Long survival after neoadjuvant and adjuvant camrelizumab plus chemotherapy and surgery in a patient with hepatoid adenocarcinoma of the lung: A case report.

Hepatoid adenocarcinoma of the lung (HAL) is a rare and aggressive subtype of lung cancer. The prognosis for patients with HAL is generally poor and currently, there are only limited treatment options. Here, we present a case of a 47-year-old male diagnosed with locally advanced-stage HAL who achieved a remarkably long disease-free survival after receiving neoadjuvant and adjuvant camrelizumab plus chemotherapy and surgery. This case highlights the potential of immunochemotherapy plus surgery in improving outcomes for patients with HAL.

Comparisons of short-term outcomes between robot-assisted, video-assisted, and open esophagectomy for resectable esophageal cancer after neoadjuvant treatment: a retrospective study.

Background: Robot-assisted esophagectomy (RAE), video-assisted minimally invasive esophagectomy (VAMIE), and open esophagectomy (OE) all have significant roles in the management of esophageal cancer (EC). Few studies have compared efficacy and safety between RAE, VAMIE, and OE for resectable EC after neoadjuvant treatment. Therefore, this study aimed to explore the short-term outcomes between RAE, VAMIE, and OE for resectable EC after neoadjuvant treatment. Methods: Ninety-eight patients were consecutively enrolled who underwent esophagectomy. A retrospective study was performed including 98 consecutive patients treated from January 2021 to August 2022 who received neoadjuvant treatment (including immunochemotherapy and chemoradiotherapy) followed by RAE, VAMIE or OE. Evaluated endpoints in the present study consisted of pathological outcomes, intraoperative and postoperative outcomes, as well as postoperative complications. Results: No significant differences were seen in the operating time, blood loss, length of intensive care unit (ICU) stay, R0 resection, and number of dissected lymph nodes between the three RAE, VAMIE, or OE groups. The achievement rate of right recurrent laryngeal nerve (RLN) lymph node removal (P=0.01) and the total cost (P<0.001) were higher in RAE. The postoperative hospital stay of OE was longer than the other two groups (P<0.05). There were no significant differences in postoperative complications. Conclusions: Compared to VAMIE, no clear benefit exists for RAE in the treatment of resectable EC after neoadjuvant therapy. OE resulted in a longer hospital stay. Although the rate of successful right RLN node removal was higher with RAE, the clinical relevance for this is yet unclear.

Efficacy of neoadjuvant immunochemotherapy and survival surrogate analysis of neoadjuvant treatment in IB-IIIB lung squamous cell carcinoma.

Until now, there are still few comparisons between neoadjuvant immunochemotherapy and chemotherapy as first-line treatment for patients with stage IB-IIIB lung squamous cell carcinoma (LUSC). In addition, the ability of pathologic response to predict long-term survival has still not been established. In this retrospective, controlled clinical trial, we ultimately enrolled 231 patients with stage IB to IIIB LUSC who received 2-4 cycles perioperative immunochemotherapy or chemotherapy alone, followed by resection. The primary endpoint of this study was pathological response. Secondary endpoints were disease-free survival (DFS), overall survival (OS), objective response rate (ORR), surgical resection rate and adverse events (AEs). The rates of major pathologic response (MPR) and pathologic complete response (pCR) in the immunochemotherapy group were 66.7% and 41.9%, respectively, which were both higher than that in the other group (MPR: 25.0%, pCR: 20.8%) (P < 0.001). The median DFS in the chemotherapy group was 33.1 months (95% CI 8.4 to 57.8) and not reached in the immunochemotherapy group (hazard ratio [HR] for disease progression, disease recurrence, or death, 0.543; 95% CI 0.303 to 0.974; P = 0.038). The median OS of the immunochemotherapy group was not achieved (HR for death, 0.747; 95% CI 0.373 to 1.495; P = 0.41), with the chemotherapy group 64.8 months (95% CI not reached to not reached). The objective response rate (ORR) of immunochemotherapy regimen was higher than that of the chemotherapy regimen (immunochemotherapy: 74.5%, chemotherapy: 42.3%, P < 0.001). About 60.8% in the immunochemotherapy group and 61.5% in the chemotherapy group eventually underwent surgery. The incidence of grade3 and 4 adverse events was 18.3% in the immunochemotherapy group and 2.6% in the chemotherapy group. MPR was significantly associated with DFS and OS (HR, 0.325; 95% CI 0.127 to 0.833; P = 0.019; and HR, 0. 906; 95% CI 0.092 to 1.008; P = 0.051, respectively). The C-index of MPR (0.730 for DFS, 0.722 for OS) was higher than the C-index of cPR (0.672 for DFS, 0.659 for OS) and clinical response (0.426 for DFS, 0.542 for OS). Therapeutic regimen (P < 0.001; OR = 7.406; 95% CI 3.054 to 17.960) was significantly correlated with MPR. In patients with stage IB to IIIB LUSC, neoadjuvant treatment with immunochemotherapy can produce a higher percentage of patients with a MPR and longer survival than chemotherapy alone. MPR may serve as a surrogate endpoint of survival to evaluate neoadjuvant therapy.

