U-Shape Pillar Strip for 3D Cell-Lumped Organoid Model (3D-COM) Mimicking Lung Cancer Hypoxia Conditions in High-Throughput Screening (HTS).

Hypoxia is a representative tumor characteristic associated with malignant progression in clinical patients. Engineered in vitro models have led to significant advances in cancer research, allowing for the investigation of cells in physiological environments and the study of disease mechanisms and processes with enhanced relevance. In this study, we propose a U-shape pillar strip for a 3D cell-lumped organoid model (3D-COM) to study the effects of hypoxia on lung cancer in a high-throughput manner. We developed a U-pillar strip that facilitates the aggregation of PDCs mixed with an extracellular matrix to make the 3D-COM in 384-plate array form. The response to three hypoxia-activated prodrugs was higher in the 3D-COM than in the 2D culture model. The protein expression of hypoxia-inducible factor 1 alpha (HIF-1α) and HIF-2α, which are markers of hypoxia, was also higher in the 3D-COM than in the 2D culture. The results show that 3D-COM better recapitulated the hypoxic conditions of lung cancer tumors than the 2D culture. Therefore, the U-shape pillar strip for 3D-COM is a good tool to study the effects of hypoxia on lung cancer in a high-throughput manner, which can efficiently develop new drugs targeting hypoxic tumors.

Segmentectomy versus lobectomy in early non-small cell lung cancer of 2 cm or less in size: A population-based study.

BACKGROUND AND OBJECTIVE: Standard surgical management for early stage lung cancer is lobectomy with mediastinal lymph node dissection. The feasibility of limited resection remains controversial; we retrospectively assessed lung cancer-specific survival (LCSS) and overall survival (OS) in early stage non-small cell lung cancer (NSCLC) to evaluate whether segmentectomy is comparable to standard lobectomy. METHODS: Patients with primary NSCLC of 20 mm or less who were diagnosed from 2000 to 2014 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. To compare the two surgical interventions, a propensity score analysis was performed between lobectomy and segmentectomy. RESULTS: Of the 15 358 patients analysed, there were 14 549 lobectomies and 809 segmentectomies. The 5-year OS was 76% for the lobectomy group and 74.4% for the segmentectomy group. There were no significant differences in OS or LCSS among patients who underwent lobectomy versus segmentectomy, as demonstrated by the propensity-matched hazard ratio (HR) for OS (HR: 1.195, 95% CI: 0.993-1.439) and LCSS (HR: 1.124, 95% CI: 0.860-1.469). The inverse propensity-weighted analysis also supported these results. Segmentectomy was more likely to be performed in elderly patients. In the subset of patients aged ≥75 years, the segmentectomy group demonstrated comparable OS (HR: 1.17, 95% CI: 0.87-1.58, P = 0.31) and LCSS (HR: 0.94, 95% CI: 0.59-1.51, P = 0.81), compared with the lobectomy group. CONCLUSION: Equivalent OS and LCSS were demonstrated in patients with primary NSCLC of 20 mm or less without lymph node or distant metastasis.

Enhanced deep learning model for precise nodule localization and recurrence risk prediction following curative-intent surgery for lung cancer.

PURPOSE: Radical surgery is the primary treatment for early-stage resectable lung cancer, yet recurrence after curative surgery is not uncommon. Identifying patients at high risk of recurrence using preoperative computed tomography (CT) images could enable more aggressive surgical approaches, shorter surveillance intervals, and intensified adjuvant treatments. This study aims to analyze lung cancer sites in CT images to predict potential recurrences in high-risk individuals. METHODS: We retrieved anonymized imaging and clinical data from an institutional database, focusing on patients who underwent curative pulmonary resections for non-small cell lung cancers. Our study used a deep learning model, the Mask Region-based Convolutional Neural Network (MRCNN), to predict cancer locations and assign recurrence classification scores. To find optimized trained weighted values in the model, we developed preprocessing python codes, adjusted dynamic learning rate, and modifying hyper parameter in the model. RESULTS: The model training completed; we performed classifications using the validation dataset. The results, including the confusion matrix, demonstrated performance metrics: bounding box (0.390), classification (0.034), mask (0.266), Region Proposal Network (RPN) bounding box (0.341), and RPN classification (0.054). The model successfully identified lung cancer recurrence sites, which were then accurately mapped onto chest CT images to highlight areas of primary concern. CONCLUSION: The trained model allows clinicians to focus on lung regions where cancer recurrence is more likely, acting as a significant aid in the detection and diagnosis of lung cancer. Serving as a clinical decision support system, it offers substantial support in managing lung cancer patients.

