Formation of pulmonary vein stump thrombus after anatomical lung resection and anticoagulant therapy.

OBJECTIVE: It has recently been suggested that the formation of pulmonary vein stump thrombus (PVST) after anatomical lung resection is an underlying cause of arterial thromboembolism including cerebrovascular infarction. This study aimed to investigate the incidence and risk factors of PVST and to evaluate the efficacy and safety of anticoagulant therapy for PVST. METHODS: Patients who underwent anatomical lung resection for malignant lung tumors were eligible for inclusion in this study. Chest contrast-enhanced (CE) computed tomography (CT) was performed after surgery to detect PVST. If PVST was observed, patients received anticoagulant therapy. The size of the PVST was followed-up by repeated chest CE-CT. RESULTS: In total, 176 patients were enrolled in this study. Chest CE-CT was performed on postoperative day 1-13 (median, postoperative day 6). PVST was detected in 22 (12.5%) patients. The median size of PVST was 9.5 (4.1-33.4) mm. Thrombus was most commonly observed in patients who underwent left upper lobectomy (9/36, 25.0%). Hypertension, dyslipidemia, arteriosclerosis, and arrhythmia were not associated with PVST formation. Anticoagulant therapy was administered to all 22 patients with PVST until the PVST disappeared. The median duration between the detection and disappearance of PVST was 77 days (range: 6-146 days). During the period between the detection and disappearance of PVST, cerebrovascular infarction or arterial thromboembolic events were not observed. CONCLUSIONS: Postoperative PVST is commonly observed, especially in patients who undergo left upper lobectomy. Anticoagulant therapy for PVST was safely introduced and was efficient to improve PVST without subsequent arterial thromboembolic events.

The Impact of Kinlessness on Survival in Patients With Advanced Non-small Cell Lung Cancer: A Single-Center Retrospective Study.

Objectives Among patients with advanced non-small cell lung cancer (NSCLC), there are those who do not have a spouse, family members, or friends to support them in their cancer treatment and daily life: the kinless patients. Therefore, we designed an exploratory study of kinlessness and the prognosis of advanced NSCLC. Methods We retrospectively analyzed the prognosis of clinical factors and treatment and kinlessness in patients with advanced NSCLC with wild-type or unknown status for epidermal growth factor receptor/anaplastic lymphoma kinase (EGFR/ALK) and who visited our hospital from November 2018 to February 2023. In addition to the survival analysis by kinlessness, a multivariable analysis of survival was performed for all clinical factors. In a secondary analysis, a multivariable analysis of the choice of best supportive care (BSC) was performed for all clinical factors. Results One hundred forty-four patients are included in our cohort. There were 131 patients with kin, with a median survival of 1.34 years (95% CI of 1.01-1.79 years). There were 13 patients has no kin, with a median survival of 0.53 years (95% CI 0.23-0.76 years). The log-rank analysis showed that kinless patients had significantly shorter overall survival than patients who have kin. A Cox regression analysis showed that age, distant metastasis, performance status, and kinlessness were associated with overall survival. Secondary analysis showed that there was no statistical association between kinlessness and the choice of BSC in our cohort. Conclusions Kinless patients had shorter survival than patients who have kin in our single-center, retrospective study of patients with advanced NSCLC with wild-type or unknown status for (EGFR/ALK). Further research to evaluate the clinical impact of kinlessness in the treatment of advanced NSCLC is needed.

Outcomes of surgical resection for pulmonary metastasis from pancreatic cancer.

PURPOSE: As the number of long-term survivors of pancreatic cancer is expected to increase thanks to recent advances in multidisciplinary treatment and earlier diagnoses of pancreatic cancer, we are likely to encounter more cases of postoperative pulmonary nodules. We analyzed the clinical course and prognosis of resection of pulmonary metastases from pancreatic cancer to clarify the prognostic implication of pulmonary metastasectomy for pancreatic cancer. METHOD: We retrospectively analyzed 35 patients who underwent resection of lung metastases after pancreatic cancer surgery. Short- and long-term outcomes and factors associated with the prognosis were analyzed. RESULTS: The observation period was 20 (range, 1-101) months, with 3- and 5-year survival rates of 88.3% and 64.5% from pancreatectomy and 44.1% and 28.3% from lung resection, respectively. A univariate analysis revealed that a period from pancreatic cancer resection to pulmonary nodule shadow detection of < 15 months was associated with a significantly lower overall survival from pancreatic resection than a longer period. Conversely, histological type, stage, size of lung metastases, and resection technique were not associated with the overall survival. CONCLUSION: A long-term prognosis may be expected in some cases with a disease-free interval of ≥ 15 months. Our findings suggest that the disease-free interval may influence the prognosis.

