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Background/aim: Sublobar resection is widely performed for early-stage non-small cell lung cancer in the clinical setting. This study evaluated the optimal surgical procedures of clinical stage 0 or IA adenocarcinoma from the perspective of recurrence., Patients and Methods: A total of 508 lung adenocarcinoma patients diagnosed as c-stage 0 or IA were retrospectively investigated., Results: The types of surgical procedures were lobectomy (n=328), segmentectomy (n=73), and wedge resection (n=107). Clinical T descriptors were cTis in 74, cT1mi in 68, cT1a in 94, cT1b in 181 and cT1c in 91 patients. Recurrence was observed in 46 cases (9%), including 3 (3.1%) with cT1a, 23 (12.7%) with cT1b and 20 (22.0%) with cT1c. The patients who received sublobar resection developed recurrence more often than the patients who received lobectomy among cT1b cases (10.1% vs. 21.4%) and cT1c cases (18.0% vs. 46.2%) (p=0.053 and p=0.023)., Conclusion: The cT1b and cT1c cases should be considered for lobectomy to prevent recurrence., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Albumin-bilirubin (ALBI) grade is an indicator of liver dysfunction and is useful for predicting postoperative prognosis of hepatocellular carcinomas. However, the significance of ALBI grade in non-small cell lung carcinoma (NSCLC) has not been elucidated., Patients and Methods: We analyzed 947 patients with pStage IA-IIIA NSCLC. We divided patients into ALBI grade 1 and grade 2/3 groups. We then analyzed the association of ABLI grade with clinicopathological characteristics and prognosis in NSCLC by using propensity-score matching., Results: ALBI grade 2/3 was significantly associated with older age, male sex, advanced pT status, and histological type. Even after propensity-score matching, ALBI grade 2/3 patients had significantly worse cancer-specific survival (CSS) than ALBI grade 1 patients (5-year CSS: 87.3% versus 92.8%; p=0.0247). In multivariate analysis, ALBI grade 2/3 was an independent predictor of CSS (HR=1.9; 95%CI=1.11-3.11; p=0.0177)., Conclusion: ALBI grade was an independent prognostic factor in surgically resected NSCLC., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Long interspersed nuclear element-1 (LINE-1) methylation status is a marker for global DNA methylation. However, the relationship between LINE-1 methylation and the biology of lung adenocarcinoma remains unclear. Here, we aimed to examine the role of LINE-1 in lung cancer., Materials and Methods: LINE-1 methylation levels were quantified by bisulfite pyrosequencing of resected tumor specimens from 162 patients with lung adenocarcinoma. The relationships of LINE-1 methylation with clinicopathological factors, gene mutations, and Ki-67 immunoreactivity were investigated., Results: LINE-1 hypomethylation was associated with tumor invasion and advanced stage. TP53 mutations were more frequently detected in the LINE-1 hypomethylation group than in the hypermethylation group. LINE-1 hypomethylation was associated with poor recurrence-free survival, high maximum standardized uptake value in positron-emission tomography, and high Ki-67 expression in tumors., Conclusion: LINE-1 hypomethylation was associated with high-grade malignancy and poor prognosis in lung adenocarcinoma, but was not related to driver mutations., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: In the new TNM classification (8th edition) of lung cancer, T category is defined based on the solid component size; therefore, part solid type (PST) with and solid type (ST) without ground glass opacity (GGO) are categorized as same T value according to their solid component sizes. However, differences between these tumors have not been clarified. Patients and Methods The study included 274 pStage I lung adenocarcinoma patients who had undergone surgery at our Institution from 2003 to 2012. Their tumors were classified as pure GGO, PST, and ST. After propensity score matching for solid component size, we compared prognoses between PST and ST., Results: The same percentage was noted for PST and ST tumors (119/274; 43.4%). After propensity score matching, the disease-free survival (DFS) was significantly worse in ST than PST (5-year DFS: 69.2% versus 88.7%; p=0.0241)., Conclusion: Prognoses of PST and ST adenocarcinomas differ even when their solid component sizes are the same., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: This study was performed to evaluate the influence of the body mass index (BMI) on disease-free survival and overall survival (DFS and OS) in patients with resected non-small cell lung cancer (NSCLC)., Patients and Methods: Overall, 546 of 780 (70%) patients with stage I to III NSCLC who underwent surgical resection were randomly selected. The patients were subdivided into three groups: low