Prognostic Factors of Pulmonary Metastasectomy for Oligometastatic Hepatocellular Carcinoma Spread to the Lungs.

Background/Objectives: Pulmonary metastasis is the most prevalent type of extrahepatic hepatocellular carcinoma (HCC) metastasis. International guidelines recommend systemic treatment for patients with HCC having pulmonary metastases. However, the role of pulmonary metastasectomy (PM) remains relatively unexplored. Therefore, we assessed the survival outcomes and the factors influencing them in patients who underwent PM for metastatic HCC. Methods: Clinical data were collected from patients with HCC who underwent PM for metastasis at a single tertiary center between January 2004 and December 2022. Recurrence-free survival and overall survival were assessed using Kaplan-Meier curves. The Cox proportional hazards model was used to identify factors associated with survival outcomes. Results: Overall, 63 patients underwent PM with a median follow-up time of 84.0 months. The cumulative survival rates after the initial PM at 1, 2, and 5 years were 79.1%, 63.9%, and 35.6%, respectively. In multivariate analysis, early intrathoracic recurrence <6 months, number and size of metastases, resection margin status, and PM bilaterality were significantly associated with overall survival. A larger size of the primary HCC, increased number of repeated PM, and frequent lobectomy were more common in patients with early (<6 months) recurrence after PM than in those without early recurrence. Conclusions: PM in patients with metastatic HCC may provide acceptable survival outcomes for those with smaller, unilateral lung metastases that can be resected with generous surgical margins. However, early recurrence with reduced overall survival is likely in patients with a larger-size initial HCC after prior PM and lobectomy.

Development of a Risk Scoring Model to Predict Unexpected Conversion to Thoracotomy during Video-Assisted Thoracoscopic Surgery for Lung Cancer.

Background: Unexpected conversion to thoracotomy during planned video-assisted thoracoscopic surgery (VATS) can lead to poor outcomes and comparatively high morbidity. This study was conducted to assess preoperative risk factors associated with unexpected thoracotomy conversion and to develop a risk scoring model for preoperative use, aimed at identifying patients with an elevated risk of conversion. Methods: A retrospective analysis was conducted of 1,506 patients who underwent surgical resection for non-small cell lung cancer. To evaluate the risk factors, univariate analysis and logistic regression were performed. A risk scoring model was established to predict unexpected thoracotomy conversion during VATS of the lung, based on preoperative factors. To validate the model, an additional cohort of 878 patients was analyzed. Results: Among the potentially significant clinical variables, male sex, previous ipsilateral lung surgery, preoperative detection of calcified lymph nodes, and clinical T stage were identified as independent risk factors for unplanned conversion to thoracotomy. A 6-point risk scoring model was developed to predict conversion based on the assessed risk, with patients categorized into 4 groups. The results indicated an area under the receiver operating characteristic curve of 0.747, with a sensitivity of 80.5%, specificity of 56.4%, positive predictive value of 1.8%, and negative predictive value of 91.0%. When applied to the validation cohort, the model exhibited good predictive accuracy. Conclusion: We successfully developed and validated a risk scoring model for preoperative use that can predict the likelihood of unplanned conversion to thoracotomy during VATS of the lung.

Pleural Carcinoembryonic Antigen and Maximum Standardized Uptake Value as Predictive Indicators of Visceral Pleural Invasion in Clinical T1N0M0 Lung Adenocarcinoma.

