Systematic Dissection Research Articles

Reclassifying the International Association for the Study of Lung Cancer Residual Tumor Classification According to the Extent of Nodal Dissection for NSCLC: One Size Does Not Fit All

IntroductionThe extent of nodal assessment may require risk-based adjustments in NSCLC. We reclassified the International Association for the Study of Lung Cancer Residual tumor classification according to the extent of nodal dissection and evaluated its long-term prognosis by tumor stage and histologic subtype. MethodsWe reclassified 5117 patients who underwent resection for clinical stages I to III NSCLC and had complete or uncertain resection by International Association for the Study of Lung Cancer classification into the following 3 groups according to compliance with three components (N1, N2, and subcarinal node) of systematic nodal dissection criteria: fully compliant group (FCG), partially compliant group (PCG), and noncompliant group (NCG). Recurrence-free survival (RFS) and overall survival (OS) were compared. ResultsOf the 5117 patients, 2806 (55%), 1959 (38%), and 359 (7%) were FCG, PCG, and NCG, respectively. PCG and NCG were more likely to be of lower clinical stage and adenocarcinoma with lepidic component than FCG. The 5-year RFS and OS were significantly better in NCG than in FCG or PCG (RFS, 86% versus 70% or 74%, p < 0.001; OS, 90% versus 80% or 83%, p < 0.001). In particular, NCG had better RFS and OS than FCG or PCG in clinical stage I and in lepidic-type adenocarcinoma. ConclusionsIn early stage NSCLC with low-risk histologic subtype, a less rigorous nodal assessment was not associated with a worse prognosis. Although surgeons should continue to aim for complete resection and thorough nodal assessment, a uniform approach to the extent and invasiveness of nodal assessment may need to be reconsidered.

Systematic trait dissection in oilseed rape provides a comprehensive view, further insight, and exact roadmap for yield determination

BackgroundYield is the most important and complex trait that is influenced by numerous relevant traits with very complicated interrelations. While there are a large number of studies on the phenotypic relationship and genetic basis of yield traits, systematic studies with further dissection focusing on yield are limited. Therefore, there is still lack of a comprehensive and in-depth understanding of the determination of yield.ResultsIn this study, yield was systematically dissected at the phenotypic, genetic to molecular levels in oilseed rape (Brassica napus L.). The analysis of correlation, network, and principal component for 21 traits in BnaZN-RIL population showed that yield was determined by a complex trait network with key contributors. The analysis of the constructed high-density single nucleotide polymorphism (SNP) linkage map revealed the concentrated distribution of distorted and heterozygous markers, likely due to selection on genes controlling the growth period and yield heterosis. A total of 134 consensus quantitative trait loci (QTL) were identified for 21 traits, of which all were incorporated into an interconnecting QTL network with dozens of hub-QTL. Four representative hub-QTL were further dissected to the target or candidate genes that governed the causal relationships between the relevant traits.ConclusionsThe highly consistent results at the phenotypic, genetic, and molecular dissecting demonstrated that yield was determined by a multilayer composite network that involved numerous traits and genes showing complex up/down-stream and positive/negative regulation. This provides a systematic view, further insight, and exact roadmap for yield determination, which represents a significant advance toward the understanding and dissection of complex traits.

Short-term outcomes of bronchoplastic lobectomies performed from video-assisted thoracoscopic and thoracotomic approaches

