Pathological Pleural Invasion is a Risk Factor for Late Recurrence in Long-Term Survivors of Non-small Cell Lung Cancer after Complete Resection.

BACKGROUND: Information regarding late recurrence after pulmonary resection for non-small cell lung cancer (NSCLC) is limited. This study aimed to analyze the risk factors for late recurrence after surgery for NSCLC in the current era. PATIENTS AND METHODS: We conducted a retrospective study of patients who underwent complete resection for pathological I-III NSCLC between 2006 and 2015. Late recurrence was defined as a recurrence that met the following conditions: (1) the patient underwent chest computed tomography (CT) at or after 54 months after surgery and recurrence was not detected at that time, and (2) recurrence that occurred more than 5 years after surgery. The factors influencing late recurrence, relapse-free survival (RFS), and overall survival (OS) after surgery were analyzed. RESULTS: A total of 1275 with 5-year relapse-free survival after surgery were enrolled in this study. The mean age of the patients was 66.4 years and 54% of the patients were men. The median interval between surgery and the latest follow-up examination was 98 months. In total, 35 patients (2.7%) experienced late recurrence and 138 patients have died thus far. The cumulative recurrence, RFS, and OS rates at 10 years were 3.9%, 84.9%, and 86.3%, respectively. A multivariate analysis revealed that pleural invasion was an independent risk factor for late recurrence. Pleural invasion was a poor prognostic factor for both RFS and OS. CONCLUSIONS: Pleural invasion was a predictor of late recurrence. Age > 67 years, preoperative serum carcinoembryonic antigen (CEA) > 5 ng/ml, non-adenocarcinoma, and pleural invasion were poor prognostic factors for RFS.

Development of a multivariable prediction model for prolonged air leak after lung resection.

OBJECTIVES: Prolonged air leak (PAL) is a common complication of lung resection. Research on predictors of PAL using a digital drainage system (DDS) remains insufficient. In this study, we investigated the predictive factors of PAL to establish a novel early postoperative prediction model for PAL. METHODS: A retrospective cohort study and validation study were conducted. We examined patients who underwent lung resection with DDS at our institute. The relationship between the clinical factors and measurements of the DDS, including the difference between the set and measured intrapleural pressure (named: additional negative pressure [ANP]) at postoperative hour (POH) 3, with PAL was analyzed. RESULTS: A total of 494 patients were enrolled, 29 of whom had PAL. Percent forced expiratory volume in 1 s <60%, ANP <1 cmH2O, air leak flow >20 mL/min and pleural adhesion findings at surgery were independent predictors of PAL according to a multivariable analysis. The PAL rate was clearly stratified according to our novel risk scoring system, which simply notes the presence of the above four factors, that is, the rate increases when the score increases. The area under the curve (AUC) of the receiver operating characteristic (ROC) analysis for this scoring system was 0.818. Analysis of the validation cohort (n = 133) revealed that this scoring system showed a sufficient ability to predict PAL. CONCLUSIONS: ANP at POH 3 is an independent predictor of PAL. Thus, the risk-scoring system proposed in this study is useful for predicting PAL in the early postoperative period.

Improving the efficiency of identifying malignant pulmonary nodules before surgery via a combination of artificial intelligence CT image recognition and serum autoantibodies.