Background: Visceral pleural invasion (VPI) is a poor prognostic factor that contributes to the upstaging of early lung cancers. However, the preoperative assessment of VPI presents challenges. This study was conducted to examine intraoperative pleural carcinoembryonic antigen (pCEA) level and maximum standardized uptake value (SUVmax) as predictive markers of VPI in patients with clinical T1N0M0 lung adenocarcinoma. Methods: A retrospective review was conducted of the medical records of 613 patients who underwent intraoperative pCEA sampling and lung resection for non-small cell lung cancer. Of these, 390 individuals with clinical stage I adenocarcinoma and tumors ≤30 mm were included. Based on computed tomography findings, these patients were divided into pleural contact (n=186) and non-pleural contact (n=204) groups. A receiver operating characteristic (ROC) curve was constructed to analyze the association between pCEA and SUVmax in relation to VPI. Additionally, logistic regression analysis was performed to evaluate risk factors for VPI in each group. Results: ROC curve analysis revealed that pCEA level greater than 2.565 ng/mL (area under the curve [AUC]=0.751) and SUVmax above 4.25 (AUC=0.801) were highly predictive of VPI in patients exhibiting pleural contact. Based on multivariable analysis, pCEA (odds ratio [OR], 3.00; 95% confidence interval [CI], 1.14-7.87; p=0.026) and SUVmax (OR, 5.25; 95% CI, 1.90-14.50; p=0.001) were significant risk factors for VPI in the pleural contact group. Conclusion: In patients with clinical stage I lung adenocarcinoma exhibiting pleural contact, pCEA and SUVmax are potential predictive indicators of VPI. These markers may be helpful in planning for lung cancer surgery.

Feasibility and performance of the chronic obstructive pulmonary disease population screener and chronic obstructive pulmonary disease screening questionnaire in a Chinese physical examination center.

Background: Chronic obstructive pulmonary disease (COPD) affects up to 13% of the Chinese population, though it is under diagnosed throughout China. Screening among asymptomatic individual as part of routine health checks in China can facilitate early diagnosis and intervention to prevent disease progress. The COPD Population Screener (COPD-PS) or COPD Screening Questionnaire (COPD-SQ) has yet to be applied in Chinese physical examination centers (PECs) for COPD screening, and their feasibility and effectiveness should be clarified before full-scale implementation. This study is the first to apply the COPD-PS and COPD-SQ in a public hospital PEC in China to assess their feasibility and effectiveness and to identify their optimal cutoff values. Methods: People aged ≥40 years who attended the Second Affiliated Hospital of Shantou University PECs from September 2021 to December 2022 were asked to complete the COPD-PS and COPD-SQ and to undergo spirometry. The optimal cutoff values of the two questionnaires at the maximal Youden index were found, and the sensitivity and specificity were calculated. Results: Data from 198 participants were analyzed; mean [standard deviation (SD)] age of patients was 63.52 (10.94) years. Twenty-five participants (12.63%) were diagnosed with COPD. The number of COPD patients classified as Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades 1 to 4 were 8, 12, 4, and 1, respectively. The area under the curves (AUCs) of the COPD-PS and COPD-SQ were 0.730 and 0.738, respectively. The optimal COPD-PS cutoff value of 4 points corresponded to a sensitivity of 72.00% and a specificity of 60.10%. The COPD-SQ optimal cutoff value of 15 points corresponded to a sensitivity of 76.00% and a specificity of 63.60%. Conclusions: Applying the COPD-PS and COPD-SQ in Chinese PECs is feasible, cost-effective and effective. COPD-PS and COPD-SQ can facilitate the early diagnosis of COPD, and whether they can improve the participants' quality of life would benefit a further study. It is recommended that the COPD-PS or COPD-SQ questionnaires be added to the screening of the physical examination program in PECs as part of health checks for people over 40 years old.

PD-L1 expression from surgically resected lung tumors predictive of early progression in patients previously treated with targeted therapy for initially unresectable non-small cell lung cancer.

