PFKP confers chemoresistance by upregulating ABCC2 transporter in non-small cell lung cancer.

Background: Chemoresistance is a significant factor contributing to tumor recurrence and treatment failure in non-small cell lung cancer (NSCLC). The phosphofructokinase, platelet (PFKP) is highly expressed in NSCLC and is associated with a poor prognosis. Exploring the molecular mechanism and identifying effective strategies to overcome chemoresistance will have important clinical significance in improving the diagnosis and treatment of NSCLC. Methods: The correlation between PFKP and cisplatin resistance in NSCLC patients was assessed by organoids and immunohistochemistry. The impact of PFKP on the prognosis of NSCLC patients was analyzed using The Cancer Genome Atlas (TCGA) database. In NSCLC cell lines, the expression of PFKP was modulated using lentivirus, and cisplatin sensitivity was assessed by flow cytometry. Subsequently, the therapeutic effect of cisplatin was tested in BALB/c nude mice implanted subcutaneously with tumor cells. We performed luciferase assay and immunohistochemistry (IHC) to investigate the correlation between PFKP and ABCC2 (ATP-binding cassette sub-family C member 2). Results: Overexpression of PFKP was correlated with poorer survival rates in NSCLC patients who received platinum-based chemotherapy. Using NSCLC organoid, we found that the expression of PFKP was elevated in cisplatin (CDDP)-resistant patients with NSCLC. Overexpression of PFKP decreased the sensitivity of NSCLC cells to CDDP, while genetic inhibition of PFKP enhanced CDDP sensitivity both in vitro and in vivo. Furthermore, we found that PFKP upregulated ABCC2 by increasing the levels of phosphorylation of IκBα and nuclear p65 NF-κB subunit protein. Conclusions: PFKP can regulate the expression of ABCC2 through the activation of NF-κB, which in turn promotes chemoresistance in NSCLC. PFKP has the potential to be a personalized therapeutic target for NSCLC patients with chemoresistance.

Deep learning-based solid component measuring enabled interpretable prediction of tumor invasiveness for lung adenocarcinoma.

BACKGROUND: The nature of the solid component of subsolid nodules (SSNs) can indicate tumor pathological invasiveness. However, preoperative solid component assessment still lacks a reference standard. METHODS: In this retrospective study, an AI algorithm was proposed for measuring the solid components ratio in SSNs, which was used to assess the diameter ratio (1D), area ratio (2D), and volume ratio (3D). The radiologist measured each SSN's consolidation to tumor ratio (CTR) twice, four weeks apart. The area under the receiver-operating characteristic (ROC) curve (AUC) was calculated for each method used to discriminate an Invasive Adenocarcinoma (IA) from a non-IA. The AUC and the time cost of each measurement were compared. Furthermore, we examined the consistency of measurements made by the radiologist on two separate occasions. RESULTS: A total of 379 patients (the primary dataset n = 278, the validation dataset n = 101) were included. In the primary dataset, compared to the manual approach (AUC: 0.697), the AI algorithm (AUC: 0.811) had better predictive performance (P =.0027) in measuring solid components ratio in 3D. Algorithm measurement in 3D had an AUC no inferior to 1D (AUC: 0.806) and 2D (AUC: 0.796). In the validation dataset, the AI 3D method also achieved superior diagnostic performance compared to the radiologist (AUC: 0.803 vs 0.682, P =.046). The two measurements of the CTR in the primary dataset, taken 4 weeks apart, have 7.9 % cases in poor consistency. The measurement time cost by the radiologist is about 60 times that of the AI algorithm (P <.001). CONCLUSION: The 3D measurement of solid components using AI, is an effective and objective approach to predict the pathological invasiveness of SSNs. It can be a preoperative interpretable indicator of pathological invasiveness in patients with lung adenocarcinoma.

The SUPER reporting guideline suggested for reporting of surgical technique.

