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OBJECTIVES To demonstrate the differences in clinical outcomes between lobectomy and segmentectomy for non-small cell lung cancer using propensity score matching. METHODS A single-centre, retrospective, matched cohort study was conducted in clinical T1N0M0 non-small cell lung cancer patients treated by surgery between 2012 and 2019. Differences in freedom from recurrence, overall survival, postoperative complications, chest drainage and preservation of pulmonary function between lobectomy and segmentectomy were evaluated using the propensity score model. Matched variables of patients were age, sex, comorbidity index and pulmonary function. Matched variables of tumours were tumour size, T-stage, fluorodeoxyglucose uptake on positron emission tomography, histopathology, lobe site and tumour distance ratio from the hilum. RESULTS Of the 112 patients treated by lobectomy and 233 patients treated by segmentectomy, 93 patients each from both groups were selected after the matching. The median tumour distance ratio from hilum was 0.7 in lobectomy and 0.8 in segmentectomy group (P = 0.59), i.e. almost outer third tumour location. There were no significant differences in freedom from recurrence (P = 0.38), overall survival (P = 0.51), postoperative complications (P = 0.94), drainage period (P = 0.53) and prolonged air leakage (P = 0.82) between the two. Median preservation of pulmonary function was 93.2% after segmentectomy, which was significantly higher than 85.9% after lobectomy (P, Pulmonary segmentectomy is expected to change the surgical treatment of clinical (c) T1N0M0 non-small cell lung cancer (NSCLC).

Adjuvant oral uracil-tegafur (UFT) has led to significantly longer postoperative survival among patients with non-small-cell lung cancer (NSCLC). Gemcitabine (GEM) monotherapy is also reportedly effective for NSCLC and has minor adverse events (AEs). This study compared the efficacy of GEM- versus UFT-based adjuvant regimens in patients with completely resected pathological stage (p-stage) IB–IIIA NSCLC. Patients with completely resected p-stage IB–IIIA NSCLC were randomly assigned to GEM or UFT. The primary endpoint was overall survival (OS); secondary endpoints were disease-free survival (DFS), and AEs. We assigned 305 patients to the GEM group and 303 to the UFT group. Baseline factors were balanced between the arms. Of the 608 patients, 293 (48.1%) had p-stage IB disease, 195 (32.0%) had p-stage II disease and 121 (19.9%) had p-stage IIIA disease. AEs were generally mild in both groups, and only one death occurred, in the GEM group. After a median follow-up of 6.8 years, the two groups did not significantly differ in survival: 5 year OS rates were GEM: 70.0%, UFT: 68.8% (hazard ratio 0.948; 95% confidence interval 0.73–1.23; P = 0.69). Although GEM-based adjuvant therapy for patients with completely resected stage IB–IIIA NSCLC was associated with acceptable toxicity, it did not provide longer OS than did UFT.

Background While the cryoablation for tumors has been conducted using argon gas, the present study conducted cryoablation using liquid nitrogen for metastatic lung cancers. The study aim is to evaluate the suitability of cryoablation using liquid nitrogen for metastatic lung cancer and to compare preserved pulmonary function according to the number of treated tumors. Methods This was a retrospective observational study including 68 patients with 121 metastatic lung tumors that were treated with cryoablation using liquid nitrogen between 2013 and 2019. The treatment was performed with a single 10-G cryoprobe under computed tomography with local anesthesia. To penetrate the tumor with cryoprobe under spontaneous breathing, a guide needle kit consisting of a 21-G guide needle and an 8-G stainless-steel coaxial system was used. Cryoablation was generally performed with repeating freeze and thaw for 3 cycles. Primary outcome was the local control and incidence of pneumothorax. Secondary outcome was whether preserved pulmonary function 6 months after cryoablation varied according to number of treated tumors. Results Cryoprobe could reach all of the 121 tumors under computed tomography. Median follow-up period was 32 months. Histological types were carcinomas in 95 tumors and sarcoma in 26. The 3-year local control rate was 73% in all tumors, and 96% and 46% in tumors

AimsTo identify factors that were associated with local control after cryoablation for metastatic lung tumors and to compare preserved pulmonary function according to tumor number.MethodsWe retrospectively evaluated 68 patients with 121 metastatic lung tumors that were treated with cryoablation using liquid nitrogen during 2013–2019. Primary outcome was whether local control was related with tumor size, histology, location, and distance to a vessel with a diameter of ≥3 mm. Secondary outcome was whether preserved pulmonary function varied according to number of treated tumors. ResultsMedian follow-up period was 32 months (range: 4–87 months).Histological types were carcinomas in 95 tumors and sarcoma in 26 tumors. Multivariate analysis revealed that local control was significantly associated with tumor size (p

