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.

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.

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.

Prognostic Analysis of Stage I Non-Small Cell Lung Cancer Abutting Adjacent Structures on Preoperative Computed Tomography.

Background: Early non-small cell lung cancer (NSCLC) that abuts adjacent structures requires careful evaluation due to its potential impact on postoperative outcomes and prognosis. We examined stage I NSCLC with invasion into adjacent structures, focusing on the prognostic implications after curative surgical resection. Methods: We retrospectively analyzed the records of 796 patients who underwent curative surgical resection for pathologic stage IA/IB NSCLC (i.e., visceral pleural invasion only) at a single center from 2008 to 2017. Patients were classified based on tumor abutment and then reclassified by the presence of visceral pleural invasion. Clinical characteristics, pathological features, and survival rates were compared. Results: The study included 181 patients with abutting NSCLC (22.7% of all participants) and 615 with non-abutting tumors (77.3%). Those with tumor abutment exhibited higher rates of non-adenocarcinoma (26.5% vs. 9.9%, p<0.01) and visceral/lymphatic/vascular invasion (30.4%/33.1%/12.7% vs. 8.5%/22.4%/5.7%, respectively; p<0.01) compared to those without abutment. Multivariable analysis identified lymphatic invasion and male sex as risk factors for overall survival (OS) and disease-free survival (DFS) in stage I NSCLC measuring 3 cm or smaller. Age, smoking history, vascular invasion, and recurrence emerged as risk factors for OS, whereas the presence of non-pure ground-glass opacity was a risk factor for DFS. Conclusion: NSCLC lesions 3 cm or smaller that abut adjacent structures present higher rates of various risk factors than non-abutting lesions, necessitating evaluation of tumor invasion into adjacent structures and lymph node metastasis. In isolation, however, the presence of tumor abutment without visceral pleural invasion does not constitute a risk factor.

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.

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 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.

Metabolic profiles of lung adenocarcinoma via peripheral blood and diagnostic model construction.

The metabolic profile of cancerous cells is shifted to meet the cellular demand required for proliferation and growth. Here we show the features of cancer metabolic profiles using peripheral blood of healthy control subjects (n = 78) and lung adenocarcinoma (LUAD) patients (n = 64). Among 121 detected metabolites, diagnosis of LUAD is based on arginine, lysophosphatidylcholine-acyl (Lyso.PC.a) C16:0, and PC-diacyl (PC.aa) C38:3. Network analysis revealed that network heterogeneity, diameter, and shortest path were decreased in LUAD. On the contrary, these parameters were increased in advanced-stage compared to early-stage LUAD. Clustering coefficient, network density, and average degree were increased in LUAD compared to the healthy control, whereas these topologic parameters were decreased in advanced-stage compared to early-stage LUAD. Public LUAD data verified that the genes encoding enzymes for arginine (NOS, ARG, AZIN) and for Lyso.PC and PC (CHK, PCYT, LPCAT) were related with overall survival. Further studies are required to verify these results with larger samples and other histologic types of lung cancer.

Prognostic value of TLR from FDG PET/CT in patients with margin-negative stage IB and IIA non-small cell lung cancer.

