Impact of Lymph Node Dissection on Survival After Neoadjuvant Chemoradiotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma: From the Results of NEOCRTEC5010, a Randomized Multicenter Study.

OBJECTIVE: To clarify whether systemic LND influences the safety of surgery and the survival of patients with locally advanced esophageal squamous cell carcinoma (ESCC) after neoadjuvant chemoradiotherapy (nCRT). SUMMARY OF BACKGROUND DATA: Prognostic impact of systemic lymphadenectomy during surgery after nCRT for ESCC is still uncertain and requires clarification. METHODS: This is a secondary analysis of NEOCRTEC5010 trial which compared nCRT followed by surgery versus surgery alone for locally advanced ESCC. Relationship between number of LND and perioperative, recurrence, and survival outcomes were analyzed in the nCRT group. RESULTS: Three-year overall survival was significantly better in the nCRT group than the S group (75.2% vs 61.5%; P = 0.011). In the nCRT group, greater number of LND was associated with significantly better overall survival (hazard ratio, 0.358; P < 0.001) and disease-free survival (hazard ratio, 0.415; P = 0.001), but without any negative impact on postoperative complications. Less LND (<20 vs ≥20) was significantly associated with increased local recurrence (18.8% vs 5.2%, P = 0.004) and total recurrence rates (41.2% vs 25.8%, P = 0.027). Compared to patients with persistent nodal disease, significantly better survival was seen in patients with complete response and with LND ≥20, but not in those with LND <20. CONCLUSIONS: Systemic LND does not increase surgical risks after nCRT in ESCC patients. And it is associated with better survival and local diseasecontrol. Therefore, systemic lymphadenectomy should still be considered as an integrated part of surgery after nCRT for ESCC.

Discovery of Quinacrine as a Potent Topo II and Hsp90 Dual-Target Inhibitor, Repurposing for Cancer Therapy.

Topo II and Hsp90 are promising targets. In this study, we first verified the structural similarities between Topo IIα ATPase and Hsp90α N-ATPase. Subsequently, 720 compounds from the Food and Drug Administration (FDA) drug library and kinase library were screened using the malachite green phosphate combination with the Topo II-mediated DNA relaxation and MTT assays. Subsequently, the antimalarial drug quinacrine was found to be a potential dual-target inhibitor of Topo II and Hsp90. Mechanistic studies showed that quinacrine could specifically bind to the Topo IIα ATPase domain and inhibit the activity of Topo IIα ATPase without impacting DNA cleavage. Furthermore, our study revealed that quinacrine could bind Hsp90 N-ATPase and inhibit Hsp90 activity. Significantly, quinacrine has broad antiproliferation activity and remains sensitive to the multidrug-resistant cell line MCF-7/ADR and the atypical drug-resistant tumor cell line HL-60/MX2. Our study identified quinacrine as a potential dual-target inhibitor of Topo II and Hsp90, depending on the ATP-binding domain, positioning it as a hit compound for further structural modification.

Prognostic Impact of Postoperative Lymph Node Metastases After Neoadjuvant Chemoradiotherapy for Locally Advanced Squamous Cell Carcinoma of Esophagus: From the Results of NEOCRTEC5010, a Randomized Multicenter Study.

OBJECTIVE: To determine the prognostic impact of pathologic lymph node (LN) status and investigate risk factors of recurrence in esophageal squamous cell carcinoma (ESCC) patients with pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (NCRT). SUMMARY BACKGROUND DATA: There are no large-scale prospective study data regarding ypN status and recurrence after pCR in ESCC patients receiving NCRT. METHODS: The NEOCRTEC5010 trial was a prospective multicenter trial that compared the survival and safety of NCRT plus surgery (S) with S in patients with locally advanced ESCC. The relationships between survival and cN, pN, and ypN status were assessed. Potential prognostic factors in patients with ypN+ and pCR were identified. RESULTS: A total of 389 ESCC patients (NCRT: 182; S: 207) were included. Patients with pN+ in the S group and ypN+ in the NCRT group had decreased overall survival (OS) and disease-free survival (DFS) compared with pN0 and ypN0 patients, respectively. Partial response at the primary site [hazard ratio (HR), 2.09] and stable disease in the LNs (HR, 3.26) were independent risk factors for lower DFS, but not OS. For patients with pCR, the recurrence rate was 13.9%. Patients with distant LN metastasis had a median OS and DFS of 16.1 months and 14.4 months, respectively. Failure to achieve the median total dose of chemotherapy was a significant risk factor of recurrence and metastasis after pCR (HR, 44.27). CONCLUSIONS: Persistent pathologic LN metastasis after NCRT is a strong poor prognostic factor in ESCC. Additionally, pCR does not guarantee a cure; patients with pCR should undergo an active strategy of surveillance and adjuvant therapy.

