MED12 controls the response to multiple cancer drugs through regulation of TGF-ß receptor signaling.

Inhibitors of the ALK and EGF receptor tyrosine kinases provoke dramatic but short-lived responses in lung cancers harboring EML4-ALK translocations or activating mutations of EGFR, respectively. We used a large-scale RNAi screen to identify MED12, a component of the transcriptional MEDIATOR complex that is mutated in cancers, as a determinant of response to ALK and EGFR inhibitors. MED12 is in part cytoplasmic where it negatively regulates TGF-ßR2 through physical interaction. MED12 suppression therefore results in activation of TGF-ßR signaling, which is both necessary and sufficient for drug resistance. TGF-ß signaling causes MEK/ERK activation, and consequently MED12 suppression also confers resistance to MEK and BRAF inhibitors in other cancers. MED12 loss induces an EMT-like phenotype, which is associated with chemotherapy resistance in colon cancer patients and to gefitinib in lung cancer. Inhibition of TGF-ßR signaling restores drug responsiveness in MED12(KD) cells, suggesting a strategy to treat drug-resistant tumors that have lost MED12.

Accurate Selection of Sublobar Resection for Small Non-small Cell Lung Cancer.

BACKGROUND: Although sublobar resection (wedge resection [Wed] or segmentectomy [Seg]) has become a standard operative procedure for clinical stages IA1 and IA2 non-small cell lung cancer (NSCLC) in Japan, the impact of this procedure on the prognosis and postoperative complications in real-world clinical practice is unknown. METHODS: This study retrospectively analyzed risk factors for a poor prognosis and postoperative complications of 470 patients with clinical stage ≤ IA2 NSCLC who underwent surgery from 2012 to 2021. RESULTS: Among the patients with a consolidation-to-tumor ratio (CTR) higher than 0.5, the 5-year relapse-free survival (RFS) rate was significantly lower in the Wed group (72.1%) than in the Seg (85.8%) and Lob (86.8%) groups (p < 0.01), but the difference between the Seg and Lob groups was not significant. Among patients with a CTR of 0.5 or lower, the 5-year RFS rate did not differ significantly among the three groups. Multivariable analysis of RFS showed that the prognosis was significantly worse in the Wed group than in the Lob group (hazard ratio, 2.83; p < 0.01), but the difference between the Wed and Seg groups or the between Seg and Lob groups was not significant. Multivariable analysis of postoperative complications showed a significantly lower risk in the Wed group than in the Seg group (odds ratio, 0.31; p < 0.01). CONCLUSIONS: Seg could become the standard operative procedure for clinical stages IA1 and IA2 NSCLC patients. Wed is suggested to be an option for patients with a CTR of 0.5 or lower and has the advantage of avoiding postoperative complications.

Predictive Value of Recurrence of Solid and Micropapillary Subtypes in Lung Adenocarcinoma.

INTRODUCTION: Although histological subtype in lung adenocarcinoma has been reported as a poor prognostic factor in several studies, its utility has not yet been revealed as an adaptation criterion of postoperative adjuvant chemotherapy. METHODS: Four hundred ninety-four lung adenocarcinoma patients were enrolled in this retrospective study. A subanalysis was performed in 420 lung adenocarcinoma patients with pathological stage 0-I disease for risk factors of postoperative recurrence. RESULTS: Maximum standardized uptake value (SUVmax) (p < 0.01), pathological stage ≥II (p < 0.04), and adjuvant chemotherapy (p < 0.01) were risk factors for recurrence in the multivariate analysis, whereas histological subtype was not a significant factor for recurrence at all stages. In the subanalysis, univariate analysis showed that carcinoembryonic antigen expression (p < 0.01), prognostic nutrition index (p = 0.03), SUVmax (p < 0.01), lymphatic invasion (p < 0.01), vascular invasion (p < 0.01), grade 3-4 differentiation (p < 0.01), pathological stage ≥IA3 (p < 0.01), and histological subtype (p = 0.03) were significant risk factors of recurrence. SUVmax (p < 0.01) was the only risk factor for recurrence in the multivariate analysis, whereas histological subtype was not (p = 0.07). Relapse-free survival (RFS) was significantly worse in the micropapillary- and solid-predominant subtype groups than in the other subtypes (p = 0.01). On the other hand, RFS with or without uracil-tegafur as adjuvant chemotherapy in lung micropapillary- or solid-predominant adenocarcinoma patients with pathological stage IA-IB disease was not significantly different. CONCLUSION: This study suggested that histological subtypes, such as micropapillary- or solid-predominant pattern, are risk factors for recurrence in pathological stage 0-I lung adenocarcinoma and may be necessary adjuvant chemotherapy instead of uracil-tegafur.