Does the time interval from neoadjuvant camrelizumab combined with chemotherapy to surgery affect outcomes for locally advanced esophageal squamous cell carcinoma?

BACKGROUND: There is currently no consensus on the optimal interval time between neoadjuvant therapy and surgery, and whether prolonged time interval from neoadjuvant therapy to surgery results in bad outcomes for locally advanced esophageal squamous cell carcinoma (ESCC). In this study, we aim to evaluate outcomes of time intervals ≤ 8 weeks and > 8 weeks in locally advanced ESCC. METHODS: This retrospective study consecutively included ESCC patients who received esophagectomy after neoadjuvant camrelizumab combined with chemotherapy at the Department of Thoracic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine. The primary endpoints were disease-free survival (DFS) and overall survival (OS), while the secondary endpoints were pathological response, surgical outcomes, and postoperative complications. RESULTS: From 2019 to 2021, a total of 80 patients were included in our study and were divided into two groups according to the time interval from neoadjuvant immunochemotherapy to surgery: ≤ 8 weeks group (n = 44) and > 8 weeks group (n = 36). The rate of MPR in the ≤ 8 weeks group was 25.0% and 27.8% in the > 8 weeks group (P = 0.779). The rate of pCR in the ≤ 8 weeks group was 11.4%, with 16.7% in the > 8 weeks group (P = 0.493). The incidence of postoperative complications in the ≤ 8 weeks group was 27.3% and 19.4% in the > 8 weeks group (P = 0.413). The median DFS in the two groups had not yet reached (hazard ratio [HR], 3.153; 95% confidence interval [CI] 1.383 to 6.851; P = 0.004). The median OS of ≤ 8 weeks group was not achieved (HR, 3.703; 95% CI 1.584 to 8.657; P = 0.0012), with the > 8 weeks group 31.6 months (95% CI 21.1 to 42.1). In multivariable analysis, inferior DFS and OS were observed in patients with interval time > 8 weeks (HR, 2.992; 95% CI 1.306 to 6.851; and HR, 3.478; 95% CI 1.481 to 8.170, respectively). CONCLUSIONS: Locally advanced ESCC patients with time interval from neoadjuvant camrelizumab combined with chemotherapy to surgery > 8 weeks were associated with worse long-term survival.

Prognostic implication of UBE2C + CD8 + T cell in neoadjuvant immune checkpoint blockade plus chemotherapy for locally advanced esophageal cancer.

BACKGROUND: Immune checkpoint blockers (ICBs) plus chemotherapy as neoadjuvant therapy for patients with esophageal cancer (EC) has gained substantial attention. This study aimed to investigate the early and mid-term outcome of neoadjuvant ICBs plus chemotherapy and discover immune-associated predictors of major pathological response (MPR) for locally advanced EC. METHOD: Patients with locally advanced EC who received neoadjuvant ICBs plus chemotherapy were retrospectively included between June 2019 to December 2021. Conjoint analysis of Bulk-RNA seq (GSE165252) and scRNA seq (GSE188900) were used to investigate potential prognostic factors and immunological mechanisms, then multiplexed immunofluorescence was applied to validate. RESULTS: 76 patients were included. A total of 21 (27.6 %) patients achieved MPR, with 13 (17.1 %) attaining a pathological complete response. Over a median follow-up of 1.8 years, 6 (7.9 %) patients died and 21 (27.6 %) experienced disease recurrence within 0.6 to 2.1 years after surgery. The overall survival rate and recurrence-free survival rate were 93.3 + 2.9 % and 84.8 + 4.2 % at 12 months, 90.8 + 3.7 % and 67.1 + 6.4 % at 24 months, and 90.8 + 3.7 % and 62.9 + 7.2 % at 36 months, respectively. Patients achieving MPR had a significantly lower risk of recurrence compared to non-responders (9.5 % vs 34.5 %, P = 0.017). Analysis of bulk-RNA seq and scRNA-seq revealed that UBE2C and UBE2C + CD8 + T cells were adverse prognostic factors. Immunohistochemistry demonstrated that the non-MPR group had a higher infiltration of UBE2C + immune cells than MPR group after neoadjuvant treatment. Multiplexed immunofluorescence confirmed that infiltrating UBE2C + CD8 + T cells in MPR group were significantly fewer than non-MPR group after neoadjuvant treatment, indicating their poor prognostic role for EC. CONCLUSIONS: Neoadjuvant ICBs plus chemotherapy shows promising efficacy in locally advanced EC, with MPR being a significant predictor of lower recurrence risk. Immunological analyses identified UBE2C + CD8 + T cells as adverse prognostic factors, suggesting their potential as biomarkers for patient stratification and treatment response.