Background: Existing reporting guidelines pay insufficient attention to the detail and comprehensiveness reporting of surgical technique. The Surgical techniqUe rePorting chEcklist and standaRds (SUPER) aims to address this gap by defining reporting standards for surgical technique. The SUPER guideline intends to apply to articles that encompass surgical technique in any study design, surgical discipline, and stage of surgical innovation. Methods: Following the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) Network approach, 16 surgeons, journal editors, and methodologists reviewed existing reporting guidelines relating to surgical technique, reviewed papers from 15 top journals, and brainstormed to draft initial items for the SUPER. The initial items were revised through a three-round Delphi survey from 21 multidisciplinary Delphi panel experts from 13 countries and regions. The final SUPER items were formed after an online consensus meeting to resolve disagreements and a three-round wording refinement by all 16 SUPER working group members and five SUPER consultants. Results: The SUPER reporting guideline includes 22 items that are considered essential for good and informative surgical technique reporting. The items are divided into six sections: background, rationale, and objectives (items 1 to 5); preoperative preparations and requirements (items 6 to 9); surgical technique details (items 10 to 15); postoperative considerations and tasks (items 16 to 19); summary and prospect (items 20 and 21); and other information (item 22). Conclusions: The SUPER reporting guideline has the potential to guide detailed, comprehensive, and transparent surgical technique reporting for surgeons. It may also assist journal editors, peer reviewers, systematic reviewers, and guideline developers in the evaluation of surgical technique papers and help practitioners to better understand and reproduce surgical technique. Trial Registration: https://www.equator-network.org/library/reporting-guidelines-under-development/reporting-guidelines-under-development-for-other-study-designs/#SUPER.

Aberrant expression of miR-33a-3p/IGF2 in postmenopausal osteoporosis patients and its role and mechanism in osteoporosis.

BACKGROUND: Postmenopausal osteoporosis (PMOP), the most frequent bone-related disease, is characterized by bone loss and fragile fractures, which is related to low bone density (BMD). This study aimed to illustrate the expression and mechanism of miR-33a-3p in osteoporosis. METHODS: TargetScan and luciferase reporter assay were applied for verifying the relevance between miR-33a-3p and IGF2. Levels of miR-33a-3p, IGF2, Runx2, ALP and Osterix were checked using RT-qPCR and western blotting. hBMSCs proliferation, apoptosis and ALP activity were analyzed by MTT, flow cytometry (FCM) analysis and ALP detection kit, respectively. Moreover, the calcification of cells was assessed using Alizarin Red S staining. The average BMD was evaluated by dual-energy X-ray absorptiometry (DEXA) assay. RESULTS: IGF2 was a target of miR-33a-3p. The level of miR-33a-3p was substantially higher and IGF2 expression was memorably lower in the serum of osteoporosis patients than that in healthy volunteers. Our results also pointed out that miR-33a-3p was reduced and IGF2 expression was enhanced during osteogenic differentiation. We concluded that miR-33a-3p negatively regulated the level of IGF2 in hBMSCs. Besides, miR-33a-3p mimic inhibited the osteogenic differentiation of hBMSCs via inhibiting the level of Runx2, ALP and Osterix and decreasing ALP activity. IGF2 plasmid dramatically reversed the influence of miR-33a-3p mimic on IGF2 expression, hBMSCs proliferation and apoptosis, and osteogenic differentiation of hBMSCs. CONCLUSION: miR-33a-3p affected osteogenic differentiation of hBMSCs by targeting IGF2, indicating a potential use of miR-33a-3p as plasma biomarker and therapeutic target for postmenopausal osteoporosis.

Development and validation of prognostic nomogram for T1-3N0M0 non-small cell lung cancer after curative resection.