Prognostic Factors among Patients with Resected Non-Adenocarcinoma of the Lung.

INTRODUCTION: Few studies have investigated the prognostic factors for non-adenocarcinoma of the lung. We retrospectively evaluated the prognostic factors on the basis of histological type of non-adenocarcinoma of the lung treated by pulmonary resection. METHODS: We enrolled 266 patients with non-adenocarcinoma of the lung in this retrospective study: 196 with squamous cell carcinoma (SCC) and 70 with non-SCC. RESULTS: Relapse-free survival (RFS) did not differ significantly between SCC and non-SCC patients (p = 0.33). For SCC patients, RFS differed significantly between patients who underwent wedge resection and non-wedge resection (p < 0.01) and between patients with Clavien-Dindo grade ≥3a and 0-2 postoperative complications (p < 0.01). For non-SCC patients, RFS rates were significantly different in the groups divided at neutrophil-to-lymphocyte ratio = 2.40 (p = 0.02), maximum standardized uptake value (SUVmax) = 8.39 (p < 0.01), between patients with pathological stage (pStage) 0-I and with pStage more than II (p < 0.01). For SCC patients, male sex (p = 0.04), wedge resection (p = 0.01), and Clavien-Dindo grade ≥3a (p = 0.02) were significant factors for RFS in multivariate analysis. For non-SCC patients, neutrophil-to-lymphocyte ratio >2.40 (p < 0.01), SUVmax >8.39 (p = 0.01), and pStage ≥II (p = 0.03) were significant factors for RFS in multivariate analysis. CONCLUSION: RFS did not differ significantly differently between SCC and non-SCC patients. It is necessary to perform more than segmentectomy and to avoid severe postoperative complications for SCC patients. SUVmax might be an adaptation criterion of adjuvant chemotherapy for patients with non-adenocarcinoma and non-SCC of the lung.

The Clinical Relevance of the Expression of SGLT2 in Lung Adenocarcinoma.

PURPOSE: We aimed to elucidate the functions and clinical relevance of sodium-glucose cotransporter 2 (SGLT2) in resected lung adenocarcinoma. METHODS: The protein expression of SGLT2 in tumor samples from 199 patients with lung adenocarcinoma was analyzed by immunohistochemistry, and the protein expression, clinical variables, and survival outcomes were compared. RESULTS: The median SGLT2 expression was significantly higher in advanced-stage and more aggressive adenocarcinomas. Age ≥70 (p < 0.01), BI ≥600 (p < 0.01), PRDX4 <25 (p < 0.01), and SGLT2 ≥12% (p = 0.03) were significant factors for RFS in multivariate analysis. Significant differences were observed in the RFS rates of the groups divided using the cutoff value of SGLT2 ≥12% (5-year RFS: 72.6% vs. 90%) (p < 0.01). CONCLUSION: The expression of SGLT2 was more frequently detected in advanced-stage and more aggressive adenocarcinomas with aggressive biological behavior than in their counterparts. The survival analysis revealed that the strong expression of SGLT2 was associated with poorer RFS. The SGLT2 expression predicts postoperative recurrence in lung adenocarcinoma patients.

Analysis of risk factors of postoperative complication for non-small cell lung cancer.