Schizandrin A induces non-small cell lung cancer apoptosis by suppressing the epidermal growth factor receptor activation.

OBJECTIVE: The purpose of this study is to explore the biological mechanism of Schizandrin A (SchA) inducing non-small cell lung cancer (NSCLC) apoptosis. METHODS: The reverse molecular docking tool "Swiss Target Prediction" was used to predict the targets of SchA. Protein-protein interaction analysis was performed on potential targets using the String database. Functional enrichment analyses of potential targets were performed with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. The conformation of SchA binding to target was simulated by chemical-protein interactomics and molecular docking. The effect of SchA on the expression and phosphorylation level of EGFR was detected by Western blot. Lipofectamine 3000 and EGFR plasmids were used to overexpress EGFR. Apoptosis was tested with Annexin V-FITC and propidium iodide staining, and cell cycle was detected by propidium iodide staining. RESULTS: The "Swiss Target Prediction" database predicted 112 and 111 targets based on the 2D and 3D structures of SchA, respectively, of which kinases accounted for the most, accounting for 24%. Protein interaction network analyses showed that molecular targets such as ERBB family and SRC were at the center of the network. Functional enrichment analyses indicated that ERBB-related signaling pathways were enriched. Compound-protein interactomics and molecular docking revealed that SchA could bind to the ATP-active pocket of the EGFR tyrosine kinase domain. Laboratory results showed that SchA inhibited the phosphorylation of EGFR. Insulin could counteract the cytotoxic effect of SchA. EGFR overexpression and excess EGF or IGF-1 had limited impacts on the cytotoxicity of SchA. CONCLUSIONS: Network pharmacology analyses suggested that ERBB family members may be the targets of SchA. SchA can inhibit NSCLC at least in part by inhibiting EGFR phosphorylation, and activating the EGFR bypass can neutralize the cytotoxicity of SchA.

The efficacy and safety of percutaneous CT-guided iodine-125 brachytherapy combined with standard chemotherapy and brachytherapy alone for lung malignant nodule: a retrospective comparative cohort study.

Background: Lung metastasis nodules and advanced-stage tumors are often considered inoperable conditions for thoracic surgery and remain major challenges to clinical decision-making. Brachytherapy has its advantages in treating localized solid tumors, which can be used in combination with other treatments to achieve good safety and efficacy. In this study, we aimed to determine the outcomes of patients who received a combination of standard chemotherapy and computed tomography (CT)-guided percutaneous brachytherapy treatment for advanced-stage lung malignant lesions. Methods: We retrospectively collected data on patients with advanced lung cancer or lung metastasis nodules who underwent percutaneous CT-guided iodine-125 (125I) brachytherapy treatment. Patients were divided into two groups: Group A (brachytherapy with chemotherapy) and Group B (brachytherapy-only). Patients were reevaluated 1 month after the operation and then followed up every 3 months. The primary endpoint of this study was overall survival. Results: Our results showed that the mean age in Group B was higher (62.32±8.79 years) than that of Group A (68.59±11.46 years; P=0.018). Patients receiving a combination of chemotherapy and brachytherapy had a median survival time of 20.5 months [95% confidence interval (CI), 16.5-24.5], while those receiving brachytherapy alone had a median survival time of 16.4 months (95% CI, 11.7-21.1) (P=0.026). Patients who received additional thermal ablation treatment and those who did not have median survival times of 16.4 (95% CI, 10.2-22.7) and 17.0 months (95% CI, 13.3-20.8) (P=0.607). The median survival time for patients with oligo lesions was 19.8 months (95% CI, 15.7-23.9), while it was 10.5 months (95% CI, 7.5-13.4) for those who had multiple lesions. Conclusions: The combination of percutaneous CT-guided 125I brachytherapy and standard chemotherapy was superior to brachytherapy alone in terms of overall survival for patients with inoperable pulmonary lesions. Our results showed no benefit from additional adjuvant thermal ablation treatment. Patients with a single oligo nodule seem to have a better prognosis than those with multiple lesions.

Treatment patterns and clinical outcomes of patients with resectable non-small cell lung cancer receiving neoadjuvant immunochemotherapy: A large-scale, multicenter, real-world study (NeoR-World).