Analytical Performance of a Highly Sensitive System to Detect Gene Variants Using Next-Generation Sequencing for Lung Cancer Companion Diagnostics.

The recent increase in the number of molecular targeted agents for lung cancer has led to the demand for the simultaneous testing of multiple genes. Although gene panels using next-generation sequencing (NGS) are ideal, conventional panels require a high tumor content, and biopsy samples often do not meet this requirement. We developed a new NGS panel, called compact panel, characterized by high sensitivity, with detection limits for mutations of 0.14%, 0.20%, 0.48%, 0.24%, and 0.20% for EGFR exon 19 deletion, L858R, T790M, BRAF V600E, and KRAS G12C, respectively. Mutation detection also had a high quantitative ability, with correlation coefficients ranging from 0.966 to 0.992. The threshold for fusion detection was 1%. The panel exhibited good concordance with the approved tests. The identity rates were as follows: EGFR positive, 100% (95% confidence interval, 95.5-100); EGFR negative, 90.9 (82.2-96.3); BRAF positive, 100 (59.0-100); BRAF negative, 100 (94.9-100); KRAS G12C positive, 100 (92.7-100); KRAS G12C negative, 100 (93.0-100); ALK positive, 96.7 (83.8-99.9); ALK negative, 98.4 (97.2-99.2); ROS1 positive, 100 (66.4-100); ROS1 negative, 99.0 (94.6-100); MET positive, 98.0 (89.0-99.9); MET negative 100 (92.8-100); RET positive, 93.8 (69.8-100); RET negative, 100 (94.9-100). The analytical performance showed that the panel could handle various types of biopsy samples obtained by routine clinical practice without requiring strict pathological monitoring, as in the case of conventional NGS panels.

Randomized Phase III Study of Gefitinib Versus Cisplatin Plus Vinorelbine for Patients With Resected Stage II-IIIA Non-Small-Cell Lung Cancer With EGFR Mutation (IMPACT).

PURPOSE: To investigate the efficacy of gefitinib as an adjuvant therapy for non-small-cell lung cancer patients with EGFR mutation. PATIENTS AND METHODS: IMPACT (WJOG6410L; University Hospital Medical Information Network Clinical Trials Registry: UMIN000006252), a randomized, open-label, phase III study, included patients with completely resected pathologic stage II-III non-small-cell lung cancer harboring EGFR mutations (exon 19 deletion or L858R) during September 2011 to December 2015. Patients were randomly assigned to receive gefitinib (250 mg once daily) for 24 months or cisplatin (80 mg/m2 on day 1) plus vinorelbine (25 mg/m2 on days 1 and 8; cis/vin) once every 3 weeks for four cycles. The primary end point was disease-free survival (DFS). RESULTS: Overall, 234 patients were randomly assigned. Among 232 eligible patients (116 each; excluding two who withdrew consent), the median DFS was 35.9 and 25.1 months in the gefitinib and cis/vin groups, respectively. However, Kaplan-Meier curves crossed around 4 years after surgery with no statistically significant difference (stratified log-rank P = .63; hazard ratio by stratified Cox proportional hazards model = 0.92; 95% CI, 0.67 to 1.28). Overall survival (OS) was also not different (stratified log-rank P = .89; hazard ratio = 1.03; 95% CI, 0.65 to 1.65), with the 5-year OS rates being 78.0% and 74.6% in the gefitinib and cis/vin groups, respectively. Treatment-related deaths occurred in 0 and three patients in the gefitinib and cis/vin groups, respectively. CONCLUSION: Although adjuvant gefitinib appeared to prevent early relapse, it did not prolong DFS or OS. However, similar DFS and OS may justify adjuvant gefitinib in the selected patient subsets, especially those deemed ineligible for platinum-doublet adjuvant therapy; however, this was not a noninferiority trial.