Background: Recent evidences showed that resection of lung tumor post-targeted therapy has shown progression-free survival (PFS) benefits in initially unresectable patients. The aim of this study is to evaluate pathologic findings of resected lung tumor samples in patients who have undergone prior epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) treatment, and also to assess the prognostic factors related to outcomes after resection. Methods: The deidentified data of non-small cell lung cancer (NSCLC) patients admitted to seven university hospitals affiliated with the Catholic University of Korea were obtained from the Clinical Data Warehouse (CDW) database. Among screened patients, 40 individuals who had previously undergone targeted therapies and later received surgical resection of a primary lung tumor were evaluated for the study. Results: All 40 patients were diagnosed with adenocarcinoma. Of these, 36 with EGFR mutations received prior EGFR TKI treatment. Only one postoperative complication, atrial fibrillation, was observed. At the time of resection, 19 patients showed primary lung tumor size regressing or unchanged, while 21 patients showed primary lung tumor regrowth or new lesions being developed before the resection. The group with no programmed death-ligand 1 (PD-L1) expression from resected samples showed significantly better post-resection PFS when compared to the other group (P=0.01). In the Model II multivariate analysis for post-resection PFS, PD-L1 detection from the resected sample was significantly associated with PFS [P=0.03; hazard ratio (HR) =5.465; 95% confidence interval (CI): 1.200-24.885]. Furthermore, an increase in PD-L1 expression compared to the baseline value was associated with an increasing lung tumor burden at the time of resection (P=0.03). Conclusions: Resected specimen following targeted therapy can provide valuable clinical information that can be used to predict the prognosis of patients with initially unresectable NSCLC.

Histo-pillar strip for optimal histogel block construction and biomarker analysis in 3D-lung cancer patient-derived organoids.

This study proposed an optimized histogel construction method for histological analysis by applying lung cancer patient-derived organoids (PDOs) to the developed histo-pillar strip. Previously, there is the cultured PDOs damage problem during the histogel construction due to forced detachment of the Matrigel spots from the 96-well plate bottom. To address this issue, we cultured PDO on the proposed Histo-pillar strips and then immersed them in 4% paraformaldehyde fixation solution to self-isolate PDO without damage. The 4µl patient-derived cell (PDC)/Matrigel mixtures were dispensed on the surface of a U-shaped histo-pillar strip, and the PDCs were aggregated by gravity and cultured into PDOs. Cultured PDOs were self-detached by simply immersing them in a paraformaldehyde fixing solution without physical processing, showing about two times higher cell recovery rate than conventional method. In addition, we proposed a method for embedding PDOs under conditions where the histogel temperature was maintained such that the histogel did not harden, thereby improving the problem of damaging the histogel block in the conventional sandwich histogel construction method. We performed histological and genotyping analyses using tumor tissues and PDOs from two patients with lung adenocarcinoma. Therefore, the PDO culture and improved histogel block construction method using the histo-pillar strip proposed in this study can be employed as useful tools for the histological analysis of a limited number of PDCs.

Prediction of TKI response in EGFR-mutant lung cancer patients-derived organoids using malignant pleural effusion.

Patient-derived organoids (PDOs) are valuable in predicting response to cancer therapy. PDOs are ideal models for precision oncologists. However, their practical application in guiding timely clinical decisions remains challenging. This study focused on patients with advanced EGFR-mutated non-small cell lung cancer and employed a cancer organoid-based diagnosis reactivity prediction (CODRP)-based precision oncology platform to assess the efficacy of EGFR inhibitor treatments. CODRP was employed to evaluate EGFR-tyrosine kinase inhibitors (TKI) drug sensitivity. The results were compared to those obtained using area under the curve index. This study validated this index by testing lung cancer-derived organoids in 14 patients with lung cancer. The CODRP index-based drug sensitivity test reliably classified patient responses to EGFR-TKI treatment within a clinically suitable 10-day timeline, which aligned with clinical drug treatment responses. This approach is promising for predicting and analyzing the efficacy of anticancer, ultimately contributing to the development of a precision medicine platform.

Pain after median sternotomy: collateral damage or mitigatable byproduct?