BACKGROUND: Neoadjuvant immunotherapy has ushered in a new era of perioperative treatment for resectable non-small cell lung cancer (NSCLC). However, large-scale data for verifying the efficacy and optimizing the therapeutic strategies of neoadjuvant immunochemotherapy in routine clinical practice are scarce. METHODS: NeoR-World (NCT05974007) was a multicenter, retrospective cohort study involving patients who received neoadjuvant immunotherapy plus chemotherapy or chemotherapy alone in routine clinical practice from 11 medical centers in China between January 2010 and March 2022. Propensity score matching was performed to address indication bias. RESULTS: A total of 408 patients receiving neoadjuvant immunochemotherapy and 684 patients receiving neoadjuvant chemotherapy were included. The pathologic complete response (pCR) and major pathologic response (MPR) rates of the real-world neoadjuvant immunochemotherapy cohort were 32.8% and 58.1%, respectively. Notably, patients with squamous cell carcinoma exhibited significantly higher pCR and MPR rates than those with adenocarcinoma (pCR, 39.2% vs 16.5% [P < .001]; MPR, 66.6% vs 36.5% [P < .001]), whereas pCR and MPR rates were comparable among patients receiving different neoadjuvant cycles. In addition, the 2-year rates of disease-free survival (DFS) and overall survival (OS) rate were 82.0% and 93.1%, respectively. Multivariate analyses identified adjuvant therapy as an independent prognostic factor for DFS (hazard ratio [HR], 0.51; 95% confidence interval [CI], 0.29-0.89; P = .018) and OS (HR, 0.28; 95% CI, 0.13-0.58; P < .001). A significantly longer DFS with adjuvant therapy was observed in patients with non-pCR or 2 neoadjuvant cycles. We observed significant benefits in pCR rate (32.4% vs 6.4%; P < .001), DFS (HR, 0.50; 95% CI, 0.38-0.68; P < .001) and OS (HR, 0.61; 95% CI, 0.40-0.94; P = .024) with immunotherapy plus chemotherapy compared to chemotherapy alone both in the primary propensity-matched cohort and across most key subgroups. CONCLUSIONS: The study validates the superior efficacy of neoadjuvant immunochemotherapy over chemotherapy alone for NSCLC. Adjuvant therapy could prolong DFS in patients receiving neoadjuvant immunochemotherapy, and patients with non-pCR or those who underwent 2 neoadjuvant cycles were identified as potential beneficiaries of adjuvant therapy.

Clinical evaluation of the impact of mediastinal tumour size on the subxiphoid approach video-assisted thoracoscopic surgery.

OBJECTIVES: The application of video-assisted thoracoscopic surgery (VATS) for relatively large mediastinal tumours (≥5.0 cm) has been a subject of debate, and few studies have investigated the subxiphoid approach VATS in different tumour size categories. The study aims to compare the efficacy of the subxiphoid approach VATS for achieving curative outcomes based on tumour size categories (<3.0, 3.0-4.9 and 5.0-10.0 cm). METHODS: A total of 165 patients with anterior mediastinal tumours who underwent surgery at our hospital between January 2018 and July 2022 were consecutively enrolled, categorized according to tumour size-group A (<3.0 cm): 58, group B (3.0-4.9 cm): 70 and group C (5.0-10.0 cm): 37. Clinical baseline data, intraoperative and postoperative outcomes, and postoperative complications were analysed. RESULTS: The study revealed significant differences in operation time among the 3 groups (group A: 103.4 ± 36.1, group B: 106.4 ± 35.2, group C: 127.4 ± 44.8; P < 0.05) as well as in the volume of drainage (group A: 273.3 ± 162.0, group B: 411.9 ± 342.6, group C: 509.7 ± 543.7; P < 0.05). However, no differences were seen in blood loss, drainage duration, postoperative hospital stay and duration of postoperative oral analgesics. Additionally, the incidence of postoperative complications did not exhibit significant differences across these groups. CONCLUSIONS: Subxiphoid approach VATS is considered a feasible and safe surgical method for large-sized anterior mediastinal tumours (5.0-10.0 cm) with no invasion to the surrounding tissues and organs.

Safety and efficacy of tislelizumab plus chemotherapy as preoperative treatment in potentially resectable locally advanced non-small-cell lung cancer patients.