OBJECTIVE: To construct a new pulmonary nodule diagnostic model with high diagnostic efficiency, non-invasive and simple to measure. METHODS: This study included 424 patients with radioactive pulmonary nodules who underwent preoperative 7-autoantibody (7-AAB) panel testing, CT-based AI diagnosis, and pathological diagnosis by surgical resection. The patients were randomly divided into a training set (n = 212) and a validation set (n = 212). The nomogram was developed through forward stepwise logistic regression based on the predictive factors identified by univariate and multivariate analyses in the training set and was verified internally in the verification set. RESULTS: A diagnostic nomogram was constructed based on the statistically significant variables of age as well as CT-based AI diagnostic, 7-AAB panel, and CEA test results. In the validation set, the sensitivity, specificity, positive predictive value, and AUC were 82.29%, 90.48%, 97.24%, and 0.899 (95%[CI], 0.851-0.936), respectively. The nomogram showed significantly higher sensitivity than the 7-AAB panel test result (82.29% vs. 35.88%, p < 0.001) and CEA (82.29% vs. 18.82%, p < 0.001); it also had a significantly higher specificity than AI diagnosis (90.48% vs. 69.04%, p = 0.022). For lesions with a diameter of ≤ 2 cm, the specificity of the Nomogram was higher than that of the AI diagnostic system (90.00% vs. 67.50%, p = 0.022). CONCLUSIONS: Based on the combination of a 7-AAB panel, an AI diagnostic system, and other clinical features, our Nomogram demonstrated good diagnostic performance in distinguishing lung nodules, especially those with ≤ 2 cm diameters. KEY POINTS: • A novel diagnostic model of lung nodules was constructed by combining high-specific tumor markers with a high-sensitivity artificial intelligence diagnostic system. • The diagnostic model has good diagnostic performance in distinguishing malignant and benign pulmonary nodules, especially for nodules smaller than 2 cm. • The diagnostic model can assist the clinical decision-making of pulmonary nodules, with the advantages of high diagnostic efficiency, noninvasive, and simple measurement.

Utility of needle biopsy in centrally located lung cancer for genome analysis: a retrospective cohort study.

BACKGROUND: It is essential to collect a sufficient amount of tumor tissue for successful next-generation sequencing (NGS) analysis. In this study, we investigated the clinical risk factors for avoiding re-biopsy for NGS analysis (re-genome biopsy) in cases where a sufficient amount of tumor tissue could not be collected by bronchoscopy. METHODS: We investigated the association between clinical factors and the risk of re-genome biopsy in patients who underwent transbronchial biopsy (TBB) or endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and required re-genome biopsy in cases enrolled in LC-SCRUM Asia, a prospective nationwide genome screening project in Japan. We also examined whether the frequency of re-genome biopsy decreased between the first and second halves of the enrolment period. RESULTS: Of the 572 eligible patients, 236 underwent TBB, and 134 underwent EBUS-TBNA. Twenty-four TBBs required re-genome biopsy, and multivariate analysis showed that the risk of re-genome biopsy was significantly increased in lesions where the tumor lesion was centrally located. In these cases, EBUS-TBNA should be utilized even if the lesion is a pulmonary lesion. However, it should be noted that even with EBUS-TBNA, lung field lesions are at a higher risk of re-canalization than mediastinal lymph node lesions. It was also found that even when tumor cells were detected in rapid on-site evaluation, a sufficient amount of tumor tissue was not always collected. CONCLUSIONS: For centrally located pulmonary mass lesions, EBUS-TBNA, rather than TBB, can be used to obtain tumor tissues that can be analyzed by NGS.

Dacomitinib overcomes afatinib-refractory carcinomatous meningitis in a lung cancer patient harbouring EGFR Ex.19 deletion and G724S mutation; a case report.

It has been reported that the efficacy of EGFR-TKI is predicted, not by which exon of the EGFR gene is mutated, but by the structural change in the EGFR protein due to the mutation. Here, we present an EGFR-mutated lung cancer patient with a 13-year history of anticancer treatment, in which EGFR ex.19 deletion (E746_S752 > V) and G724S mutations were detected by liquid biopsy during 12th line afatinib treatment, and switching to dacomitinib showed improvement of cancerous meningitis. We choose dacomitinib as 14th line chemotherapy based on ex.19 deletion and G724S mutant EGFR structure and its penetration rate to cerebral fluid, which successfully prolonged her life by 6 months. The optimal EGFR-TKI may be selected by understanding the EGFR compound mutation profile by next generation sequencing and predicting the effect based on the structure. Dacomitinib may be effective choice in afatinib-refractory carcinomatous meningitis harboring G724S mutation. This is the first case report showing that a change to dacomitinib responded to afatinib refractory cancerous meningitis.

Heterogeneity of cancer-associated fibroblasts: Opportunities for precision medicine.

