PPP1r18 promotes tumor progression in esophageal squamous cell carcinoma by regulating the calcineurin-mediated ERK pathway.

Esophageal cancer is one of the most common malignant tumors, and the 5-year overall survival rate is only 20%. Esophageal squamous cell carcinoma (ESCC) is the primary histological type of esophageal carcinoma in China. Protein phosphatase 1 regulatory subunit 18 (PPP1r18) is one of the actin-regulatory proteins and is able to bind to protein phosphatase 1 catalytic subunit alpha (PPP1CA). Yet, little is known about the role of PPP1r18 in esophageal squamous cell carcinoma (ESCC). This study aimed to elucidate the biological functions of PPP1r18 in the ESCC progression. Clinical samples first confirmed that PPP1r18 expression was upregulated in ESCC, and PPP1r18 was correlated with tumor invasion depth, lymph node metastasis, distant metastasis, and reduced overall survival. We then observed that PPP1r18 overexpression enhanced cell proliferation in vitro and in vivo. Mechanistically, PPP1r18 regulated tumor progression of ESCC through activating the calcineurin-mediated ERK pathway, rather than binding to PPP1CA. Collectively, our results suggest that PPP1r18 promotes ESCC progression by regulating the calcineurin-mediated ERK pathway. PPP1r18 might be a potential target for the diagnosis and treatment of ESCC.

Opioid-Free Versus Opioid-Based Anesthesia on Postoperative Pain After Thoracoscopic Surgery: The Use of Intravenous and Epidural Esketamine.

BACKGROUND: The effectiveness and safety of opioid-free anesthesia (OFA) regimens in distinct types of surgeries remain controversial. In this study, we investigated whether OFA could reduce the occurrence of chronic postoperative pain in patients receiving video-assisted thoracoscopic surgery (VATS). METHODS: We conducted a 2-center, randomized, controlled trial from September 2021 to January 2022. A total of 162 lung tumor patients scheduled to undergo VATS were randomly divided into an opioid-based anesthesia (OA) group and an OFA group. The OA group received general anesthesia combined with thoracic epidural block using morphine, while the OFA group received general anesthesia combined with thoracic epidural block using esketamine. Patient-controlled epidural analgesia (PCEA) was used after surgery (ropivacaine and morphine for the OA group versus ropivacaine and esketamine for the OFA group). The primary end point was chronic pain rates at 3 months after VATS, which were analyzed using a logistic regression model. The secondary end points were chronic pain rates at 6 months, acute pain rates at 24 hours and 48 hours postoperatively, postoperative side effects, and perioperative variables. RESULTS: The final analysis included 159 patients. Acute postoperative pain at 24 hours occurred in 0 of the 79 (0%) patients in the OA group and 10 of the 80 (17.5%) patients in the OFA group (odds ratio, 52.14; 95% confidence interval [CI], 6.47-420.10; P < .001). Acute postoperative pain at 48 hours occurred in 3 of the 79 (3.8%) patients in the OA group and 2 of the 80 (2.5%) patients in the OFA group (odds ratio, 2.07; 95% CI, 0.99-4.32; P = .053). In this study, none of the patients had moderate or severe pain in either group at 3 and 6 months postsurgically. Mild chronic postoperative pain at 3 months occurred in 27 of the 79 (34.2%) patients in the OA group and 14 of the 80 (17.5%) patients in the OFA group (odds ratio, 3.52; 95% CI, 1.49-8.31; P = .004). At 6 months, mild chronic pain still occurred in 23 of the 79 (29.1%) patients in the OA group and 9 of the 80 (11.3%) patients in the OFA group (odds ratio, 5.55; 95% CI, 2.01-15.33; P = .001). In addition, the OFA group included fewer patients with side effects, including nausea, vomiting, and pruritus, within 48 hours after surgery. CONCLUSIONS: Replacement of opioids by esketamine, intraoperatively as intravenous injection and epidural infusion and postoperatively as epidural infusion, reduces the incidence of mild chronic postoperative pain and side effects in patients after VATS.

Expression of PD-L1 through evolution phase from pre-invasive to invasive lung adenocarcinoma.