Prognosis beyond 5 years after segmentectomy for non-small cell lung cancer (NSCLC) has not been well studied.This study is a retrospective analysis of a previous prospective cohort study of patients with peripheral cT1 N0 M0 NSCLC who underwent segmentectomy between 2005 and 2009. Exclusion criteria were right middle lobe tumors, multiple tumors in same lobe, patients having considerable risk for segmentectomy, and patients requesting lobectomy rather than segmentectomy. The median follow-up period was 108 months. Study outcomes included overall survival, recurrence-free probability, and local recurrence.Of 179 patients with cT1 N0 M0 who were treated by segmentectomy, clinical T stages were Tis in 57 patients, T1mi or T1a in 34, T1b in 57, and T1c in 31. All tumors were pathologic N0 tumors. The 10-year recurrence-free probability rates in each clinical stage were 100% in Tis, 97% in T1mi or T1a, 90% in T1b, and 69% in T1c, which were significantly lower in advanced T stages (p0.001). Fourteen patients (8%) experienced recurrences after segmentectomy; these were local in 8 patients (five recurrences at the surgical margin and three in the preserved lobe) and nonlocal in 6 patients. Six of the eight local recurrences developed more than 5 years after segmentectomy. All eight local recurrences were treated by local therapy, resulting in 6 patients surviving without disease at 55 months of median follow-up after the additional treatments.Although segmentectomy may be a viable curative option for treating T1 N0 M0 NSCLC, monitoring for local recurrence should be continued beyond 5 years after segmentectomy to avoid missing opportunities to effect a cure.

S-1 plus oxaliplatin(SOX)chemotherapy is now widely used for the treatment of unresectable gastric cancer but there are few case reports about conversion surgery following SOX. Hereby, we report a case of type 4 gastric cancer with peritoneal dissemination successfully treated with conversion surgery after intensive SOX chemotherapy. A 69-year-old female was diagnosed of type 4 gastric cancer by upper endoscopy(por1, HER2 negative)and peritoneal disseminations were identified on left diaphragm and mesentery under direct vision. After 11 courses of SOX chemotherapy, CT revealed that primary tumor markedly decreased in size. Therefore, staging laparoscopy was performed and peritoneal disseminated lesions disappeared. Peritoneal cytology also turned negative. Subsequently, total gastrectomy and splenectomy were performed. Histology revealed that tumor was categorized as por2, ypT2N3M0, ypStage ⅢA, and Grade 2 in histological evaluation criteria. SOX was continued as an adjuvant chemotherapy for another 6 months and the patients remain healthy without recurrence. Unresectable gastric cancer with peritoneal dissemination can be successfully treated with conversion surgery following SOX chemotherapy and staging laparoscopy was useful to evaluate peritoneal dissemination. When conversion surgery is indicated for gastric cancer with peritoneal dissemination, downstaging should be confirmed by staging laparoscopy.

Objectives: To examine the differences in clinical response, pathological response, recurrence, and survival between lung adenocarcinoma (AD) and squamous cell carcinoma (SQ) after induction chemoradiotherapy (ICRT) followed by surgery. Methods: Ninety-five patients with N1-2 or T3-4 non-small cell lung cancer were treated with ICRT followed by surgery between 2012 and 2018; 55 patients had AD and 40 had SQ. Differences in reductions of tumor size and fluorodeoxyglucose uptake on positron emission tomography after ICRT, as well as the pathological response, histological distribution of residual tumors, time to recurrence, and overall survival were compared between AD and SQ. Median follow-up period was 51 months. Results: After ICRT, SQ showed significantly more reduction in both the tumor size and fluorodeoxyglucose uptake than AD (p

This study sought to clarify the extent of segmentectomy that achieves greater lung preservation than lobectomy.This was a single-center retrospective cohort study involving 374 patients with lung cancer who were treated with either lobectomy or segmentectomy between 2013 and 2018. The percentage of preserved pulmonary function (%PPF) after surgery was compared among patients who underwent lobectomy (n = 164), segmentectomy of 2 or more segments (Seg ≥2S; n = 42), and segmentectomy of less than 2 segments (Seg2S; n = 168). Using perfusion scintigraphy, forced expiratory volume in 1 second of the preserved target lobe was measured to examine its effect on the %PPF. The number of resected subsegments (SSs) in segmentectomy that made the %PPF higher than that observed with lobectomy was also examined.Mean %PPF was lowest in those patients who underwent lobectomy (86%), followed by Seg ≥2S (89%) and Seg2S (95%) (P.001), but the difference between the lobectomy and Seg ≥2S was not significant (P = .21). The forced expiratory volume in 1 second of the preserved target lobe was significantly lower in the Seg ≥2S group than in the Seg2S group (P.001). The number of resected SSs was 6 to 12 in lobectomy, 4 to 7 in Seg ≥2S, and 1 to 4 in Seg2S. Although the %PPF after segmentectomy of less than 5 SSs (Seg5SS) was significantly higher than that after lobectomy (P.001), the %PPF after segmentectomy of 5 or more SSs (Seg ≥5SS) was not significantly different from that after lobectomy (P = .68).Both the Seg ≥2S and Seg ≥5SS groups did not differ from lobectomy in %PPF because of the low function of preserved target lobe.