A cross-population atlas of genetic associations for 220 human phenotypes.

Current genome-wide association studies do not yet capture sufficient diversity in populations and scope of phenotypes. To expand an atlas of genetic associations in non-European populations, we conducted 220 deep-phenotype genome-wide association studies (diseases, biomarkers and medication usage) in BioBank Japan (n = 179,000), by incorporating past medical history and text-mining of electronic medical records. Meta-analyses with the UK Biobank and FinnGen (ntotal = 628,000) identified ~5,000 new loci, which improved the resolution of the genomic map of human traits. This atlas elucidated the landscape of pleiotropy as represented by the major histocompatibility complex locus, where we conducted HLA fine-mapping. Finally, we performed statistical decomposition of matrices of phenome-wide summary statistics, and identified latent genetic components, which pinpointed responsible variants and biological mechanisms underlying current disease classifications across populations. The decomposed components enabled genetically informed subtyping of similar diseases (for example, allergic diseases). Our study suggests a potential avenue for hypothesis-free re-investigation of human diseases through genetics.

Effects of Prophylaxis with Oral Supportive Care for Peri-implantitis in Patients Undergoing Malignancy Chemotherapy.

PURPOSE: Dental implants without proper maintenance may lead to serious consequences, such as peri-implantitis. Peri-implantitis in patients undergoing antitumour chemotherapy can negatively affect the prognosis of treatment. The purpose of this study was to examine the association between the onset of peri-implantitis and the effects of oral hygiene management in patients with dental implants undergoing antitumour chemotherapy. MATERIALS AND METHODS: Twenty-three patients (n = 23) with dental implants who received oral supportive care during malignancy chemotherapy were included. They were categorised into two groups based on the presence of peri-implantitis and were analysed for oral hygiene conditions, maintenance after implant insertion, and adverse effects such as febrile neutropenia. Statistical analysis was performed using the Fisher's exact test and the Mann-Whitney U-test, with p < 0.05 considered statistically significant. RESULTS: The average number of implants was higher in patients with peri-implantitis; these implants generally did not receive appropriate maintenance. There were statistically significantly fewer peri-implantitis sites in patients receiving continuous implant maintenance therapy than those who did not (p < 0.05). The severity of febrile neutropenia was reduced by dental interventions. CONCLUSION: Dental intervention before malignancy chemotherapy effectively prevented peri-implantitis and contributed to alleviating febrile neutropenia, even when it was initiated amidst chemotherapy. Dental intervention before chemotherapy seems essential in malignancy patients with dental implants.

Phase III study of adjuvant gemcitabine compared with adjuvant uracil-tegafur in patients with completely resected pathological stage IB-IIIA non-small cell lung cancer (WJTOG0101).

BACKGROUND: 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 AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Long-term survival in thymic carcinoma with postoperative pleural dissemination.

BACKGROUND: We report a patient with thymic squamous cell carcinoma who underwent multiple rounds of surgical resection and definitive radiotherapy for both primary tumor and postoperative recurrence. However, the patient remains well and healthy 18 years after initial diagnosis. Since long-term survival after postoperative recurrence of thymic carcinoma is extremely rare, we also present her immunohistochemical staining results, which suggested indolent disease. CASE PRESENTATION: A 42-year-old woman with thymic squamous cell carcinoma underwent en bloc resection of the tumor and thymus gland. Pleural dissemination was noted in the right thoracic cavity 3, 10, and 16 years postoperatively. Where possible, the nodules were resected surgically: during the postoperative 3rd and 16th years. Definitive radiotherapy was administered for all nodules that could not be excised during the postoperative 3rd and 10th years. Disease-free survival is 25 months. CONCLUSIONS: Local control of pleural dissemination may be beneficial in the treatment of postoperative recurrence of thymic carcinoma in limited cases of indolent disease.

Preoperative AminoIndex Cancer Screening (AICS) abnormalities predict postoperative recurrence in patients undergoing curative resection for non-small cell lung cancer.