OBJECTIVES: To evaluate the prognostic value of TLR from PET/CT in patients with resection margin-negative stage IB and IIA non-small cell lung cancer (NSCLC) and compare high-risk factors necessitating adjuvant treatment (AT). METHODS: Consecutive FDG PET/CT scans performed for the initial staging of NSCLC stage IB and IIA were retrospectively reviewed. The maximum standardized uptake value (SUVmax) of the primary tumor and mean SUV of the liver were acquired. The tumor-to-liver SUV ratio (TLR) was also calculated. Charts were reviewed for basic patient characteristics and high-risk factors for considering AT (poor differentiation, visceral pleura invasion, vascular invasion, tumors > 4 cm, and wedge resection). Statistical analysis was performed using Cox regression analysis and the Kaplan-Meier method. RESULTS: Of the 112 patients included, 15 (13.4%) died, with a median overall survival (OS) of 43.8 months. Twenty-two patients (19.6%) exhibited recurrence, with median disease-free survival (DFS) of 36.0 months. In univariable analysis, pathology, poor differentiation, and TLR were associated with shorter DFS and OS. In multivariable analysis, TLR (hazard ratio [HR] = 1.263, p = 0.008) and differentiation (HR = 3.087, p = 0.012) were associated with shorter DFS. Also, TLR (HR = 1.422, p < 0.001) was associated with shorter OS. CONCLUSION: TLR from FDG PET/CT was an independent prognostic factor for recurrence and survival. PET parameters constitute risk factors for consideration in the decision-making for AT in margin-negative stage IB and IIA NSCLC. CLINICAL RELEVANCE STATEMENT: In this study, TLR from FDG PET/CT was an independent prognostic factor in stage IB-IIA non-small cell cancer patients. Although additional validation studies are warranted, TLR has the potential to be used to determine the need for adjuvant therapy. KEY POINTS: • High TLR is an independent poor prognostic factor in stage IB-IIA NSCLC. • Adjuvant treatment should be considered in patients with high TLR following complete tumor resection.

Clinical significance of tumor necrosis and viability in non-small cell lung cancer.

Background: We included tumor necrosis (TN) and tumor viability (TV) in our prognostic assessment of patients with non-small cell lung cancer (NSCLC) and investigated their clinical significance. Methods: Medical records of all consecutive subjects who underwent a lobectomy with standard mediastinal lymph node dissection for NSCLC between 2015 to 2016, were reviewed retrospectively. We analyzed the associations of TN and TV with various parameters associated with prognosis as well as survival in NSCLC patients. All analyses were performed regarding neoadjuvant therapy status [the group without neoadjuvant therapy (WON) vs. the group with neoadjuvant therapy (WN)]. Results: A consecutive 154 patients (mean age: 65.0±10.1 years) were included into the present study. Fifteen patients underwent neoadjuvant therapy. Final pathologic stages were IA1 (n=13), IA2 (n=30), IA3 (n=32), IB (n=40), IIA (n=9), IIB (n=18), and IIIA (n=12). WN significantly showed higher TN (P=0.005) and lower TV (P<0.001) than WON. Tumors with vascular, lymphatic, and perineural invasion showed significantly lower TV and higher TN than cases without these features (P=0.014, P=0.019, and P=0.012 for TV; P=0.001, P<0.001, and P<0.001 for TN, respectively). Tumors with poorer differentiation had lower TV (P<0.001) and higher TN (P<0.001) than more differentiated tumors. There was a positive correlation between TN and tumor size (P<0.001) and a negative correlation between TV and tumor size (P=0.031). TN significantly increased as pathologic stage increased (P=0.001), and TV significantly decreased as pathologic stage increased (P=0.038). The group without TN survived significantly longer than the group with TN (P=0.016) in N0 disease and presence of TN and pT stage were independent prognostic factors for survival in N0 disease (P=0.037 and P=0.021, respectively). There was a positive correlation between TN and Ki-67 level (P=0.027). In WN, TN was significantly associated with differentiation (P=0.035), tumor size (P=0.008), and pT stage (P=0.031) but not overall pathologic stage or survival. Conclusions: Presence of histological TN was associated with prognosis of NSCLC, especially in N0 disease, and its usage as a diagnostic or prognostic tool and determination of resection extent could potentially provide prognostic information that can facilitate better management of NSCLC.

DeepRePath: Identifying the Prognostic Features of Early-Stage Lung Adenocarcinoma Using Multi-Scale Pathology Images and Deep Convolutional Neural Networks.

The prognosis of patients with lung adenocarcinoma (LUAD), especially early-stage LUAD, is dependent on clinicopathological features. However, its predictive utility is limited. In this study, we developed and trained a DeepRePath model based on a deep convolutional neural network (CNN) using multi-scale pathology images to predict the prognosis of patients with early-stage LUAD. DeepRePath was pre-trained with 1067 hematoxylin and eosin-stained whole-slide images of LUAD from the Cancer Genome Atlas. DeepRePath was further trained and validated using two separate CNNs and multi-scale pathology images of 393 resected lung cancer specimens from patients with stage I and II LUAD. Of the 393 patients, 95 patients developed recurrence after surgical resection. The DeepRePath model showed average area under the curve (AUC) scores of 0.77 and 0.76 in cohort I and cohort II (external validation set), respectively. Owing to low performance, DeepRePath cannot be used as an automated tool in a clinical setting. When gradient-weighted class activation mapping was used, DeepRePath indicated the association between atypical nuclei, discohesive tumor cells, and tumor necrosis in pathology images showing recurrence. Despite the limitations associated with a relatively small number of patients, the DeepRePath model based on CNNs with transfer learning could predict recurrence after the curative resection of early-stage LUAD using multi-scale pathology images.