BACKGROUND: Postoperative acute pain can cause anxiety and decrease the quality of life in patients. Acute sternal bone pain after cardiac surgery can persist for long time. OBJECTIVE: The aim of this study is to explore the relationships between the degree of sternal misalignment and the degree of acute sternal pain after coronary artery bypass grafting surgery (CABG). METHODS: We retrospectively reviewed postoperative coronary computed tomographic (CT) angiography and medical records in 104 patients who received CABG between May 1, 2009 and January 31, 2011. CT scan was classified into five categories, and we compared the degree of misalignment and subjective pain via numerical rating scale (NRS) system. RESULTS: Positive correlation was noted between NRS and the degree of sternal misalignment (Pearson correlation coefficient 0.660, p = 0.000). CONCLUSION: Postoperative sternal pain is related to the degree of misalignment of the sternal halves. It would be appropriate for surgeons to approximate the sternal halves accurately to decrease the postoperative sternal wound pain in the first place.

Enlarging pulmonary cyst: a rare form of alveolar adenoma.

BACKGROUND: Alveolar adenoma is a rare benign tumour, usually presenting as a peripherally located solid mass, sometimes mimicking malignancy. CASE PRESENTATION: A 37-year-old woman presented with chronic intermittent vague chest discomfort. The chest x-ray showed a simple cyst in the left lower lung field, and serial computed tomography (CT) over the following 2-year period showed rapid growth of the cyst, from 3.5 to 9.0 cm in diameter. The CT scan suggested bronchiolar communication, which was suspected to be the cause of growth, via check-valve mechanism. Thoracoscopic surgery was performed, and we found a thin-walled cyst in the lingular segment. Wedge resection was performed and the pathology was an unexpected alveolar adenoma which had grown on the terminal bronchiole, causing the alveolus to rupture and the cyst to grow. In 48 months of follow-up, there was no evidence of recurrence and the patient's symptoms resolved. CONCLUSIONS: Rapidly growing pulmonary cysts can lead to complications including rupture with pneumothorax and haemothorax, and surgery is always indicated. Abnormally rapid growth may indicate an underlying pathology such as alveolar adenoma. Surgical resection is the treatment of choice and there have been no reported cases of recurrence. Here we present a rare form of alveolar adenoma, which was a form of rapidly growing pulmonary cyst.

Long-term clinical outcomes after initial secondary pneumothorax surgery.

Background: Given the heterogeneity of underlying lung disease and the higher morbidity and mortality associated with surgery for secondary pneumothorax (SP), treatment standardization and evidence-based early surgical management are challenging pursuits. Our aim was to document the clinical course of SP after initial surgical intervention and analyse related recurrence risk. Methods: We conducted a retrospective review of 160 patients, each with SP, using clinical records housed in an institutional database. Clinical, imaging, and operative data were retrieved, and Cox proportional hazards (PH) analysis was undertaken to identify risk factors for recurrence. Results: During a mean follow-up of 58.7 months, the overall recurrence rate in this cohort was 18.75% (ipsilateral, 14; contralateral, 16). A total of 24 patients had ≥3 ipsilateral episodes <6 months prior to surgery, marked by initial index episodes. In multivariate Cox PH analysis, the strongest risk factor for recurrence was underlying lung pathology other than chronic obstructive pulmonary disease [COPD: hazard ratio (HR) =5.3; P<0.001]. Conclusions: In this setting, underlying lung disease of a non-COPD nature is a proven risk factor for postsurgical recurrence. There is also a tendency in some patients for multiple episodes of pneumothorax within short periods of time, especially in the absence of COPD. Underlying disease processes may thus merit consideration in treatment planning.

Cancer Research Line (CAREL): Development of Expanded Distributed Research Networks for Prostate Cancer and Lung Cancer.