The possibility of endoscopic treatment of cN0 submucosal esophageal cancer: results from a surgical cohort.

BACKGROUND: We analyzed the pathological characteristics and recurrence pattern of cN0 submucosal esophageal cancer after esophagectomy and conducted risk stratification to determine the feasibility of performing endoscopic resection for cN0pT1b esophageal squamous cell malignancies. METHODS: We retrospectively enrolled 167 patients who underwent right-sided transthoracic esophagectomy and extended thoracic/abdominal two-field lymphadenectomy. Patients with pathologically confirmed lymph node metastasis or tumor recurrence constituted the high-risk group for endoscopic submucosal resection, and the remainder were defined as low risk. Factors affecting lymphatic metastasis and long-term recurrence were identified by univariate and multivariate analyses. RESULTS: Postoperative pathology showed that five patients (5/167; 3%) had lymph node metastases. Follow-up ranged from 12-60 months, with a median of 29 months. A total of 17 patients (10.2%) had recurrences during follow-up, including three patients with pathologic nodal metastasis (pN +) found at surgery. Invasion depth, differentiation, and tumor size differed significantly in high-risk patients. Overall 3-year survival rates were 94.2% (low-risk) and 40.9% (high-risk) (p < 0.01). Twenty-one patients with sm1 cancer, high tumor differentiation, and tumor length < 2 cm had no lymph node metastasis or lymphovascular invasion, and none of these patients experienced recurrence. CONCLUSIONS: Endoscopic submucosal resection alone may be feasible for patients with small (≤ 2 cm) clinically N0 submucosal esophageal squamous cell carcinoma with low invasion depth (sm1) and higher differentiation, but prospective studies are required for confirmation. Other patients require surgical resection with extended two-field thoracic/abdominal lymphadenectomy.

Effect of Camrelizumab vs Placebo Added to Chemotherapy on Survival and Progression-Free Survival in Patients With Advanced or Metastatic Esophageal Squamous Cell Carcinoma: The ESCORT-1st Randomized Clinical Trial.