The OBJECTIVE of this study was to evaluate the short-term outcomes of bronchoplastic lobectomies performed from video-assisted thoracoscopic (VATS) and thoracotomic approaches and to identify factors affecting the course of the early postoperative period.METHODS AND MATERIALS. Out of 398 patients underwent surgical resection in the Center for Intensive Pulmonology and Thoracic Surgery of the SPbSBHI «City multidisciplinary hospital № 2» from 2014 to 2021 for malignant lung neoplasms, 27 patients with bronchoplastic lobectomy were included in the retrospective study. Patients were divided into two groups depending on surgical approach: group I (n=17) included patients operated via thoracotomic approach; group II (n=10) included patients who underwent VATS surgeries. The groups were similar in gender, age, smoking history, Body Mass Index, concomitant pathology, functional status and stage of the disease. Surgical intervention included ipsilateral systematic lymph dissection and bronchoplastic lobectomy.RESULTS. There were no significant differences in time of operation, blood loss, duration of drainage of the pleural cavity, incidence of postoperative complications, length of hospital stay, number of dissected lymph nodes between the groups. Factor analysis of the influence of pre- and intraoperative factors on the development of postoperative complications showed that the risk of a complicated course of the postoperative period significantly decreased at normal values of FEV1 and FVC (OR=0.942, p&lt;0.05; OR=0.932, p&gt;&lt;0.05) and increased in the presence of adhesions (obliteration of the pleural cavity more than 50%), requiring total pneumolysis, and the absence of interlobar fissures (OR=5.5, p&gt;&lt;0.05; OR=6.5, p&gt;&lt;0.05). In multivariate analysis, strong adhesions in the pleural cavity turned out to be an independent unfavorable prognostic factor for the development of postoperative complications (OR=8.567, p&gt;&lt;0.05). CONCLUSION. The use of VATS approach does not increase the incidence of complications after bronchoplastic lobectomies. In patients with FEV1&gt;84.9 %)CONCLUSION. The use of VATS approach does not increase the incidence of complications after bronchoplastic lobectomies. In patients with FEV1&gt;84.9 % and FVC&gt;101.2 %, the risk of complications after bronchoplastic lobectomies is confirmed lower. Adhesions in pleural cavity requiring total pneumolysis is an independent unfavorable factor in the development of postoperative complications.

Prognostic impact of micropapillary and solid histological subtype on patients undergoing curative resection for stage I lung adenocarcinoma according to the extent of pulmonary resection and lymph node assessment

BackgroundWe aimed to evaluate the impact of micropapillary and/or solid (MPSOL) components on survival and recurrence of patients with resected stage I lung adenocarcinoma (LUAD) according to the extent of surgery and completeness of lymph node assessment (LNA). MethodsWe retrospectively reviewed 1886 consecutive patients who underwent surgical resection for pathologic stage I LUAD between 2009 and 2014. The patients were classified by the presence (≥1%) of MPSOL into the MPSOL(+) (n = 489) and MPSOL(−) (n = 1397) group.We analyzed the outcomes according to the extent of surgery (sublobar resection [SR] vs. lobectomy) and the LNA (complete vs. incomplete). Complete LNA was defined as systematic LN dissection according to European Society of Thoracic Surgeons guideline. ResultsIn the MPSOL(+) patients, there was no significant difference in adjusted overall survival (OS), recurrence-free survival (RFS), and recurrence pattern between the lobectomy and SR group. Of note, patients with complete LNA had higher adjusted OS and RFS than those with incomplete LNA (aOS, 86.3% vs. 78%, p = 0.002; aRFS, 70% vs 63.1%, p = 0.06). In the MPSOL(−) patients, adjusted RFS of the SR group was better than the lobectomy group (95% vs. 90.5%, p = 0.021), although there was no difference in survival regarding to the LNA. Complete LNA was a favorable prognostic factor for RFS in the MPSOL(+) patients (HR = 0.463, 95% CI: 0.227–0.944, p = 0.034). ConclusionsIn MPSOL(+) patients, complete LN assessment affects the OS and RFS rather than the extent of lung resection. In patients with solid tumor or tumor>2 cm, a complete LN assessment would be required, even if sublobar resection is unavoidable.

Analysis of treatment failure phenotype and prognostic factors of stage Ⅰ non-small cell lung cancer

Non-small cell lung cancer (NSCLC) is one of the most severe malignant tumors worldwide. Lobectomy and systematic nodal dissection remain the standard treatment for stageⅠNSCLC. Stereotactic body radiotherapy (SBRT) has become the standard treatment for medically inoperable patients. Though the prognosis of stage Ⅰ NSCLC patients is generally good, there are still about 20% of patients with local recurrence and distant metastasis. There is significant heterogeneity in the prognosis and failure phenotype of patients, which cannot be precisely distinguished by the pathological TNM classification system. Identification of the risk factors for the prognosis of patients with stage Ⅰ NSCLC is a key step to realize the treatment from experience to precision. Screening the high-risk patients will facilitate to individually develop the adjuvant therapy strategy after surgery or SBRT and improve the overall curative effect. There are many factors that are significantly related to the prognosis of stage Ⅰ NSCLC including individual factors such as gender, age, and systemic inflammatory biomarkers; treatment-related factors such as the extent of surgical resection of the primary tumor and lymph nodes, the choice of different radiation rays, and different dose fractionation; and tumor-related factors such as imaging information, pathology information; and molecular biology information. This review will analyze the treatment failure phenotype and prognostic factors of stageⅠ NSCLC in various perspectives such as individual-, tumor- and treatment-related factors.