BACKGROUND: The relationship between risk factors of common postoperative complications after pulmonary resection, such as air leakage, atelectasis, and arrhythmia, and patient characteristics, including nutritional status or perioperative factors, has not been sufficiently elucidated. METHODS: One thousand one hundred thirty-nine non-small cell lung cancer patients who underwent pulmonary resection were retrospectively analyzed for risk factors of common postoperative complications. RESULTS: In a multivariate analysis, male sex (P = 0.01), age ≥ 65 years (P < 0.01), coexistence of chronic obstructive pulmonary disease (COPD) (P < 0.01), upper lobe (P < 0.01), surgery time ≥ 155 min (P < 0.01), and presence of lymphatic invasion (P = 0.01) were significant factors for postoperative complication. Male sex (P < 0.01), age ≥ 65 years (P = 0.02), body mass index (BMI) < 21.68 (P < 0.01), coexistence of COPD (P = 0.02), and surgery time ≥ 155 min (P = 0.01) were significant factors for severe postoperative complication. Male sex (P = 0.01), BMI < 21.68 (P < 0.01), thoracoscopic surgery (P < 0.01), and surgery time ≥ 155 min (P < 0.01) were significant risk factors for postoperative air leakage. Coexistence of COPD (P = 0.01) and coexistence of asthma (P < 0.01) were significant risk factors for postoperative atelectasis. Prognostic nutrition index (PNI) < 45.52 (P < 0.01), lobectomy or extended resection more than lobectomy (P = 0.01), and surgery time ≥ 155 min (P < 0.01) were significant risk factors for postoperative arrhythmia. CONCLUSION: Low BMI, thoracoscopic surgery, and longer surgery time were significant risk factors for postoperative air leakage. Coexistence of COPD and coexistence of asthma were significant risk factors for postoperative atelectasis. PNI, surgery time, and surgical procedure were revealed as risk factors of postoperative arrhythmia. Patients with these factors should be monitored for postoperative complication. TRIAL REGISTRATION: The Institutional Review Board of Kanazawa Medical University approved the protocol of this retrospective study (approval number: I392), and written informed consent was obtained from all patients.

The Utility of SUVmax as an Adaptation Criterion for Limited Resection in Stage IA Non-Small Cell Lung Cancer.

INTRODUCTION: Although the consolidation diameter of a tumor on computed tomography (CT) is an adaptation criterion for limited resection in early-stage non-small cell lung cancer (NSCLC), whether the maximum standardized uptake value (SUVmax) is also an adaptation criterion for limited resection has not been evaluated. METHODS: In total, 478 NSCLC patients with clinical stage IA disease were analyzed, among whom 383 were used to perform a sub-analysis. RESULTS: Multivariate analysis showed that consolidation diameter (odds ratio [OR]: 3.05, p = 0.01), SUVmax (OR: 10.74, p = 0.02), and lymphatic invasion (OR: 10.34, p < 0.01) were risk factors for lymph node metastasis in clinical stage IA NSCLC patients. Furthermore, age (OR: 2.98, p = 0.03), SUVmax (OR: 13.07, p = 0.02), and lymphatic invasion (OR: 5.88, p = 0.02) were risk factors for lymph node metastasis in clinical stage IA lung adenocarcinoma patients according to multivariate analysis. CONCLUSION: Consolidation diameter of a tumor on CT, SUVmax, and lymphatic invasion are risk factors for lymph node metastasis. However, SUVmax was a risk factor for lymph node metastasis rather than consolidation diameter on CT in lung adenocarcinoma patients. These results suggest that for early-stage lung adenocarcinoma patients, SUVmax is more important for deciding the indication of limited resection than consolidation diameter of the tumor on CT.

Association between lower lobe location and early recurrence for non-small cell lung cancer.

OBJECTIVES: It is unclear whether a lower lobe origin is a risk factor for early recurrence of non-small cell lung cancer (NSCLC) in patients who underwent pulmonary resection. MATERIALS AND METHODS: The risk factors for early recurrence, defined as recurrence occurring within 1 year after surgery, were analyzed in 476 patients with NSCLC who underwent pulmonary resection without wedge resection. RESULTS: The proportion of men, Brinkman's index, carcinoembryonic antigen levels, and the maximum standardized uptake value (SUVmax) were significantly higher in patients with early recurrence than in those without early recurrence. Furthermore, the rates of lower lobe origin, extended resection beyond lobectomy, lymphatic invasion, vascular invasion, and advanced-stage disease were significantly higher in patients with early recurrence. Age (odds ratio [OR] = 4.46, p < 0.01), SUVmax (OR = 5.78, p = 0.02), a lower lobe origin (OR = 3.06, p = 0.01), and pathological stage (OR = 3.34, p = 0.01) were risk factors for early recurrence in multivariate analysis. Furthermore, only early recurrence (OR = 3.34, p = 0.01) was a risk factor for overall survival in multivariate analysis, and overall survival outcomes and prognoses significantly differed between patients with and without early recurrence (p < 0.01). CONCLUSIONS: Age, SUVmax, a lower lobe origin, and pathological stage are risk factors for early recurrence. These results suggest that for patients with NSCLC who underwent pulmonary resection, SUVmax and a lower lobe origin are important for deciding the indication for adjuvant chemotherapy in addition to pathological stage.