Despite marked development in cancer therapies during recent decades, the prognosis for advanced cancer remains poor. The conventional tumor-cell-centric view of cancer can only explain part of cancer progression, and thus a thorough understanding of the tumor microenvironment (TME) is crucial. Among cells within the TME, cancer-associated fibroblasts (CAFs) are attracting attention as a target for cancer therapy. However, CAFs present a heterogeneous population of cells and more detailed classification of CAFs and investigation of functions of each subset is needed to develop novel CAF-targeted therapies. In this context, application of newly developed approaches to single-cell analysis has already made an impact on our understanding of the heterogeneity of CAFs. Here, we review the recent literature on CAF heterogeneity and function, and discuss the possibility of novel therapies targeting CAF subsets.

Long-Term Outcomes of Pulmonary Metastasectomy for Uterine Malignancies: A Multi-institutional Study in the Current Era.

BACKGROUND: Information on pulmonary metastasectomy (PM) for uterine malignancies in the current era is limited. In the present study, we analyzed the clinical course and results of PM for uterine malignancies in the era of modern imaging diagnostics to clarify the role of PM in the current era in a multi-institutional setting. METHODS: Fifty-seven patients who underwent PM for uterine malignancies between 2006 and 2015 were retrospectively reviewed. The short- and long-term outcomes, along with factors associated with the prognosis, were analyzed. Details of the clinical course after PM were described. RESULTS: The mean age of patients was 59.4 years. The primary tumor was located in the uterus corpus in 34 cases (60%) and in the uterus cervix in 23 cases (40%). The median disease-free interval (DFI) was 32 months. Forty patients (70%) received fluorine-18-2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography before PM, and complete resection was achieved in 52 patients (91%). Postoperative complications occurred in 4 patients (7%). Of the 52 patients who underwent complete resection of pulmonary metastases, 28 experienced recurrence, and among these, 17 (60%) underwent local therapy, including six repeat PMs. Among the 52 patients who underwent complete resection, the 5-year relapse-free survival rate was 40.7% and the 5-year overall survival (OS) rate was 68.8%. The univariate analysis revealed that a DFI of ≤ 24 months was associated with significantly poorer OS. CONCLUSIONS: PM for uterine malignancies is safe and provides favorable long-term outcomes in selected patients. Patients with a DFI of > 24 months have better OS and are good candidates for PM.

Long-Term Outcomes After Surgical Resection for Pleural Dissemination of Thymoma.

BACKGROUND: Cases of thymoma with pleural dissemination are occasionally encountered, and their management is difficult. Some reports have noted that surgical treatment for dissemination is effective, although the long-term results and clinical course details remain unclear. The current study investigated the short- and long-term outcomes of surgical resection of pleural dissemination. METHODS: A retrospective review examined the medical records for 38 patients who underwent surgical resection for pleural dissemination occurring synchronously with a primary thymoma or metachronously after complete surgical resection of a primary thymoma between 1996 and 2017 at the authors' institution. Clinical characteristics and prognostic factors were analyzed. RESULTS: The patients were classified into synchronous (n = 21) and metachronous (n = 17) groups. The 10-year overall survival rate was 59% for the synchronous group and 88% for the metachronous group. The median follow-up period for all the patients was 61 months (range 4-225 months). No perioperative deaths occurred. For all the patients, the 5- and 10-year overall survival rates were respectively 91% and 82%, and the 5- and 10-year relapse-free survival rates were respectively 29% and 19%. A significantly worse prognosis was observed for patients 50 years of age or older than for those younger than 50 years (p = 0.02). For 13 patients who underwent repeat resection for pleural dissemination, the prognosis was better than for those without repeat resection (p < 0.01). CONCLUSION: Surgical resection of thymoma with pleural disseminated nodules can be safely performed and provides a favorable long-term outcome. Repeat resection is considered to be effective for achieving a good prognosis.

Long-Term Outcomes of Pulmonary Resection for Lung Cancer Patients with Chronic Kidney Disease.