OBJECTIVES: Locally advanced non-small-cell lung cancer (LA-NSCLC) requires more preoperative regiments in the era of immunotherapy. Tislelizumab was approved for first-line treatment for advanced lung cancer, bringing hope for preoperative therapy in LA-NSCLC. The aim of this study was to investigate the safety and efficacy of preoperative tislelizumab plus chemotherapy in LA-NSCLC. METHODS: The medical records at the First Affiliated Hospital of Zhejiang University were examined retrospectively from September 2019 to June 2022 for this descriptive single-arm cohort study. Patients with LA-NSCLC were treated with tislelizumab plus platinum-based dual-drug regimens for 2-6 cycles and regular imaging assessments were performed every 1-2 cycles. Data including demographic characteristics, clinicopathological staging, adverse events and surgery-related details were recorded in specifically designed forms. RESULTS: Forty patients met the inclusion criteria of the study and 23 patients underwent curative intent surgeries. Significantly clinical and pathological downstaging was observed, with the objective response rate being 65.00%, leading to a major pathological remission (MPR) rate of 56.52% and a pathological complete remission (pCR) rate of 34.78%. Grade 3-4 treatment-related adverse events occurred in 4 patients and no perioperative death occurred. The 1-year progress-free survival rate and the 1-year overall survival rate were 85.0% and 90.0%, respectively. CONCLUSIONS: Tislelizumab plus chemotherapy as preoperative therapy demonstrates promising antitumour activity for potentially resectable LA-NSCLC with high MPR, pCR and acceptable toxicity and survival.

The implications of N6-methyladenosine (m6A) modification in esophageal carcinoma.

Esophageal carcinoma (EC) is always diagnosed at advanced stage and its the mortality rate remains high. The patients usually miss the best opportunity for treatment because of non-specific symptoms and the survival rates are low. N6-methyladenosine (m6A) the predominant modification in eukaryotic messenger RNA(mRNA), serves vital roles in numerous bioprocess. This chemical modification is dynamic, reversible and consists of three regulators: m6A methyltransferases (writers), demethylases (erasers) and m6A-binding proteins (readers). Recently, a growing number of evidences have indicated relationships between m6A and EC. Whereas, lacking of cognition about the molecular mechanism of m6A modification in esophageal carcinoma. We will focus on the biological function roles of m6A modification in the tumorigenesis and development of EC. Recent studies showed that immunotherapy had a positive impact on EC. The relationship between m6A and immunotherapy in EC deserves further research and discussion. We will also discuss the potential clinical applications regarding diagnosis, treatment and prognosis of m6A modification for EC and provide perspectives for further studies.

Minimally invasive surgery for pleuroperitoneal communication complicating peritoneal dialysis.

OBJECTIVE: Pleuroperitoneal communication (PPC) is an uncommon but serious complication of continuous ambulatory peritoneal dialysis (CAPD). At present, there are many kinds of treatment options, with different effects. We describe our single-institutional experiences in the minimally invasive surgery of pleuroperitoneal communication complicating continuous ambulatory peritoneal dialysis in detail. METHODS: Our study consecutively enrolled 12 pleuroperitoneal communication patients complicating CAPD. All patients underwent direct closure of the defective diaphragm and mechanical rub pleurodesis under video-assisted thoracoscopy. What is more, pseudomonas aeruginosa injection was infused into the thoracic cavity postoperatively to further promote pleural adhesion, which was the innovation of our study. RESULTS: After 1.0-8.3 months of CAPD, all 12 patients presented hydrothorax in the right side. All these patients received surgery 7-179 days (18.0 ± 49.5 days) after onset. Bleb-like lesions situated on the diaphragm were discovered in all patients and three patients also had obvious hole on the surface of diaphragm. Pseudomonas aeruginosa injection was infused into the thoracic cavity postoperatively, and three cases showed fever with remission after 2-3 days of symptomatic treatment. The time from surgery to restarting CAPD ranged from 14 to 47 days, with a median of 20 days. There was no recurrence of hydrothorax and transformation to hemodialysis during the follow-up period (median: 7.5 months). CONCLUSIONS: Video-assisted thoracoscopic direct closure of the defective diaphragm and mechanical rub pleurodesis plus chemical pleurodesis using pseudomonas aeruginosa injection postoperatively is a safe and effective option for the treatment of pleuroperitoneal communication complicating continuous ambulatory peritoneal dialysis with 100% success rate.

The Safety and Efficacy of Preoperative Immunotherapy Combined with Chemotherapy in Patients with Stage IIIA-IIIB Lung Squamous Cell Carcinoma.