BACKGROUND: AminoIndex™ Cancer Screening (AICS (lung)) was developed as a screening test for lung cancer using a multivariate analysis of plasma-free amino acid (PFAA) profiles. According to the developed index composed of PFAA, the probability of lung cancer was categorized into AICS (lung) ranks A, B, and C in order of increasing risk. The aim of the present study was to investigate the relationship between the preoperative AICS (lung) rank and surgical outcomes in patients who underwent curative resection for non-small cell lung cancer (NSCLC). METHODS: Preoperative blood samples were collected from 297 patients who underwent curative resection for NSCLC between 2006 and 2015. PFAA concentrations were measured. The relationship between the preoperative AICS (lung) rank and clinicopathological factors was examined. The effects of the preoperative AICS (lung) rank on postoperative outcomes were also analyzed. RESULTS: The AICS (lung) rank was A in 93 patients (31.3%), B in 82 (27.6%), and C in 122 (41.1%). The AICS (lung) rank did not correlate with any clinicopathological factors, except for age. Based on follow-up data (median follow-up period of 6 years), postoperative recurrence was observed in 22 rank A patients (23.7%), 15 rank B (18.3%) and 49 rank C (40.2%). In the univariate analysis, preoperative AICS (lung) rank C was a worse factor of recurrence-free survival (p = 0.0002). The multivariate analysis identified preoperative AICS (lung) rank C (HR: 2.17, p = 0.0005) as a significant predictor of postoperative recurrence, particularly in patients with early-stage disease or adenocarcinoma. CONCLUSION: Preoperative AICS (lung) rank C is a high-risk predictor of postoperative recurrence in patients undergoing curative resection for NSCLC.

[Perioperative Management for Patients Undergoing General Thoracic Surgery with Metabolic or Endocrine Disorders].

By improvement of surgical procedures and advances in perioperative management, the patients with various comorbidity diseases have been able to undergo pulmonary resection. In particular, the patients with endocrine and metabolic disorders are relatively frequent and often underwent pulmonary resection. Most of them are chronic diseases and often controlled for a long time. However, they sometimes have drastic changes due to surgical stress during perioperative periods. Failure to properly perioperative management for them may result in postoperative morbidity or mortality. Therefore, we have to well know perioperative changes by surgical stress for them. Among endocrine and metabolic disorders, following is frequent, diabetes, hyperthyroidism and hypothyroidism, steroid administration. We describe perioperative management of them. When operating on them, it is important to ① proper evaluation before surgery, ② careful postoperative management, and ③ close coordination with the department of endocrinology and anesthesiology.

Novel imprint cytological classification is correlated with tumor spread through air spaces in lung adenocarcinoma.

OBJECTIVES: Spread through air spaces (STAS) is a risk factor for local recurrence after sublobar resection in lung cancer patients. We recently proposed the novel Nakayama-Higashiyama imprint cytological classification (N-H classification) based on small-sized lung adenocarcinoma surgical specimens, which correlated with histological patterns and nodal involvement. This study aimed to evaluate the correlation between STAS and the N-H classification and to validate the N-H classification as an intraoperative predictor of the presence of STAS. MATERIALS AND METHODS: We retrospectively analyzed 164 intraoperative imprint cytologies and their paired histologic specimens from patients undergoing surgical resection for lung adenocarcinoma in our institute in 2017-2019. Using the NH classification, imprint cytological findings were classified into 5 groups (Groups I to V) based on cell cluster shape, cell and nucleus size, and the existence of necrosis. We examined the characteristics of imprint cytology and STAS in the resected tissues and analyzed the relationship between them. RESULTS: Tumor STAS was observed in 29 (17.7 %) cases. The presence of STAS was significantly associated with the NH classification (P < 0.0001). STAS was present in 6 of 57 cases (10.5 %) in NH classification Group II, 11 of 42 cases (26.2 %) in Group III, and 12 of 28 cases (42.9 %) in Group IV/V; STAS was not observed in any case in Group I. Logistic regression analysis revealed that tumors with a ground glass opacity rate of <50 % on computed tomography (P = 0.00867) and Groups III-V of the NH classification (P = 0.00201) were significant independent predictors for STAS. CONCLUSION: Intraoperative imprint cytology with the N-H classification for lung adenocarcinoma is well correlated with the STAS status of the tumor and might have applications as an intraoperative predictive marker of STAS. This classification may be useful for intraoperative detection of STAS and in the decision-making process for the surgical procedure.