Non-small cell lung cancer (NSCLC) involving the chest wall is usually treated with en bloc rib resection or parietal pleurectomy; however, the former causes chest wall deformity and the latter is associated with local recurrence. To prevent both these sequalae, we performed the “ribcage” procedure for tumors involving the chest wall after induction chemoradiotherapy. This was a single center retrospective study conducted from 2012 to 2018. The “ribcage” procedure is designed to preserve the ribs of patients with lung tumors involving chest wall and involves peeling the intercostal muscles and periosteum from the ribs, resulting in a birdcage-like appearance. Seventeen patients with NSCLC clearly involving the chest wall, but not destroying the ribs, were treated with induction chemoradiotherapy, followed by the ribcage procedure. A negative margin at the ribs was confirmed by intraoperative frozen sections in 16 of these patients, who then underwent the ribcage procedure. Complete resection was achieved in all 16 patients, none of whom experienced major postoperative complications. After a median follow-up period of 37 months, there was no evidence of local recurrence in any of the patients. Our findings suggest that the ribcage procedure is the preferable surgical option as it can prevent chest wall deformities as well as local recurrence.

OBJECTIVES To clarify differences in postoperative changes in systemic and regional pulmonary functions between segmentectomy and lobectomy in patients with lung cancer, we compared the 2 procedures using lung perfusion scintigraphy with a fusion image of single-photon emission computed tomography and computed tomography. METHODS This study is a retrospective matched cohort study of consecutively acquired data. Pulmonary function tests and perfusion single-photon emission computed tomography/computed tomography were conducted before surgery and 6 months after surgery to measure changes in forced expiratory volume in 1 s of a whole lung, contralateral lung and a lobe. After exactly matching the site of the resected lobe between the 2 procedures, propensity scores for age, sex, smoking status and pulmonary function were used to match them. RESULTS Of the 184 patients treated with segmentectomy and the 208 patients treated with lobectomy between 2013 and 2016, 103 patients were selected from each group after the matching. Whole lung function was significantly more preserved after segmentectomy than after lobectomy (P

The aim was to investigate the relationship of age for recovery of six-minute walking distance (6MWD), pulmonary function, and health-related quality of life (HRQOL) after lung cancer surgery. Primary outcome was the 6MWD recovery until 6 months after surgery. Secondary outcome was the recoveries of forced expiratory volume in 1 s (FEV1) and HRQOL until 6 months after surgery. Linear mixed-effects model was used to estimate the association of age to the outcomes. A total of 311 lung cancer patients were included. All the 6MWD, FEV1, and HRQOL decreased after surgery (− 32 m, − 0.39L, and − 2 scores, respectively, p = 0.027—p

Background To predict pathological response and survival in T3/T4 non-small cell lung cancer after induction chemoradiotherapy by assessing fluorodeoxyglucose uptake with positron emission tomography. Methods In this retrospective observational study, standard uptake values of whole tumors and extrapulmonary involvement sites were measured after induction chemoradiotherapy. The values were then compared with pathological responses and recurrence-free survival. Results Fifty-seven patients with clinical T3/T4 tumors were treated by chemoradiotherapy followed by surgery. Pathological complete response was observed in 33% of patients (19 of 57). With the cutoff value of 3.3 for whole tumor fluorodeoxyglucose uptake for estimating complete response, 38% patients (9 of 24) with values lower than the cutoff value were false-negative. Tumor remission at extrapulmonary involvement sites was observed in 82% patients (47 of 57), and the cutoff value of the extrapulmonary uptake was 3.0 without any false negatives. Recurrence-free survival was significantly better in patients with values lower than both the whole- and extrapulmonary-uptake cutoff values than in patients with higher values (P = .016 and P = .001, log-rank test, respectively). Among 7 patients who avoided en bloc resections of involved structures because of lowered extrapulmonary uptakes and negative findings in intraoperative frozen sections, none experienced margin recurrence. Conclusions Even when whole tumor uptakes in patients with T3/T4 tumors markedly decrease after induction chemoradiotherapy, surgical treatment is still indicated because of possible residual tumors. Tumor remission at extrapulmonary involvement sites could be predicted by extrapulmonary uptake values. Both whole- and extrapulmonary-uptake values after induction chemoradiotherapy could be used to predict prognosis.

To evaluate local control and complications of cryoablation for T1N0M0 non-small cell lung cancer using liquid nitrogen.This is a retrospective observational study on 101 patients with T1N0M0 NSCLC who underwent cryoablation between 2013 and 2019. Exclusion criteria included tumors without pathological diagnosis. The study population was divided into 4 groups according to the quartile of maximum tumor diameter. The study outcomes included local control, recurrence-free survival (RFS), treatment complications, and change in pulmonary function. Median follow-up period was 35 months.Tumor diameter was divided into ≤0.9 cm (n = 21), 1.0-1.2 (n = 29), 1.3-1.7 (n = 24), and ≥1.8 (n = 27). Ten patients experienced local recurrences, which were observed none in both the groups of ≤0.9 cm and 1.0-1.2 cm (0%), one in the group of 1.3-1.7 cm (4%), and the other 9 in the group of ≥1.8 cm (33 %), indicating the local control to be better in smaller tumors (p 0.001). The 3-year RFS was 86 % in ≤0.9 cm, 97 % in 1.0-1.2 cm, 92 % in 1.3-1.7 cm, and 53 % in≥1.8 cm, indicating the survival to be better in smaller tumors (p 0.001). No patient had treatment-related mortality. The most frequent complication was pneumothorax, with a rate of 24 %. Forced expiratory volume in 1 s at 6 months after cryoablation was 97 ± 10 % of the pretreatment one.The local control and recurrence-free survival of cryoablation for T1N0M0 NSCLC was satisfactory for tumors1.8 cm. While main complication was pneumothorax, the decrease of pulmonary function was just 3%.