BACKGROUND: This study evaluated programmed cell death-ligand 1 (PD-L1) expression from pre-invasive adenocarcinoma to invasive lung adenocarcinoma, aimed to investigate the potential association of PD-L1 pathway with lung adenocarcinoma early evolution. METHODS: We evaluated PD-L1 expression in 1123 resected lung specimens of adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IAC) of stage IA1-IA3. PD-L1 expression was defined based on the proportion of stained tumor cells using the tumor proportion score: < 1% (negative), ≥ 1% (positive) and ≥ 50% (strongly positive). Correlations between PD-L1 expression and T stage, pathological subtype, adenocarcinoma grade, spread through air space (STAS), vascular invasion, lymphatic invasion and driven genes were analyzed. RESULTS: There was almost no PD-L1 expression in AIS or MIA. However, PD-L1 expression was correlated with invasiveness of lung adenocarcinoma. The percentages of PD-L1 positive in IA1-IA3 were 7.22%, 11.29%, and 14.20%, respectively. The strongly positive rates of PD-L1 were 0.38%, 1.64%, and 3.70% in IA1-IA3, respectively. PD-L1 expression and positive rate were also associated with poor pathological subtype and poor biological behavior, such as adenocarcinoma Grade 3, micropapillary or solid dominant subtype, STAS and vascular invasion. Finally, PD-L1 positive rate seems also corrected with driven gene ALK, ROS-1 and KRAS. CONCLUSIONS: PD-L1 expression was positively correlated with the emergence of invasiveness and poor pathological subtype or biological behavior of early-stage lung adenocarcinoma. PD-L1 pathway may be involved in the early evolution of lung adenocarcinoma from AIS to IAC.

B4GALNT1 promotes progression and metastasis in lung adenocarcinoma through JNK/c-Jun/Slug pathway.

Lung adenocarcinoma (LUAD) is one of the most common types of cancer and has a low survival rate. ß-1,4-N-Acetyl galactosaminyltransferase 1 (B4GALNT1), which is involved in the synthesis of complex gangliosides, is highly expressed in the progression of various cancers. This study aimed to elucidate the biological functions of B4GALNT1 in LUAD progression and metastasis. We observed that B4GALNT1 overexpression showed enhanced cell migration and invasion in vitro, and promoted tumor metastasis, with reduced survival in mice. Mechanistically, B4GALNT1 regulated metastatic potential of LUAD through activating the JNK/c-Jun/Slug pathway, and with the form of its enzymatic activity. Clinical samples confirmed that B4GALNT1 expression was upregulated in LUAD, and B4GALNT1 was correlated with c-Jun/Slug expression, lymph node involvement, advanced clinical stage, and reduced overall survival. Collectively, our results suggest that B4GALNT1 promotes progression and metastasis of LUAD through activating JNK/c-Jun/Slug signaling, and with the form of its enzymatic activity.

Identification of immune-related gene signature predicting survival in the tumor microenvironment of lung adenocarcinoma.

The tumor microenvironment (TME) plays an essential role in the occurrence and progression of malignancy. The potential prognostic TME-related biomarkers of lung adenocarcinoma (LUAD) remained unclear, which were investigated in this research. The RNA-sequencing profiles and corresponding clinical parameters were extracted from TCGA and GEO databases, based on which the stromal and immune scores were calculated through the ESTIMATE algorithm. Overlapping differentially expressed genes between stromal and immune score group were analyzed by the LASSO and Random Forrest algorithms and validated in cases from our center. And a prognostic 8-gene signature was constructed using Cox regression. The infiltration of 22 hematopoietic cell phenotypes was assessed by the CIBERSORT algorithms. We found that female, elder patients, and solid predominant subtype had obviously higher stromal and immune scores. And patients with early stage LUAD received a prominently higher immune score. A high stromal or immune score meant a good prognosis. Subsequently, eight TME-related prognostic genes (ATAD5, CYP4F3, CYP4F12, ESPNL, FXYD2, GPX2, NLGN4Y, and SERPINC1) were identified by both LASSO regression and Radom Forest algorithms. High 8-gene signature group exhibited worse overall survival. Furthermore, B cell naïve, plasma cells, T cell follicular helper, and macrophages M1 were prominently more in high signature group. Nevertheless, fewer T cells CD4 memory resting, monocytes, and dendritic cell resting were identified in the high signature group. The composition of the tumor microenvironment significantly affected the prognosis of LUAD patients. We provided a new strategy for the exploration of prognostic TME-related biomarkers and immunotherapy.

Preoperative Computed Tomography-Guided Localization for Pulmonary Nodules with Glue and Dye.