BACKGROUND: The survival outcome in lung cancer patients with chronic kidney disease (CKD) has not been well evaluated. The aim of this study was to evaluate the survival outcomes following non-small cell lung cancer (NSCLC) surgery in patients with CKD as a preoperative comorbidity. METHODS: Among 671 patients who underwent surgery for NSCLC between 2007 and 2014 at our hospital, 55 (8%) had CKD and we retrospectively analyzed the survival outcomes of these patients. RESULTS: Most patients with CKD were elderly and male. Patients with CKD had a higher frequency of smoking habit, cardiovascular disease, and pulmonary diseases, and a notably lower pulmonary function, resulting in receiving limited pulmonary resection. There were no marked differences in the frequency of surgical complications between patients with and without CKD (p = 0.16). Squamous cell carcinoma was more frequently diagnosed in patients with CKD than in those without it. The 5-year disease-free survival rates in patients with and without CKD were 60.0% and 69.7% (p = 0.06), respectively, and the 5-year overall survival rates were 68.9% and 80.0%, respectively, showing significant differences (p = 0.01). The rate of receiving supportive care was higher in patients with CKD when recurrence observed. CONCLUSION: CKD is associated with a poorer overall survival in patients who undergo lung cancer resection for recurrent disease. As patients with CKD tend to have a poor respiratory function, thoracic surgeons should carefully select the resection type to balance the therapeutic benefit and invasiveness.

Proposal of a Useful Surrogate Endpoint of the Overall Survival in Patients Undergoing Pulmonary Metastasectomy: The Time to Local Therapy Failure.

BACKGROUND: A recent study demonstrated remarkable discrepancy between the relapse-free survival (RFS) and overall survival (OS) after pulmonary metastasectomy (PM) in the current era. As the RFS may not be a suitable parameter after PM, a more suitable parameter is needed for PM as a surrogate marker for OS. METHODS: A total of 134 consecutive patients who underwent PM were retrospectively analyzed. In the present study, we introduced a new endpoint, time to local treatment failure (TLTF). This endpoint was defined as the time interval between the first PM and the first untreatable recurrence by local treatment with curative intent or death due to any cause. We analyzed the correlation between the RFS and OS and between the TLTF and OS to validate whether or not the TLTF is a better parameter than the RFS after PM. RESULTS: Thus far, 78 patients have experienced relapse. Of these, 37 patients (47%) underwent local therapy with curative intent, 29 of whom are alive without local treatment failure. The 5-year OS, RFS and TLTF were 70.9%, 36.5%, and 57.6%, respectively. The concordance proportions for the RFS and OS and for the TLTF and OS were 0.634 and 0.851 for all patients, respectively. The Spearman's rank correlation coefficient for the RFS and OS was 0.639, while that for the TLTF and OS was 0.875. CONCLUSIONS: The TLTF may be a good surrogate parameter for the OS after PM in the current era.

Long-term outcomes and prognostic factors of pulmonary metastasectomy for osteosarcoma and soft tissue sarcoma.

BACKGROUND: The prognostic factors of pulmonary metastasectomy in patients with osteosarcoma and soft tissue sarcoma remain controversial. The purpose of our analysis was to explore the prognostic factors and outcomes of patients with osteosarcoma and soft tissue sarcoma who underwent pulmonary metastasectomy at our institution. METHODS: We reviewed the data of 44 patients who underwent resection of pulmonary metastases from 1996 to 2016 at our institution. The Kaplan-Meier method, log-rank test and multivariate Cox hazard model were used for comparison and survival analyses. RESULTS: There was no perioperative mortality. The median post-metastasectomy overall survival was 24.8 months, and the 5-year overall survival rate of all patients was 43.5%. The 5-year survival rate of the patients who underwent repeat thoracotomies was 60.0%. Incomplete resection, a largest tumor size > 2 cm and a disease-free interval < 12 months were associated with poor survival in multivariate analyses. Among eight patients, who underwent repeat pulmonary resection, two remain alive with no evidence of disease. These patients had the longest DFI and DFI-2 (time from first pulmonary metastasectomy to the diagnosis of recurrent pulmonary metastasis), respectively. CONCLUSION: The survival of patients with a relatively long disease-free interval, small tumor size and complete resection was favorable following the treatment of osteosarcoma and soft tissue sarcoma with pulmonary metastasectomy. Repeat pulmonary metastasectomies also provide favorable prognosis in select patients.

Carnosol suppresses interleukin-6 production in mouse lungs injured by ischemia-reperfusion operation and in RAW264.7 macrophages treated with lipopolysaccharide.