Objective Segmentectomy includes numerous kinds of procedures that may result in decreased postoperative pulmonary function. This causes controversy regarding the functional advantage of segmentectomy over lobectomy. To clarify the difference between the procedures, systemic and regional pulmonary functions of the resected segments must be examined. Methods Pulmonary function tests and lung perfusion single-photon emission computed tomography (SPECT) were prospectively conducted before and after segmentectomy in 117 patients who were divided into groups based on resection of 1 ) of segment and lobe were measured from a fusion image of SPECT and computed tomography. Results Percentage of postoperative/preoperative pulmonary function was the highest in the P 1 of preserved lobes were significantly lower than the predicted value in all segmentectomy groups ( P P P = .02, respectively). Conclusions Segmentectomy decreased the pulmonary function with increasing number of resected segments. LUD segmentectomy decreased both systemic and lobar function significantly due to not only large resection, but also marked depression of the preserved lobe, resulting in similar decrease as lobectomy.

To examine the efficiency of cryoablation using liquid nitrogen in lung tissue, we measured the size and temperature distribution of the frozen area (iceball) in gel and in the ex vivo pig lungs. Cryoprobes with diameters of 2.4 and 3.4 mm (2.4D and 3.4D, respectively) were used. Three temperature sensors were positioned at the surface of the cryoprobe and at distances of 0.5 and 1.5 cm from the cryoprobe. The ex vivo pig lungs were perfused with 37 °C saline and inflated using ventilator to simulate in vivo lung conditions. In gel, the 2.4D and 3.4D probes made iceballs of 3.9 ± 0.1 and 4.8 ± 0.3 cm in diameter, respectively, and the temperature at 1.5 cm from those probes reached −32 ± 8 and −53 ± 5 °C, respectively. In the pig lung, the 2.4D and 3.4D probes made iceballs of 5.2 ± 0.1 and 5.5 ± 0.4 cm in diameter, respectively, and the temperature at 1.5 cm from these probes reached −49 ± 5 and −58 ± 3 °C, respectively. Liquid nitrogen cryoablation using both 2.4D and 3.4D probes made iceballs that were of sufficient size, and effective temperatures were reached in both gel and the ex vivo pig lung.

It is often difficult to expose the pulmonary artery buried in a scar tissue, especially in lung cancer patients that responded well to neoadjuvant chemoradiotherapy. Difficulty to access pulmonary artery branches may lead to potentially unnecessary pneumonectomy. To complete lobectomy in such cases, a technique with preceding bronchial cutting for exposure of the pulmonary artery is presented. After dissecting the pulmonary vein, the lobar bronchus is cut from the opposite side of the pulmonary artery with scissors. The back wall of the lobar bronchus is cut using a surgical knife from the luminal face, which can expose the pulmonary artery behind the bronchial stump and then complete lobectomy. Fourteen patients have been treated using the present technique, enabling complete resection by lobectomy (including sleeve lobectomy in 3 patients) without major bleeding. The present procedure can expose pulmonary artery buried in scar tissue, resulting in making the lobectomy safer.

To assess whether a video-assisted thoracoscopic surgery (VATS) procedure is superior to limited thoracotomy (LT) for segmentectomy; postoperative pain was compared between VATS-lobectomy (VATS-L) and LT-segmentectomy (LT-S). Widely opened anterolateral thoracotomy segmentectomy (WT-S) was used as a control. This study was a retrospective analysis of prospectively collected data for 220 consecutive patients with stage I NSCLC treated between 2012 and 2015 at a single institute using VATS-L (n = 58), LT-S (n = 93), or WT-S (n = 69). Pain scores from postoperative days (POD) 1–4 were measured using a visual analog scale three times a day. Chronic pain was assessed by the need for analgesics at 1, 2, and 3 months postoperatively. No significant differences in pain from POD 1 to 4 were observed between VATS-L and LT-S, whereas WT-S showed significantly higher pain scores than these two procedures (p = 0.0001–0.02). Chronic pain did not differ significantly among the procedures. Postoperative pain does not differ significantly between VATS-L and LT-S. LT may be preferable to VATS for segmentectomy to identify the anatomy, dissect the hilar nodes, and establish surgical margins.