BACKGROUND: This study was aimed to describe a new localization technique developed using medical glue and methylene blue dye, and characterized the localization results and postoperative outcome to evaluate its safety and usefulness. METHODS: This retrospective study was conducted at our center from January 2016 to April 2018. Totally 346 consecutive patients with 383 nodules who underwent preoperative computed tomography (CT)-guided medical glue and methylene blue dye localization, followed by lung resection, were enrolled in this study. RESULTS: Mean nodule size was 7.7 ± 3.7 mm (range: 2-30 mm), with a mean depth from pleura or fissure of 9.4 ± 9.3 mm (range: 0-60 mm). The success rate of CT-guided localization for pulmonary nodules was 99.5% (381/383) of the nodules. Localization-related complications included mild pneumothorax in 16 (4.6%) patients, mild hemothorax in 7 (2.0%) patients, and hemoptysis in 1 (0.3%) patient. Pleural reaction occurred in 7 (2.0%) and pain in 25 (7.2%) patients. All 383 nodules were resected successfully, with conversion to thoracotomy only required in two patients for adhesion and calcification of lymph nodes. All patients recovered well postoperatively, with a short postoperative hospital stay (3.7 ± 2.0 days) and a low complication rate (2.6%, 9/346). CONCLUSION: CT-guided medical glue and methylene blue dye localization prior to video-assisted thoracoscopic surgery (VATS) lung resection was a novel, safe, and technically feasible method, with a high-technical success rate and a low-complication rate. It allowed surgeons to easily locate and detect the nodules and estimate the surgical margin.

Video-assisted thoracoscopic total thymectomy: two-lung ventilation with artificial pneumothorax.

Objectives: Double-lumen endotracheal tube (DLET) and one-lung ventilation (OLV) have been generally accepted as the classic anesthetic method in video-assisted thoracoscopic total thymectomy (VATT). However, there are still some disadvantages of DLET. Two-lung ventilation (TLV) with single-lumen endotracheal tube (SLET) is considered to be an alternative in VATT to avoid these disadvantages. This study evaluated the safety and feasibility of TLV in VATT by comparing it with OLV cases.Material and methods: We retrospectively screened 198 patients who received TLV unilateral thoracic incision VATT and 117 patients who received OLV unilateral thoracic incision VATT. Perioperative data were analyzed, including surgical variables, intraoperative hemodynamic parameters, and postoperative complications and hospital stay.Results: No significant differences with regard to operative time (p = .146), postoperative hospital stay (p = .553), complications (p = .254), hemodynamic parameters and pulse oxygen saturation (SpO2) were found between TLV group and OLV group. However, end-tidal CO2 (EtCO2) was higher in TLV group at 15 min (39.95 ± 5.03 vs 38.70 ± 4.57, p = .021) and 30 min (41.91 ± 5.50 vs 38.91 ± 4.51, p < .001) after initiation of the operation.Conclusions: It is safe and feasible to adopt TLV using SLET with CO2 insufflation artificial pneumothorax in unilateral thoracic incision VATT.

Attenuation and Morphologic Characteristics Distinguishing a Ground-Glass Nodule Measuring 5-10 mm in Diameter as Invasive Lung Adenocarcinoma on Thin-Slice CT.

OBJECTIVE. The purpose of this study is to comprehensively investigate the role of multiple features seen on thin-section CT (TSCT) in the differential diagnosis of ground-glass nodules (GGNs) measuring 5-10 mm in diameter as invasive adenocarcinoma (IAC). MATERIALS AND METHODS. The TSCT features of 313 surgically diagnosed GGNs from 288 patients were retrospectively reviewed. A logistic regression model was applied, and the AUC values for the model and the size and attenuation of the lesions were compared using ROC curve analysis. RESULTS. A total of 247 lung adenocarcinomas in situ (AISs) and minimally invasive adenocarcinomas (MIAs) (hereafter referred to as the AIS-MIA group) and 66 invasive adenocarcinomas (IACs) were identified. Compared with the AIS-MIA group, the IAC groups were significantly larger in size and had higher attenuation values, a higher frequency of mixed GGNs (all p < 0.001), bubblelike appearance, spiculation, pleural indentation, different locations, and a lower frequency of clear tumor-lung interface (all p < 0.05). The logistic model included size and attenuation (both p < 0.001; odds ratio [OR], 1.872 and 1.009, respectively) as well as tumor-lung interface (p = 0.001; OR, 0.242), bubblelike appearance (p < 0.05; OR, 2.205), and type of nodule. The AUC value for the logistic model was 0.847 (sensitivity, 80.3%; specificity, 81.0%) and was significantly higher than that for size or attenuation (both p < 0.01). CONCLUSION. Radiologic features could help in the differential diagnosis of a GGN that was 5-10 mm in diameter as IAC versus AIS or MIA. GGNs larger than 8.12 mm and with attenuation greater than -449.52 HU were more likely to be IAC.