BMI (<18.5 kg/m 2 ), normal BMI (18.5 to <25.0 kg/m 2 ), and high BMI (≥25.0 kg/m 2 ). Cox proportional hazards regression analyses were performed to identify variables associated with survival., Results: In all patients, a low BMI was an independent prognostic factor for both DFS and OS (p=0.0175 and p=0.0134, respectively). In patients with stage I, a low BMI was also an independent prognostic factor for both DFS and OS (p=0.0066 and p<0.0001, respectively)., Conclusion: A low BMI was an independent prognostic factor after surgical resection of stage I NSCLC. Molecular targeted therapies, such as epidermal growth factor receptor inhibitors, anaplastic lymphoma kinase-tyrosine kinase inhibitors, and immune checkpoint inhibitors targeting the programmed cell death-1/programmed cell death-ligand 1 (PD-L1) pathway have greatly improved the clinical course for patients with non-small cell lung cancer (NSCLC), especially advanced-stage NSCLC (1-7). However, lung cancer remains the leading cause of cancer-related death worldwide (8). Even in patients with stage I to IIIA NSCLC, the clinical course is unsatisfactory despite the fact that surgical resection is the main treatment option (9). Therefore, it is important to identify useful, simple, and inexpensive prognostic markers in patients with resectable NSCLC., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Alterations of microRNA expression in three-dimensional spheroids were examined to identify novel microRNAs that might be associated with tumorigenesis., Materials and Methods: Using microRNA microarray analysis, we screened for microRNAs that were dramatically up-regulated inside three-dimensional spheroids in genetically-modified HCT116 human colon cancer cells expressing Copepoda Green Fluorescent Protein under hypoxia., Results: miR-3148 was identified as a possible candidate onco-microRNA. A growth advantage of HCT116 cells stably expressing miR-3148 (HCT116-miR3148) was observed compared to parental cells in vivo, but not in vitro. Additionally, no change in growth under hypoxic or starvation conditions was seen in these cells cultured two-dimensionally; however, HCT116-miR3148 cells maintained as three-dimensional spheroids were highly resistant to hypoxic conditions. HCT116-miR3148 cells were more sensitive to mitogen-activated protein kinase (MAPK) kinase inhibitors and extracellular signal-regulated kinase (ERK) inhibitors., Conclusion: MiR-3148 may be a novel onco-microRNA that protects cancer cells from serious stress conditions through the MAPK/ERK pathway, especially in vivo., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: To investigate the role of programmed cell death-ligand 2 (PD-L2) expression as a predictive biomarker for response to anti-programmed cell death-1 (PD-1) drugs in patients with non-small cell lung cancer (NSCLC)., Patients and Methods: Ten patients who had undergone curative lung resection and received the anti-PD-1 drugs for the recurrence were enrolled. The cut-off value for PD-L2 (antibody clone 176611) expression on tumor cells was set at 50%. Tumor response was evaluated according to immune-related response criteria., Results: Seven patients (70.0%) were positive for PD-L2. The response rates were 28.6% (2/7) and 33.3% (1/3) in patients with PD-L2-positive and PD-L2-negative NSCLC, respectively. Disease control was obtained in 2 patients despite the programmed cell death-ligand 1 (PD-L1)-negativity (antibody clone 22C3: 0%, antibody clone SP142: 0%), and these tumors expressed PD-L2 (≥1%)., Conclusion: PD-L2 expression may be a target of immunotherapy in patients with PD-L1-negative NSCLC., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Although some previous studies suggested that programmed cell death-ligand 1 (PD-L1) expression was significantly associated with a favorable postoperative prognosis in patients with small-cell lung cancer (SCLC), the prognostic significance of PD-L2 expression remains unknown. The aim of the current study was to investigate the prognostic significance of PD-L2 expression in patients with SCLC., Patients and Methods: Thirty-eight patients who underwent resection of SCLC were analyzed. A monoclonal anti-human PD-L1 antibody (clone SP142) and a monoclonal anti-human PD-L2 antibody (clone 176611) were used as the primary antibodies. Cut-off value for PD-L1 and PD-L2 expression was set to 1%., Results: Among 38 patients, 15 (39.5%) were positive for PD-L2 expression. No significant associations between PD-L2-positivity and clinicopathological factors, including PD-L1 positivity or prognosis were identified. No significant differences in disease-free survival and overall survival were observed between PD-L2-positive patients and PD-L2-negative patients (p=0.367 and p=0.726, respectively)., Conclusion: PD-L2 expression is not related to