Complete Lymphadenectomy for Clinical Stage I Lepidic Adenocarcinoma of the Lung: Is it justified?

The role of a systematic lymphadenectomy in patients undergoing surgery for clinical stage I lung lepidic adenocarcinoma is still unclear. In the last years, some authors have advocated the possibility to avoid a complete lymph-node dissection in this setting. Results of patients who received systematic hilar-mediastinal nodal dissection for this oncologic condition are here reported. Between 2012 and March 2019, 135 consecutive patients underwent lung resection for clinical stage I lepidic adenocarcinoma, at our institution. Only patients (n = 98) undergoing lobectomy or sublobar resection associated with systematic hilar-mediastinal nodal dissection were retrospectively enrolled in the study. Patients' mean age was 67.8 ± 8.7 years (range 37-84). Three were 52 females and 46 males. Resection was lobectomy in 77.6% (n = 76) and sublobar in 22.4% (n = 22). All the resections were complete (R0). Histology was lepidic predominant adenocarcinoma in 85 cases and minimally invasive adenocarcinoma in 13 cases. At pathologic examination, N0 was confirmed in 78 patients (79.6%), while N+ was found in 20 cases (20.4%), (N1 in 12, 12.2% and N2 in 8, 8.2%). No mortality occurred. Complication rate was 8.2%. At a median follow-up of 45.5 months, recurrence rate was 26.5%. Disease-free 5-year survival was 98.6% for stage I, 75% for stage II and 45% for stage III, p < 0.001. A complete nodal dissection can reveal occult nodal metastases in lepidic adenocarcinoma patients and can increase the accuracy of pathologic staging. N1/N2 disease is a negative prognostic factor for this histology. A systematic lymph-node dissection should be considered even in this setting.

Sentinel lymph node mapping versus sentinel lymph node mapping with systematic lymphadenectomy in endometrial cancer: an open-label, non-inferiority, randomized trial (ALICE trial)

BackgroundGrowing evidence suggest that sentinel lymph node (SLN) biopsy in endometrial cancer accurately detects lymph node metastasis. However, prospective randomized trials addressing the oncological outcomes of SLN biopsy in endometrial...

Up-regulation of miR-335 and miR-674-3p in the rostral ventrolateral medulla contributes to stress-induced hypertension.

The rostral ventrolateral medulla (RVLM) is known as the vasomotor center that plays a crucial role in mediating the development of stress-induced hypertension (SIH). MicroRNAs (miRNAs) are involved in many different biological processes and diseases. However, studies that evaluated the roles of miRNAs in the RVLM during SIH do not exist. Here, we performed RNA sequencing to explore the genome-wide miRNA profiles in RVLM in an SIH rat model established by administering electric foot-shocks and noises. The function of miRNAs in blood pressure regulation was determined in vivo via the intra-RVLM microinjection of the agomir or antagomir. Furthermore, the underlying mechanisms of miRNAs on SIH were investigated through in vitro and in vivo experiments, like gain-of-function. We discovered 786 miRNA transcripts among which 4 were differentially expressed. The over-expression of miR-335 and miR-674-3p in RVLM dramatically increased the heart rate (HR), arterial blood pressure (ABP), systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) levels of normotensive rats, whereas the knockdown of miR-335 and miR-674-3p in RVLM markedly reduced the HR, ABP, SBP, DBP, and MAP levels of SIH rats. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation revealed that miR-335 and miR-674-3p participated in regulating the development of SIH from different aspects, like apoptosis-multiple species pathway. Sphk1, whose expression was markedly decreased in SIH, was identified as a novel target of miR-335. MiR-335 over-expression substantially reduced the expression of Sphk1 and promoted neural apoptosis, and its inhibition had opposite effects. Re-introduction of Sphk1 dramatically abrogated the apoptosis induced by miR-335. This study provides the first systematic dissection of the RVLM miRNA landscape in SIH. MiR-335 and miR-674-3p act as SIH promoters, and the identified miR-335/Sphk1/apoptosis axis represents one of the possible mechanisms. These miRNAs can be exploited as potential targets for the molecular-based therapy of SIH.