Relative space-based GIS data model to analyze the group dynamics of moving objects.

The relative motion of moving objects is an essential research topic in geographical information science (GIScience), which supports the innovation of geodatabases, spatial indexing, and geospatial services. This analysis is very popular in the domains of urban governance, transportation engineering, logistics and geospatial information services for individuals or industrials. Importantly, data models of moving objects are one of the most crucial approaches to support the analysis for dynamic relative motion between moving objects, even in the age of big data and cloud computing. Traditional geographic information systems (GIS) usually organize moving objects as point objects in absolute coordinated space. The derivation of relative motions among moving objects is not efficient because of the additional geo-computation of transformation between absolute space and relative space. Therefore, current GISs require an innovative approach to directly store, analyze and interpret the relative relationships of moving objects to support their efficient analysis. This paper proposes a relative space-based GIS data model of moving objects (RSMO) to construct, operate and analyze moving objects' relationships and introduces two algorithms (relationship querying and relative relationship dynamic pattern matching) to derive and analyze the dynamic relationships of moving objects. Three scenarios (epidemic spreading, tracker finding, and motion-trend derivation of nearby crowds) are implemented to demonstrate the feasibility of the proposed model. The experimental results indicates the execution times of the proposed model are approximately 5-50% those of the absolute GIS method for the same function of these three scenarios. It's better computational performance of the proposed model when analyzing the relative relationships of moving objects than the absolute methods in a famous commercial GIS software based on this experimental results. The proposed approach fills the gap of traditional GIS and shows promise for relative space-based geo-computation, analysis and service.

CMISG1701: a multicenter prospective randomized phase III clinical trial comparing neoadjuvant chemoradiotherapy to neoadjuvant chemotherapy followed by minimally invasive esophagectomy in patients with locally advanced resectable esophageal squamous cell carcinoma (cT3-4aN0-1M0) (NCT03001596).

BACKGROUND: Neoadjuvant chemoradiation is not recommended as an approach for treatment of esophageal squamous cell carcinoma due to its significant postoperative mortality. However, it is assumed the combination of neoadjuvant chemoradiation with minimally invasive esophagectomy (MIE) may reduce postoperative mortality, which can revive preoperative chemoradiation. No randomized controlled studies comparing neoadjuvant chemoradiation plus MIE with neoadjuvant chemotherapy plus MIE have been performed so far. The present trial is initiated to obtain valid information whether neoadjuvant chemoradiation plus MIE yields better survival without worse postoperative morbidity and mortality in the treatment of locally advanced resectable esophageal squamous cell carcinoma(cT3-4aN0-1M0). METHODS/DESIGN: CMISG1701 is a multicenter, prospective, randomized, phase III clinical trial, investigating the safety and efficacy of neoadjuvant chemoradiation plus MIE compared with neoadjuvant chemotherapy plus MIE. Patients with locally advanced resectable esophageal squamous cell carcinoma (cT3-4aN0-1M0) are eligible for the study. A total of 264 patients are randomly assigned to neoadjuvant chemoradiation (arm A) or neoadjuvant chemotherapy (arm B) with a 1:1 allocation ratio. The primary outcome is overall survival assessed with a minimum follow-up of 36 months. Secondary outcomes are progression-free survival, recurrence-free survival, postoperative pathologic stage, treatment-related complications, postoperative mortality as well as quality of life. DISCUSSION: The objective of this trial is to identify the superior protocol with regard to patient survival, treatment morbidity/mortality and quality of life between neoadjuvant chemoradiation plus MIE and neoadjuvant chemotherapy plus MIE. TRIAL REGISTRATION: NCT03001596 (December 17, 2016).

Prognostic value of visceral pleural invasion in non-small cell lung cancer: A propensity score matching study based on the SEER registry.