Number of metastatic lymph nodes and zones as prognostic factors in non-small-cell lung cancer.

OBJECTIVES: Characterizing pathological nodes (pNs) by location alone is sometimes inadequate as patients with pN1 or pN2 non-small-cell lung cancer (NSCLC) show prognostic heterogeneity. We aimed to assess the relationship of the number of metastatic lymph nodes (LNs) and zones with prognosis in NSCLC patients. METHODS: We analysed 1393 patients who underwent lobectomy with mediastinal LN dissection for NSCLC at the Osaka International Cancer Institute between January 2006 and December 2015. Patients were classified into 3 groups according to the number of LNs: n1-3, n4-6 and n7-. We investigated the relationship of prognosis with the number of metastatic LNs and metastatic zones. RESULTS: In the multivariable analyses, the number of metastatic LNs and zones were not independent factors for overall survival or recurrence-free survival in patients with pN1 disease after adjustment for age, sex, tumour histology and tumour diameter. However, n4-6 (ref. n1-3) was an independent prognostic factor for overall survival [hazard ratio (HR) 4.148, P < 0.001] in those with pN2 disease. There were no significant differences in overall survival and recurrence-free survival between pN1 (HR 0.674, P = 0.175) and pN2n1-3 disease (HR 1.056, P = 0.808). Moreover, patients with pN2 disease with a higher number of metastatic zones had a poor prognosis for recurrence-free survival [3 zones (ref. 1): HR 1.774, P = 0.051, and 4 zones (ref. 1): HR 2.173, P < 0.047]. CONCLUSIONS: The number of metastatic LNs and metastatic zones were useful prognostic factors in NSCLC patients. The findings could help in establishing a new pN classification.

Intraoperative Diagnosis and Surgical Procedure with Imprint Cytology for Small Pulmonary Adenocarcinoma.

Objectives: For patients with multiple small-sized pulmonary cancers, a lobectomy can disrupt future therapeutic options for other lesions. It was recently reported that limited pulmonary resections were not inferior to lobectomy for the management of selected peripheral small-sized pulmonary adenocarcinomas. Patients with adenocarcinoma in situ or minimally invasive adenocarcinoma, as proposed by the International Association for the Study of Cancer classification, have been reported to have 100% survival after 5 years. However, that classification can be applied postoperatively. Since 2005, we have been intentionally performing limited pulmonary resection procedures for small-sized adenocarcinoma cases based on intraoperative imprint cytological diagnosis and our classification (Nakayama-Higashiyama's classification). Materials and Methods: A total of 120 consecutive cases were included in this study. Lung tumors were removed intraoperatively by wedge resection, and stump smear cytology was performed, from which the cases were classified into 5 groups based on our classification. When the tumor was classified as Group I or II, the operation was finished. When diagnosed as a more advanced classification, a lobectomy and lymph node dissection were additionally performed. Results: The 5-year survival rate for Group I and II was 100%, while those for Group III and IV-V were 95.8% and 94.4%, respectively. The 5-year disease-free survival rates for Group I and Group II were 100% and 97.1%, respectively, and for Group III and IV-V they were 100% and 94.1%, respectively. Conclusion: Use of cytological findings along with Nakayama-Higashiyama's classification for determining operation procedure is effective for treatment of patients with small-sized pulmonary adenocarcinoma.

Novel Imprint Cytological Classification for Small Pulmonary Adenocarcinoma Using Surgical Specimens: Comparison with the 8th Lung Cancer Staging System and Histopathological Classification.