Interim analysis of the efficiency and safety of neoadjuvant PD-1 inhibitor (sintilimab) combined with chemotherapy (nab-paclitaxel and carboplatin) in potentially resectable stage IIIA/IIIB non-small cell lung cancer: a single-arm, phase 2 trial.

While some clinical studies have shown that PD-1 and PD-L1 can also be an effective neoadjuvant treatment for early-stage non-small cell lung cancer (NSCLC), no evidence has been available for the use of the PD-1 inhibitor sintilimab combined with chemotherapy as a neoadjuvant treatment for potentially resectable NSCLC in the Chinese population. This prospective, single-center, single-arm, phase 2 clinical trial (registration number: NCT04326153) included treatment-naive patients with potentially resectable NSCLC (stage IIIA/IIIB) who received sintilimab plus nab-paclitaxel and carboplatin for two to three cycles before systematic nodal dissection 30 to 45days after neoadjuvant treatment. After surgery, patients needed to complete two cycles of adjuvant chemoimmunotherapy (sintilimab + nab-paclitaxel + carboplatin). The primary endpoint was disease-free survival rate at 24months, whereas secondary endpoints included major pathological response (MPR) and pathologic complete response (pCR) rates, the proportion of patients who achieved tumor downstaging, overall survival, objective response rate (ORR), and adverse effects. PD-L1 status before and after treatment was also determined. Among the 20 patients who received neoadjuvant chemoimmunotherapy, 16 underwent radical resection. The disease control rate and ORR were 90% and 70%, respectively. Among the 16 patients who underwent surgery, 10 (62.5%) and 5 (31.25%) achieved MPR and pCR, respectively. Squamous cell NSCLC exhibited superior response rates compared to adenocarcinoma (pCR 35.7% vs. 0%). Moreover, 14 patients (70%) experienced grade 1 or 2 neoadjuvant treatment-related adverse events (TRAEs), whereas 6 (30%) experienced grade 3 TRAEs. Bronchopleural fistula (BPF) was found in the current study as an adverse reaction of concern. The rate of BPF was 20% (4/20), of which three patients were in grade 1-2, and one patient died. The occurrence of BPF had no significant correlation with basic disease history, nutritional status, anemia, hypoalbuminemia, surgical procedure, pathological remission, and PD-L1 expression. However, during neoadjuvant treatment, no adverse events prompted dose reduction, treatment discontinuation, surgery delay, or death. Although PD-L1 expression may change after chemoimmunotherapy, no regular pattern was noted. PD-L1 expression, neither at baseline nor after neoadjuvant chemoimmunotherapy, was associated with pathological remission. The current study found similar ORR, slightly lower MPR and pCR rates, and lower grade 3 TRAEs among patients with potentially resectable stage IIIA/IIIB NSCLC compared to the NADIM trial, as well as a greater ORR, MPR rate, pCR rate, and grade 3 TRAEs compared to Gao's study involving sintilimab for Chinese patients with resectable stage IA-IIIB NSCLC. Though neoadjuvant chemoimmunotherapy had been found to promote a high risk of BPF for patients with stage IIIA/IIIB disease, it offered greater potential for radical cure. Therefore, the current study suggests that neoadjuvant chemoimmunotherapy can be a safe approach in increasing the efficiency of treatment and hopefully improving the prognosis of patients with potentially resectable locally advanced NSCLC.

Quantitative Dissection of the Proximal Ciona brachyury Enhancer.