Relative efficacies of EGFR-TKIs and immune checkpoint inhibitors for treatment of recurrent non-small cell lung cancer after surgery.

INTRODUCTION: The relative efficacies of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and immune checkpoint inhibitors (ICIs) for the treatment of recurrent non-small cell lung cancer (NSCLC) after surgery remain unclear. METHODS: Among 801 patients with NSCLC who underwent pulmonary resection at Kanazawa Medical University between 2017 and 2021, 64 patients had recurrence. We retrospectively compared the efficacies of EGFR-TKIs and ICIs in these patients with recurrent NSCLC who underwent pulmonary resection. RESULTS: The 3-year overall survival rates after recurrence were 79.3% in patients who received EGFR-TKIs, 69.5% in patients who received ICIs, and 43.7% in patients who received cytotoxic agents. There was no significant difference in overall survival between patients treated with EGFR-TKIs and ICIs (p=0.14) or between patients treated with ICIs and cytotoxic agents (p=0.23), but overall survival was significantly higher in patients treated with EGFR-TKIs compared with cytotoxic agents (p<0.01) The probabilities of a 2-year response were 88.5%, 61.6%, and 25.9% in patients treated with EGFR-TKIs, ICIs, and cytotoxic agents, respectively. There was no significant difference in response periods between patients treated with EGFR-TKIs and ICIs (p=0.18), but the response period was significantly better in patients treated with EGFR-TKIs (p<0.01) or ICIs (p=0.03) compared with cytotoxic agents. Percent-predicted vital capacity (p=0.03) and epidermal growth factor receptor gene mutation (p<0.01) were significant factors affecting the overall response to chemotherapy in multivariate analysis. CONCLUSION: EGFR-TKIs and ICIs are effective for treating recurrent NSCLC after surgery. Although adjuvant chemotherapy for completely resected pathological stage II to IIIA NSCLC, atezolizumab or Osimertinib, has also been recently approved as adjuvant chemotherapy, there is a risk that patients who relapse after adjuvant chemotherapy will have less choice.

Improvements in perioperative outcomes for non-small cell lung cancer: a decade-long analysis.

BACKGROUND: Video-assisted thoracic surgery (VATS) procedures for non-small cell lung cancer (NSCLC) have steadily increased and have become the gold standard, but their prognostic advantage compared with thoracotomy has not been elucidated. This study retrospectively evaluated perioperative characteristics of VATS for NSCLC over time. METHODS: We collected the clinical data of 760 patients with NSCLC who underwent pulmonary resection over the past decade, classifying patients into early (2011-2015) and late (2016-2020) periods. Changes in NSCLC patient characteristics, surgical approaches, perioperative factors, postoperative morbidities, and prognoses were analyzed. RESULTS: Patients in the late period were older (p = 0.01), had more comorbidities (p = 0.01), and had earlier-stage cancer (p < 0.01) than those in the early period. The late period had significantly fewer surgical procedures for lobectomy or extended resection beyond lobectomy (p < 0.01), open thoracotomies (p < 0.01), postoperative (p = 0.02) and severe morbidities (p < 0.01), and a significantly shorter postoperative hospital stay than the early period. Surgical procedures of lobectomy or extended resection beyond lobectomy (p < 0.01) were significant risk factors for postoperative morbidity, and being in the early period (p < 0.01) and surgical procedures of lobectomy or extended resection beyond lobectomy (p < 0.01) were significant risk factors for severe postoperative morbidities. The overall survival prognosis significantly differed between the groups (p = 0.02) but progression-free survival did not (p = 0.89). CONCLUSIONS: The incidence of postoperative morbidities decreased over time in older patients and patients with more comorbidities. The prognosis of patients with NSCLC did not change with increasing VATS or sublobar resection.