Importance: Standard first-line therapy for advanced or metastatic esophageal carcinoma is chemotherapy, but the prognosis remains poor. Camrelizumab (an anti-programmed death receptor 1 [PD-1] antibody) showed antitumor activity in previously treated advanced or metastatic esophageal squamous cell carcinoma. Objective: To evaluate the efficacy and adverse events of camrelizumab plus chemotherapy vs placebo plus chemotherapy as a first-line treatment in advanced or metastatic esophageal squamous cell carcinoma. Design, Setting, and Participants: This randomized, double-blind, placebo-controlled, multicenter, phase 3 trial (ESCORT-1st study) enrolled patients from 60 hospitals in China between December 3, 2018, and May 12, 2020 (final follow-up, October 30, 2020). A total of 751 patients were screened and 596 eligible patients with untreated advanced or metastatic esophageal squamous cell carcinoma were randomized. Interventions: Patients were randomized 1:1 to receive either camrelizumab 200 mg (n = 298) or placebo (n = 298), combined with up to 6 cycles of paclitaxel (175 mg/m2) and cisplatin (75 mg/m2). All treatments were given intravenously every 3 weeks. Main Outcomes and Measures: Coprimary end points were overall survival (significance threshold, 1-sided P < .02) and progression-free survival (significance threshold, 1-sided P < .005). Results: Of the 596 patients randomized (median age, 62 years [interquartile range, 56-67 years]; 523 men [87.8%]), 1 patient in the placebo-chemotherapy group did not receive planned treatment. A total of 490 patients (82.2%) had discontinued the study treatment. The median follow-up was 10.8 months. The overall survival for the camrelizumab-chemotherapy group was a median of 15.3 months (95% CI, 12.8-17.3; 135 deaths) vs a median of 12.0 months (95% CI, 11.0-13.3; 174 deaths) for the placebo-chemotherapy group (hazard ratio [HR] for death, 0.70 [95% CI, 0.56-0.88]; 1-sided P = .001). Progression-free survival for camrelizumab plus chemotherapy was a median of 6.9 months (95% CI, 5.8-7.4; 199 progression or deaths) vs 5.6 months (95% CI, 5.5-5.7; 229 progression or deaths) for the placebo-chemotherapy group (HR for progression or death, 0.56 [95% CI, 0.46-0.68]; 1-sided P < .001). Treatment-related adverse events of grade 3 or higher occurred in 189 patients (63.4%) in the camrelizumab-chemotherapy group and 201 (67.7%) in the placebo-chemotherapy group, including treatment-related deaths among 9 patients (3.0%) and 11 patients (3.7%), respectively. Conclusions and Relevance: Among patients with advanced or metastatic esophageal squamous cell carcinoma, the addition of camrelizumab to chemotherapy, compared with placebo and chemotherapy, significantly improved overall survival and progression-free survival. Trial Registration: ClinicalTrials.gov Identifier: NCT03691090.

Robot-assisted esophagectomy (RAE) versus conventional minimally invasive esophagectomy (MIE) for resectable esophageal squamous cell carcinoma: protocol for a multicenter prospective randomized controlled trial (RAMIE trial, robot-assisted minimally invasive Esophagectomy).

BACKGROUND: Currently, there are three main surgical approaches for resectable esophageal cancer: open transthoracic esophagectomy (OTE), conventional minimally invasive esophagectomy (MIE) and robot-assisted esophagectomy (RAE). Previous studies had demonstrated the better short-term outcomes in MIE or RAE when compared to OTE, respectively. However, to date, no prospective study was designed to compare these two minimally invasive approaches (MIE and RAE). The primary objective of this study is to compare the outcomes on survival, safety and efficacy, quality of life between RAE and MIE in the treatment for resectable esophageal squamous cell carcinoma (ESCC). METHODS: This study is designed as a multicenter, prospective, randomized, non-inferiority phase III clinical trial, investigating the safety and efficacy of RAE compared with MIE in the treatment of resectable ESCC. Eligible patients are randomly assigned to either RAE (n = 180) or MIE (n = 180) group. The follow-up visits will be scheduled at 3, 6, 9, and 12 months in the first two years, and then every 6 months until the end of the study. During the follow-up period, clinical data and quality of life questionnaires will be examined. The primary endpoint is the 5-year overall survival (OS). The secondary endpoints are 3-year OS, 5-year disease-free survival (DFS), short-term outcomes as well as quality of life. DISCUSSION: This is the first prospectively randomized controlled trial designed to compare RAE with MIE as surgical treatment for resectable ESCC. According to our hypothesis, RAE will result in at least similar oncologic outcomes and long-term quality of life, but with a shorter operation time, lower percentage of perioperative complications, lower blood loss, and shorter hospital stay when compared with MIE. This study started in July 2017. Follow-up will terminate after 5 years from the time when the last patient was enrolled. TRIAL REGISTRATION: ClinicalTrial.gov: NCT03094351 (March 29, 2017). The trial was prospectively registered.

Characterization of candidate odorant-binding proteins and chemosensory proteins in the tea geometrid Ectropis obliqua Prout (Lepidoptera: Geometridae).