A major goal in biology is to understand the rules by which cis-regulatory sequences control spatially and temporally precise expression patterns. Here we present a systematic dissection of the proximal enhancer for the notochord-specific transcription factor brachyury in the ascidian chordate Ciona. The study uses a quantitative image-based reporter assay that incorporates a dual-reporter strategy to control for variable electroporation efficiency. We identified and mutated multiple predicted transcription factor binding sites of interest based on statistical matches to the JASPAR binding motif database. Most sites (Zic, Ets, FoxA, RBPJ) were selected based on prior knowledge of cell fate specification in both the primary and secondary notochord. We also mutated predicted Brachyury sites to investigate potential autoregulation as well as Fos/Jun (AP1) sites that had very strong matches to JASPAR. Our goal was to quantitatively define the relative importance of these different sites, to explore the importance of predicted high-affinity versus low-affinity motifs, and to attempt to design mutant enhancers that were specifically expressed in only the primary or secondary notochord lineages. We found that the mutation of all predicted high-affinity sites for Zic, FoxA or Ets led to quantifiably distinct effects. The FoxA construct caused a severe loss of reporter expression whereas the Ets construct had little effect. A strong Ets phenotype was only seen when much lower-scoring binding sites were also mutated. This supports the enhancer suboptimization hypothesis proposed by Farley and Levine but suggests that it may only apply to some but not all transcription factor families. We quantified reporter expression separately in the two notochord lineages with the expectation that Ets mutations and RBPJ mutations would have distinct effects given that primary notochord is induced by Ets-mediated FGF signaling whereas secondary notochord is induced by RBPJ/Su(H)-mediated Notch/Delta signaling. We found, however, that ETS mutations affected primary and secondary notochord expression relatively equally and that RBPJ mutations were only moderately more severe in their effect on secondary versus primary notochord. Our results point to the promise of quantitative reporter assays for understanding cis-regulatory logic but also highlight the challenge of arbitrary statistical thresholds for predicting potentially important sites.

Functional dissection of inherited non-coding variation influencing multiple myeloma risk

Thousands of non-coding variants have been associated with increased risk of human diseases, yet the causal variants and their mechanisms-of-action remain obscure. In an integrative study combining massively parallel reporter assays (MPRA), expression analyses (eQTL, meQTL, PCHiC) and chromatin accessibility analyses in primary cells (caQTL), we investigate 1,039 variants associated with multiple myeloma (MM). We demonstrate that MM susceptibility is mediated by gene-regulatory changes in plasma cells and B-cells, and identify putative causal variants at six risk loci (SMARCD3, WAC, ELL2, CDCA7L, CEP120, and PREX1). Notably, three of these variants co-localize with significant plasma cell caQTLs, signaling the presence of causal activity at these precise genomic positions in an endogenous chromosomal context in vivo. Our results provide a systematic functional dissection of risk loci for a hematologic malignancy.

Techniques of Minimally Invasive Posterior Basal (S10) Segmentectomies of the Lower Lobes

Now, the standard treatment for clinical stage I non-small cell lung cancer (NSCLC) is lobectomy with systematic nodal dissection. Sublobar resections, such as segmentectomy and wedge resection are often performed in compromised patients with peripheral small-sized NSCLC who are unfit or at high risk for standard lobectomy or even in those with indolent NSCLC who are fit for lobectomy. Anatomical segmentectomy rather than non-anatomical wedge resection as sublobar resection is usually recommended. Segmentectomy could be subdivided according to the number and shape of intersegmental plane. Segmentectomy that creates one, linear intersegmental plane, with a relatively easier procedure, could be considered simple segmentectomy, that is, resection of the superior segmentectomy of the lower lobe, the upper division, or lingula segment of the left upper lobe. Segmentectomy that creates several, or intricate intersegmental planes, with more a complex procedure, could be considered complex segmentectomy, that is, one other than simple segmentectomy, such as non-superior segmentectomy of the basilar segment of the lower lobe. Because of procedural complexity and risk of increased complications and incurability, compared with simple segmentectomy, some general thoracic surgeons may have concerns to perform complex segmentectomies. In this article, we show the technique of posterior basal segmentectomies, which is one of the most challenging procedures in complex segmentectomy, through a hybrid video-assisted thoracic surgery approach.

Comparison of Perioperative Outcomes of Modified Blumgart Pancreaticojejunostomy with Dunking Pancreaticojejujostomy Following Pancreaticoduodenectomy at a Tertiary Referral Centre of a Low-Middle Income Country