clinicopathological factors or postoperative prognosis in patients with SCLC, though this should be further investigated in studies involving larger populations., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Aim: A combination of immune-checkpoint inhibitors that target the programmed cell death 1 (PD1)/programmed cell-death ligand 1 (PDL1) pathway and indoleamine 2,3-dioxygenase 1 (IDO1) is a promising treatment for non-small-cell lung cancer. Herein, we investigated clinical features of IDO1 + /PDL1 + primary lung adenocarcinoma., Materials and Methods: IDO1 and PDL1 expression in 388 resected primary lung adenocarcinoma samples was evaluated using immunohistochemistry, and the radiological features of patients with IDO1 + /PDL1 + lung adenocarcinoma were analyzed., Results: Of 388 specimens, 229 (59.0%) were IDO1 + , 131 (33.8%) were PDL1 + , and 109 (28.1%) were IDO1 + /PDL1 + In multivariate analysis, vascular convergence and the absence of surrounding ground glass opacity were significantly associated with IDO1 + /PDL1 + tumors. Fisher's exact test showed high consolidation/tumor ratio was also significantly associated with IDO1 + /PDL1 + tumors. Moreover, maximum standardized uptake in 18 F-fluorodeoxyglucose positron-emission tomography/computed tomography was significantly higher in patients with IDO1 + /PDL1 + tumors than in those with IDO1 - or PDL1 - tumors., Conclusion: IDO1/PDL1 co-expression was significantly related to radiological invasiveness and malignancy in lung adenocarcinoma. This study may help select patients likely to benefit from combination therapy using immune-checkpoint inhibitors., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase that is deeply involved in cancer pathogenesis. Although clinicopathological significance of EZH2 in non-small cell lung cancer has been gradually elucidated, such significance in small cell lung cancer (SCLC) has yet to be fully investigated., Patients and Methods: Forty patients with resected SCLC were analyzed for EZH2. EZH2 expression was evaluated using the Allred score (0-8) and was classified into negative (0-6) and positive (7 and 8). We evaluated the association between EZH2 and the clinicopathological characteristics and postoperative survivals., Results: Among 40 patients, 15 (37.5%) and 25 (62.5%) were classified as being negative and positive for EZH2, respectively. Fisher's exact test demonstrated no significant associations between the positivity for EZH2 and clinicopathological characteristics. No significant differences were observed in recurrence-free and overall survivals between EZH2-negative/low and EZH2-high patients., Conclusion: EZH2 was frequently observed in patients with resected SCLC, but no significant associations were found between its expression and the clinicopathological characteristics and postoperative survivals., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Aim: To investigate the radiological features on computed tomography (CT) of brain metastasis (BM) from epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC)., Patients and Methods: Thirty-four patients with NSCLC with BMs who underwent surgical resection of the BMs at the Department of Neurosurgery, Kyushu University from 2005 to 2016 were enrolled in the study. The EGFR statuses of the 34 BMs were investigated. Radiological features, including the number, size, and location of the tumor, were delineated by CT., Results: Patients with EGFR-mutated BMs had significantly higher frequencies of multiple metastases than those with the non-EGFR-mutated type (p=0.042). BMs harboring mutations in EGFR were more frequently observed in the central area of the brain compared to those without mutations in EGFR (p=0.037)., Conclusion: Careful follow-up of patients with EGFR-mutated NSCLC may be necessary given the high frequencies of multiple BMs and their location in the central area of the brain., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Takotsubo cardiomyopathy (TC) is a syndrome characterized by transient local systolic dysfunction of the left ventricle with no evidence of coronary artery disease or acute plaque rupture. We present the case of 71-year-old woman who developed TC after two-stage surgery for double primary lung cancer. On computed tomography, lung nodules were identified in the left upper and right middle lobes. Based on the diagnosis of double primary lung cancer, we performed two-stage surgery (left upper lobectomy followed by right middle lobectomy). One day after the second surgery, respiratory failure developed. Electrocardiography showed ST segment elevation, serum troponin levels were elevated, and chest x-ray showed acute pulmonary edema. Cardiac catheterization showed no coronary artery disease and apical akinesia. Based on these findings, we diagnosed TC and the patient recovered