Insects rely heavily on their sophisticated chemosensory systems to locate host plants and find conspecific mates. Although the molecular mechanisms of odorant recognition in many Lepidoptera species have been well explored, limited information has been reported on the geometrid moth Ectropis obliqua Prout, an economically important pest of tea plants. In the current study, we first attempted to identify and characterize the putative olfactory carrier proteins, including odorant-binding proteins (OBPs) and chemosensory proteins (CSPs). By analyzing previously obtained transcriptomic data of third-instar larvae, five OBPs and 14 CSPs in E. obliqua were identified. Sequence alignment, conserved motif identification, and phylogenetic analysis suggested that candidate proteins have typical characteristics of the insect OBP or CSP family. The expression patterns regarding life stages and different tissues were determined by quantitative real-time PCR. The results revealed that four transcripts (OBP2, OBP4 and CSP8, CSP10) had larvae preferential expression profiles and nine candidate genes (PBP1, OBP1 and CSP2, CSP4, CSP5, CSP6, CSP7, CSP11, and CSP13) were adult-biased expressed. Further specific tissue expression profile evaluation showed that OBP1, OBP2, OBP4, and PBP1 were highly expressed at olfactory organs, implying their potential involvement in chemical cue detection, whereas CSPs were ubiquitously detected among all of the tested tissues and could be associated with multiple physiological functions. This study provided a foundation for understanding the physiological functions of OBPs and CSPs in E. obliqua and will help pave the way for the development of a new environmental friendly pest management strategy against the tea geometrid moth.

Internal jugular vein pressure monitoring guided venous reconstruction could improve perioperative safety after superior vena cava resection for mediastinal tumors: a cohort study.

INTRODUCTION: After superior vena cava (SVC) resection, the decision on unilateral or bilateral reconstruction was mostly based on the expertise of surgeons without objective measurements. This study explored the use of internal jugular vein pressure (IJVP) monitoring to guide the SVC reconstruction strategy. METHODS: In a retrospective cohort, perioperative outcomes of unilateral and bilateral reconstruction based on surgeons' experience were compared. Then, IJVP threshold was measured when temporarily clamping the left innominate vein in a testing cohort. Venous reconstruction according to IJVP monitoring was performed in a prospective validation cohort afterward. Perioperative outcomes were compared between the prospective and the retrospective cohorts. For some interested variables, intuitive explanations would be given using Bayesian methods. Potential risk factors for postoperative complications were investigated by multivariable analysis. RESULTS: From March 2009 to September 2022, 57 patients underwent SVC reconstruction based on surgeons' experience. Bayesian analysis indicated a posterior probability of 80.49% that unilateral reconstruction had less blood loss than bilateral reconstruction (median 550 ml vs. 1200 ml). Cerebral edema occurred in two patients after unilateral reconstruction. In the testing cohort, median IJVP was 22.7 (18-27) cmH 2 O after temporary left innominate vein clamping in 10 patients. In the prospective cohort, unilateral reconstruction only was performed if the contralateral IJVP was <30 cmH 2 O in 16 patients. Bilateral reconstruction was performed if IJVP was ≥30 cmH 2 O after unilateral bypass in nine patients. No cerebral edema occurred in the prospective cohort. Less postoperative complications occurred in the prospective cohort than the retrospective cohort (12.0 vs. 38.6%, P =0.016). Upon multivariable analysis, IJVP-monitoring guided SVC reconstruction was associated with significantly less postoperative complications ( P =0.033). CONCLUSIONS: Intraoperative IJVP-monitoring is a useful strategy for selection of unilateral or bilateral SVC reconstruction and improving perioperative safety in patients with mediastinal tumors.

China Anti-Cancer Association Guidelines for the diagnosis, treatment, and follow-up of thymic epithelial tumors (2023).

Background: Thymic epithelial tumors (TETs) are a relatively rare type of thoracic tumors with higher incidence in Asians. The diagnosis and treatment pattern has long been based mainly on clinical experience and expert consensus. In recent years, with an increasing number of TETs detected in physical examinations, there is an urgent need to develop the guidelines that apply to the Chinese population. Thus, we intend to develop a holistic integrative guideline for TETs. Methods: Under the leadership of the Chinese Anti-Cancer Association (CACA) Mediastinal Tumor Committee, a multidisciplinary guideline development group was established. Systemic literature review and two rounds of questionnaires regarding key clinical issues were carried out. The grading of recommendations assessment, development and evaluation (GRADE) approach was used to rate the quality of evidence and the strength of recommendations. Results: The CACA guideline provides recommendations for the clinical differential diagnosis of anterior mediastinal lesions, management of asymptomatic small anterior mediastinal nodules, pathological classification and staging systems of TETs, as well as principles of surgery, neoadjuvant and adjuvant therapies, systemic therapies for advanced TETs, and follow-up strategies after surgical resection. Conclusions: This guideline provides holistic integrative management strategies for TETs and would be a useful tool for clinicians on decision-making.