OBJECTIVE: Data on preoperative immunotherapy combined with chemotherapy in potentially resectable lung squamous cell carcinoma (LUSC) remain scarce. This study was designed to investigate the safety and efficacy of preoperative immunotherapy and chemotherapy for stage IIIA-IIIB LUSC. METHODS: This study consecutively enrolled stage IIIA-IIIB LUSC who received preoperative immunotherapy combined with chemotherapy between January 2019 and July 2021. Patients received two to four cycles of immunotherapy combined with platinum-based doublet chemotherapy (platinum + paclitaxel) before surgery. Patients were assessed radiographically every one to two cycles until surgery. Postoperative pathological evaluation was also performed. Follow-up was performed until at least 3 months after surgery. RESULTS: Sixty-five patients with stage IIIA-IIIB LUSC were enrolled. The objective response rate was 78.46% (51/65), and no patients had progressive disease. Fifty-seven patients underwent surgery, and 55 patients achieved R0 resection. There were no perioperative deaths. The rate of pathological complete response (pCR) was 31.58% (18/57) and major pathological response was 68.42% (39/57). The incidence of grade 3 and 4 adverse reactions was 21.21 and 1.54%, respectively. CONCLUSION: Perioperative immunotherapy combined with chemotherapy followed by surgical resection for male patients with stage IIIA-IIIB LUSC was effective with a tolerable toxicity profile.

Safety and effectiveness of neoadjuvant immunotherapy combined with chemotherapy followed by surgical resection in patients with stage I-IIIA small-cell lung cancer: a retrospective single-arm clinical trial.

Background: Immunotherapy, chemotherapy and surgery all have significant roles in the management of small-cell lung cancer (SCLC). Neoadjuvant immunotherapy combined with chemotherapy followed by surgery has shown encouraging efficacy for resectable SCLC with a good tolerability and considerable survival benefit. However, there are still few data on whether surgery for stage I-IIIA SCLC can be performed after immunotherapy with chemotherapy. Therefore, we investigated the safety and effectiveness of neoadjuvant immunotherapy combined with chemotherapy followed by surgery in patients with stage I-IIIA SCLC in the hope of adding new ideas to the treatment of SCLC. Methods: The study group comprised 19 patients with stage I-IIIA SCLC who received neoadjuvant immunotherapy and chemotherapy between 2019 and 2021. Patients received 2-4 cycles of immunotherapy combined with platinum-containing dual-drug chemotherapy (platinum + paclitaxel) before surgery. Imaging evaluation was performed every two cycles until surgery. Tumor response to neoadjuvant therapy, neoadjuvant treatment related adverse events, perioperative and postoperative complications, surgical resection rate, and degree of tumor regression were evaluated. We obtained follow-up data from the patients' regular examination or treatment in hospital. If we can't complete it, contacting patients by telephone or WeChat would be adopted by us. The follow-up was not terminated until 3 months after surgery. Results: The objective response rate (ORR) was 84.2% (16/19), and no patients had progressive disease (PD). Of the 10 patients who underwent surgery, and approximately 9 (90.0%) had R0 resection. There were no perioperative deaths, and 1 case of pyothorax. The rate of pathological complete remission (pCR) and major pathological response (MPR) was 30.0% (3/10), and 40.0% (4/10) respectively. Grade 3-4 adverse reactions comprised 1 case of anemia and 1 case of constipation. Conclusions: Neoadjuvant immunotherapy combined with chemotherapy followed by surgical resection for patients with stage I-IIIA SCLC is effective and safe with a high ORR and MPR rate, as well as a high R0 resection rate and a tolerable toxicity profile. Whether this regimen gives a survival benefit should be confirmed by further follow-up and larger, randomized controlled trials are required to confirm our findings.

Evaluation of the safety and effectiveness of neoadjuvant combined chemoimmunotherapy in the treatment of locally advanced esophageal squamous cell carcinoma: a retrospective single-arm cohort study.

Background: Transforming potentially resectable advanced esophageal squamous cell carcinoma (ESCC) into resectable ESCC through preoperative induction therapy is an important component of ESCC comprehensive treatment. Immune checkpoint inhibitor (ICI) therapy has been shown to have significant effects in the treatment of advanced ESCC, but its role in the neoadjuvant treatment of potentially resectable ESCC is unclear. This study aims to investigate the safety and effectiveness of camrelizumab combined with chemotherapy in the neoadjuvant treatment of ESCC. Methods: We recruited consecutive patients with potentially resectable ESCC who received preoperative camrelizumab in combination with chemotherapy. Data including demographic data, clinicopathological characteristics, neoadjuvant treatment regimens, lesion changes observed by imaging, and surgical details were retrospectively collected through specially designed forms. Toxic effects of neoadjuvant therapy on hematology, gastrointestinal tract, liver, kidney, skin, and thyroid were also collected. Imaging assessments were performed every 1-2 treatment cycles. Follow-up is based on the patient's regular admission to the hospital for examination and treatment, at least 3 months after surgery. Results: A total of 66 patients with locally advanced ESCC were included in this study, including 8 patients with stage II, 29 patients with stage III, and 29 patients with stage IVA. The objective response rate (ORR) of the neoadjuvant immunotherapy combined with chemotherapy was 75.76% (50/66), and no one developed disease progression. A total of 60 patients underwent surgery, and the R0 resection rate was 98.3% (59/60). The pathological complete remission (pCR) rate and the major pathological response (MPR) rate was 6.7% (4/60) and 20% (12/60), respectively. There were 14 cases of treatment-related adverse reactions >3, but no perioperative deaths occurred. Conclusions: Neoadjuvant immunotherapy combined with chemotherapy followed by surgical resection may be an available treatment for patients with locally advanced ESCC.

