CONCLUSIONS: Mutational signatures can predict the cause of lung squamous cell carcinoma. Tobacco smoking is the mutagen most related with TMB.

[Primary pulmonary synovial sarcoma confirmed by gene expression analysis].

We report a patient who was diagnosed with synovial sarcoma based on gene expression analysis. A 39-year-old male visited a local hospital due to left chest pain. Chest compued tomography (CT) showed a lung tumor located mainly at the lingula of the left lung, and extending to the bifurcation of the upper and lower lobar bronchi. Left pneumonectomy was performed. Pathological examination showed a mesenchymal tumor consisting of short-spindle, small, round cells, and the differentiation between synovial sarcoma and peripheral neuroectodermal tumor was necessary. RT-PCR to examine the gene expression of cells revealed a SYT-SSX fusion gene, and a diagnosis of primary synovial sarcoma of the lung was made.

[Iterative surgical resections for second primary and local recurrent lung cancer; comparison of lobectomy and limited resection].

During a 24-year period (1986-2009), 74 patients (3.5%) underwent iterative surgical resections for 2nd primary and recurrent lung cancer. Patients are classified to 5 groups: 20 2nd primary lung cancer patients undergoing lobectomy (A), 24 2nd primary lung cancer patients undergoing limited resection (B), 11 2nd primary bronchioloalveolar carcinoma (BAC) patients undergoing limited resection (C), 8 recurrent lung cancer patients undergoing lobectomy (D), and 11 recurrent lung cancer patients undergoing limited resection (E). There were 13 (65%) patients with pathological stage IA in group A, 20 (83%) in B, 11 (100%) in C, 2 (25%) in D, and 8 (73%) in E. There were 18 (90%) patients with adenocarcinoma in group A, 15 (63%) in B, 11 (100%) in C, 5 (63%) in D, and 9 (82%) in E. Overall hospital mortality was 5%, including 3 deaths in A and 1 death in D. Five-year and 10-year survival after the 2nd surgery was 55% and 55% in A, 63% and 50% in B, 100% and 100% in C, 57% and 37% in D, and 70% and 53% in E. These data showed that limited resections had low surgical risk and good long-term results. Limited resection appears to achieve better outcomes for 2nd primary and recurrent lung cancer and should be chosen whenever possible.

Characteristics and risk factors of recurrence in clinical stage I non-small cell lung cancer patients undergoing anatomic segmentectomy.

OBJECTIVE: Although lobectomy is the standard surgical procedure for small-sized non-small cell lung cancer (NSCLC), segmentectomy has been performed for various reasons. The aim of this study was to investigate the characteristics of and risk factors for recurrence in early-stage NSCLC patients undergoing segmentectomy. METHODS: We retrospectively reviewed 179 patients with clinical stage I NSCLC who underwent segmentectomy. Preoperative factors were analyzed using the log-rank test for univariate analyses. Multivariate analyses were performed using a Cox proportional hazards regression model to identify independent risk factors for recurrence. For the significant factors, optimal cutoff points were determined by receiver operating characteristic (ROC) analysis. RESULTS: During the follow-up period of 51 months, 18 patients developed recurrence; 5 had locoregional (including 2 with margin recurrences only), 9 had distant, and 4 had both locoregional and distant recurrence. Multivariate and ROC analysis identified radiologic solid tumor size with a cutoff point of 1.5 cm as an independent risk factor for recurrence. Three patients in the solid size < 1.5 cm group (n = 119) developed recurrence, 2 of whom had surgical margin recurrence, compared to 15 patients in the solid size ≥ 1.5 cm group (n = 60). CONCLUSIONS: The indication for segmentectomy should be decided upon with caution, and the segments to be resected should be carefully considered to secure an appropriate surgical margin in this low-risk subgroup of patients because they may have a relatively higher risk of surgical margin recurrence, despite being at decreased risk.

Frequent Germline and Somatic Single Nucleotide Variants in the Promoter Region of the Ribosomal RNA Gene in Japanese Lung Adenocarcinoma Patients.

Ribosomal RNA (rRNA), the most abundant non-coding RNA species, is a major component of the ribosome. Impaired ribosome biogenesis causes the dysfunction of protein synthesis and diseases called "ribosomopathies," including genetic disorders with cancer risk. However, the potential role of rRNA gene (rDNA) alterations in cancer is unknown. We investigated germline and somatic single-nucleotide variants (SNVs) in the rDNA promoter region (positions -248 to +100, relative to the transcription start site) in 82 lung adenocarcinomas (LUAC). Twenty-nine tumors (35.4%) carried germline SNVs, and eight tumors (9.8%) harbored somatic SNVs. Interestingly, the presence of germline SNVs between positions +1 and +100 (n = 12; 14.6%) was associated with significantly shorter recurrence-free survival (RFS) and overall survival (OS) by univariate analysis (p < 0.05, respectively), and was an independent prognostic factor for RFS and OS by multivariate analysis. LUAC cell line PC9, carrying rDNA promoter SNV at position +49, showed significantly higher ribosome biogenesis than H1650 cells without SNV. Upon nucleolar stress induced by actinomycin D, PC9 retained significantly higher ribosome biogenesis than H1650. These results highlight the possible functional role of SNVs at specific sites of the rDNA promoter region in ribosome biogenesis, the progression of LUAC, and their potential prognostic value.