BACKGROUND: Radical resection plus lymph node dissection is a common treatment for patients with T1-3N0M0 non-small cell lung cancer (NSCLC). Few models predicted the survival outcomes of these patients. This study aimed to developed a nomogram for predicting their overall survival (OS). MATERIALS AND METHODS: This study involved 3002 patients with T1-3N0M0 NSCLC after curative resection between January 1999 and October 2013. 1525 Patients from Sun Yat-sen University Cancer Center were randomly allocated to training cohort and internal validation cohort in a ratio of 7:3. 1477 patients from ten institutions were recruited as external validation cohort. A nomogram was constructed based on the training cohort and validated by internal and external validation cohort to predict the OS of these patients. The accuracy and practicability were tested by Harrell's C-indexes, calibration plots and decision curve analyses (DCA). RESULTS: Age, sex, histological classification, pathological T stage, and HI standard were independent factors for OS and were included in our nomogram. The C-index of the nomogram for OS estimates were 0.671 (95% CI, 0.637-0.705),0.632 (95% CI, 0.581-0.683), and 0.645 (95% CI, 0.617-0.673) in the training cohorts, internal validation cohorts, and external validation cohort, respectively. The calibration plots and DCA for predictions of OS were in excellent agreement. An online version of the nomogram was built for convenient clinical practice. CONCLUSIONS: Our nomogram can predict the OS of patients with T1-3N0M0 NSCLC after curative resection. The online version of our nomogram offer opportunities for fast personalized risk stratification and prognosis prediction in clinical practice.

Prognostic impact of tumor spread through air spaces for T2aN0 stage IB non-small cell lung cancer.

BACKGROUND: Spread through air spaces (STAS) is a pattern of invasion recently identified in non-small cell lung cancer (NSCLC), with a poor prognosis. However, the predictive impact of STAS in stage IB NSCLC is not well understood. This investigation aims to assess the prognostic influence of STAS in stage IB NSCLC. METHODS: We reviewed 130 resected stage IB NSCLC between 2010 and 2015. Beyond the central tumor edge, lung parenchymal air gaps containing cancer cells were identified as STAS. In order to estimate recurrence-free survival (RFS) and overall survival (OS), Cox models and Kaplan-Meier techniques were utilized. Logistic regression analysis was employed to define the factors influencing STAS. RESULTS: Of 130 patients, 72 (55.4%) had STAS. STAS was a significant prognosticator. Kaplan-Meier method showed that STAS-positive patients had a significantly lower OS and RFS than STAS-negative patients (5-year OS, 66.5% vs. 90.4%, p = 0.02; 5-year RFS, 59.5% vs. 89.7%, p = 0.004) In a semiquantitative assessment, the RFS and OS were shorter in survival analysis when STAS increased (5-year RFS, 89.7%, no STAS, 61.8%, low STAS, 57.2%, high STAS, p = 0.013; 5-year OS, 90.4%, no STAS, 78.3%, low STAS, 57.2%, high STAS, p = 0.002). The association between STAS and poor differentiation, adenocarcinoma, and vascular invasion (p value was <0.001, 0.047, and 0.041, respectively) was statistically significant. CONCLUSIONS: The STAS is an aggressive pathological feature. RFS and OS could be significantly reduced by STAS, while it also serves as an independent predictor.

Prognosis and surgical outcomes of the total thymectomy versus thymomectomy in non-myasthenic patients with early-stage thymoma: A systematic review and meta-analysis.

Whether thymectomy (TM) or thymomectomy (TMM) is better for non-myasthenic patients with early-stage thymoma. We conducted a meta-analysis to compare the clinical outcomes and prognoses of non-myasthenic patients with early-stage thymoma treated using thymectomy versus thymomectomy. PubMed, Embase, Cochrane Library and CNKI databases were systematically searched for relevant studies on the surgical treatment (TM and TMM) of non-myasthenic patients with early-stage thymoma published before March 2022. The Newcastle-Ottawa scale was used to evaluate the quality of the studies, and the data were analyzed using RevMan version 5.30. Fixed or random effect models were used for the meta-analysis depending on heterogeneity. Subgroup analyses were performed to compare short-term perioperative and long-term tumor outcomes. A total of 15 eligible studies, including 3023 patients, were identified in the electronic databases. Our analysis indicated that TMM patients might benefit from a shorter duration of surgery (p = 0.006), lower blood loss volume (p < 0.001), less postoperative drainage (p = 0.03), and a shorter hospital stay (p = 0.009). There were no significant differences in the overall survival rate (p = 0.47) or disease-free survival rate (p = 0.66) between the two surgery treatment groups. Likewise, TM and TMM were similar in the administration of adjuvant therapy (p = 0.29), resection completeness (p = 0.38), and postoperative thymoma recurrence (p = 0.99). Our study revealed that TMM might be a more appropriate option in treating non-myasthenic patients with early-stage thymoma.