Background: Pancreaticojejunostomy (PJ) is considered as the Achilles heel of Pancreaticoduodenectomy (PD) that determines the perioperative outcomes. Although various studies have not shown superiority of any techniques of PJ, duct to mucosa PJ is associated with less incidence of postoperative pancreatic fistula (POPF). Methods: A retrospective comparative study of prospectively maintained database of patients undergoing PD at Tribhuvan University Teaching Hospital, Kathmandu, Nepal. Continuous dunking PJ (control group) was performed routinely in our unit, but since 2020 we started doing Modified Blumgart PJ (study group). The preoperative variables and perioperative variables like duration of surgery, intraoperative blood loss, overall complications as graded by Clavien Dindo grading of complications, procedure-specific complications as defined and graded by ISGPS and 30-day mortality were analyzed between the two groups. The statistical analysis was done with SPSS version 23.0. Results: Thirty-nine consecutive patients underwent systematic mesopancreas dissection PD between January 2018 to May 2021. Continuous dunking PJ was performed in 24 patients, while Modified Blumgart PJ was performed in 15 patients. The most common indication for PD was ampullary carcinoma (21 out of 39 patients, 53.8%). The two groups were comparable in terms of demography, type of tumour, pancreatic texture and pancreatic duct diameter. Results are give in the Table below.Tabled 1EP02D-180Perioperative variablesModified Blumgart PJ (n=15)Dunking PJ (n=24)p valueDuration of surgery, mins, Mean±SD394.00±45.17372.50±57.120.225Intraoperative blood loss, ml, Mean±SD436.67±175.73508.33±184.550.237CR-POPF, n (%)1 (7.7%)7 (29.1%)0.130Major complications, n (%)2 (15.4%)9 (37.5%)0.103Reoperation, n (%)0 (0%)2 (8.3%)0.25130-day mortality, n (%)0 (0%)3 (12.5%)0.154Length of hospital stay, days, Mean±SD12.13±1.9516.04±5.790.016 Open table in a new tab Conclusion: Our retrospective comparative study showed, better perioperative outcomes in terms of POPF, overall major complications and 30-day mortality, but did not reach the statistical significance. We need a larger number of patients to demonstrate the benefit of modified Blumgart PJ over Dunking PJ.

Systematic screen of potential circular RNA biomarkers of Hirschsprung's disease.

BackgroundHirschsprung’s disease (HSCR) is a developmental disorder of the enteric nervous system in which enteric ganglia are missing along a portion of the intestine. Aberrant expression of several circular RNAs (circRNAs) has been identified in the disease, but the full range of dysregulated circRNAs and their potential roles in its pathogenesis remain unclear. We used microarray profiling to systematically screen for circRNAs that were differentially expressed in HSCR, and we comprehensively analyzed the potential circRNA-miRNA-mRNA regulatory network to identify molecular mechanisms involved in the disorder.MethodsWe identified circRNAs that were differentially expressed between diseased tissue and paired normal intestinal tissues from patients with HSCR. The most strongly upregulated circRNAs were then validated by quantitative reverse-transcription-PCR (RT-PCR). We also constructed a circRNA-miRNA-mRNA interaction network to determine functional interactions between miRNAs and mRNAs.ResultsWe identified 17 circRNAs that were upregulated and 10 that were downregulated in HSCR tissue compared with normal tissues. The five circRNAs that showed the greatest upregulation were verified by RT-PCR: hsa_circRNA_092493, hsa_circRNA_101965, hsa_circRNA_103118, hsa_circRNA_103279, and hsa_circRNA_104214. These five circRNAs were successfully adopted to diagnose HSCR based on receiver operating characteristic curves, and they were used to generate a circRNA-miRNA-mRNA network. The network revealed a potential function of the circRNAs as molecular sponges targeting miRNAs and mRNAs in HSCR.ConclusionsThis first-ever systematic dissection of the circRNA profile in HSCR may provide useful insights into improving diagnosis and therapy.

Impact on quality of life after vagus nerve and phrenic nerve guided systematic nodal dissection for non-small cell lung cancer patients: a prospective, single-arm clinical trial