Fate decisions of breast cancer stem cells in cancer progression.

Breast cancer has a marked recurrence and metastatic trait and is one of the most prevalent malignancies affecting women's health worldwide. Tumor initiation and progression begin after the cell goes from a quiescent to an activated state and requires different mechanisms to act in concert to regulate t a specific set of spectral genes for expression. Cancer stem cells (CSCs) have been proven to initiate and drive tumorigenesis due to their capability of self-renew and differentiate. In addition, CSCs are believed to be capable of causing resistance to anti-tumor drugs, recurrence and metastasis. Therefore, exploring the origin, regulatory mechanisms and ultimate fate decision of CSCs in breast cancer outcomes has far-reaching clinical implications for the development of breast cancer stem cell (BCSC)-targeted therapeutic strategies. In this review, we will highlight the contribution of BCSCs to breast cancer and explore the internal and external factors that regulate the fate of BCSCs.

Construction and validation of a two-gene signature based on SUMOylation regulatory genes in non-small cell lung cancer patients.

BACKGROUND: Post-translational modification plays an important role in the occurrence and development of various tumors. However, few researches were focusing on the SUMOylation regulatory genes as tumor biomarkers to predict the survival for specific patients. Here, we constructed and validated a two-gene signature to predict the overall survival (OS) of non-small cell lung cancer (NSCLC) patients. METHODS: The datasets analyzed in this study were downloaded from TCGA and GEO databases. The least absolute shrinkage and selection operator (LASSO) Cox regression was used to construct the two-gene signature. Gene set enrichment analysis (GSEA) and Gene Ontology (GO) was used to identify hub pathways associated with risk genes. The CCK-8 assay, cell cycle analysis, and transwell assay was used to validate the function of risk genes in NSCLC cell lines. RESULTS: Firstly, most of the SUMOylation regulatory genes were highly expressed in various tumors through the R package 'limma' in the TCGA database. Secondly, our study found that the two gene signature constructed by LASSO regression analysis, as an independent prognostic factor, could predict the OS in both the TCGA training cohort and GEO validation cohorts (GSE68465, GSE37745, and GSE30219). Furthermore, functional enrichment analysis suggests that high-risk patients defined by the risk score system were associated with the malignant phenomenon, such as DNA replication, cell cycle regulation, p53 signaling pathway. Finally, the results of the CCK-8 assay, cell cycle analysis, and transwell assay demonstrated that the two risk genes, SAE1 and UBA2, could promote proliferation and migration in non-small cell lung cancer cells. CONCLUSIONS: The two-gene signature constructed in our study could predict the OS and may provide valuable clinical guidance for the treatment of NSCLC patients.

Value of Contrast-Enhanced Ultrasound in Adjusting the Classification of Chinese-TIRADS 4 Nodules.

OBJECTIVES: To explore the value of applying contrast-enhanced ultrasound (CEUS) in adjusting the classification of category 4 nodules in the Chinese-Thyroid Imaging Report and Data System (C-TIRADS). METHODS: The data of preoperative conventional ultrasound and CEUS examinations of 125 C-TIRADS 4 nodules in 109 patients were retrospectively analyzed. We divided the thyroid nodules into two groups based on whether recommend by the guide fine-needle aspiration (FNA). Group I included C-TIRADS 4A nodules with a maximum diameter ≤15 mm and C-TIRADS 4B and 4C nodules with a maximum diameter ≤10 mm, and Group II included C-TIRADS 4A nodules with a maximum diameter >15 mm and C-TIRADS 4B and 4C nodules with a maximum diameter >10 mm. In CEUS, thyroid nodules showing suspicious malignant features such as hypoenhancement or early washout were adjusted to a level higher in the C-TIRADS classification; thyroid nodules showing possible benign features such as iso- or hyperenhancement were adjusted to a level lower; and thyroid nodules showing no enhancement were adjusted to C-TIRADS 3. Taking the pathological results as the gold standard, the receiver operating characteristic (ROC) curves of the C-TIRADS classification before and after the adjustment based on CEUS were plotted, and the diagnostic efficiency was compared. RESULTS: The sensitivity, specificity, accuracy, and positive and negative predictive values of the C-TIRADS classification for the diagnosis of thyroid nodule malignancy before the adjustment based on the CEUS results were 83.6%, 63.8%, 74.4%, 72.7%, and 77.1%, respectively, and these values were 91.0%, 82.8%, 87.2%, 85.9%, and 88.9%, respectively, after the adjustment. The area under the ROC curve (AUC) was 0.737 and 0.869, respectively, showing a significant difference (Z = 3.288, P=0.001). The diagnostic efficiency of C-TIRADS classification after the adjustment based on the CEUS results in both groups was improved compared with the result before the adjustment, and the difference in Group II was significant (Z = 2.931, P=0.003). CONCLUSIONS: CEUS significantly improved the diagnostic performance in the adjustment of C-TIRADS 4 nodule classification, especially for the nodules which needs FNA recommended by the C-TIRADS.