A Re-Examination of Neoadjuvant Therapy for Thymic Tumors: A Long and Winding Road.

For most patients with advanced thymic epithelial tumors (TETs), a complete resection is a strong indicator of a better prognosis. But sometimes, primary surgery is unsatisfactory, and preoperative therapy is needed to facilitate complete resection. Neoadjuvant chemotherapy is the most used form of preoperative therapy. But studies on neoadjuvant chemotherapy have included mainly patients with thymoma; its efficacy in patients with thymic carcinoma is less known. Neoadjuvant chemoradiation has also been explored in a few studies. Novel therapies such as immunotherapy and targeted therapy have shown efficacy in patients with recurrent/metastatic TETs as a second-line option; their role as preoperative therapy is still under investigation. In this review, we discuss the existing evidence on preoperative therapy and the insight it provides for current clinical practice and future studies.

Clinical characteristics and survival of esophageal cancer patients: annual report of the surgical treatment in Shanghai Chest Hospital, 2017.

Background: Esophageal cancer remains a significant burden of lethal cancers worldwide, particularly in China. This is an annual report of Shanghai Chest Hospital (SCH) on surgical treatment for esophageal cancer patients in 2017. Methods: All patients who received surgical treatment for esophageal cancer at SCH in 2017 were given a detailed summary of clinical information based on the database of SCH. Kaplan-Meier method was used to present their survival, subgroup analyses, and multivariate Cox regression analysis were used to estimate the potential risk factors for prognosis. Results: In 2017, a total of 663 patients received surgical treatment (628 esophagectomies and 35 endoscopic resections) for esophageal cancer at SCH. Of the patients who underwent esophagectomy, 292 patients received perioperative treatment, majority of which was postoperative treatment (47.9%). Only 69 (10.4%) patients received preoperative treatment. Minimally invasive techniques were used in 444 (70.7%) patients and robotic-assisted esophagectomies were used in 130 (20.7%) patients. Complete resection (R0) was achieved in 90.3% of esophagectomy patients. The 5-year overall survival (OS) rate after esophagectomy was 52.5%. Conclusions: The 5-year OS of patients with esophageal cancer can reach 52.5% after surgical treatment in 2017 at SCH. The exact beneficiaries of neoadjuvant therapy are still unclear in the 2017 cohort.

Final analysis of camrelizumab plus chemotherapy for untreated advanced or metastatic esophageal squamous cell carcinoma: The ESCORT-1st trial.

BACKGROUND: The interim analysis of the randomized phase 3 ESCORT-1st study demonstrated significantly longer overall survival (OS) and progression-free survival (PFS) for camrelizumab-chemotherapy than placebo-chemotherapy in untreated advanced/metastatic esophageal squamous cell carcinoma (ESCC). Here, we present the final analysis of this study and investigate potential indicators associated with OS. METHODS: Patients were randomized 1:1 to receive camrelizumab (200 mg) or placebo, both in combination with up to six cycles of paclitaxel (175 mg/m2) and cisplatin (75 mg/m2). All treatments were administered intravenously every 3 weeks. The co-primary endpoints were OS and PFS assessed by the independent review committee. FINDINGS: As of April 30, 2022, the median OS was significantly longer in the camrelizumab-chemotherapy group compared to the placebo-chemotherapy group (15.6 [95% confidence interval (CI): 14.0-18.4] vs. 12.6 months [95% CI 11.2-13.8]; hazard ratio [HR]: 0.70 [95% CI 0.58-0.84]; one-sided p < 0.0001), with 3-year OS rates of 25.6% and 12.8% in the two groups, respectively. The 2-year PFS rates were 20.4% in the camrelizumab-chemotherapy group and 3.4% in the placebo-chemotherapy group. Adverse events were consistent with those reported in the interim analysis. Higher PD-L1 expression correlated with extended OS, and multivariate analysis identified sex and prior history of radiotherapy as independent indicators of OS. CONCLUSIONS: The sustained and significant improvement in efficacy with camrelizumab-chemotherapy compared to placebo-chemotherapy, along with the absence of accumulating or delayed toxicities, supports the long-term use of camrelizumab-chemotherapy as a standard therapy in untreated advanced/metastatic ESCC. FUNDING: This study was funded by Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Proteomic and comparative genomic analysis of two Brassica napus lines differing in oil content.