PD-L1 Expression is not a Predictive Factor for Recurrence in Resected Non-small Cell Lung Cancer.

PURPOSE: Although targeting programmed death-1 (PD-1) and its ligand, programmed death-ligand 1 (PD-L1), is an established treatment modality for non-small cell lung cancer (NSCLC), the prognostic relevance of PD-L1 expression in NSCLC patients who undergo pulmonary resection is controversial. METHODS: Two hundred thirty-seven NSCLC patients who underwent pulmonary resection were enrolled and the relationship between PD-L1 and various clinicopathological factors, as well as the prognostic relevance of PD-L1, was evaluated. RESULTS: PD-L1 expression was significantly higher in male patients (p < 0.01), lymphatic invasion (p < 0.01), vascular invasion (p < 0.01), grade 3-4 differentiation (p < 0.01), squamous cell carcinoma (p < 0.01), and pathological stage > II (p < 0.01), but significantly lower in those who were epithelial growth factor receptor (EGFR) mutation negative (p < 0.01). Relapse-free survival was significantly worse in patients with PD-L1 expression (p = 0.04). Univariate analysis showed that male sex (p = 0.04), carcinoembryonic antigen expression (CEA) (p < 0.01), maximum standardized uptake value (p < 0.01), lymphatic invasion (p < 0.01), vascular invasion (p < 0.01), grade 3-4 differentiation (p < 0.01), lower lobe disease (p = 0.04), PD-L1 expression (p = 0.03), and pathological stage (p < 0.01) were significant risk factors of recurrence. In multivariate analysis, CEA expression (p = 0.01), lymphatic invasion (p = 0.04), and pathological stage (p < 0.01) were risk factors for recurrence, whereas PD-L1 expression was not a significant factor of recurrence (p = 0.62). CONCLUSION: PD-L1 expression was not a risk factor of recurrence but tumor progression tended to increase PD-L1 expression. TRIAL REGISTRATION: The Institutional Review Board of Kanazawa Medical University approved the protocol of this retrospective study (approval number: I392), and written informed consent was obtained from all patients.

Prognostic Impact of Cancer Inflammation Prognostic Index for Non-small Cell Lung Cancer.

PURPOSE: Cancer-inflammation prognostic index (CIPI) is calculated by multiplying the concentration of carcinoembryonic antigen by neutrophil-to-lymphocyte ratio. CIPI has been reported as a prognostic factor for colorectal cancer. Although carcinoembryonic antigen and neutrophil-to-lymphocyte ratio have been reported as prognostic factors for non-small cell lung cancer (NSCLC), it has not been investigated whether CIPI is a useful marker. METHODS: We analyzed the prognostic factors, including CIPI, in 700 NSCLC patients treated by pulmonary resection. We also analyzed a subgroup of 482 patients with pathological stage I NSCLC. RESULT: CIPI > 14.59 (P < 0.01), maximum standardized uptake value (SUVmax) > 5.35 (P < 0.01), lymphatic invasion (P = 0.01), and pathological stage (P < 0.01) were significant factors for relapse-free survival (RFS) in multivariate analysis. SUVmax > 5.35 (P < 0.01) and pathological stage (P < 0.01) were revealed as significant factors for overall survival in the multivariate analysis. In the subanalysis, CIPI > 14.88 (P = 0.01) and SUVmax > 5.07 (P < 0.01) were significant factors for RFS of pathological stage I NSCLC in multivariate analysis. CONCLUSION: CIPI was a significant factor for RFS in NSCLC patients treated surgically, even in those with pathological stage I disease. SUVmax was also a significant factor for RFS and overall survival in NSCLC patients treated surgically, and for RFS in patients with pathological stage I NSCLC. TRIAL REGISTRATION: The Institutional Review Board of Kanazawa Medical University approved the protocol of this retrospective study (Approval Number: I392), and written informed consent was obtained from all patients.