BACKGROUND AND OBJECTIVES: Visceral pleural invasion (VPI) is considered a poor prognostic factor in non-small cell lung cancer (NSCLC). We aimed to analyze the effect of VPI on cancer-specific survival, using propensity score matching (PSM) based on the Surveillance, Epidemiology, and End Results database. METHODS: We identified 9901 patients with T1-2N0-2M0 who received segmentectomy, lobectomy, or pneumonectomy. Ten covariates were included in PSM. The effect of VPI on survival was assessed, stratified by nodal status and tumor size. RESULTS: One-thousand and eighty-three pairs of patients were matched with standardized differences of covariates <10% after matching. We found that VPI was associated with a significantly worse survival (3-year survival rate: 84.6% vs. 75.9%, P = 0.005), especially in N0 (P < 0.001), but not in N1 or N2. No significant difference was observed between the extent of VPI. Moreover, VPI conferred a significantly worse survival in tumors >1-2 (P = 0.034) and >2-3 cm (P < 0.001), not ≤1, >3-4, or >4-5 cm in N0. CONCLUSIONS: VPI is a poor prognostic factor; but with increasing tumor size and nodal stage, its negative effect disappears. Our findings support current staging system which assigns higher T-stage for early >1-2 and >2-3 cm tumors.

Is minimally invasive esophagectomy beneficial to elderly patients with esophageal cancer?

BACKGROUND: Open esophagectomy (OE) in elderly patients with esophageal cancer is hazardous due to high surgical mortality and limited survival. The aim of this study was to explore whether minimally invasive esophagectomy (MIE) has perioperative or long-term benefits in elderly patients with esophageal cancer compared with OE. METHODS: Between February 2005 and June 2013, 407 patients older than 70 years underwent esophagectomy for esophageal cancer, including 89 who received MIE and 318 who received OE. A retrospective pair-matched study was performed to compare 116 patients (58 pairs) who underwent either OE or MIE. Patients were matched by age, sex, comorbidity, tumor location, histology, TNM stage, and operative approach. Perioperative and long-term outcomes were compared between the two groups. RESULTS: The overall incidence of postoperative complications was significantly lower in the MIE group than in the OE group (37.9 vs. 60.3 %, P = 0.016), especially incidence of pulmonary complications (20.7 vs. 39.7 %, P = 0.026). The mean length of hospital stay was also significantly shorter (10 days [range 7-70] vs. 12 days [range 8-106], P = 0.032). The perioperative mortality rate trended lower in the MIE group but was not significantly different (3.4 vs. 8.6 %, P = 0.435). Kaplan-Meier analysis showed that the median disease-specific survival time in the MIE group was significantly longer than in the OE group (>27 months [range 1-82] vs. 24 months [range 1-99], P = 0.003). No difference was found in overall survival (39 ± 8.9 vs. 22 ± 3.4 months, P = 0.070). CONCLUSION: In surgical management of elderly patients with esophageal cancer, MIE is associated with lower rates of morbidity and pulmonary complications as well as longer disease-specific survival time. Whether it provides benefit to patients' long-term survival requires further research.

PLK1 regulating chemoradiotherapy sensitivity of esophageal squamous cell carcinoma through pentose phosphate pathway/ferroptosis.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is the most common pathological type of esophageal cancer in China, accounting for more than 90 %. Most patients were diagnosed with advanced-stage ESCC, for whom new adjuvant therapy is recommended. Therefore, it is urgent to explore new therapeutic targets for ESCC. Ferroptosis, a newly discovered iron-dependent programmed cell death, has been shown to play an important role in carcinogenesis by many studies. This study explored the effect of Polo like kinase 1 (PLK1) on chemoradiotherapy sensitivity of ESCC through ferroptosis METHODS: In this study, we knocked out the expression of PLK1 (PLK1-KO) in ESCC cell lines (KYSE150 and ECA109) with CRISPR/CAS9. The effects of PLK1-knock out on G6PD, the rate-limiting enzyme of pentose phosphate pathway (PPP), and downstream NADPH and GSH were explored. The lipid peroxidation was observed by flow cytometry, and the changes in mitochondria were observed by transmission electron microscopy. Next, through the CCK-8 assay and clone formation assay, the sensitivity to cobalt 60 rays, paclitaxel, and cisplatin were assessed after PLK1-knock out, and the nude mouse tumorigenesis experiment further verified it. The regulation of transcription factor YY1 on PLK1 was evaluated by dual luciferase reporter assay. The expression and correlation of PLK1 and YY1, and their impact on prognosis were analyzed in more than 300 ESCC cases from the GEO database and our center. Finally, the above results were further proved by single-cell sequencing. RESULTS: After PLK1 knockout, the expression of G6PD dimer and the level of NADPH and GSH in KYSE150 and ECA109 cells significantly decreased. Accordingly, lipid peroxidation increased, mitochondria became smaller, membrane density increased, and ferroptosis was more likely to occur. However, with the stimulation of exogenous GSH (10 mM), there was no significant difference in lipid peroxidation and ferroptosis between the PLK1-KO group and the control group. After ionizing radiation, the PLK1-KO group had higher lipid peroxidation ratio, more cell death, and was more sensitive to radiation, while exogenous GSH (10 mM) could eliminate this difference. Similar results could also be observed when receiving paclitaxel combined with cisplatin and chemoradiotherapy. The expression of PLK1, G6PD dimer, and the level of NADPH and GSH in KYSE150, ECA109, and 293 T cells stably transfected with YY1-shRNAs significantly decreased, and the cells were more sensitive to radiotherapy and chemotherapy. ESCC patients from the GEO database and our center, YY1 and PLK1 expression were significantly positively-correlated, and the survival of patients with high expression of PLK1 was significantly shorter. Further analysis of single-cell sequencing specimens of ESCC in our center confirmed the above results. CONCLUSION: In ESCC, down-regulation of PLK1 can inhibit PPP, and reduce the level of NADPH and GSH, thereby promoting ferroptosis and improving their sensitivity to radiotherapy and chemotherapy. Transcription factor YY1 has a positive regulatory effect on PLK1, and their expressions were positively correlated. PLK1 may be a target for predicting and enhancing the chemoradiotherapy sensitivity of ESCC.