Carnosol is a naturally occurring herbal compound, known for its antioxidative properties. We previously found that carnosol protected mouse lungs from ischemia-reperfusion injury in ex vivo cultures. To elucidate the molecular mechanisms underpinning carnosol-mediated lung protection, we analyzed modes of interleukin-6 (IL-6) gene expression, which is associated with lung ischemia-reperfusion injury. Microarray analysis of mouse lungs suggested that IL-6 mRNA levels were elevated in the mouse lungs subjected to clamp-reperfusion, which was associated with elevated levels of other inflammatory modulators, such as activating transcription factor 3 (ATF3). Carnosol pretreatment lowered the IL-6 protein levels in mouse lung homogenates prepared after the clamp-reperfusion. On the other hand, the ATF3 gene expression was negatively correlated with that of IL-6 in RAW264.7 cells. IL-6 mRNA levels and gene promoter activities were suppressed by carnosol in RAW264.7 cells, but rescued by ATF3 knockdown. When RAW264.7 cells were subjected to hypoxia-reoxygenation, carnosol treatment lowered oxygen consumption after reoxygenation, which was coupled with a correlation with a transient production of mitochondrial reactive oxygen species and following ATF3 gene expression. These results suggest that carnosol treatment could be a new strategy for protecting lungs from ischemia-reperfusion injury by modulating the ATF3-IL-6 axis.

Stromal PDGFR-ß Expression is Associated with Postoperative Survival of Non-Small Cell Lung Cancer Patients Receiving Preoperative Chemo- or Chemoradiotherapy Followed by Surgery.

BACKGROUND: PDGFR-ß is used as a stromal biomarker and is functional in mesenchymal cells of the tumor microenvironment. The significance of stromal PDGFR-ß expression in non-small cell lung cancer (NSCLC) in patients undergoing preoperative chemo- or chemoradiotherapy had not been determined. METHODS: Patients with NSCLC undergoing preoperative chemo- or chemoradiotherapy between 1996 and 2014 were assessed for expression of stromal PDGFR-ß by immunohistochemistry using resected specimens. Relationships between stromal PDGFR-ß expression and survival after operation were analyzed. Forty-three patients who underwent surgery without preoperative treatment in 2005 were also analyzed as a chemo-naïve control group. RESULTS: The mean age of the 92 patients was 60.2 years. Seventy-eight (85%) were male, and 14 (15%) were female. Fifty-four patients (59%) underwent preoperative chemoradiotherapy, and 38 patients (41%) underwent preoperative chemotherapy. Regimens for preoperative chemotherapy were cisplatin (CDDP) based in 48 patients (52%) and carboplatin (CBDCA) based in 43 (42%). While stromal cells expressed PDGFR-ß in 21 chemo-naïve patients (49%), stromal cells expressed PDGFR-ß in 65 patients who underwent preoperative therapy (p = 0.02). The 5-year disease-free survival rate (DFS) of the PDGFR-ß-positive group was significantly worse than that of the negative group (27 vs. 48%, p = 0.04). The 5-year disease-specific survival rate (DSS) in the stromal PDGFR-ß-positive group was also significantly worse than in the negative group (43 vs. 70%, p = 0.01). On the other hand, stromal PDGFR-ß expression did not influence survival in chemo-naïve patients. CONCLUSIONS: Stromal PDGFR-ß expression is negatively associated with DFS and DSS in patients with NSCLC undergoing preoperative chemo- or chemoradiotherapy.

Podocalyxin influences malignant potential by controlling epithelial-mesenchymal transition in lung adenocarcinoma.