Epidemiological and therapeutic profiles of lung cancer patients in the Hokushin Region Japan: a retrospective hospital administrative database study.

OBJECTIVE: This study was performed to validate the epidemiology, initial treatment, and clinical practice of lung cancer patients in the Hokushin region, Japan. METHODS: We retrospectively surveyed data of 5503 newly diagnosed and registered lung cancer patients in 22 principal hospital-based cancer registries in Hokushin region linked with health insurance claims data for registered patients between 2016 and 2017. RESULTS: The patients consisted of 3677 (66.8%) men and 1826 (33.2%) women with a mean (range) age of 72.2 (27-103) years). Diagnoses were small cell lung cancer (n = 512, 9.4%), squamous cell carcinoma (n = 1083, 19.7%), and non-squamous non-small cell lung cancer (NSCLC; n = 3906, 70.9%). The population with stage I disease in Toyama prefecture (41.1%) was smaller than in the other three prefectures associated with reduced selection of initial surgical therapy and increased frequencies of stage IV disease (33.2%) and best supportive care (18.6%). Initial chemotherapy for stage IV non-squamous NSCLC consisted of tyrosine kinase inhibitors in 39.3% of cases for EGFR and 4% of cases for ALK-positive non-squamous NSCLC, followed by platinum compounds (25.9%) non-platinum compounds (12.9%), and immune checkpoint inhibitors (10.2%). Carboplatin was the commonly prescribed first-line cytotoxic chemotherapeutic agent (65.4% of patients under 75 years and in 96.7% of patients over 75 years). CONCLUSION: This study revealed real-world data on epidemiological and treatment status in lung cancer in four prefectures in Hokushin region, Japan. Simultaneous analysis of nationwide registry and insurance data could provide valuable insights for the development of lung cancer screening and medical treatment strategies. In addition, the comparative data analysis with other lesions or countries will be useful for evaluating the differences in clinical practice of cancer managements.

The consecutive impact of COVID-19 on thoracic surgical procedures in Japan: an analysis of data from the National Clinical Database.

PURPOSE: The current study was designed to analyze the impact of the COVID-19 pandemic on general thoracic surgeries in Japan. METHODS: Changes in surgeries for lung cancer and metastatic lung tumors were evaluated based on National Clinical Database data regarding cancer screening. RESULTS: In 2021, surgeries for primary lung cancer increased by 3.4% compared to 2020, which, given the increase from 2014 to 2019, indicates an overall 11.1% decrease. In contrast, surgeries for metastatic lung tumors in 2021 decreased by 5.8% compared to 2020, which, given the increase from 2014 to 2020, indicates an overall 9.2% decrease. Half of the primary diseases for metastatic lung tumor were cases of colorectal cancer. Low anterior resection procedures in 2020 decreased by 5.5% compared to 2019. Lung and colon cancer screening examinees in 2021 were increased compared to 2020; however, they still showed respective decreases of 11% and 9.0% compared to 2019. CONCLUSIONS: Surgeries for primary lung cancer still decreased substantially during the COVID-19 pandemic. The continued stagnation of screening was responsible for this decrease. Surgeries for metastatic lung tumors decreased profoundly, and the decrease in screening for primary tumors was responsible for this reduction. Our findings emphasize the significance of maintaining cancer screening efforts, even during a pandemic.

[Pulmonary Nodule Localization by Pleural Marking Using Virtual Thoracoscopic Imaging].

Percutaneous or transbronchial markings are performed to localize pulmonary nodules preoperatively. We present a novel intraoperative procedure that utilizes virtual thoracoscopic imaging-assisted pleural marking. In this procedure, a virtual thoracoscopic image is created preoperatively, and the coordinates of the pleural point above the tumor are determined. The pleural marker is intraoperatively placed on the coordinates, and dye is transferred to the visceral pleura with two lung ventilations. We present the specific procedures and countermeasures for cases when nodules are not palpable. Additionally, we present a comparison between the various methods of preoperative marking and this method.

Analysis of risk factors for postoperative complications in non-small cell lung cancer: comparison with the Japanese National Clinical Database risk calculator.