Objectives: Big data-based multicenter medical research is expected to bring significant advances to cancer treatment worldwide. However, there are concerns related to data sharing among multicenter networks. Clinical data can be shielded by firewalls using distributed research networks (DRNs). We attempted to develop DRNs for multicenter research that can be easily installed and used by any institution. Patients and Methods: We propose a DRN for multicenter cancer research called the cancer research line (CAREL) and present a data catalog based on a common data model (CDM). CAREL was validated using 1723 patients with prostate cancer and 14 990 patients with lung cancer in a retrospective study. We used the attribute-value pairs and array data type JavaScript object notation (JSON) format to interface third-party security solutions such as blockchain. Results: We developed visualized data catalogs of prostate and lung cancer based on the observational medical outcomes partnership (OMOP) CDM, from which researchers can easily browse and select relevant data. We made the CAREL source code readily available for download and application for relevant purposes. In addition, it is possible to realize a multicenter research network using CAREL development sources. Conclusion: CAREL source can enable medical institutions to participate in multicenter cancer research. Our technology is open source, so small institutions that cannot afford to spend high costs can use it to develop a platform for multicenter research.

Effect of total intravenous versus inhalation anesthesia on long-term oncological outcomes in patients undergoing curative resection for early-stage non-small cell lung cancer: a retrospective cohort study.

BACKGROUND: Propofol-based total intravenous anesthesia (TIVA) improves long-term outcomes after cancer surgery compared with inhalation anesthesia. However, its effect on patients undergoing non-small cell lung cancer (NSCLC) surgery remains unclear. We aimed to compare the oncological outcomes of TIVA and inhalation anesthesia after curative resection of early-stage NSCLC. METHODS: We analyzed the medical records of patients diagnosed with stage I or II NSCLC who underwent curative resection at a tertiary university hospital between January 2010 and December 2017. The primary outcomes were recurrence-free survival (RFS) and overall survival (OS) according to anesthesia type. RESULTS: We included 1,508 patients with stage I/II NSCLC. The patients were divided into the TIVA (n = 980) and Inhalation (n = 528) groups. The two groups were well-balanced in terms of baseline clinical characteristics. The TIVA group demonstrated significantly improved RFS (7.7 years, 95% CI [7.37, 8.02]) compared with the Inhalation group (6.8 years, 95% CI [6.30, 7.22], P = 0.003). Similarly, TIVA was superior to inhalation agents with respect to OS (median OS; 8.4 years, 95% CI [8.08, 8.69] vs. 7.3 years, 95% CI [6.81, 7.71]; P < 0.001). Multivariable Cox regression analysis revealed that TIVA was an independent prognostic factor related to recurrence (hazard ratio [HR]: 1.24, 95% CI [1.04, 1.47], P = 0.014) and OS (HR: 1.39, 95% CI [1.12, 1.72], P = 0.002). CONCLUSIONS: Propofol-based TIVA was associated with better RFS and OS than inhalation anesthesia in patients with stage I/II NSCLC who underwent curative resection.

Exploration of a novel prognostic model based on nomogram in non-small cell lung cancer patients with distant organ metastasis: implications for immunotherapy.

Background: Evidence for the effects of immunotherapy in non-small cell lung cancer (NSCLC) patients with distant organ metastasis is insufficient, and the predictive efficacy of established markers in tissue and blood is elusive. Our study aimed to determine the prognostic factors and develop a survival prognosis model for these patients. Methods: A total of 100 advanced NSCLC patients with distant organ metastases, who received single or combination immune checkpoint inhibitors (ICIs) in Xijing Hospital between June 2018 and June 2021, were enrolled for retrospective analysis. The major clinicopathological parameters were collected, and associated survival outcomes were followed up by telephone or inpatient follow-up for nearly 3 years to assess prognoses. The survival prognosis model was established based on univariate and multivariate Cox regression analyses to determine the candidate prognostic factors. Results: From the start of immunotherapy to the last follow-up, 77 patients progressed and 42 patients died, with a median follow-up of 18 months [95% confidence interval (CI): 15-19.9]. The median progression-free survival (PFS) and overall survival (OS) were 8 months (95% CI: 5.6-10.4) and 21 months (95% CI: 8.9-33.1), respectively. Multivariate Cox proportional hazards analysis showed Eastern Cooperative Oncology Group performance status (ECOG PS), body mass index (BMI), age-adjusted Charlson comorbidity index (ACCI), lactate dehydrogenase (LDH), and absolute neutrophil count (ANC) were correlated significantly with OS. Based on these five predictive factors, a nomogram and corresponding dynamic web page were constructed with a concordance index (C-index) of 0.81 and a 95% CI of 0.778-0.842. Additionally, the calibration plot and time-receiver operating characteristic (ROC) curve validated the precision of the model at 6-, 12-, and 18-month area under the curves (AUCs) reached 0.934, 0.829, and 0.846, respectively. According to the critical point of the model, patients were further divided into a high-risk total point score (TPS) >258, middle-risk (204< TPS ≤258), and low-risk group (TPS ≤204), and significant OS differences were observed among the three subgroups (median OS: 4.8 vs. 13.0 vs. 32.9 months). Conclusions: A feasible and practical model based on clinical characteristics has been developed to predict the prognosis of NSCLC patients with distant organ metastasis undergoing immunotherapy.