BackgroundPatients with non-small cell lung cancer (NSCLC) suffer a decrease in quality of life (QOL) after receiving curative lobectomy and mediastinal lymph node dissection via video-assisted thoracoscopic surgery (VATS). We aimed to explore the preliminary influence of our modified approach called the duo-nerve-guided systematic nodal dissection (SND) on patients’ QOL.MethodsBetween October 2018 and March 2019, 21 patients were enrolled from the First Affiliated Hospital of Sun Yat-sen University and received curative lobectomy and duo-nerve-guided SND for clinical stage I to IIIA NSCLC. Participants’ QOL was evaluated by Functional Assessment of Cancer Therapy-Lung (FACT-L) questionnaire before operation and at 1- and 3-month postoperatively.ResultsThe overall QOL scores at 1 month after surgery were significantly lower than those before surgery (116.13 vs. 126.63, P=0.001), while there was no significant difference in the overall QOL score between preoperative and 3 months after surgery. In particular, among the 5 subscales, physical well-being (PWB), functional well-being (FWB), and trial outcome index (TOI) significantly declined at 1 month after surgery. However, each subscale showed significant improvement at 3 months after operation compared with that at 1 month and basically returned to the level at baseline. In addition, there was a significant improvement in the emotional well-being (EWB) domain 3 months after surgery (23.00 vs. 18.00, P=0.001).ConclusionsAs evidenced by patients’ QOL at 3 months after receiving duo-nerve-guided SND being not significantly different from that at baseline, the improved SND procedure has positive effects on the fast recovery of NSCLC patients.

A modified approach of port-access lymphadectomy for locally advanced non-small cell lung cancer: A single center experience.

Systematic nodal dissection (SND) is an important component of locally advanced non-small cell lung cancer (NSCLC), but modification of this procedure is rarely reported. In this paper, we reported a modified technique of systematic mediastinal lymph node dissection (MLND) of operable lung cancer by video-assisted thoracic surgery (VATS). Parallel upward dissection (the PUD technique) was named due to this modification and the efficacy of the PUD technique was evaluated as well. We summarized the tips of the PUD technique and its version was updated in surgical aspect. The design and procedure sequence of the PUD technique were introduced in detail as well as its pros and cons. A retrospective study was performed on 998 cases of locally advanced NSCLC which accepted the PUD procedure in Department of Thoracic Surgery, Second Xiangya Hospital, Central South University, from 2012 to 2020. The perioperative mortality and the incidence of general and serious complications (such as recurrent laryngeal nerve injury, bronchopleural fistula) were analyzed. All the 998 cases were operated successfully with the PUD technique and few post-operation complications were found. There was no perioperative mortality and severe complication such as recurrent laryngeal nerve injury and bronchopleural fistula. The PUD technique is safe and convenient and it can be a good supplement to the existing surgical techniques for locally advanced lung cancer.

Site-Specific and Stable Conjugation of the SARS-CoV-2 Receptor-Binding Domain to Liposomes in the Absence of Any Other Adjuvants Elicits Potent Neutralizing Antibodies in BALB/c Mice.

Understanding immune responses toward viral infection will be useful for potential therapeutic intervention and offer insights into the design of prophylactic vaccines. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the COVID-19 pandemic. To understand the complex immune responses toward SARS-CoV-2 infection, here we developed a method to express and purify the recombinant and engineered viral receptor-binding domain (RBD) to more than 95% purity. We could encapsulate RNA molecules into the interior of a virion-sized liposome. We conjugated the purified RBD proteins onto the surface of the liposome in an orientation-specific manner with defined spatial densities. Both the encapsulation of RNAs and the chemical conjugation of the RBD protein on liposome surfaces were stable under physiologically relevant conditions. In contrast to soluble RBD proteins, a single injection of RBD-conjugated liposomes alone, in the absence of any other adjuvants, elicited RBD-specific B cell responses in BALB/c mice, and the resulting animal sera could potently neutralize HIV-1 pseudovirions that displayed the SARS-CoV-2 spike proteins. These results validate these supramolecular structures as a novel and effective tool to mimic the structure of enveloped viruses, the use of which will allow systematic dissection of the complex B cell responses to SARS-CoV-2 infection.

LOBE-SPECIFIC METASTASIS IN NON-SMALL CELL LUNG CANCER

Aim: to identify the pathways of lymph node metastases in non-small cell lung cancer (NSCLC).Material and Methods. The frequency of mediastinal lymph node metastases and treatment outcomes were analyzed in 327 patients with stage I–III non-small cell lung carcinoma (NSCLC), who underwent lung resection with systematic lymph node dissection (SLND) between 2007 and 2011.Results. In cases with tumor location in any lobe of the right lung, metastasis occurred in the superior and inferior mediastinal lymph nodes. In left-side tumors, the main pathways of lymphatic spread of tumors were superior and inferior mediastinal nodes as well as aortic lymph nodes. Left lower lobe tumors metastasized most often to inferior mediastinal lymph nodes. Skip metastases were observed at any location of the tumor. Routine examination of all ipsilateral mediastinal lymph nodes overstaged NSCLC in 19.5 % of cases. The overall 5-and 10-year survival rates in patients with stage I–III NSCLC with SND were 61.5 % and 49.2 %, respectively. The median survival time was 103 months.Conclusion. Despite typical metastatic patterns of mediastinal lymph nodes in patients with NSCLC, non-specific metastasis was observed at any location of the tumor, which required mandatory systematic nodal dissection.