Sleeve Lobectomy After Neoadjuvant Chemoimmunotherapy Versus Chemotherapy for Squamous Cell Lung Cancer: A Multicenter, Retrospective Study.

Introduction: To analyze the feasibility and efficacy of sleeve lobectomy after neoadjuvant immunotherapy in multicenter patients with squamous cell lung cancer. Methods: We retrospectively identified patients who received neoadjuvant immunotherapy (n = 14) or chemotherapy alone (n = 33) at five thoracic surgery centers between 2018 and 2020. The primary end point was 30-day major complications. The secondary end point was major pathologic response. Multivariate analysis was performed with a log-binomial regression model adjusting potential risk factors. Results: All patients received induction therapy and underwent sleeve lobectomy without 90-day postoperative deaths. The distribution of age, sex, nutrition status, pulmonary and cardiac function, tumor stage, surgical approach, and location of the pulmonary lobe was well balanced between the two cohorts. In the immunotherapy cohort, two patients (14.3%) experienced a pulmonary major complication, whereas nine pulmonary major complications and one cardiac major complication (30.3%) occurred in the chemotherapy cohort (p = 0.302). Conclusions: Neoadjuvant immunotherapy in addition to chemotherapy did not increase 30-day risk of postoperative complications, and immunotherapy is a favorable factor affecting pathologic downstage and response. Therefore, sleeve lobectomy after induction chemoimmunotherapy appears safe and feasible.

Efficacy and safety of immune checkpoint inhibitors versus chemotherapy in the second-line treatment of advanced esophageal squamous cell carcinoma: a meta-analysis and systematic review.

Background: Esophageal cancer (EC) is the seventh most common cancer in the world, with 604,000 new cases diagnosed each year. Immune checkpoint inhibitors (ICIs) including programmed death ligand-1 (PD-L1) inhibitors have demonstrated a considerable survival advantage over chemotherapy in numerous randomized controlled trials (RCTs), particularly in patients with advanced esophageal squamous cell carcinoma (ESCC). In this analysis, we aimed to demonstrate that ICIs are more safe and effective than chemotherapy when used as a second-line treatment for advanced ESCC. Methods: Publications on the safety and efficiency of ICIs in advanced ESCC that were available prior to February 2022 were searched in the Cochrane Library, Embase, and PubMed databases. Studies with missing data were eliminated, and studies that compared the treatments between the immunotherapy group and chemotherapy group were included. Statistical analysis was carried out using RevMan 5.3, and risk and quality were evaluated with relevant evaluation tools. Results: Five studies met the inclusion criteria were selected, involving 1,970 patients with advanced ESCC. We compared chemotherapy and immunotherapy in the second-line treatment of advanced ESCC. ICIs considerably enhanced both the objective response rate (P=0.007) and overall survival (OS; P=0.001). However, the effect of ICIs on progression-free survival (PFS) was not significant (P=0.43). ICIs presented fewer grade 3-5 treatment-related adverse events (TRAEs), and there was also a suggested linkage between both PD-L1 expression and the effectiveness of the therapeutic intervention. Conclusions: For patients with advanced ESCC, ICIs are more effective and safer than chemotherapy, and thus have a higher treatment value.

Effect of preoperative radiotherapy on the prognosis of patients with stage cTxN0M0 esophageal squamous cell carcinoma: propensity score matching analysis based on SEER database.