Purpose To investigate local control and survival after bronchial artery embolization (BAE) using N-butyl-2-cyanoacrylate (NBCA) for pulmonary hilar or mediastinal tumors that are refractory to chemotherapy or chemoradiotherapy. Method This is a single center retrospective study involving 42 patients treated between 2015 and 2018 for pulmonary hilar or mediastinal tumors (primary tumors in 5 and metastatic ones in 37). Tumor histology was sarcoma in 22 and carcinoma in 20 patients. All patients had shown tumor progression regardless of previous chemotherapy (n = 37) or chemoradiotherapy (n = 5). Thirty-seven patients (88 %) had respiratory symptoms, such as cough, dyspnea, and hemoptysis. BAE was performed using NBCA to shrink tumors for extending life expectancy. Target tumors were followed with computed tomography at 1,3, and 6 months after BAE. Endpoints included the best tumor response within 6 months as well as overall survivals in patients with and without tumor responses. Results Best local responses within 6 months were complete response (CR) in 1 patient, partial response (PR) in 16, stable disease (SD) in 24, and progressive disease (PD) in 1; the CR/PR rate was 40 % (17/42). Median follow-up period was 13 months (range:1−43). Overall survival in patients with CR/PR was significantly better than in those with SD/PD (p = 0.006); with 3-year survival rates of 45 % (8/17) and 0% (0/25), respectively. Conclusions BAE using NBCA has potential promise for shrinking hilar and/or mediastinal tumors that are refractory to chemotherapy or chemoradiotherapy, and may also improve overall survival in patients who respond.

Background: The 2-year overall survival (OS) of c-Stage IIIA/B non-small cell lung cancer (NSCLC) is each 53% and 34% in IASLC Staging Project (7th) and the treatments remain controversial. Especially, multimodal treatment at stage III (T3/4-AOI) is poorly studied. Method: This retrospective observational study aimed to elucidate the efficacy and safety of tri-modality therapy in pts with stage III NSCLC (T3/4-AOI). We included all pts who received ICRT (2 cycles of DOC/CDDP or PAC/CBDCA plus 40–46 Gy of thoracic radiation) between 2014 and 2017 at our institution. Results: 35 pts (mean age, 66y) with stage III NSCLC (T3/4-AOI, any-N proven by EBUS-TBNA) judged as pre-ICRT resectable by a multidisciplinary tumor board, were enrolled. There were 21 T3 and 14 T4 cases; and 17 adenocarcinoma, 17 squamous cell carcinoma, and 1 not-otherwise-specified case. One pneumonectomy and 28 lobectomies; and 11 tracheobronchial, 6 chest wall, 7 great vessel, and 6 cardiac resections were performed. 26 pts (90%) achieved R0 resection. 6 pts did not undergo surgery due to disease progression (n=3), performance status decline (n=1), and severe radiation pneumonitis (n=2). No pts died during ICRT or within 6 months post-surgery. The 2-year OS and recurrence-free survival (RFS) rate in those who completed the 2-year follow-up was each 74% (17/23) and 68% (15/22), respectively. In total, each 12 and 13 pts have not reached 2-year follow-up yet. Conclusion: Surgery after ICRT in pts with stage III NSCLC (T3/4-AOI) was well tolerated and potentially benefitted survival.

Diffusion-weighted magnetic resonance imaging (DWI) frequently shows heterogeneity of signal intensity (SI) in non-small cell lung cancer (NSCLC). The purpose of our study was to examine the association of SI and DWI patterns with histology, tumor invasiveness, lymph node metastasis, and (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) uptake in NSCLC.One hundred forty-five patients with NSCLC underwent preoperative DWI and FDG-PET. DWI patterns were visually classified as homogenous (HOM) (n = 81) or heterogeneous (HET) (n = 64). The former was further classified as faint (faint-HOM) (n = 27) or dark (dark-HOM) (n = 54) according to a cutoff value of SI. Associations of SI and DWI patterns with tumor histology, lymphatic or vascular invasion, pleural invasion, lymph node metastasis, and FDG uptake were evaluated.All faint-HOM tumors were well-differentiated adenocarcinoma, whereas dark-HOM and HET tumors were less-differentiated adenocarcinoma or non adenocarcinoma. Although the dark areas in HET tumors showed a dense aggregation of tumor cells, their faint areas showed abundant fibrovascular stroma or necrosis, or a well-differentiated part of adenocarcinoma. Tumor size and the frequencies of lymphatic or vascular invasion, pleural invasion, and nodal metastasis were highest in HET tumors, followed by dark-HOM and faint-HOM (P = .1-P.001) tumors. Sixty-five tumors having at least 1 of the invasions or metastasis showed significantly higher SI than the 81 tumors without (P.001). HET tumors had the highest FDG uptake, followed by dark-HOM and faint-HOM tumors; differences between the groups were significant (P.01 to P.001).The SI and heterogeneity of DWI reflect the histologic heterogeneity, tumor aggressiveness, and FDG-PET uptake in NSCLC.

11071 Background: Soft tissue sarcoma (STS) is well-known rare cancer with few therapeutic options. Although recent genomic analyses of sarcoma revealed few somatic mutations, massive copy number variations (CNV) and chromoplexy which correlate with worse clinical outcomes, their molecular and genomic mechanisms remain to be understood. Methods: We recruited 116 patients (102 female and 14 male, mean age 50, 80 LMS, 14 LPS, 3 AS and others) and performed whole exome sequencing with the methods as reported in ASCO2018. In addition to somatic mutations, we evaluated germline and CNV contributions in tumor to find LOH mutations by Strelka and Virmid analysis softwares. Results: Of the total of 135-4717 (mean 1129) mutations in tumors, 3-111 (mean 32) mutations were found in 595 COSMIC genes including both somatic and LOH mutations. Less than 33% LOH in the total of somatic and LOH mutations significantly correlated with improved 5-year survival rate as compared with patients with more LOH (81% vs 52%, P=0.01). Among the 224 genes reported in somatic mutations of sarcoma, damaging mutations in ARHGAPs, Rho GTPase signal inactivating genes, were most frequently detected in 59% of total (n=116) and 63% of leiomyosarcoma (n=80) patients as in somatic and/or LOH mutations. Patients with ARHGAP mutations were significantly reduced 5-year survival rates as compared with patients without mutation (51% vs 76%, P=0.007). Among the 163 genes involved in autophagy, a key silencing process for active RhoGTPase, one or more damaging mutations as in somatic and/or LOH mutations were found in 87% in total and 96% in leimyosarcoma patients. Conclusions: Our results, for the first time, suggest an important role of mutations in genes involved in Rho GTPase and autophagy signaling, both well known regulator of chromosomal stability, invasion and metastasis of tumor cells, and thus implicate a potential therapeutic target in STS.