Cancer organoid-based diagnosis reactivity prediction (CODRP) index-based anticancer drug sensitivity test in ALK-rearrangement positive non-small cell lung cancer (NSCLC).

BACKGROUND: Recently, cancer organoid-based drug sensitivity tests have been studied to predict patient responses to anticancer drugs. The area under curve (AUC) or IC50 value of the dose-response curve (DRC) is used to differentiate between sensitive and resistant patient's groups. This study proposes a multi-parameter analysis method (cancer organoid-based diagnosis reactivity prediction, CODRP) that considers the cancer stage and cancer cell growth rate, which represent the severity of cancer patients, in the sensitivity test. METHODS: On the CODRP platform, patient-derived organoids (PDOs) that recapitulate patients with lung cancer were implemented by applying a mechanical dissociation method capable of high yields and proliferation rates. A disposable nozzle-type cell spotter with efficient high-throughput screening (HTS) has also been developed to dispense a very small number of cells due to limited patient cells. A drug sensitivity test was performed using PDO from the patient tissue and the primary cancer characteristics of PDOs were confirmed by pathological comparision with tissue slides. RESULTS: The conventional index of drug sensitivity is the AUC of the DRC. In this study, the CODRP index for drug sensitivity test was proposed through multi-parameter analyses considering cancer cell proliferation rate, the cancer diagnosis stage, and AUC values. We tested PDOs from eight patients with lung cancer to verify the CODRP index. According to the anaplastic lymphoma kinase (ALK) rearrangement status, the conventional AUC index for the three ALK-targeted drugs (crizotinib, alectinib, and brigatinib) did not classify into sensitive and resistant groups. The proposed CODRP index-based drug sensitivity test classified ALK-targeted drug responses according to ALK rearrangement status and was verified to be consistent with the clinical drug treatment response. CONCLUSIONS: Therefore, the PDO-based HTS and CODRP index drug sensitivity tests described in this paper may be useful for predicting and analyzing promising anticancer drug efficacy for patients with lung cancer and can be applied to a precision medicine platform.

Surgical treatment of facial blushing: Patient selection and operative technique (retrospective observational study).