Objective: The aim of this study was to investigate the effect of preoperative radiotherapy (RT) on overall survival (OS) in patients with stage cTxN0M0 esophageal squamous cell carcinoma (ESCC). Methods: A total of 467 patients with ESCC diagnosed as cTxN0M0 and undergoing esophagectomy between 2004 and 2016 were downloaded from the Surveillance, Epidemiology, and End Results (SEER) database. According to the presence or absence of preoperative RT, the patients were divided into preoperative RT group and non-preoperative RT group. Propensity score matching (PSM) was performed to equalize baseline levels between groups. Univariate and multivariate Cox regression analyses were used to compare the survival differences between the two groups. Results: Using PSM, 162 pairs of patients were selected. Preoperative RT was not a prognostic factor for OS in all patients with cTx stage. After PSM, for patients with cT1-2 stage, univariate Cox regression analysis showed that preoperative RT was an influencing factor of OS, and multivariate Cox regression analysis confirmed that preoperative RT was an independent predictor of OS. Compared with non-preoperative RT, preoperative RT significantly decreased OS (HR = 1.556, 95%CI 1.008-2.464, p = 0.046). For patients with cT3-4, univariate Cox regression analysis showed that preoperative RT was an influencing factor for OS, and multivariate Cox regression analysis determined that preoperative RT was independent predictors of survival. Compared with non-preoperative RT, preoperative RT significantly improved the OS (HR = 0.479, 95%CI 0.272-0.841, p = 0.010). Conclusion: For ESCC, preoperative RT can improve the OS of patients with cT3-4N0M0. However, preoperative RT is not suitable for patients with cT1-2N0M0.

Effects of Carbohydrase Supplementation on Growth Performance, Intestinal Digestive Enzymes and Flora, Glucose Metabolism Enzymes, and glut2 Gene Expression of Hybrid Grouper (Epinephelus fuscoguttatus♀ × E. lanceolatus♂) Fed Different CHO/L Ratio Diets.

An optimal carbohydrate-to-lipid (CHO: L) ratio facilitates fish growth and protein conservation, and carbohydrase promotes nutrient absorption. Therefore, an 8-week feeding trial was conducted to investigate the effects of carbohydrase supplementation on growth performance, intestinal digestive enzymes and flora, glucose metabolism enzymes and glut2 gene expression in juvenile hybrid grouper (Epinephelus fuscoguttatusâ™€× Epinephelus lanceolatus♂) fed different CHO: L ratios diets. L, M, and H represent CHO:L ratios of 0.91, 1.92 and 3.91, respectively. LE, ME, and HE represent CHO:L ratios of 0.91, 1.92, 3.91, respectively, supplemented with the same ratio of carbohydrase. Results showed that weight gain rate (WGR) and specific growth rate (SGR) reached a maximum in group M and were significantly enhanced by carbohydrase (p < 0.05). Crude lipid content decreased significantly with an increase in the dietary CHO:L ratio (p < 0.05). Significant increases in the trypsin (TRY) and amylase (AMS) activities and significant decreases in the lipase (LPS) activity were observed with increasing dietary CHO:L ratio, and the former two were significantly promoted by carbohydrase (p < 0.05). The content of liver and muscle glycogen increased significantly with the increasing dietary CHO:L ratio but decreased significantly after carbohydrase supplementation (p < 0.05). The glucokinase (GK), pyruvate kinase (PK), Phosphate 6 fructokinase-1 (PFK-1) and phosphoenolpyruvate kinase (PEPCK) activities increased significantly with increasing dietary CHO:L ratio (p < 0.05). Glut2 mRNA expression decreased significantly in liver and increased significantly in intestine with increasing dietary CHO:L ratio (p < 0.05). By linear discriminant analysis (LDA), the abundance of Alistipe was significantly higher in Group ME than in Group M. These results suggested that hybrid grouper can only moderately utilize dietary carbohydrate and lipid in diet, and a certain amount of high glycemic lipids occurred when fed with high-carbohydrate diets. By the weight gain for basis, the supplementation of carbohydrase in Group H with amylase, glycosylase, and pullulanase in a 1:1:1 ratio effectively lowered glycemic lipids, promoted the growth of grouper, digestive enzymes activities and carbohydrate metabolic enzyme, and glut2 gene expression in intestine, effectively balancing the negative effects of high-carbohydrate diet and improving the utilization of carbohydrate.

Survival Outcomes of Sublobectomy and Lobectomy in Elderly Patients with Peripheral Solid-Dominant Non-small Cell Lung Cancer.