Effects of lower thoracic sympathicotomy on plantar hyperhidrosis.

BACKGROUND: The purpose of this study was to investigate whether performing lower thoracic sympathicotomy (LTS) from T10 to T12 affects plantar hyperhidrosis in patients with palmo-plantar (PP) or palmo-axillary-plantar (PAP) hyperhidrosis. METHODS: Between January 2015 and January 2020, all consecutive patients with primary hyperhidrosis who underwent bilateral thoracoscopic sympathicotomy and met the inclusion criteria were included. Sympathicotomy was performed using one of the following two methods: the conventional upper thoracic vs. expanded thoracic sympathicotomy. In the expanded thoracic sympathicotomy, we expanded the level of sympathicotomy ranging from R5 to R12 in addition to the conventional upper thoracic sympathicotomy (R3 or R4). In cases of the expanded thoracic sympathicotomy, we defined the LTS as a sympathicotomy of the levels ranging from R10 to R12, which are related to plantar hyperhidrosis. RESULTS: A total of 103 subjects with PP (71 cases) or PAP (32 cases) hyperhidrosis were included. Palmar or axillary hyperhidrosis in all patients were alleviated after sympathicotomy. There was no difference in sweating decrease or CH according to the hyperhidrosis types or sympathicotomy techniques. In addition, no-LTS was performed in 77 cases and LTS was performed in 26 cases. In the no-LTS group, there were 65 and 12 cases of low and high degrees of CH, respectively. In the LTS group, there were 22 and four cases of low and high degrees of CH, respectively. There was no significant difference in CH between the no-LTS and LTS groups (P=0.981). Improvement in plantar hyperhidrosis in the no-LTS group was observed in 29 of 77 cases, while improvement in plantar hyperhidrosis in the LTS group was observed in 16 of 26 cases. The addition of LTS lead to significant improvement in plantar hyperhidrosis (P=0.034). CONCLUSIONS: Performing LTS is a safe and feasible procedure that improved plantar sweating more so than it did in cases that did not undergo LTS. Therefore, we cautiously suggest that adding LTS helps in the treatment of plantar hyperhidrosis combined with palmar hyperhidrosis. Further studies on LTS are needed to validate these findings and will be helpful in establishing management guidelines.

Thoracic Chordoma Misdiagnosed as Primary Adenocarcinoma of the Mediastinum.

Chordoma is a rare malignant bone tumor originating from the embryonic notochord. Herein, we present a case of thoracic chordoma located at T3-T5 that was misdiagnosed as primary mediastinal adenocarcinoma. The patient underwent neoadjuvant chemoradiation and the disease showed little response. Due to vertebral body invasion, we performed en bloc mass removal and partial corpectomy (T4-5) in collaboration with orthopedic surgeons.

Heart rate variability as a potential diagnostic tool to predict compensatory hyperhidrosis after sympathectomy in patients with primary focal hyperhidrosis.