A Nomogram Based on Consolidation Tumor Ratio Combined with Solid or Micropapillary Patterns for Postoperative Recurrence in Pathological Stage IA Lung Adenocarcinoma.

BACKGROUND: Patients with pathological stage IA lung adenocarcinoma (LUAD) are at risk of relapse. The value of the TNM staging system is limited in predicting recurrence. Our study aimed to develop a precise recurrence prediction model for stage IA LUAD. MATERIALS AND METHODS: Patients with pathological stage IA LUAD who received surgical treatment at Zhongshan Hospital Fudan University were retrospectively analyzed. Multivariate Cox proportional hazards regression models were used to create nomograms for recurrence-free survival (RFS). The predictive performance of the model was assessed using calibration plots and the concordance index (C-index). RESULTS: The multivariate Cox regression analysis revealed that CTR (0.75 < CTR ≤ 1; HR = 9.882, 95% CI: 2.036-47.959, p = 0.004) and solid/micropapillary-predominance (SMPP; >5% and the most dominant) (HR = 4.743, 95% CI: 1.506-14.933, p = 0.008) were independent prognostic factors of RFS. These risk factors were used to construct a nomogram to predict postoperative recurrence in these patients. The C-index of the nomogram for predicting RFS was higher than that of the eighth T-stage system (0.873 for the nomogram and 0.643 for the eighth T stage). The nomogram also achieved good predictive performance for RFS with a well-fitted calibration curve. CONCLUSIONS: We developed and validated a nomogram based on CTR and SMP patterns for predicting postoperative recurrence in pathological stage IA LUAD. This model is simple to operate and has better predictive performance than the eighth T stage system, making it suitable for selecting further adjuvant treatment and follow-up.

Impact of a Ground-glass Opacity Component on c-Stage IA Lung Adenocarcinoma.

Studies have shown that tumors with ground-glass opacity (GGO) components are associated with favorable outcomes. However, this view should be confirmed in an international cohort. We aimed to verify the impact of a GGO component on clinical (c)-stage IA lung adenocarcinoma and to describe the biological discrepancies between the part-solid and pure-solid groups. We evaluated 1333 cases of surgically resected c-stage IA lung adenocarcinomas, including 484 part-solid and 849 pure-solid tumors. Furthermore, we matched the solid size between the 2 groups and examined 470 patients. We compared the prognoses between the 2 groups before and after matching. The prognostic and biological differences were described before and after matching. Compared with the pure-solid group, the part-solid group was associated with favorable outcomes [5-year overall survival (OS) 99.4% vs 87.6%, P < 0.001; 5-year recurrence-free survival (RFS) 96.9% vs 82.2%, P < 0.001]. Similar results were obtained after matching (5-year OS 98.9% vs 92.2%, P = 0.012; 5-year RFS 95.0% vs 88.5%, P = 0.007). Multivariable analyses revealed that GGO component appearance was a factor of better OS and RFS. The part-solid tumor, regardless of the size of the solid component, had a similar outcome to the pure-solid tumor of c-stage T1a classification. Also, more epidermal growth factor receptor, human epidermal growth factor receptor-2 mutations, and receptor tyrosine kinase ROS-1-positive were observed in the part-solid group. In comparison, more wild types and Kirsten-Ras were observed in the pure-solid group. Adenocarcinomas with a GGO component were associated with superior outcomes. The GGO component should be considereda new clinical T descriptor. Early-stage lung adenocarcinomas with and without a GGO component may be 2 distinct tumor types.