BACKGROUND: According to the JCOG0802 study, there were many non-cancer-related deaths in the lobectomy group. Meanwhile, the median age of the enrolled patients in the JCOG0802 study was 67 years old. Whether this difference in perioperative outcomes and survival outcomes is related to age remains unknown. We aim to investigate whether the sublobectomy was comparable to lobectomy in elderly (≥ 75 years old) patients with peripheral solid-dominant [50% ≤ consolidation tumor ratio (CTR) ≤ 1] and diameter ≤ 2 cm non-small cell lung cancer (NSCLC). METHODS: We retrospectively included 10,830 patients who underwent surgery treatment at two large-volume medical centers, Taizhou Hospital of Zhejiang Province and Shanghai Chest Hospital, from January 2016 to January 2018. Of these, 164 patients aged ≥ 75 years, tumor ≤ 2 cm, and 50% ≤ CTR ≤ 1 who received lobectomy or sublobectomy were included in our study. The perioperative outcomes, survival analyses, analysis of death patterns, tumor recurrence patterns, and Cox regression analyses were performed. RESULTS: On perioperative outcomes, sublobectomy was associated with a shorter operation time (p < 0.001), and in terms of survival outcomes, the 5-year overall survival (OS, p = 0.85) and 5-year disease-free surivial (DFS, p = 0.58) did not differ significantly between the two groups. The Cox regression analyses showed that CTR value, visceral pleural infiltration, and smoking were independent risk factors for worse OS. Furthermore, tumor recurrence pattern and death patterns between the two groups did not differ significantly. CONCLUSIONS: Sublobectomy could achieve superior perioperative outcomes and equivalent oncological efficacy in comparison with lobectomy in elderly patients (≥ 75 years old) with peripheral solid-dominant and diameter ≤ 2 cm NSCLC.

Neoadjuvant Immunotherapy in Oncogene-Positive Non-Small Cell Lung Cancer: A Multicenter Study.

BACKGROUND: Preoperative immunotherapy has shed light on the management of resectable non-small cell lung cancer (NSCLC). However, whether neoadjuvant immunotherapy benefits patients with oncogene-positive NSCLC remains unknown. METHODS: Data were retrieved from 4 institutions in the period from August 2018 to May 2021. Eligible patients were aged ≥18 years with histologically confirmed stage IIA to stage IIIB (T1-2 N1-2 or T3-4 N0-2) NSCLC that was deemed to be surgically resectable. The neoadjuvant regimen included immune checkpoint inhibitors alone or in combination with platinum-based doublets. Surgical resection was performed 4 to 6 weeks after the first day of the last cycle of treatment. The primary end point was major pathologic response (MPR; ≤10% viable tumor cells). Analyses were categorized according to the patients' oncogene (EGFR, ALK, KRAS, MET, BRAF, ROS1, RET) status. RESULTS: Overall, 137 patients were identified; 46 (33%) patients had nonsquamous cell cancer, and 114 (83%) had stage IIIA/B disease. Oncogene alterations were identified in 22 (16%) patients, of whom only 2 patients (2/22 [9%]) had an MPR compared with 65 (65/115 [56.5%]) in the oncogene-negative population (P < .001). Similar results were retained after propensity score matching for age, sex, smoking status, histologic type, stage, and cycles of neoadjuvant treatment. Squamous cell carcinoma (odds ratio, 2.54; 95% CI, 1.08-5.99) and positive oncogene status (odds ratio, 0.13; 95% CI, 0.03-0.64) were found to be indicators for MPR by logistic regression. The 1-year event-free survival rate was 75.4% in the oncogene-positive group, which was not significantly different from 85.5% in the oncogene-negative population (P = .23). CONCLUSIONS: Patients with stage II-III oncogene-positive NSCLCs respond less than patients with oncogene-negative NSCLCs after neoadjuvant immunotherapy.

Reporting guidelines for surgical technique could be improved: a scoping review and a call for action.