Purpose: Reduction in the level of vascular endothelial growth factor (VEGF) has been implicated in the pathogenesis of pulmonary emphysema. To this end, pharmacological VEGF receptor blockade, and the Cre-lox system models have been utilized to study the effects of VEGF depletion in the lung. These models generally reproduce air space enlargement resembling clinical emphysema. Here we report a potentially more readily available model of lung targeted VEGF depletion by airway administration of VEGF small inhibitory RNA oligonucleotides (siRNAs) in mice. Methods: Airway administration of VEGF siRNAs were done in C57BL/6 mice. The lungs were removed for histology and protein analysis 2, and 4 days later. Airspace enlargement was evaluated by lung volume measurement, and histological analyses. VEGF levels were analyzed by western blot and immunohistochemistry. Results: Airway administration of VEGF siRNAs induced transient air space enlargement in the mouse lung morphologically resembling the previously reported models of pulmonary emphysema. VEGF expression was significantly reduced in the lung, particularly in the alveolar septal cells. We also found that in this particular model, sequential airway administration of recombinant VEGF protein attenuated this air space enlargement. Additionally, we found that airway administration of DCI, a combination of dexamethasone, 3'-5'-cyclic adenosine monophosphate, and isobutylmethylxanthine attenuated the air space enlargement in this particular model, at least in part through the recovery of lung VEGF expression. Conclusions: The pathogenesis of pulmonary emphysema is likely to be multifaceted, but the present mouse model may be useful in dissecting the involvement of VEGF in pulmonary emphysema.

Resistance to erlotinib in lung cancer cases includes T790M mutant epidermal growth factor receptor and c-Met gene amplification, but other unknown mechanisms account for about 30% of the resistance. Activation of the nuclear factor kappa B (NFkappaB)-related pathways in association with the reduction in ikappaB level may be one of such potential mechanisms. It is known that curcumin inhibits the inducible activation of NFkappaB at least in part by sustaining ikappaB expression level. Therefore, we evaluated the effects of coadministration of erlotinib and curcumin on lung cancer cells. We found that erlotinib and curcumin augmentatively reduced cell viability. Studies in PC9 cells showed that induction of apoptosis was involved. Expression of ikappaB was elevated in PC9 cells by curcumin administration, and pretreatment with siRNAs for ikappaB significantly attenuated the reduction in cell viability after coadministration of erlotinib and curcumin. Furthermore, coadministration of erlotinib and/or curcumin augmentatively attenuated the growth of PC9 tumors in mice. These results suggested the existence of an augmentative tumor growth inhibitory effect between erlotinib and curcumin, and this effect was at least in part mediated by the increase in the expression of ikappaB induced by curcumin. Copyright © 2013 John Wiley & Sons, Ltd.

Objective During cryoablation, cells are destroyed at temperatures less than −20°C. The determining factors for local cancer control in pulmonary cryoablation were assessed using computed tomography (CT), isothermal curves, and histologic findings in pigs. Experimental findings were compared with clinical CT findings and were extrapolated to local cancer control outcomes. Methods Cryoablation was performed with thermal monitoring, and the ablated areas were divided into 3 zones: less than −20°C, −20°C to 0°C, and greater than 0°C and were compared with histologic findings. CT findings with multiplanar reconstruction in 36 nodules were compared with the porcine histologic findings. The relationship between CT findings and 3-year local cancer control was evaluated in 98 nodules. Results The 3 concentric thermal zones correlated with histologic findings as follows: less than −20°C zone, complete tissue destruction (zone D); −20°C to 0°C zone (which surrounded zone D), hemorrhage with air trapping and maintenance of alveolar structures (zone H); and greater than 0°C zone (outermost), edema with sustained alveolar structures (zone E). The CT findings in 36 nodules showed a central solid zone, a surrounding air-containing zone, and an outside solid zone, corresponding to zones D, H, and E, respectively. Local cancer control at 3 years in 80 nodules contained within the central solid zone was significantly greater compared with the 18 nodules that were not (82% vs 33%, P = .0002). Conclusions Pulmonary cryoablation should be performed such that tumors are contained within the central solid zone on CT, which represents the less than −20°C zone.