BACKGROUND: Primary focal hyperhidrosis (PFH) is associated with autonomic nervous activity, and studies investigating this association in patients with PFH are very important. Heart rate variability (HRV) is a simple and noninvasive electrocardiographic test showing activity and balance in the autonomic nervous system, which consists of sympathetic and parasympathetic components. The aims of this study are to investigate associations between autonomic nervous activity and hyperhidrosis characteristics using HRV and to investigate the association between HRV findings and compensatory hyperhidrosis (CH) after sympathectomy. METHODS: From March 2017 to March 2020, 105 subjects with PFH who underwent preoperative HRV tests and sympathectomy were analyzed. All subjects underwent bilateral thoracoscopic sympathectomy. T2 sympathectomy was conducted for craniofacial hyperhidrosis, and T3 sympathectomy was conducted for palmar hyperhidrosis. The following HRV parameters chosen to investigate the association between hyperhidrosis and autonomic nervous activity were measured by time and frequency domain spectral analysis: (I) time domain: standard deviation of normal-to-normal interval (SDNN) and square root of mean squared differences of successive normal-to-normal intervals (RMSSD), (II) frequency domain: total power (TP) of power spectral density, very low frequency (VLF), low frequency (LF), and high frequency (HF). HRV parameters were analyzed according to hyperhidrosis type (craniofacial vs. palmar type), sweat reduction, and CH after sympathectomy. In addition, the independent HRV parameters influencing CH after sympathectomy were investigated with multivariate analysis. RESULTS: Craniofacial hyperhidrosis was significantly more prevalent in the old age group (P<0.001). Sweat reduction after sympathectomy was significantly more prominent in palmar hyperhidrosis (P=0.037), and CH after sympathectomy was more prominent in craniofacial hyperhidrosis (P<0.001). Palmar type patients exhibited significantly larger SDNN, RMSSD, TP, LF, and HF than craniofacial type patients (all P<0.001). There were no significant differences in any HRV parameters according to sweat reduction after sympathectomy. Low-degree CH was associated with significantly larger SDNN, RMSSD, TP, LF, and HF than high-degree CH (P<0.001, P<0.001, P=0.002, P=0.001, and P<0.001, respectively). Multivariate analysis showed that HF and age group were associated with CH after sympathectomy (P=0.007 and P=0.010, respectively). CONCLUSIONS: This study shows that HRV can provide useful insight into the pathophysiology of PFH and enhance preoperative risk stratification of CH. Large-scale, prospective studies are required to determine the predictive value of HRV in patients at risk for subsequent CH after sympathectomy.

Impact of Sarcopenia on Early Postoperative Complications in Early-Stage Non-Small-Cell Lung Cancer.

BACKGROUND: Risk assessment for pulmonary resection in patients with early-stage non-small-cell lung cancer (NSCLC) is important for minimizing postoperative morbidity. Depletion of skeletal muscle mass is closely associated with impaired nutritional status and limited physical ability. We evaluated the relationship between skeletal muscle depletion and early postoperative complications in patients with early-stage NSCLC. METHODS: Patients who underwent curative lung resection between 2016 and 2018 and who were diagnosed with pathological stage I/II NSCLC were included, and their records were retrospectively analyzed. The psoas volume index (PVI, cm3/m3) was calculated based on computed tomography images from routine preoperative positron emission tomography-computed tomography. Early postoperative complications, defined as those occurring within 90 days of surgery, were compared between the lowest sex-specific quartile for PVI and the remaining quartiles. RESULTS: A strong correlation was found between the volume and the cross-sectional area of the psoas muscle (R2=0.816). The overall rate of complications was 57.6% among patients with a low PVI and 32.8% among those with a normal-to-high PVI. The most common complication was prolonged air leak (low PVI, 16.9%; normal-to-high PVI, 9.6%), followed by pneumonia (low PVI, 13.6%; normal-to-high PVI, 7.9%) and recurrent pleural effusion (low PVI, 11.9%; normal-to-high PVI, 6.8%). The predictors of overall complications were low PVI (odds ratio [OR], 2.18; 95% confidence interval [CI], 1.07-4.09; p=0.03), low hemoglobin level (OR, 0.686; 95% CI, 0.54-0.87; p=0.002), and smoking history (OR, 3.93; 95% CI, 2.03-7.58; p<0.001). CONCLUSION: Low PVI was associated with a higher rate of early postoperative complications in patients with early-stage NSCLC.

Nodal Outcomes of Uniportal versus Multiportal Video-Assisted Thoracoscopic Surgery for Clinical Stage I Lung Cancer.