OBJECTIVES: To identify reporting guidelines related to surgical technique and propose recommendations for areas that require improvement. STUDY DESIGN AND SETTING: A protocol-guided scoping review was conducted. A literature search of MEDLINE, the EQUATOR Network Library, Google Scholar, and Networked Digital Library of Theses and Dissertations was conducted to identify surgical technique reporting guidelines published up to December 31, 2021. RESULTS: We finally included 55 surgical technique reporting guidelines, vascular surgery (n = 18, 32.7%) was the most common among the clinical specialties covered. The included guidelines generally showed a low degree of international and multidisciplinary cooperation. Few guidelines provided a detailed development process (n = 14, 25.5%), conducted a systematic literature review (n = 13, 23.6%), used the Delphi method (n = 4, 7.3%), or described post-publication strategy (n = 6, 10.9%). The vast majority guidelines focused on the reporting of intraoperative period (n = 50, 90.9%). However, of the guidelines requiring detailed descriptions of surgical technique methodology (n = 43, 78.2%), most failed to provide guidance on what constitutes an adequate description. CONCLUSION: Our study demonstrates significant deficiencies in the development methodology and practicality of reporting guidelines for surgical technique. A standardized reporting guideline that is developed rigorously and focuses on details of surgical technique may serve as a necessary impetus for change.

Prognostic value of recurrence pattern in locally advanced esophageal squamous cell carcinoma: Results from the phase III trial NEOCRTEC5010.

OBJECTIVES: The prognosis of patients with locally advanced esophageal squamous cell carcinoma with different recurrence backgrounds is highly heterogeneous. This study aims to explore the effects of recurrence patterns on prognosis. METHODS: The phase III, multicenter, prospective NEOCRTEC5010 trial enrolled 451 patients with stage IIB-III esophageal squamous cell carcinoma randomly assigned to neoadjuvant chemoradiotherapy combined with surgery (NCRT group) or surgery alone (S group) and followed them long-term. We investigated the effects of recurrence patterns on survival in patients undergoing radical esophagectomy. RESULTS: In total, 353 patients were included in the study. The 5-year overall survival of patients with different recurrence patterns was significantly different: recurrence versus recurrence-free (17.8% vs 89.2%; P < .001), early recurrence versus late recurrence (4.6% vs 51.2%; P < .001), and distant metastasis versus locoregional recurrence (17.0% vs 20.0%; P = .666). Patients with early recurrence had significantly shorter survival after recurrence than those with late recurrence (hazard ratio, 1.541; 95% confidence interval, 1.047-2.268, P = .028). There was no significant difference in postrecurrence survival between patients with distant metastasis and locoregional recurrence (hazard ratio, 1.181; 95% confidence interval, 0.804-1.734; P = .396). Multivariate logistic analysis showed that pN1 stage, lymph node dissection <20, and lack of response to NCRT were independent risk factors for postoperative early recurrence. Multivariate Cox regression suggested that NCRT, age ≥60 years, early recurrence, and the pN1 stage were independent risk factors for shortened survival after recurrence. CONCLUSIONS: Prerecurrence primary tumor stage is inaccurate in predicting postrecurrence survival. In contrast, recurrence patterns can guide follow-up while also predicting postrecurrence survival. NCRT prolongs disease-free survival but is associated with a worse prognosis in patients with recurrence, especially early recurrence.

Factors influencing surgical choice and anxiety in patients with pulmonary nodules smaller than 8 mm.