The Value of Chinese Thyroid Imaging Report and Data System Combined With Contrast-Enhanced Ultrasound Scoring in Differential Diagnosis of Benign and Malignant Thyroid Nodules.

OBJECTIVES: To explore the diagnostic value of contrast-enhanced ultrasound (CEUS) combined with the Chinese Thyroid Imaging Reporting and Data System (C-TIRADS) for differentiation of benign and malignant thyroid nodules. METHODS: A retrospective analysis of the conventional ultrasound and CEUS data of 388 nodules in 355 patients who had undergone thyroid nodule resection was conducted. All nodules had clear pathological results. The CEUS observation indexes included the enhancement degree in the arterial phase (no enhancement, scant punctate-linear enhancement, mild enhancement, moderate enhancement, and high enhancement) and wash-out patterns (rapid wash-out, slow wash-out, and isochronous wash-out). Chi-square test between groups and receiver operating characteristic curves (ROC) were used to determine the malignant (+1 point) and benign (-1 point) observation indexes that were statistically significant for the differentiation between benign and malignant thyroid nodules. The CEUS and C-TIRADS malignant and benign indexes were combined to score and draw the ROC curve, which was compared with the ROC curve scored by C-TIRADS alone to compare the diagnostic efficacy of the two methods for differentiating between benign and malignant thyroid nodules. RESULTS: Among the CEUS observation indexes, mild enhancement and rapid wash-out were malignant indexes, while isochronous wash-out was a benign index. The best diagnostic cut-off value for the differentiation of benign and malignant thyroid nodules using the C-TIRADS score and the C-TIRADS and CEUS combined score (C-TIRADS + CEUS score) was 2. The sensitivity, specificity, positive predictive values (PPV), and negative predictive values (NPV) of the two methods were 79.97, 75.48, 82.9, 70.5%, and 89.7, 72.9, 83.3, 82.5%, respectively. The area under the curve values were 0.840 and 0.877 (P < .001), respectively. CONCLUSIONS: The CEUS feature of mild enhancement in the arterial phase and rapid wash-out pattern are suggestive of malignancy and isochronous wash-out pattern is suggestive of benignity. The C-TIRADS + CEUS score has a higher value for distinguishing benign from malignant thyroid nodules than the C-TIRADS score alone.

The Influence of Different Treatment Strategies on the Long-Term Prognosis of T1 Stage Esophageal Cancer Patients.

OBJECTIVE: To compare the long-term prognosis effects of non-esophagectomy and esophagectomy on patients with T1 stage esophageal cancer. METHODS: All esophageal cancer patients in the study were included from the National Surveillance Epidemiology and End Results (SEER) database between 2005-2015. These patients were classified into non-esophagectomy group and esophagectomy group according to therapy methods and were compared in terms of esophagus cancer specific survival (ECSS) and overall survival (OS) rates. RESULTS: A total of 591 patients with T1 stage esophageal cancer were enrolled in this study, including 212 non-esophagectomy patients and 111 esophagectomy patients in the T1a subgroup and 37 non-esophagectomy patients and 140 esophagectomy patients in the T1b subgroup. In all T1 stage esophageal cancer patients, there was no difference in the effect of non-esophagectomy and esophagectomy on postoperative OS, but postoperative ECSS in patients treated with non-esophagectomy was significantly better than those treated with esophagectomy. Cox proportional hazards regression model analysis showed that the risk factors affecting ECSS included race, primary site, tumor size, grade, and AJCC stage but factors affecting OS only include tumor size, grade, and AJCC stage in T1 stage patients. In the subgroup analysis, there was no difference in either ECSS or OS between the non-esophagectomy group and the esophagectomy group in T1a patients. However, in T1b patients, the OS after esophagectomy was considerably better than that of non-esophagectomy. CONCLUSIONS: Non-esophagectomy, including a variety of non-invasive procedures, is a safe and available option for patients with T1a stage esophageal cancer. For some T1b esophageal cancer patients, esophagectomy cannot be replaced at present due to its diagnostic and therapeutic effect on lymph node metastasis.