with supportive treatment., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Growing teratoma syndrome (GTS) of the lung is extremely rare, and there are very few reports on this condition. This is a case report of GTS of the lung that was successfully treated by resection. A 19-year-old man, who had been diagnosed with a testicular tumor, lung metastases and left hilar lymph node metastasis, underwent surgical resection for left testicular cancer. After orchiectomy and chemotherapy, the patient was successfully treated with wedge resection of the right upper lobe and left upper lobectomy. In conclusion, the current case suggests that some patients with GTS might be successfully treated by surgical resection., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Aim: We investigated the safety of simultaneous bilateral lung resection for lung metastases., Patients and Methods: We retrospectively analyzed 185 patients with pulmonary metastases who underwent unilateral or bilateral pulmonary resection from August 2009 to December 2016 at a single institution., Results: Single-stage bilateral lung resection was undertaken in 19 patients, and the other 166 patients underwent unilateral pulmonary resection, including 20 patients who underwent repeated resections for synchronous or metachronous metastases. Operative time and drainage days in the bilateral group were significantly longer than those in the unilateral group (220±20 vs. 152±6.9 min: p<0.01, and 2.79±0.3 vs. 2.08±0.1 days: p<0.01). Incidence of postoperative complications and postoperative in-hospital days did not differ between the two groups (p=0.33 and 0.66, respectively). The bilateral group was further divided into two groups, namely, those who underwent wedge resection on both sides (WW) and those who underwent wedge resection on one side and segmentectomy or lobectomy on an opposite side (WSL). Operative time in the WSL group was significantly longer than that in the WW group (260±19 vs. 201±18 min: p=0.03). However, there was no significant difference in duration of chest tube use and postoperative hospital days between the two groups (p=0.26 and p=0.89). No severe postoperative complications occurred in either group., Conclusion: One-stage bilateral pulmonary metastasectomy appears to be safe as long as only wedge resection is performed on at least one side., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Spread through air spaces (STAS) is a novel invasive pattern of lung cancer, especially adenocarcinoma and squamous cell carcinoma. However, its frequency and significance in patients with resected small cell lung cancer (SCLC) remains unclear., Patients and Methods: A total of 30 patients with resected SCLC were analyzed for STAS. STAS was classified as either no STAS, low STAS (1-4 single cells or clusters of STAS), or high STAS (≥5 single cells or clusters of STAS). We evaluated the association between STAS and clinicopathological characteristics and postoperative survivals., Results: Among 30 patients, 5 (17%), 6 (20%) and 19 (63%) were classified as having no, low and high STAS, respectively. Fisher's exact test demonstrated no significant associations between the positivity for STAS and clinicopathological characteristics. No significant differences were observed in recurrence-free and overall survival between STAS-negative/low and STAS-high patients., Conclusion: STAS was frequently observed in patients with resected SCLC., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The aim of this study was to assess the appropriateness of pulmonary metastasectomy (MT), with a focus on the primary organ., Patients and Methods: The pathological status of the primary organ, outcome of the MT, disease-free interval, and overall survival were assessed., Results: The primary organ was the most significant prognostic factor analyzed, with a relative risk of 4.6 (95% confidence interval: 1.69-12.56, p=0.003). Patients with colorectal carcinoma had a better survival than those with another primary organ (p=0.003). The hazard ratios by primary organ in comparison to colorectal carcinoma were 3.2 for head and neck carcinoma, 3.5 for soft tissue sarcoma, 8.3 for hepatocellular carcinoma, and 8.9 for urinary carcinoma., Conclusion: Colorectal carcinoma is associated with a greater survival benefit than cancer of other primary organs. Colorectal carcinoma cases should be more aggressively considered for MT than other primary organ cases., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Aim: To investigate the association between positivity for programmed cell death-ligand 1 (PD-L1) in brain metastases (BM) and the prognosis or clinical factors in patients with non-small cell lung cancer (NSCLC)., Materials and Methods: Thirty-two patients with surgically resected brain-metastatic NSCLC were enrolled. The