Purpose To describe the computed tomographic (CT) appearance of lung tumors treated with cryoablation to establish a reliable reference profile. Materials and Methods CT images of 56 patients who underwent follow-up CT for at least 1 year for treatment with cryoablation of 79 tumors from 2003 to 2010 were retrospectively reviewed. Patients had a follow-up CT scan immediately after the procedure; 1 day, 1 week (two-phase dynamic CT), and 1 month later; and then at 3-month intervals. The appearance of ablation zones on CT images was classified into five patterns, and bidimensional diameters and other imaging features were evaluated. Results Seventy-eight percent of ablation zones (62 of 79) showed transformation similar to the following: a consolidation or nodular pattern was seen within the 1-week follow-up, involution and a "stripe" pattern was shown at 1 month or later, and zones later became indistinct. Eighty percent of cases of local progression (eight of 10) arose from the stripe pattern on follow-up CT 6 months or later, after the ablation zones showed a transformation opposite the aforementioned pattern. Ice balls could not always be visualized exactly because of dense peritumoral hemorrhage. Internal and marginal enhancement of the ablation zone within the 3-month follow-up did not show a direct relationship with local progression. In total, cavitation and peritumoral ground-glass opacity were seen in 35% (n = 28) and 85% (n = 66) of ablation zones, respectively. Conclusions The reference profile of CT appearance, which is mandatory for follow-up, has been established. No single indicator of complete ablation was proven throughout this study. Careful long-term follow-up with CT is indispensable.

Background To examine whether segmentectomy is radical for cT1N0M0 non–small cell lung cancer (NSCLC), a prospective single-arm study was performed at a single institution. Methods The criteria for segmentectomy were as follows: (1) peripheral-type cT1N0M0 NSCLC; (2) intraoperative frozen sections of sentinel nodes identified with isotope showing no metastasis; (3) surgical margins greater than 2 cm; (4) patient choice for segmentectomy; and (5) exclusion of right middle lobe tumors. From 2005 to 2009, of 245 patients with cT1N0M0 NSCLC, 195 (80%) were enrolled in the present study. Of these 195 patients, 179 ultimately underwent segmentectomy with systematic lymph node dissection. Of these 179 patients, 134 (75%) had tumors 2 cm or smaller, and 45 (25%) had tumors 2.1 cm to 3 cm. The median follow-up period was 43 months. Results All 181 tumors from 179 patients were stage pN0. Of the 179 patients, 6 developed distant site recurrence and 3 local recurrence (ie, 1 developed pulmonary metastases within the same lobe 21 months after segmentectomy and 2 developed local recurrence at the surgical margin 60 and 62 months after segmentectomy, respectively). The 5-year overall survival was 94% for patients with tumors 2 cm or smaller and 81% for those with 2.1-cm to 3-cm tumors. Postoperative pulmonary function was preserved at 90% ± 12% of preoperative levels. Conclusions Segmentectomy with systematic lymph node dissection with a sufficient surgical margin could be a radical treatment for selected cT1N0M0/pN0 NSCLC while preserving pulmonary function. The surgical margin should be monitored for the development of local recurrence for a long period after segmentectomy.

Salvage surgery after gefitinib therapy in a 66-year-old female with cT4N1M1a lung adenocarcinoma in the right middle lobe, which had gene mutation of epidermal growth factor receptor, is presented. The patient had bulky hilar lymph nodes, pleural dissemination, and pulmonary metastases in the ipsilateral lobes. After 3 courses of chemotherapy, the patient was treated with gefitinib, resulting in partial response, i.e. only the primary tumor and the middle lobe atelectasis remained. We performed the middle lobe lobectomy aimed at local control and pathological confirmation of the remaining tumor. Because the hilum of the middle lobe was occupied with scar tissue, its pulmonary vein had to be cut within the pericardium and its pulmonary artery and bronchus had to be transected simultaneously with a stapler. Pathological stage was yp-T2aN0N0 with Ef 2. For salvage surgery after good response to gefitinib therapy, it should be taken care to expose pulmonary vessels.

Strategies to inhibit metastasis have been mainly unsuccessful in part due to insufficient mechanistic understanding. Here, we report evidence of critical role for the angiopoietin-like protein 2 (ANGPTL2) in metastatic progression. In mice, Angptl2 has been implicated in inflammatory carcinogenesis but it has not been studied in human tumors. In patients with lung cancer, elevated levels of ANGPTL2 expression in tumor cells within the primary tumor were associated with a reduction in the period of disease-free survival after surgical resection. Transcription factors NFATc, ATF2, and c-Jun upregulated in aggressive tumor cells promoted increased Angptl2 expression. Most notably, tumor cell–derived ANGPTL2 increased in vitro motility and invasion in an autocrine/paracrine manner, conferring an aggressive metastatic tumor phenotype. In xenograft mouse models, tumor cell–derived ANGPTL2 accelerated metastasis and shortened survival whereas attenuating ANGPTL2 expression in tumor cells–blunted metastasis and extended survival. Overall, our findings showed that tumor cell–derived ANGPTL2 drives metastasis and provided an initial proof of concept for blockade of its action as a strategy to antagonize the metastatic process. Cancer Res; 72(7); 1784–94. ©2012 AACR.