BACKGROUND: Although the risk calculator of the National Clinical Database (RC-NCD) has been widely used to predict the occurrence of mortality and major morbidity in Japan, it has not been demonstrated whether a correlation between the calculated RC-NCD risk score and the actual occurrence of mortality and severe morbidity exists. METHODS: The clinical data of 585 patients who underwent pulmonary resection for non-small cell lung cancer were collected, and the risk factors for postoperative morbidity were analyzed to verify the validity of the RC-NCD. RESULTS: The coexistence of asthma (p = 0.02), nutrition lymphocyte ratio (p = 0.04), and pulmonary lobe (p < 0.01) were significant risk factors for postoperative morbidity in the present study, and the percent-predicted vital capacity (p < 0.01), pulmonary lobe (p = 0.03), and type of operative procedure (p = 0.01) were significant risk factors for severe postoperative morbidity. Furthermore, in patients received lobectomy, coexistence of asthma (p = 0.01) and pulmonary lobe (p < 0.01) were identified as significant risk factors for postoperative morbidity. Meanwhile, male sex (p = 0.01), high BMI (p < 0.01), low vital capacity (p = 0.04), and pulmonary lobe (p = 0.03) were identified as significant risk factors for severe postoperative morbidity. CONCLUSIONS: Given that the pulmonary lobe was a significant risk factor for postoperative morbidity in patients received pulmonary resection and for severe postoperative morbidity in patients received lobectomy, the RC-NCD for postoperative morbidity needs to be modified according to high-risk lobes. TRIAL REGISTRATION: The Institutional Review Board of Kanazawa Medical University approved the protocol of this retrospective study (approval number: I392), and written informed consent was obtained from all patients.

Overexpression of Teashirt Homolog 2 suppresses cell proliferation and predicts the favorable survival of Lung Adenocarcinoma.

Background: Teashirt homolog 2 (TSHZ2) is essential for maintaining cellular homeostasis and regulating transcription on neoplasia development. However, the regulation of TSHZ2 in lung tumorigenesis and the underlying mechanisms remain unclear. Objective: To evaluate the relationship between TSHZ2 expression in patients' tumor tissue and prognosis in lung adenocarcinoma. Methods: TSHZ2 expression in different lung adenocarcinoma cell lines and human tissue were detected by Western blotting. The effect of TSHZ2 on cell proliferation, apoptosis and migration in lung adenocarcinoma cells was measured by CCK8, colony formation, flowcytometric analyses and wound-healing, respectively. TSHZ2 expression in different lung adenocarcinoma cell lines and human tissue from patients was detected using Western blotting and immunohistochemical staining. We also retrospectively analyzed 226 lung adenocarcinoma patients after surgical resection using immunohistochemical staining, and the association of TSHZ2 expression with the patient survival was evaluated. Results: TSHZ2 was lowly expressed in certain lung adenocarcinoma cell lines (PC9 and B203L), but other cells showed a high expression. Low expression of TSHZ2 was also observed in most lung adenocarcinoma tissues compared with adjacent tissues. Furthermore, we found that the overexpression of TSHZ2 plasmids led to the dramatic inhibition of cell proliferation, colony formation ability, migration and apoptosis induction in PC9 lung adenocarcinoma cells. In contrast, no obvious effect was found when the TSHZ2 expression was down-regulated by si-TSHZ2. An elevated TSHZ2 expression was observed in 155(68.6%) tumor tissues samples of lung adenocarcinoma patients. Notably, the lung adenocarcinoma patients with a high TSHZ2 expression tended to have EGFR mutations less frequently and a preferable prognosis to those with a lower expression. Conclusion: A high TSHZ2 expression inhabited cell proliferation and predicted a better prognosis of lung adenocarcinoma, possibly representing a useful therapeutic target for lung adenocarcinoma.

Multi-institutional survey of cancer disparities in disabled patients in the region of northwestern Japan.