Epithelial-mesenchymal transition (EMT) plays an important role in the progression of lung carcinoma. Podocalyxin (PODXL), which belongs to the CD34 family and regulates cell morphology, has been linked to EMT in lung cancer, and PODXL overexpression is associated with poor prognosis in several different classes of cancers. The aim of this study was to clarify the role of PODXL overexpression in EMT in lung cancer, and to determine the prognostic value of PODXL overexpression in tumors from lung cancer patients. The morphology, EMT marker expression, and migration and invasion abilities of engineered A549 PODXL-knockdown (KD) or PODXL-overexpression (OE) lung adenocarcinoma cells were examined. PODXL expression levels were assessed by immunohistochemistry in 114 human clinical lung adenocarcinoma specimens and correlated with clinical outcomes. PODXL-KD cells were epithelial in shape, whereas PODXL-OE cells displayed mesenchymal morphology. Epithelial markers were upregulated in PODXL-KD cells and downregulated in PODXL-OE cells, whereas mesenchymal markers were downregulated in the former and upregulated in the latter. A highly selective inhibitor of phosphatidylinositol 3-kinase-Akt signaling attenuated EMT of PODXL-OE cells, while a transforming growth factor inhibitor did not, suggesting that PODXL induces EMT of lung adenocarcinoma cells via the phosphatidylinositol 3-kinase pathway. In lung adenocarcinoma clinical specimens, PODXL expression was detected in minimally invasive and invasive adenocarcinoma, but not in non-invasive adenocarcinoma. Disease free survival and cancer-specific survival were significantly worse for patients whose tumors overexpressed PODXL. PODXL overexpression induces EMT in lung adenocarcinoma and contributes to tumor progression.

Outcomes of lung cancer surgery in patients with coronary artery disease: a decade of experience at a single institution.

PURPOSE: The aim of this study is to investigate the surgical outcomes of surgery for non-small cell lung cancer (NSCLC) in patients with coronary artery disease (CAD). METHODS: Among 805 patients who underwent surgery for NSCLC at our hospital within a recent 10-year period, 43 (5.3 %) had a history of CAD. We analyzed the surgical outcomes and risk factors for postoperative complications in these 43 patients. RESULTS: The postoperative mortality and morbidity rates were 2 and 42 %, respectively. The morbidity rate was significantly higher in the patients with CAD than in those without CAD (P < 0.01). Postoperative cerebrovascular or cardiovascular events occurred in four patients (9 %). Having two of the following was significantly associated with the development of postoperative complications: decreased cardiac function, respiratory dysfunction, or deteriorated renal function (p = 0.04). The 5-year overall and disease-free survival rates of the patients with CAD were 75.6 and 64.5 %, respectively; comparable with those of the patients without CAD; at 77.9 % and 72.5 %, respectively (p = 0.46 and 0.69). CONCLUSIONS: Patients with NSCLC and a history of CAD are at higher risk of complications after pulmonary resection. Combined decreased organ function is a risk factor for postoperative complications. CAD did not influence the long-term outcomes of patients after pulmonary resection for NSCLC.

Outcomes of surgery for lung cancer in patients with atrial fibrillation as a preoperative comorbidity: a decade of experience at a single institution in Japan.

PURPOSE: To investigate the surgical outcomes of surgery for non-small cell lung cancer (NSCLC) in patients with atrial fibrillation (AF) as a preoperative comorbidity. METHODS: Among 805 patients who underwent surgery for NSCLC, 27 (3.4%) had a history of AF. We analyzed the perioperative and long-term outcomes of these 27 patients. RESULTS: Fourteen patients (52%) had chronic AF and 13 (48%) had paroxysmal AF; being high rates of a comorbid illness. Nineteen patients (70%) underwent lobectomy, and 8 (30%) underwent sublobar resection. Ten patients (37%) received perioperative heparinization. There was no mortality. Other non-AF postoperative complications developed in 8 patients (30%), this incidence being higher than among the patients without AF (16%, 127 out of 778, p = 0.09). A thromboembolic event occurred in one patient (4%). With respect to the long-term outcomes, the 5-year overall survival and disease-free survival rates among the patients with AF were 70.3 and 60.8%, respectively, which were similar to those in the patients without AF (79.8 and 72.6%, p = 0.30 and 0.31). CONCLUSIONS: Lung cancer surgery in patients with AF is safe and provides favorable long-term outcomes; however, thoracic surgeons should monitor these patients carefully for postoperative thromboembolic events.

Role of pulmonary metastasectomy in colorectal cancer in the era of modern multidisciplinary therapy.