Surgeons are often reluctant to offer further intervention to patients with medically intractable facial blushing. This is mainly because of the relatively high failure rate of blushing resolution and a high incidence of compensatory hyperhidrosis. In this study, we sought to identify the type of blushing that would benefit from surgery and minimize compensatory hyperhidrosis by applying diffuse sympathicotomy (DS). This study was a retrospective review of 62 patients who underwent R2 endoscopic thoracic sympathicotomy (ETS) and preemptive DS for facial blushing. Facial blushing was classified as autonomic-mediated blushing (thermoregulatory, emotional) and vasodilator-mediated blushing (constant) based on the history and precipitating factors for blushing. DS was performed at lower-thoracic levels in the form of limited DS (right R5/7/9/11, left R5/6/8/10) or extended DS (bilateral R5-11). Resolution of blushing (described as "almost disappeared") was achieved in 48% of patients with a median follow-up of 19.6 months. There was a significant difference in resolution among 3 types of blushing (emotional: 55%, thermoregulatory: 28%, constant: 15%, P = .03). Multivariate analysis confirmed thermoregulatory and constant type blushing as a potential independent predictor of blushing resolution. Even though there was no difference between the DS procedures with respect to compensatory hyperhidrosis, intolerable compensatory hyperhidrosis (Hyperhidrosis Disease Severity Scale = 4) occurred in only 11% of patients. DS redistributed sweating area, being predominantly on the chest and mid-back (89%), also seen on the abdomen-waist-groin-buttocks-thighs (63%). Overall, 77% of patients experienced satisfactory results. Emotional blushing proved to be an established indication of ETS where good long-term results can be expected. Expansion of surgical indication to thermoregulatory or constant type blushing needs to be validated in future studies. Additionally, compensatory hyperhidrosis, another hurdle for ETS, can be minimized by preemptive DS, resulting in redistribution and decrease of sweating.

Comparison of clinical results between high grade patterns in stage I lung adenocarcinoma.

BACKGROUND: The histological subtype has been introduced in invasive lung adenocarcinoma. The predominant micropapillary and solid subtypes are categorized as high-grade patterns and provide a worse prognosis. However, the prognostic analysis of high-grade patterns has not previously been fully investigated. Thus, this study aimed to investigate the prognostic role of high-grade patterns in pathological stage I lung adenocarcinoma. METHODS: Patients with stage I lung adenocarcinoma and micropapillary or solid components were reviewed. Clinicopathological features and clinical course were compared in these subtypes, and prognostic factors were analyzed in high-grade patterns. RESULTS: The patients were classified into five groups based on the presence of micropapillary or solid subtypes, namely, micropapillary predominant, solid predominant, both nonpredominant subtypes, only minor micropapillary subtype, and only minor solid subtype present. Disease-free interval was significantly different, and the micropapillary predominant group showed worse disease-free interval (p = 0.001). Contrastingly, the solid predominant group showed significantly worse overall survival among high-grade patterns (p = 0.035). The multivariate analysis revealed an association between smoking, micropapillary predominant, blood vessel invasion, and visceral pleural invasion with recurrence and more association between solid predominant and visceral pleural invasion with overall survival. CONCLUSIONS: Clinical results were different in stage I high-grade adenocarcinoma. The predominant micropapillary subtype is the independent prognostic factor for recurrence. However, the solid subtype is the significant factor for overall survival. Furthermore, the predominant subtype is the most valuable and independent prognostic factor for predicting recurrence or survival.

Predicting prognosis using a pathological tumor cell proportion in stage I lung adenocarcinoma.

BACKGROUND: Tumor size is a valuable prognostic factor because it is considered a measure of tumor burden. However, it is not always correlated with the tumor burden. This study aimed to identify the prognostic role of pathological tumor proportional size using the proportion of tumor cells on the pathologic report after curative resection in pathologic stage I lung adenocarcinoma. METHODS: We retrospectively reviewed the medical records of 630 patients with pathologic stage I lung adenocarcinoma after lung resection for curative aims. According to the pathologic data, the proportion of tumor cells was reviewed and pathological tumor proportional size was estimated by multiplying the maximal diameter of the tumor by the proportion of tumor cells. We investigated the prognostic role of pathological tumor proportional size. RESULTS: The median tumor size was 2 cm (range: 0.3-4), and the median pathological tumor proportional size was 1.5 (range: 0.12-3.8). This value was recategorized according to the current tumor-node-metastasis (TNM) classification, and 184 patients showed down staging compared with the current stage. The survival curve for disease-free survival using pathological tumor proportional size showed more distinction than the current stage classification. Multivariate analysis revealed that a down stage indicated a favorable prognostic factor. CONCLUSION: Pathological tumor cell proportional size may be associated with prognosis in stage I lung adenocarcinoma. If the pathological tumor proportional size shows a downward stage, it may indicate a smaller tumor burden and better prognosis.