PD-L1 expression in BM was analyzed using the antibody against human PD-L1 (clone SP142). The PD-L1 positivity was defined as PD-L1 expression on brain-metastatic tumor cells of ≥5%., Results: Seven (21.9%) out of 32 patients showed PD-L1 positivity in BM. The PD-L1-positive BM group had a significantly shorter brain-specific disease-free survival than the PD-L1-negative BM group (p<0.05). PD-L1 positivity in BM was significantly associated with a heavy smoking history and the administration of radiotherapy for BM before surgery (p<0.05 and p<0.05, respectively)., Conclusion: The PD-L1 expression in BM from NSCLC may be associated with local recurrence following surgery, and the smoking- or radiotherapy-derived effects., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Aim: We evaluated the metabolic characteristics of small-sized lung cancer using 18 F-fluorodeoxyglucose positron-emission tomography/computed tomography ( 18 F-FDG PET/CT) with regard to programmed cell death ligand 1 (PD-L1) expression., Materials and Methods: PD-L1 expression was evaluated by immunohistochemistry with the antibody clone SP142 in 263 patients with surgically resected primary small-sized lung cancer. Specimens with <5% tumor membrane staining were considered negative. We examined the association between the frequency of PD-L1 expression and the maximum standardized uptake value (SUVmax) in preoperative 18 F-FDG PET/CT., Results: Among patients with non-small cell lung cancer (NSCLC), the SUVmax was significantly higher in those with PD-L1 expression than in those without (p<0.0001). However, there was no correlation between SUVmax and PD-L1 expression in patients with neuroendocrine tumors (p=0.9638). Multivariate analysis revealed that smoking and a high SUVmax were independent predictors of PD-L1 expression., Conclusion: PD-L1 expression was related to high glucose metabolism in small-sized NSCLC., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Few studies have so far described the conversion of programmed death-ligand 1 (PD-L1) after treatment. In particular, the effect of nivolumab on the PD-L1 expression has never been reported. We investigated the changes in PD-L1 expression after chemotherapy and nivolumab treatment and herein describe the detailed clinical course., Patients and Methods: We retrospectively examined the PD-L1 expression in resected specimens and in the re-biopsy specimens of patients with non-small cell lung cancer by immunohistochemical analysis., Results: Four patients underwent a re-biopsy after treatment. Of those, three showed positive conversion of the PD-L1 expression. One patient underwent a re-biopsy after chemotherapy and nivolumab treatment, and the other two cases underwent a re-biopsy after chemotherapy, radiotherapy and nivolumab treatment., Conclusion: These cases suggest the positive conversion of PD-L1 expression after treatments including nivolumab, suggesting that PD-L1 expression must be assessed in not only the resected specimens, but also in the re-biopsied ones., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Women with breast cancer are at increased risk of subsequent primary malignancies, specifically lung cancer. The aim of this study was to report the frequency of lung cancer in patients with breast cancer, and patients' characteristics and surgical outcomes., Patients and Methods: We investigated 1,066 consecutive female patients undergoing surgical resection for breast cancer and 666 undergoing surgical resection for lung cancer., Results: Lung cancer with breast cancer was observed in 14 patients (1.3% of breast cancer and 2.1% of lung cancer cases; mean age=65 years), and 3/14 (21.4%) patients were smokers. Sixteen lung cancer lesions in 14 patients were adenocarcinomas and one was squamous cell carcinoma. All 14 patients were alive at the time of this report; 4/14 (28.6%) patients had recurrent breast cancer and 1/14 (7.1%) had recurrent lung cancer. In synchronous cases, 5/6 (83.3%) patients received concomitant surgery for both breast cancer and lung cancer. Patients' postoperative courses were uneventful. In metachronous cases, eight patients had lung cancer a mean of 33 months after breast cancer surgery. All eight patients received adjuvant therapies and 4/8 (50%) patients received adjuvant therapies for recurrent breast cancer, including chemotherapy, radiotherapy, hormonal therapy, and anti-HER2 therapy. All patients had early-stage lung adenocarcinoma and underwent surgical resection., Conclusion: Concomitant surgery for synchronous lung and breast cancer was feasible and safe. In metachronous cases, lung cancers tended to be detected within 3 years after surgery for breast cancer. Careful follow-up for postoperative breast cancer may contribute to the detection of early-stage lung