BACKGROUND: Potential disparities between cancer patients with and without disabilities remained to be validate in Japan. METHODS: We surveyed retrospective data on hospital cancer registration as well as information on disability certificates obtained through the Hokushin Ganpro database. In total, 93,545 cancer patients in 10 principal hospitals covering the region of northwestern Japan were registered with the Hokushin Ganpro database between 2010 and 2015. The database included the following data: diagnosis date, cancer type, staging, treatment, cancer detection process, and possession of a disability certificate. RESULTS: We found that 2983 patients, which accounted for 3.2% of the total patients, had disabilities. No significant differences in gender, age at diagnosis, cancer stage distribution, and cancer incidence rates were observed between the disabled and non-disabled patients. Even though the proportion of early-stage cancer among disabled patients differed only slightly from that in non-disabled patients, early-stage cancer was more frequently diagnosed in patients with disabilities during their regular hospital visits than in those without disabilities, who had more opportunity for early cancer detection during cancer screening. According to in-house data reflecting treatment period and process from a single hospital, all 16 disabled patients treated with chemotherapy completed the treatment until disease progression or end of predetermined cycles. CONCLUSION: These results indicate that deep disparities between cancer patients with and without disabilities are not apparent and that the disabled patients in the region of northwestern Japan receive appropriate hospital follow-up.

Repeat pulmonary resection for lung malignancies does not affect the postoperative complications: a retrospective study.

BACKGROUND: Although repeat pulmonary resection (RPR) for multiple lung cancer has been performed for non-small cell lung cancer and metastatic lung tumor, with the prognostic benefit detailed in several reports, the risk of RPR has not been well analyzed. METHODS: Patients with lung malignancies who underwent complete resection at Kanazawa Medical University between January 2010 and October 2019 were analyzed. The relationship between postoperative complications and preoperative and perioperative factors was analyzed. Postoperative complications were categorized into five grades according to the Clavien-Dindo classification system. RESULTS: A total of 41 patients who were received RPR were enrolled in this study. Primary lung tumor was found in 31 patients, and metastatic lung tumor was found in 10 patients. The postoperative complication rate of the first operation was 29%, and that of the second operation was 29%. While there were no significant factors for an increased incidence of postoperative complication in a multivariate analysis, an operation time over 2 h at the second operation tended to affect the incidence of postoperative complication (p = 0.06). Furthermore, the operation time was significantly longer (p = 0.02) and wound length tended to be longer (p = 0.07) in the ipsilateral group than in the contralateral group. The rate of postoperative complications and the length of the postoperative hospital stay were not significantly different between the two groups. CONCLUSION: RPR is safely feasible and is not associated with an increased rate of postoperative complications, even on the ipsilateral side.

First case of lung cancer with pneumoconiosis and endobronchial leiomyoma complicating the diagnosis.

BACKGROUND: In the treatment of lung cancer, the presence or absence of mediastinal lymph node involvement has a significant bearing on the indication for surgery. In addition, if a tumor is found in the trachea during preoperative scrutiny of lung cancer, the possibility of intratracheal metastasis should be considered, since this kind of metastasis is a contraindication for surgery. In the present study, we experienced a case of lung cancer associated with pneumoconiosis and a rare intratracheal leiomyoma. In this case, preoperative staging was difficult, but endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and intratracheal tumor biopsy were helpful in determining the treatment strategy. CASE PRESENTATION: A 65-year-old man was referred to our hospital for evaluation of abnormal chest X-ray shadows. Sputum cytology indicated squamous cell carcinoma. PET-CT scan showed fluorodeoxyglucose uptake in a right upper lobe mass and the hilar, mediastinal and right supraclavicular lymph nodes, and bronchoscopy revealed a protuberant lesion in the left bronchus. Hence, EBUS-TBNA for the mediastinal lymph nodes and simultaneous evaluation of the protuberant lesion in the left bronchus were performed. The bronchial tumor was histopathologically diagnosed as leiomyoma. Since mediastinal lymph node biopsy showed no malignant cells, a right upper lobectomy and a right S6 segmentectomy were performed. Postoperative pathological evaluation of the dissected lymph nodes revealed pneumoconiosis but no metastasis. He was, thus, diagnosed with squamous cell lung carcinoma (pT2bN0M0, pStage IIA). CONCLUSIONS: We report a patient with lung cancer and coexistence of a rare endobronchial leiomyoma and pneumoconiosis, who underwent surgery after preoperative evaluation using EBUS-TBNA.