Ultrastructural observations, combined with proteomic and comparative genomic analyses, were applied to interpret the differences in protein composition and oil-body characteristics of mature seed of two Brassica napus lines with high and low oil contents of 55.19% and 36.49%, respectively. The results showed that oil bodies were arranged much closer in the high than in the low oil content line, and differences in cell size and thickness of cell walls were also observed. There were 119 and 32 differentially expressed proteins (DEPs) of total and oil-body proteins identified. The 119 DEPs of total protein were mainly involved in the oil-related, dehydration-related, storage and defense/disease, and some of these may be related to oil formation. The DEPs involved with dehydration-related were both detected in total and oil-body proteins for high and low oil lines and may be correlated with the number and size of oil bodies in the different lines. Some genes that corresponded to DEPs were confirmed by quantitative trait loci (QTL) mapping analysis for oil content. The results revealed that some candidate genes deduced from DEPs were located in the confidence intervals of QTL for oil content. Finally, the function of one gene that coded storage protein was verified by using a collection of Arabidopsis lines that can conditionally express the full length cDNA from developing seeds of B. napus.

[Comparison of surgical approaches for thymic disorders: feasibility of VATS thymectomy and comparison with small incision and median sternotomy].

OBJECTIVES: To evaluate the feasibility and safety of video-assisted thoracoscopic surgery (VATS), and to compare surgical results of VATS with standard median sternotomy (MS) and other minimal invasive approaches through various small incisions (SI). METHODS: Totally 111 patients underwent surgery for thymic disorders (maximun diameter ≤ 5 cm, clinical stage I-II for thymic tumors) during March 2010 to June 2012 was retrospectively reviewed. There were 46 male and 65 female patients with a mean age of (51 ± 15) years.Resection via VATS was carried out in 47 patients, via SI in 26 patients, and via MS in 38 patients. Demographic characteristics, operation time, number and cause of conversion, blood loss during operation, duration and amount of chest tube drainage, transfusion, morbidity, and length of hospital stay (LHS) were compared between the three groups. RESULTS: Of the 111 patients, 79 patients had thymic epithelia tumors (stage I 32 patients, stage II 39 patients, stage III 8 patients), 31 patients had benign cysts and 1 patient had tuberculosis.In the VATS group, there were 3 conversions among 38 patients through right-side approach, and 4 conversions among 9 patients through left-side approach. The causes for conversion included dense pleura adhesion, invasion of tumor into adjacent structures (pericardium, lung, or great vessels), and injury of the left inominate vein. There was no significant difference in operative time, blood loss or transfusion during operation, duration or amount of postoperative chest tube drainage among the 3 groups (P > 0.05). Average LHS was significantly shorter in the VATS group (5.7 ± 1.7) days than in the SI group (7.5 ± 2.2) days and the MS group (8.2 ± 1.9) days (F = 3.759, P = 0.002). Total thymectomy was performed in 74 patients, 25 patients (53.2%, 25/47) in VATS group, 11 patients (42.3%, 11/26) in SI group, and 38 patients (100%, 38/38) in MS group. The reset of the patients received tumor resection and partial thymectomy. Among all the subgroups, LHS was the shortest in VATS total thymectomy patients (5.0 ± 1.4) days (F = 5.844, P = 0.001). There was no perioperative mortality. The only major morbidity was a postoperative bleeding necessitating reintervention in SI group. CONCLUSIONS: VATS for benign thymic lesions and early-stage thymic tumors is safe and feasible.It is associated with shorter hospital stay compared with other minimal invasive approaches or standard sternotomy.