PURPOSE: To clarify the role of pulmonary metastasectomy in colorectal cancer in the era of modern multidisciplinary therapy. METHODS: The characteristics and outcomes of the patients who underwent pulmonary metastasectomy for colorectal cancer through 2002 (n = 26) and from 2003 (n = 68) were compared. RESULTS: The patients treated from 2003 had a smaller tumor size and more frequently had a history of extra-pulmonary relapses than did those treated through 2002. There was a significant improvement in the 5-year overall survival (42.0% vs. 73.1%, p = 0.03) but not the 5-year relapse-free survival (41.4% vs. 37.5%, p = 0.85) after pulmonary metastasectomy from 2003. The rate of patients who received local therapy with curative intent after the first pulmonary metastasectomy was significantly higher in patients treated from 2003 than in those treated through 2002 [4/13, (31%) vs. 25/39 (64%), p = 0.04]. The survival after relapse after the first pulmonary metastasectomy was significantly longer in patients treated from 2003 than in those treated through 2002 (median survival time: 14 vs. 47 months). CONCLUSIONS: Pulmonary metastasectomy for colorectal cancer remains an important treatment option in the sense that it can achieve a good relapse-free survival.

Treatment of simultaneously discovered lung cancer and cardiovascular disease: a 20-year single-institution experience.

PURPOSE: To propose a treatment strategy for simultaneously discovered non-small cell lung cancer (NSCLC) and cardiovascular disease (CVD). METHODS: Of 1302 patients who underwent surgery for NSCLC, CVD requiring invasive treatment was simultaneously discovered in 33 (3 %). The details of the treatments as well as the short- and long-term outcomes of pulmonary resection were analyzed. RESULTS: CVD included coronary artery disease in 20 patients, valvular disease in 6, abdominal aortic aneurysm in 5, and congenital heart disease in 2. Twenty-six patients underwent two-stage treatment, while seven received simultaneous surgery. In 23 patients whose treatment for CVD preceded that for lung cancer, the median interval between those treatments was 78 days (range 18-197 days). Postoperative complications occurred in 8 (31 %) of 26 patients who underwent 2-stage treatment and in 3 (43 %) of 7 who underwent simultaneous surgery. Notably, of 3 patients who underwent lobectomy or bilobectomy, 2 (67 %) experienced respiratory dysfunction that required intubation. The 5-year overall survival rate of all 33 patients was 84.5 %. CONCLUSION: The outcomes of two-stage treatment in the present cohort were favorable. Given our experience, simultaneous surgery for lung cancer and CVD should, therefore, be selected only for patients who may benefit from that strategy.

PSF1 (Partner of SLD Five 1) is a Prognostic Biomarker in Patients with Non-small Cell Lung Cancer Treated with Surgery Following Preoperative Chemotherapy or Chemoradiotherapy.

BACKGROUND: PSF1 (Partner of SLD Five 1) is an evolutionarily conserved DNA replication factor that is part of the GINS (Go, Ichi, Nii, and San) complex . The objective of this study was to evaluate the relationship between PSF1 expression and prognosis in patients with non-small cell lung cancer (NSCLC) treated with surgery following preoperative chemotherapy or chemoradiotherapy. METHODS: Sixty-nine patients with NSCLC treated with surgery following preoperative chemotherapy or chemoradiotherapy who did not achieve pathologic complete response were enrolled. The status of PSF1 expression was evaluated by immunohistochemistry, and the relationship between expression of PSF1 and Ki-67 was determined, as well as correlations between PSF1 expression and prognosis. RESULTS: We found that 27 of 69 patients' tumors (39 %) were positive for PSF1 expression. The Ki-67 index was significantly higher in the PSF1-positive versus the PSF1-negative group (p = 0.0026). Five-year, disease-free survival of the PSF1-positive group was significantly worse (17.7 vs. 44.3 %, p = 0.0088), and the 5-year overall survival also was worse (16.6 vs. 47.2 %, p = 0.0059). Moreover, PSF1 expression was found to be a significant independent prognostic factor for shorter survival by Cox multivariate analysis (hazard ratio 2.43, 95 % confidence interval 1.27-4.60, p = 0.0076). CONCLUSIONS: PSF1 is a useful prognostic biomarker to stratify NSCLC patients treated with surgery following preoperative chemotherapy or chemoradiotherapy.