Ground glass nodules with scattered or eccentric island-shaped consolidations may have poor outcomes.

Background: To explore the effect of scattered or eccentric shaped types of ground glass opacity (GGO) on outcomes of patients with solid-dominant peripheral lung adenocarcinoma. Methods: We evaluated patients with solid-dominant peripheral lung adenocarcinoma, who underwent radical surgery at Zhongshan Hospital, Fudan University, between January 2013 and December 2015. Morphologically heterogeneous solid-dominant lung adenocarcinoma in imaging findings was based on the last preoperative computed tomography (CT) scans. Endpoints were recurrence-free survival (RFS) and overall survival (OS). Kaplan-Meier analysis and the log-rank test were used to estimate survival differences. Impact factors were assessed by univariable logistic regression analysis. Results: We retrospectively collected data from 200 patients, including 170 patients with central island-shaped CT imaging, 18 patients with scattered shaped CT imaging, and 12 patients with eccentric shaped CT imaging. Eleven patients experienced recurrence or metastases. Kaplan-Meier survival curves showed significant survival differences between the central island-shaped type and scattered shaped or eccentric shaped type for OS (c-stage IA: 5-year OS: 100% vs. 92.1%; HR = 0.019, p = 0.0025; p-stage IA: 100% vs. 95.2%; HR = 0.146, p = 0.1139) and RFS (c-stage IA: 5-year RFS: 100% vs. 59.7%; HR = 0.001, p < 0.0001; p-stage IA: 100% vs. 64.5%; HR < 0.001, p < 0.0001). Univariable logistic regression analysis showed that scattered and eccentric shaped types were related to poor outcomes (p < 0.012, odds ratio = 18.8). Conclusions: Relative spatial position of GGO and solid components may affect patient outcomes. Patients with scattered or eccentric shaped GGO may have a poor prognosis.

The development and validation of pathological sections based U-Net deep learning segmentation model for the detection of esophageal mucosa and squamous cell neoplasm.

Background: Deep learning methods have demonstrated great potential for processing high-resolution images. The U-Net model, in particular, has shown proficiency in the segmentation of biomedical images. However, limited research has examined the application of deep learning to esophageal squamous cell carcinoma (ESCC) segmentation. Therefore, this study aimed to develop deep learning segmentation systems specifically for ESCC. Methods: A Visual Geometry Group (VGG)-based U-Net neural network architecture was utilized to develop the segmentation models. A pathological image cohort of surgical specimens was used for model training and internal validation, with two additional endoscopic biopsy section cohort for external validation. Model efficacy was evaluated across several metrics including Intersection over Union (IOU), accuracy, positive predict value (PPV), true positive rate (TPR), specificity, dice similarity coefficient (DSC), area under the receiver operating characteristic curve (AUC), and F1-Score. Results: Surgical samples from ten patients were analyzed retrospectively, with each biopsy section cohort encompassing five patients. Transfer learning models based on U-Net weights yielded optimal results. For mucosa segmentation, the in internal validation achieved 93.81% IOU, with other parameters exceeding 96% (96.96% accuracy, 96.45% PPV, 96.65% TPR, 98.41% specificity, 96.81% DSC, 96.11% AUC, and 96.55% F1-Score). The tumor segmentation model attained an IOU of 91.95%, along with other parameters surpassing 95% (95.90% accuracy, 95.62% PPV, 95.71% TPR, 97.88% specificity, 95.81% DSC, 94.92% AUC, and 95.67% F1-Score). In the external validation for tumor segmentation model, IOU was 59.86% for validation database 1 (72.74% for accuracy, 76.03% for PPV, 77.17% for TPR, 83.80% for specificity, 74.89% for DSC, 71.83% for AUC, and 76.60% for F1-Score), and 50.88% for validation cohort 2 (68.03% for accuracy, 59.02% for PPV, 66.87% for TPR, 78.48% for specificity, 67.44% for DSC, 64.68% for AUC, and 62.70% for F1-Score). Conclusions: The models exhibited satisfactory results, paving the way for their potential deployment on standard computers and integration with other artificial intelligence models in clinical practice in the future. However, limited to the size of study, the generalizability of models is impaired in the external validation, larger pathological section cohort would be needed in future development to ensure robustness and generalization.

Mechanisms and characteristics of subcapsular sinus macrophages in tumor immunity: a narrative review.