18F-Acetate (18F-Ace) was synthesized by a simple and quick halogen phase exchange catalysis. solvent extraction method was employed to purify 18F-Ace directly from the reaction vessel. These all simple synthesis and purification method make reactions short and quick so that all synthesis time takes less than 30 minutes. 2- Iodo-acetic ethylester (ICH2COOC2H5) dissolved in anhydrous acetylnirile reacted with 18F-fluorine in Kriptfix-222 and produce 2-18F-acetic ethylester in acetylinitrile. Final product 18F-Ace was obtained by hydrolysis of 2-18F-acetic ethylester in 0.25N NaOH. 18F-Actate radiochemical yield was 48.7% ± 5.2% (n-5). Pyrogen test and sterility check were all negative. With these new simple synthesis and quick purification. 18F-Ace will be more employed to diagnose tumors such as well differentiate one then 18FDG.

Malignant pleural mesothelioma is known to be widely resistant to therapy and new treatment strategies are needed. Curcumin, which has a long history as a dietary spice is known to suppress the growth of multiple cancer lines, but the effects on mesothelioma cells are not well defined. In the present study we examined the effects of curcumin on ACC-MESO-1, which is a human derived mesothelioma cell line. We found that curcumin dose-dependently reduced cell viability but did not induce apoptosis. Curcumin administration increased LC3B-II/LC3B-I expression, and induced the formation of autophagosomes on electron microscopy. These changes were attenuated by RNA silencing of atg5. From these findings it was speculated that induction of autophagy was at least in part involved in the reduction of cell viability by curcumin.

To evaluate the safety and feasibility of cryoablation for lung tumors as well as the incidence of, and risk factors for, complications.This study included 193 cryoablation sessions for 396 lung tumors in 117 consecutive patients. Univariate and multivariate analyses were performed to assess risk factors for common complications. Changes in laboratory values were analyzed the day after cryoablation.Pneumothorax, pleural effusion, and hemoptysis occurred after 119 (61.7%), 136 (70.5%), and 71 (36.8%) sessions, respectively. Phrenic nerve palsy, frostbite, and empyema occurred after one session each (0.52%). Proximal tumor implantation was observed in one of 471 punctures (0.20%). Of 119 sessions with pneumothorax, 21 (17.6%) required chest tube insertion and two (1.7%) required pleurodesis. Delayed and recurrent pneumothorax occurred in 15 of 193 sessions each (7.8%). A greater number of cryoprobes was a significant (P = .001) predictor of pneumothorax. Male sex (P = .047) and no history of ipsilateral surgery (P = .012) were predictors for the need for chest tube insertion, and no history of ipsilateral surgery (P = .021) was a predictor for delayed/recurrent pneumothorax. Greater number of cryoprobes (P = .001) and no history of ipsilateral surgery (P = .004) were predictors for pleural effusion. Greater number of cryoprobes (P.001) and younger age (P = .034) were predictors for hemoptysis. Mean changes in white blood cell count, platelet count, hemoglobin level, and C-reactive protein level were 2,418/μL ± 2,260 (P.001), -2.0 × 10(4)/μL ± 3.2 (P.001), -0.77 mg/dL ± 0.89 (P.001), and 3.0 mg/dL ± 2.9 (P.001), respectively.Percutaneous cryoablation could be performed minimally invasively with acceptable rates of complications.

Lung cancers in the residual lungs of patients who have undergone pneumonectomies are often unresectable, primarily because of the risks of overt pulmonary function losses. Percutaneous cryoablation of lung tumors is a potentially minimally invasive technique that has recently been used in the treatment of lung cancers and metastatic lung tumors. Here, we present two patients who had previously undergone pneumonectomies, in whom lung cancers in the residual lungs were treated by cryoablation. In both patients, the procedures were performed safely without any complications, such as airway bleeding, hemothoraces, or pneumothoraces. The changes in pulmonary functions after the procedures were minimal: % vital capacity (−1% and −4%), and %FEV 1 (−1% and +10%) in the first and second patients, respectively. The performance statuses were maintained at zero in both patients after cryoablation. In the first patient, local control has been maintained for 4 years. In the second patient, local control was maintained for 2 years until the patient died of distant metastases. This is, to our knowledge, the first reported case of lung cryoablation in residual lungs of patients who have previously undergone pneumonectomies. Application of percutaneous cryoablation may represent a new treatment option for lung tumors in patients who have previously undergone pneumonectomies.

We report a case of lung cancer producing granulocyte-macrophage colony-stimulating factor (GM-CSF). The patient, a 55-year-old woman, was found to have leukocytosis (leukocytes 28.8 × 10(3)/mm3) with eosinophilia (eosinophils 24.5%) without any evidence of infection or allergy. The serum concentration of GM-CSF was elevated to 44 pg/ml (normal range2.0 pg/ml), which might have induced the leukocytosis and eosinophilia. We performed left pneumonectomy and diagnosed a pleomorphic carcinoma with p-T2bN0M0, based on histological examination of the resected tumor. Immunohistochemical examination revealed GM-CSF. The serum level of GM-CSF decreased to within the normal range 8 days after surgery. At the time of writing, 16 months after the surgery, she was alive without disease. To our knowledge, this represents the first case report of a GM-CSF-producing tumor effectively treated by surgical resection.