cancer., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Aim: To determine the efficacy of surgery for non-small cell lung cancer in patients who had previously undergone surgery for pancreaticobiliary cancer., Patients and Methods: Seven patients who underwent pulmonary resection for primary lung cancer after curative surgery for pancreaticobiliary cancer at our Institution from 2006 to 2016 were retrospectively evaluated., Results: Five patients had metachronous and two patients had synchronous cancer of pancreaticobiliary and lung origin. The median time between surgeries for the two cancers was 35 months. All patients underwent complete resection of both cancers. The 5-year survival was 68.6% after pulmonary resection. Two patients had recurrence after lung surgery, with a mean recurrence-free interval of 6.5 months., Conclusion: Surgery should be considered for lung cancer in patients who have undergone curative surgery for pancreaticobiliary cancer., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Aim: To determine the efficacy of pulmonary metastasectomy for pancreatic and biliary tract cancer., Patients and Methods: Ten patients who underwent therapeutic pulmonary metastasectomy after resection for pancreatic and biliary tract cancer at our Institution from 2006 to 2016 were retrospectively evaluated., Results: The primary site was the pancreas in four patients and biliary tract in six. Nine patients had single metastasis, and one patient had bilateral multiple metastases. The median time from surgery for the primary tumor to pulmonary resection was 23.3 months (range= 0-47.1 months). One patient underwent lobectomy, while nine patients underwent partial resection. One patient had incomplete resection due to pleural dissemination. There were no postoperative mortalities or major morbidities. The mean follow-up period was 26.0 months. The median survival time was 38.5 months, and the estimated 5-year overall survival was 38.9% after pulmonary resection. Five patients had recurrent disease after pulmonary resection, with a median recurrence-free interval of 6.0 months. One patient underwent second pulmonary resection for a solitary lung recurrence., Conclusion: Despite the poor prognoses of these cancer types, pulmonary metastasectomy can significantly prolong survival in selected patients with pancreatic and biliary tract cancer., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Aim: The purpose of this study was to investigate the prognostic significance of epidermal growth factor receptor (EGFR) sensitizing mutations in patients with lung adenocarcinoma who underwent complete surgical resection., Patients and Methods: We retrospectively reviewed the clinical records of 164 patients with lung adenocarcinoma who underwent surgery from 2003 to 2010. Seventy-four patients harbored EGFR mutations; two with exon 18 mutations, 27 with exon 19 mutations, and 45 with exon 21 mutations., Results: There were more female patients and more never-/light smokers among patients with EGFR mutations than among patients without EGFR mutations. Patients with EGFR mutations had a trend for better disease-free survival and overall survival compared to patients without EGFR mutations (p=0.068 and p=0.049, respectively). Patients with exon 21 mutations had significantly better disease-free survival than patients with exon 19 mutations (p=0.027)., Conclusion: Adenocarcinomas harboring EGFR exon 21 mutation were less malignant than adenocarcinomas harboring exon 19 mutation., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: With the recent popularization of living-donor liver transplantation (LDLT), it has become important to provide treatment for comorbidities in recipients. We report the case of a patient who was successfully treated with LDLT, followed by left upper lobectomy for lung cancer concomitant with decompensated liver cirrhosis., Case Report: A 67-year-old female was admitted for treatment for severe liver cirrhosis. The lung cancer was identified preoperatively using computed tomography. We initially performed LDLT to improve liver function and coagulopathy; the patient was discharged postoperatively on day 39 without complication. Three months after LDLT, we performed a left upper lobectomy., Results: The patient's postoperative course was uneventful and she was discharged after 11 days., Conclusion: We conclude that an aggressive and appropriate surgical strategy, including LDLT, is an effective curative treatment in patients with controllable malignancy, concomitant with severe liver dysfunction., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background/aim: Patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) gene mutations or echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) rearrangement often have a better prognosis when they are treated with specific inhibitors