Background: The detection of pulmonary nodules significantly impacts the lives and mental health of patients. Although the 2020 National Comprehensive Cancer Network (NCCN) guidelines recommend scheduled surveillance for nodules ≤8 mm, patients often opt to have their nodules surgically removed. Methods: A cross-sectional questionnaire was administered to patients with small pulmonary nodules who presented to a local grade 3 hospital with small pulmonary nodules and decided to receive surgery versus prescribed monitoring. The questionnaire included four aspects: (I) patient characteristics; (II) nodule-specific knowledge; (III) doctor-patient communication; and (IV) nodular-specific distress. Nodular-specific distress was measured by the Impact of Event Scale-Revised (IES-R). Results: A total of 234 (69%) patients responded to the survey and were included in the final analysis. Poor performance in activities of daily living (ADLs), the presence of solid nodules, multifocal disease, and a family history of lung cancer were significantly associated with reported anxiety. Most notably, facilitating patient choice for surgery was the computed tomography (CT) scan results, with reference to lung nodule size and number of nodules, where concerns related to lung nodule, cancer risk, and fear of surgery or death had a significant psychological impact on patients. Conclusions: In this cohort of patients who elected to have their small pulmonary nodules surgically removed, we identified key factors underlying their anxiety toward guideline recommended surveillance. Our findings will be useful for clinicians when discussing treatment options with their patients.

Extracorporeal membrane oxygenation (ECMO)-assisted surgery for traumatic bronchial rupture: a report of three cases.

Background: Traumatic tracheal rupture is a severe closed chest injury that often causes major respiratory and circulatory disturbances requiring emergency surgery. We have found that veno-venous extracorporeal membrane oxygenation (VV-ECMO) employs lung-protective ventilation strategies to facilitate lung rest, aiming to minimize the risk of ventilator-induced lung injury, while ensuring adequate oxygenation. Case Description: We presented 3 critically ill patients who presented with traumatic bronchial rupture between 2019 and 2021, and underwent emergency thoracic surgery with the help of VV-ECMO. The ECMO support time, the operative time, the duration of postoperative hospital stay, and the postoperative mechanical ventilation time were collected in this study. All patients were successfully treated and discharged home. The duration of surgery ranged from 135 to 180 min, the duration of ECMO use ranged from 98 to 123 h, the duration of postoperative ventilator use ranged from 5 to 8 days, and the duration of postoperative hospital stay ranged from 14 to 30 days. All 3 patients had good postoperative pulmonary re-expansion, with no residual tracheal or bronchial stenosis, and good physical activity following the surgery. Conclusions: We reported successful use of VV-ECMO in critically ill patients with traumatic bronchial rupture presenting in acute respiratory and circulatory failure. Performing emergency surgery with ECMO-assisted support can provide more time to stabilize the patient and ensure the safety of the procedure. However, considering the small sample size of this study, larger cohorts with long-term follow-up data are needed to further evaluate its application.

Silencing the expression of lncRNA SNHG15 may be a novel therapeutic approach in human breast cancer through regulating miR-345-5p.

Background: Long noncoding RNA (lncRNA) short nucleolar RNA host gene 15 (SNHG15) has been found to have an oncogenic function in numerous malignancies. Nevertheless, the biological function and regulatory mechanisms of SNHG15 in breast cancer have not been fully elucidated. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of SNHG15 and in MDA-MB-231 breast cancer cells. The expression of SNHG15 was silenced using small interfering RNA (siRNA) technology. The proliferation and migration of the cells were examined by colony formation assays, cell counting kit 8 (CCK-8) assays, and transwell assays. For the zebrafish xenograft injection experiments, cultured cells labelled with the fluorescent dye CM-DiI were injected into the perivitelline space of the larvae. Results: This present study revealed that the expression of lncRNA SNHG15 (lnc-SNHG15) was significantly upregulated in breast cancer cells, and its overexpression was associated with the tumor. The relative expression of lnc-SNHG15 could be downregulated using siRNAs, and silencing lnc-SNHG15 inhibited the proliferation and the migration of MDA-MB-231 cells. In vivo experiments using the zebrafish xenograft model showed similar results. Mechanistically, the knockdown effect of lnc-SNHG15 could be restored by inhibiting the expression of the miR-345-5p, confirming the negative regulation between lnc-SNHG15 and miR-345-5p. Interestingly, cisplatin treatment combined with SNHG15 knockdown effectively inhibited MDA-MB-231 cell proliferation and migration in the zebrafish xenograft compared to negative controls. Conclusions: In conclusion, lnc-SNHG15 knockdown increased miR-345-5p expression and negated cisplatin resistance in breast cancer cells, and thus, lnc-SNHG15 may be a potential novel target for breast cancer therapy.