[Recurrence pattern of histological node-negative squamous cell carcinoma of the thoracic esophagus after extended radical esophagectomy with lymphadenectomy].

OBJECTIVE: To analyze the clinical and pathologic influencing factors of early recurrence in patients with histological node-negative (pN0 stage) esophageal squamous cell carcinoma after radical esophagectomy. METHODS: A retrospective study on 112 consecutive pN0 stage esophageal squamous cell carcinoma patients who underwent esophagectomy with lymphadenectomy by the same surgical team from January 2004 to December 2010. There were 92 male and 20 female patients, aging from 36 to 80 years with a mean age of 60.3 years. The Cox proportional hazards model was used to determine the independent risk factors for recurrence within 3 years after the operation. RESULTS: Recurrence was recognized in 45 patients (40.2%) within 3 years after operation. The median time to tumor recurrence was 17.4 months. Locoregional recurrence was found in 38 patients (33.9%), and hematogenous metastasis in 7 patients (6.3%). Recurrence closely correlated with tumor location, grade of differentiation, pT stage and pathologic stage (χ(2) = 6.380 to 18.837, P < 0.05). The Cox multivariate analysis showed that tumor location (RR = 1.092, P = 0.049) and pT3-4a stage (RR = 3.296, P = 0.017) were independent risk factors for postoperative locoregional recurrence. CONCLUSIONS: The most common recurrence pattern of patients with pN0 esophageal squamous cell carcinoma would develop recurrence within 3 years after operation is locoregional recurrence. Upper/middle thoracic location and pT3-4a stage are independent risk factors for locoregional recurrence of pN0 esophageal squamous cell carcinoma after operation.

A uniport subxiphoid approach with a modified sternum retractor is safe and feasible for anterior mediastinal tumors.

Background: Minimally invasive surgery has been used to treat anterior mediastinal tumors. This study sought to describe a single team's experience of uniport subxiphoid mediastinal surgery using a modified sternum retractor. Methods: Patients who underwent uniport subxiphoid video-assisted thoracoscopic surgery (USVATS) or unilateral video-assisted thoracoscopic surgery (LVATS) from September 2018 to December 2021 were retrospectively enrolled in this study. A 5-cm vertical incision approximately 1-cm caudal to the xiphoid process was usually made followed by the installment of a modified retractor, which was able to raise the sternum by 6-8 cm. Next, the USVATS was performed. In the unilateral group, 3 1-cm incisions were usually made, among which, 2 are made in the 2nd or 3rd and 5th intercostal anterior axillary line, and the 3rd was made in the 5th intercostal midclavicular line. In some instances, an additional subxiphoid incision was made to remove the large tumors. All the clinical and perioperative data, including the prospectively recorded visual analogue scale (VAS) score, were analyzed. Results: In total, 16 patients who underwent USVATS and 28 patients who underwent LVATS were enrolled in this study. With the exception of tumor size (USVATS 7.9±1.6 cm vs. LVATS 5.1±2.4 cm, P<0.001), the baseline data of the patients in the 2 groups were comparative. Blood loss in surgery, conversion, draining duration, postoperative stay, postoperative complications, pathology and tumor invasion were similar between the 2 groups. Although the operation time was significantly longer in the USVATS group than the LVATS group (115±19 vs. 83±30 min, P<0.001), the VAS score at 1st postoperative day (1.9±1.1 vs. 3.1±1.1, P<0.001) and moderate pain level (a VAS score >3) (6.3% vs. 32.1%, P=0.049) were better in the USVATS group than the LVATS group. Conclusions: Uniport subxiphoid mediastinal surgery is a feasible and safe procedure, especially for large tumors. Our modified sternum retractor is especially helpful during uniport subxiphoid surgery. Compared to lateral thoracic surgery, this approach has the advantages of less injury and lower postoperative pain, which may lead to a faster recovery. However, its long-term follow-up outcomes need to be observed.

Minimally Invasive Thymectomy Could Be Attempted for Locally Advanced Thymic Malignancies: A Real-World Study With Propensity Score-Matched Analysis.