than when treated with cytotoxic agents. However, the associations between gene mutations and cytotoxic chemosensitivity are still unclear. The objective of the present study was to identify which clinicopathological factors, including genetic mutations, influence chemosensitivity, determined using the succinate dehydrogenase inhibition (SDI) test in patients with NSCLC., Materials and Methods: The chemosensitivity of tumor tissues from 96 patients with NSCLC who underwent surgical resection was evaluated using the SDI test., Results: In patients with adenocarcinoma, tumors with EGFR gene mutations were significantly more sensitive to 5-fluorouracil (5-FU) than tumors without EGFR gene mutations (p<0.0149)., Conclusion: Our data suggest that patients with adenocarcinoma harboring EGFR gene mutations may be susceptible to 5-FU., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Aim: To analyse the prognostic factors for patients with non-small cell lung cancer (NSCLC) who underwent cytotoxic chemotherapy with third generation agents or epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) for recurrence., Patients and Methods: Between 1997 and 2005, 479 patients underwent a complete resection for NSCLC. Of these, 112 patients underwent chemotherapy for postoperative recurrence., Results: Median postrecurrence survival time for these 112 patients was 25.6 months. Univariate analysis showed female gender, age younger than 65 years, ECOG performance status of 0-1, never-smoker status, and adenocarcinoma prolonged survival, whereas metastasis to the liver or adrenal gland shortened survival. Multivariate analysis revealed age, performance status, cell type and metastasis to the adrenal gland to be independent prognostic factors., Conclusion: Age, performance status, cell type, and metastasis to the adrenal were independent prognostic factors in NSCLC patients treated with third-generation agents or EGFR-TKI for recurrence.

Background: Eleven phosphodiesterase (PDE) gene families (PDE1-11) have been identified, and some PDE isoforms are selectively expressed in various cell types. Previously, we reported PDE1, PDE3 and PDE4 expressions in human malignant melanoma cells. However, the expression and role of PDE5 in malignant melanoma cells is not clear. Therefore, we characterized PDE5 in human malignant melanoma MAA cells., Materials and Methods: PDE5 activity and PDE5A mRNA expression were investigated in MAA cells. The full open reading frames for human PDE5A1 were sequenced. Effects of PDE5 inhibitors on cell growth were determined by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assays., Results: PDE5 activity and PDE5A1 mRNA expression were detected in MAA cells. The nucleotide sequence of PDE5A1 was identical to that of human PDE5A1, previously published. Two PDE5 inhibitors inhibited the growth of cells., Conclusion: PDE5A1 mRNA is expressed and may play an important role in the growth of human malignant melanoma MAA cells.

Background: Differentiation-inducing factor 1 [DIF-1; 1-(3,5-dichloro-2,6-dihydroxy-4-methoxyphenyl) hexan-1-one] from Dictyostelium discoideum exhibits antiproliferative activity in mammalian cells. We have previously shown that phosphodiesterase 1 (PDE1) is a pharmacological target of DIF-1, but there are no reports of PDE1 in human malignant melanoma cells. Therefore, we characterized PDE1 in human malignant melanoma MAA cells., Materials and Methods: PDE1 mRNA expression was investigated in MAA cells. The full open reading frames for human PDE1C1 and PDE1C3 were cloned. Cell growth was determined by MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt] assay., Results: PDE1C mRNA expression was detected in MAA cells. The nucleotide sequence of PDE1C1 was identical to that of human PDE1C1, previously published. At nucleotide 2246 in PDE1C3, A was replaced by G, but this did not change the encoded amino acid. Cell growth was inhibited by the PDE1 inhibitor vinpocetin., Conclusion: PDE1C mRNA is expressed and may play an important role in human malignant melanoma MAA cells.

Little is known concerning the expression, distribution and function of phosphodiesterase (PDE) 3s in malignant tumor cells, including human malignant melanoma HMG and osteosarcoma HOSM-1 cells. PDE3 activity was detected in homogenates of HMG cells; however, much less activity was found in HOSM-1 cells. In HMG cells, most of the PDE3 activity was in the particulate fraction. PDE3A and 3B mRNAs were detected by RT-PCR in RNA from HMG cells only. The nucleotide sequences of the fragments were identical to those of human PDE3A and 3B. The PDE3-specific inhibitors, trequinsin and cilostamide, did not inhibit the proliferation of HMG or HOSM-1 cells. Although two PDE3 isoforms may be expressed in human malignant melanoma cells, their functional importance is not known.