Background and Objective: Lymph nodes constitute an integral component of the secondary lymphoid organs, housing a diverse population of macrophages. Macrophages exhibit heterogeneity in terms of localization, phenotype and ontogeny. Recent evidence has established that subcapsular sinus macrophages (SCSMs) are the initial cells exposed to antigens from afferent lymph vessels, playing a crucial role in the host immune response against invading pathogens and tumor cells. In order to summarize the role and mechanisms of SCSM in tumor immunity, this study systematically reviews research on SCSMs in tumor immunity. Methods: A systematic search was conducted in PubMed and Web of Science to identify articles investigating clinical significance and mechanisms of SCSMs. Study eligibility was independently evaluated by two authors based on the assessment of titles, abstracts and full-texts. Key Content and Findings: The narrative review included a total of 17 studies. Previous research consistently showed that a high level of SCSM in patients with various carcinomas is associated with a favorable long-term prognosis. SCSM acts as the front-line defender in antitumor activity, engaging in intricate communication with other immune cells. Moreover, SCSM could directly and indirectly modulate tumor immunity, and the integrity of SCSM layer is interrupted in disease status. Several studies explored the feasibility of targeting SCSM to activate immunity against tumors. However, the direct molecular interactions and alternation in signal pathway in the tumor immunity of SCSM are less well established in previous researches. Conclusions: This narrative review underscores the critical role of SCSM in tumor immunity. Future studies should focus on the deeper mechanism underlying SCSMs and explore their clinical applications.

Minimally invasive esophagectomy for esophageal squamous cell carcinoma: a case-control study of thoracoscope versus mediastinoscope assistance.

OBJECTIVE: Minimally invasive esophagectomy (MIE) has been widely applied for esophageal carcinoma treatment. Thoracoscope-assisted transthoracic esophagectomy (TATTE) and mediastinoscope-assisted transhiatal esophagectomy (MATHE) are two kinds of MIE. The objective of this study is to compare these two methods with respect to surgical safety and survival. METHODS: Single-institution experience with MATHE and TATTE was analyzed to assess morbidity, adequacy of tumor clearance, and survival. A pair-matched case-control study was performed to compare 54 patients who underwent either MATHE or TATTE between July 2000 and December 2009. Patients were matched by age, sex, comorbidity, forced expiratory volume in 1 s (FEV1), tumor location, and stage. RESULTS: Statistically significant differences between the MATHE group and the TATTE group were: shorter operative time for MATHE (194.4 min) versus TATTE (228.1 min), less blood loss during operation in the TATTE group (142.6 ml) versus the MATHE group (214.6 ml), and more lymph nodes retrieved in the TATTE group (19.1 nodes) versus the MATHE group (11.4 nodes). There was no difference in survival between the groups. CONCLUSIONS: MATHE and TATTE are both technically feasible. TATTE can provide better visibility. TATTE has less blood loss compared with MATHE. More adequate tumor clearance in terms of lymph node dissection can be achieved with TATTE.

Low dose theophylline showed an inhibitory effect on the production of IL-6 and IL-8 in primary lung fibroblast from patients with COPD.

Chronic obstructive pulmonary disease (COPD) is characterized by the abnormal and chronic lung inflammation. We hypothesized that lung fibroblasts could contribute to the local inflammation and investigated whether low dose theophylline had a beneficial effect on fibroblasts inflammation. Subjects undergoing lobectomy for bronchial carcinoma were enrolled and divided into COPD and control groups according to spirometry. Primary human lung fibroblasts were cultured from peripheral lung tissue distant to tumor tissue. There was a significant increase in both the mRNA expressions and protein levels for IL-6 and IL-8 in fibroblasts in COPD group, and the values were negatively correlated with lung function (P < 0.05). For COPD fibroblasts, the protein levels of IL-6 and IL-8 decreased from 993.0 ± 738.9 pg/mL to 650.1 ± 421.9 pg/mL (P = 0.014) and from 703.1 ± 278.0 pg/mL to 492.0 ± 214.9 pg/mL (P = 0.001), respectively, with 5 µg/mL theophylline treatment. In addition, theophylline at the dose of 5 µg/mL reduced the increased production of IL-6 and IL-8 induced by 1 µg/mL LPS in primary human lung fibroblasts. Our data suggest that lung fibroblasts participate in the chronic inflammation in COPD by releasing IL-6 and IL-8, and low dose theophylline can alleviate the proinflammatory mediators' production by fibroblasts.