Objectives: Small-size lung lesions suspected of being cancer are now often being identified on computed tomography. Correspondingly, a new lung cancer staging system has been proposed by the International Association for the Study of Lung Cancer (IASLC), in which the T1 factor and adenocarcinoma are re-subclassified. Previously, we proposed an intraoperative cytological diagnosis and its classification of small-size lung adenocarcinoma, which correlated significantly with clinical malignancy, to be used for selecting the surgical strategy. In the current study, the correlation of our intraoperative cytological classification with the new 8th IASLC classification was investigated. Materials and Methods: A total of 139 consecutive small-size lung adenocarcinoma cases were surgically resected from 2000 to 2006 and included in this study. Intraoperative stump imprint cytology using these specimens was performed, and the cases were classified into 5 groups based on our classification. The cytological classification was compared with the IASLC classification and the WHO histopathological grading. Results: According to our classification, 32 patients were in Group I, 38 in Group II, 24 in Group III, 27 in Group IV, and 18 in Group V. Compared with the IASLC classification, most of Group I was pTis or pT1mi, and most of Group II was pT1mi or pT1a (p<0.001). There was also a significant relationship between lymph node metastasis and our cytological classification (p<0.001). The histological patterns according to the WHO classification also had a significant relationship with our classification (p<0.001). Conclusion: Our cytological classification correlated not only with the T classification, but also with the adenocarcinoma subclassification of the 8th IASLC classification.

Rapid progressive lung cancers harbouring multiple clonal driver mutations with big bang evolution model.

INTRODUCTION: Next-generation sequencing (NGS) of multiple metastases in an advanced cancer patient reveals the evolutional history of the tumor. The evolutionary model is clinically valuable because it reflects the future course of the tumorigenic process and prognosis of the patient. MATERIALS AND METHODS: We experienced two lung cancer patients whose clinical courses were abruptly deteriorating resulting in very poor prognosis. To investigate the evolutionary model of these patients, we performed targeted sequencing covering whole exons of 53 significantly mutated genes associated with lung cancer of multiple metastases by autopsy. We conducted PyClone analysis to infer subclonal archtecture of multi-lesional samples. RESULTS: The NGS analysis revealed both patients harboring multiple clonal driver mutations. In Case.1, KRAS Q61H, KEAP1 G333C, STK11 K312*, RBM10 Q320* and MGA I1429V and in Case.2, TP53 R337L, TP53 Q192*, PTEN W274C, RB1 P29fs and CREBBP P696L with high allele fraction were detected in all lesions. These mutations were clustered and occupied major population across multi-lesional tumor samples. Our data suggested their lung cancers progressed with punctuated and big bang evolutional model. CONCLUSION: We should pay attention to clinical course of lung cancer patients harboring multiple clonal driver mutations in their primary lesions. Their punctuated and big bang evolutionary process could develop systemic clinically undetectable metastases with an unexpected speed.

Feasibility of postoperative adjuvant chemotherapy using carboplatin plus S-1 in completely resected non-small cell lung cancer patients.

Feasibility is one of the major concerns during adjuvant chemotherapy in patients with completely resected non-small cell lung cancer. A phase II clinical trial of adjuvant chemotherapy with four courses of carboplatin (AUC 5 at day 1) and S-1 (80 mg/m2/day for 2 weeks followed by a 2-week rest) was performed to evaluate the feasibility (UMIN 9101). The primary endpoint was the completion rate and the secondary endpoints were adverse events, 2-year overall survival and disease-free rates. Thirty-five non-small cell lung cancer patients were enrolled. The adjuvant chemotherapy completion rate was 85.3% (29/34); 17/34 (50%) patients completed 4 courses without dose reduction. There were no treatment-related deaths, and Grade 3/4 adverse events included neutropenia (38.2%), leukocytopenia (14.7%), anemia (20.6%), thrombocytopenia (20.6%), anorexia (5.9%), fatigue (5.9%), and oral mucositis (2.9%). Two-year overall and disease-free survival rates were 96.3% and 53.3%, respectively. Adjuvant chemotherapy with carboplatin plus S-1 is safe and feasible.

Post-operative AICS status in completely resected lung cancer patients with pre-operative AICS abnormalities: predictive significance of disease recurrence.