INTRODUCTION: Increasing evidence supports minimally invasive thymectomy (MIT) for early stage thymic malignancies than open median sternotomy thymectomy (MST). Nevertheless, whether MIT could be attempted for locally advanced disease remains unclear. METHODS: The clinical data of consecutive patients with stage T2-3NxM0 (eighth edition TNM staging) thymic malignancies who underwent MIT or MST were identified from a prospectively maintained database. The co-resected structures were rated with a resection index to evaluate surgical difficulty. The impact of surgical approach on treatment outcomes was investigated through propensity score-matched analysis and multivariable analysis. RESULTS: From January 2008 to December 2019, a total of 128 patients were included; MIT was initially attempted in 58 (45.3%) cases, and eight (13.8%) were converted to MST during surgery. The conversion group had similar perioperative outcomes to the MST group, except for a longer operation time. After propensity score matching, the resection index scores were similar between the MIT and MST groups (3.5 versus 3.7, p = 0.773). The MIT group had considerably less blood loss (p < 0.001), fewer postoperative complications (p = 0.048), a shorter duration of chest drainage (p < 0.001), and a shorter hospitalization duration (p < 0.001) than the MST group. The 5-year freedom from recurrence rate was not different between the two groups (78.2% versus 78.5%, p = 0.942). In multivariable analysis, surgical approach was not associated with freedom from recurrence (p = 0.727). CONCLUSIONS: MIT could be safely attempted in carefully selected patients with locally advanced thymic tumors. Conversion did not compromise the surgical outcomes. Patients may benefit from the less traumatic procedure and thus better recovery, with comparable long-term oncologic outcomes.

[Microbial remediation of cadmium-contaminated soils and its mechanisms: a review].

Excessive levels of cadmium (Cd) in soil exert serious negative impacts on soil ecosystems. Microorganisms are a common component of soil and show great potential for mitigating soil Cd. This review summarizes the application and remediation mechanisms of microorganisms, microbial-plants, and microbial-biochar in Cd-contaminated soil. Microorganisms such as Bacillus, Acinetobacter, Pseudomonas, and arbuscular mycorrhizal fungi (AMF) can change the biological validity of Cd through adsorption, mineralization, precipitation and dissolution. Different factors such as pH, temperature, biomass, concentration, and duration have significant effects on Cd bioavailability by microorganisms. Pseudomonas, Burkholderia, and Flavobacterium can promote the uptake of Cd2+ by hyperaccumulator through promotion and activation. Biochar, a soil amendment, possesses unique physicochemical properties and could act as a shelter for microorganisms in agriculture. The use of combined microbial-biochar can further stabilize Cd compared to using biochar alone.

Effect of Different Modification Methods on the Adsorption of Manganese by Biochar from Rice Straw, Coconut Shell, and Bamboo.

The adsorption capacity of pristine biochar without modification is usually low. In this experiment, we comprehensively evaluated the adsorption of Mn(II) by biochar with different modification methods from different biomass. The biochar from rice straw, coconut shell, and bamboo was produced by pyrolysis at 600 °C under nitrogen and then modified with HNO3, NaOH, and Na2S, respectively. The results showed that the adsorption capacities of these modified biochar samples were in the order Biochar-NaOH > Biochar-Na2S > Biochar-HNO3. Among the three modification methods, biochar modified with NaOH is the optimum for the adsorption of Mn(II). However, the same method of modification has different effects on different biomass feedstocks. Rice straw: R-C > R-NaOH-C > R-Na2S-C > R-HNO3-C; coconut shell: C-NaOH-C > C-Na2S-C > C-HNO3-C > C-C; bamboo: B-NaOH-C > B-Na2S-C > B-C > B-HNO3-C. At the pH of 5 and 30 °C, R-C, C-NaOH-C, and B-NaOH-C showed the highest maximum adsorption capacity for Mn(II). Equilibrium data were evaluated by Langmuir, Freundlich, and Temkin isotherm models, and the results suggested that the Langmuir model is the most suitable to expound the adsorption behavior of Mn(II) on R-C, C-NaOH-C, and B-NaOH-C. Overall, the results from this work suggest that the key for preparing biochar adsorbents with high capacity is to choose the appropriate biomass feedstock and modification method.

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.