BACKGROUND: Accurate intraoperative assessment of mediastinal lymph nodes is a critical aspect of lung cancer surgery. The efficacy and potential for upstaging implicit in these dissections must therefore be revisited in the current era of uniportal video-assisted thoracoscopic surgery (VATS). METHODS: A retrospective study was conducted in which 544 patients with stage I (T1abc-T2a, N0, M0) primary lung cancer were analyzed. To assess risk factors for nodal upstaging and to limit any imbalance imposed by surgical choices, we constructed an inverse probability of treatment-weighted (IPTW) logistic regression model (in addition to non-weighted logistic models). We also evaluated risk factors for early locoregional recurrence using IPTW logistic regression analysis. RESULTS: In the comparison of uniportal and multiportal VATS, the resected lymph node count (14.03±8.02 vs. 14.41±7.41, respectively; p=0.48) and rate of nodal upstaging (6.5% vs. 8.7%, respectively; p=0.51) appeared similar. Predictors of nodal upstaging included tumor size (odds ratio [OR], 1.74; 95% confidence interval [CI], 1.12-2.70), carcinoembryonic antigen level (OR, 1.11; 95% CI, 1.04-1.18), and histologically confirmed pleural invasion (OR, 3.97; 95% CI, 1.89-8.34). The risk factors for locoregional recurrence within 1 year were found to be number of resected N2 nodes, age, and nodal upstaging. CONCLUSION: Uniportal and multiportal VATS appear similar with regard to accuracy and thoroughness, showing no significant difference in the extent of nodal dissection.

Atypical Thymic Carcinoid in a Patient with Zollinger-Ellison Syndrome.

Atypical thymic carcinoid is an extremely rare tumor with a poor prognosis. In addition to its known association with multiple endocrine neoplasia type 1, its hallmark characteristics include local invasion and early distant metastasis. In this report, we share our experience treating atypical thymic carcinoid in a patient with Zollinger-Ellison syndrome.

Preliminary results of entire pleural intensity-modulated radiotherapy in a neoadjuvant setting for resectable malignant mesothelioma.

PURPOSE: The purpose of this study is to evaluate the safety and efficacy of the multimodality treatment with neoadjuvant intensitymodulated radiotherapy (IMRT) for resectable clinical T1-3N0-1M0 malignant pleural mesothelioma (MPM). MATERIALS AND METHODS: A total of eleven patients who received neoadjuvant chemotherapy and radiotherapy between March 2016 and June 2018 were reviewed. Patients received 25 Gy in 5 fractions to entire ipsilateral hemithorax with helical tomotherapy. RESULTS: All of patients were men with a median age of 56 years. Epithelioid subtype was found in 10 patients. All patients received neoadjuvant chemotherapy with pemetrexed-cisplatin regimen. Ten patients (90.9%) completed 25 Gy/5 fractions and one (9.0%) completed 20 Gy/4 fractions of radiotherapy. IMRT was well tolerated with only one acute grade 3 radiation pneumonitis. Surgery was performed 1 week (median, 8 days; range, 1 to 15 days) after completing IMRT. Extrapleural pneumonectomy was performed in 4 patients (36.3%), extended pleurectomy/decortication in 2 (18.2%) and pleurectomy/decortications in 5 (63.6%). There was no grade 3+ surgical complication except two deaths after EPP in 1 month. Based on operative findings and pathologic staging, adjuvant chemotherapy was delivered in 7 patients (63.6%), and 2 (18.2%) were decided to add adjuvant radiotherapy. After a median follow-up of 14.6 months (range, 2.8 to 30 months), there were 3 local recurrence (33.3%) and 1 distant metastasis (11.1%). CONCLUSION: Neoadjuvant entire pleural IMRT can be delivered with a favorable radiation complication. An optimal strategy has to be made in resectable MPM patients who would benefit from neoadjuvant radiation and surgery. Further studies are needed to look at long-term outcomes.

Early detection of complications: anastomotic leakage.

Anastomotic leakage (AL) is one of the most critical and detrimental complications in esophageal surgery. Early diagnosis and timely therapeutic action are necessary if patients are to avoid AL-related problems. However, there is no gold standard or consensus for early diagnosis. In this review, we focus on summarizing the definition and types of AL and modalities for early diagnosis of AL after esophagectomy.