The AminoIndexTM Cancer Screening (AICS) system, a plasma-free amino acid (PFAA)-based multivariate discrimination index, is a blood screening test for lung cancer based on the comparison of PFAA concentrations between patients with lung cancer and healthy controls. Pre- and post-operative AICS values were compared among 72 patients who underwent curative resection for lung cancer. Post-operative changes in PFAA concentrations were also evaluated. AICS values were classified as rank A (0.0-4.9), B (5.0-7.9), or C (8.0-10.0). Rank B-C patients were evaluated for outcomes and post-operative changes in their AICS values. Twenty-three of the 44 pre-operative rank B-C patients experienced post-operative reductions in AICS rank. Only one patient experienced cancer recurrence. Post-operative changes in PFAA concentrations were associated with the risk of post-operative cancer recurrence (p = 0.001). Multivariate analysis revealed that the absence of a post-operative reduction in AICS rank independently predicted cancer recurrence (hazard ratio: 14.28; p = 0.012). The majority of patients had high pre-operative AICS values and exhibited a reduction in AICS rank after curative resection. However, the absence of a post-operative reduction in AICS rank was associated with cancer recurrence, suggesting that AICS rank may be a sensitive marker of post-operative recurrence.

Surgical Treatment following Chemo-Targeted Therapy with Bevacizumab for Lung Metastasis from Colorectal Carcinoma: Analysis of Safety and Histological Therapeutic Effects in Patients Treated at a Single Institution.

BACKGROUND: Recently, therapeutic strategies for a metastasectomy from colorectal carcinoma after chemo-targeted therapy with bevacizumab have been presented, with which some uncommon but serious adverse events have been reported. However, only few reports have investigated the safety of lung resection after such therapy or the histological effects. We retrospectively analyzed the both of them at our institute. METHODS: Of 69 colorectal carcinoma patients who underwent pulmonary metastasectomy procedures from 2009 to 2014, we investigated 11 who also received chemo-targeted therapy prior to surgery. RESULTS: In addition to bevacizumab, 5 fluorouracil (FU)/leucovorin + oxaliplatin or capecitabine was given in 6 cases and 5 FU/leucovorin + irinotecan in 5 cases. The mean period from the end of chemo-targeted therapy to surgery was 2.7 ± 0.9 months. The response to therapy shown in imaging findings was progressive disease in 6, stable disease in 3, and partial response in 2 (response rate, 18.2%). The operation modes were wedge resection (n = 8, 72.3%), segmentectomy (n = 2, 1 in bilateral lobes, 1 in the right lobe, 18.2%), and lobectomy (n = 1, left lower lobectomy, 9.1%). All patients safely underwent a complete resection. As for postsurgical complications, chylothorax occurred in 1 case and prolonged pulmonary air leakage in 1 case. The histological effects of chemo-targeted therapy were slight. There was no relationship between histological findings with imaging findings obtained prior to the operation (p = 0.63). The 5-year disease-free survival rate after metastasectomy was 10.9%. CONCLUSIONS: Pulmonary metastasectomy after chemo-targeted therapy for colorectal carcinoma patients obtained acceptable results. In addition, there was no correlation between imaging and histopathologic results following chemo-targeted therapy.

HER3 expression is enhanced during progression of lung adenocarcinoma without EGFR mutation from stage 0 to IA1.

BACKGROUND: Activating EGFR mutations, HER2, and HER3 are implicated in lung cancer; however, with the exception of EGFR gene amplification in lung adenocarcinoma harboring EGFR mutations, their involvement in disease progression during the early stages is poorly understood. In this paper, we focused on which receptor is correlated with lung adenocarcinoma progression in the presence or absence of EGFR mutation from stage 0 to IA1. METHODS: HER2 and HER3 expression and activating EGFR mutations in surgically resected lung adenocarcinoma exhibiting ground glass nodules on chest computed tomography and re-classified to stage 0 and IA1 were examined by immunohistochemistry and peptide nucleic acid-locked nucleic acid PCR clamp method, respectively. RESULTS: HER2 and HER3 expression was detected in 22.2% and 86.1% of samples, respectively. The frequency of EGFR mutation was 45.7% and was not significantly different between stage 0 and IA1 (40.0% and 48.0%, respectively), suggesting that EGFR mutation does not correlate with cancer progression from stage 0 to IA1. HER2 expression also did not correlate to progression. However, not only the frequency, but also the intensity of HER3 expression was increased in stage IA1 lung adenocarcinoma, particularly in lung adenocarcinoma without EGFR mutation. CONCLUSION: HER3 tends to be intensively expressed during the progression of lung adenocarcinoma without EGFR mutation from carcinoma in situ to invasive carcinoma.