Prognostic impact of spread through air spaces in lung adenocarcinoma.

Spread through air spaces (STAS) is a pattern of invasion present in some adenocarcinomas (ADC). The goal of this study was to assess the impact of STAS in patients treated with different types of surgical resections and on the clinical outcome in patients with ADC of different diameters and with different degrees of nodal involvement. A total of 109 patients were reviewed. Complete surgical resection with systematic nodal dissection was achieved in all patients. The median follow-up was 65 months (3-90 months). STAS was observed in 70 cases (64.2%); 13 patients (18.5%) had lymph node involvement (N1 and N2). Overall survival and progression-free survival were higher in patients without STAS (P = 0.042; P = 0.027). The presence of STAS in tumours ≤2 cm was a predictor of worse progression-free survival following sublobar resection compared to major resections (P = 0.011). Sublobar resection of N0 STAS-positive tumours was associated with worse long-term survival compared to a major resection (P = 0.04). Statistical analyses showed that age >70 years and recurrence were independent variables for survival; smoking pack-years >20, sublobar resection and nodal involvement were independent variables for recurrence; and smoking pack-years >20 were independent variables for a history of cancer and pleural invasion for local recurrence. STAS seems to play a role in long-term survival, particularly for patients with N0 and tumours smaller than 2 cm. Further studies are necessary to validate this hypothesis.

Clinical and morphological factors that increase the risk of locoregional metastasis of papillary thyroid cancer

Background. The sensitivity of the ultrasound method to determine lymph node metastases of papillary thyroid cancer (PTC) to the central lymphatic collector of the neck at the preoperative stage is low, 49 % only, therefore assessment of the factors leading to the prolongation of the process is of great importance in the development of surgical treatment tactics.Aim — to evaluate factors that increase the risk of locoregional metastases of papillary thyroid cancer and substantiate the advisability of systematic central neck dissection (SCND).Materials and methods. A retro-prospective single center study of the risk of PTC prolongation in the form of locoregional metastases (LRM) was carried out. The data of 514 patients operated for papillary thyroid disease were processed. The main group included 240 patients in whom LRM was found according to the results of histopathological examination (HPE), control group consisted of 274 patients without LRMsigns. The following signs were taken into account: multifocal lesions of the thyroid gland, the patients’age, gender, presence of thyroiditis, the size of the dominant tumor, invasion of adipose tissue. In order to substantiate the expediency of the SCND, retrospective processing of the data of 514 patients, operated from 2018 to 2020, was carried out for PTC, in which the presence of metastases was not cytologically confirmed at the preoperative stage (cN0).Results. The mean age of patients of the main group was lower than in the control group (p &lt; 0.001). The median size of the primary tumor in patients of the main group was significantly higher than in the control group (p &lt; 0.001). The men portion in the main group was significantly higher than in the control group, and the part of women vice versa (p &lt; 0.05). Invasion of the tumor into the adipose tissue in the main group occurred almost twice as often (p &lt; 0.01). The number of patients with multifocal lesions in both groups was practically the same and did not differ statistically (p &gt; 0.05). Ipsilateral and contralateral localization of tumors in both groups did not differ significantly (p &gt; 0.05). The presence of thyroiditis in the control group was higher than in the main group (p &lt; 0.05). The diagnostic efficiency (DE) of accounting for the factor of invasion into adipose tissue was 64.8 %, tumor size over 1.3 cm — 66.7 %, age up to 47 years — 60.0 %. The frequency of detecting metastases with cN0 at the preoperative stage, according to HPE results, was 25.8 %.Conclusions. The reliability of preoperative imaging and diagnostic methods does not allow to ignore the likelihood of LRM and not perform SCND. According to the obtained data, in 25.8 % of casesmetastases were verified based on HPE owing to thesystematic central neck dissection. Male gender (p &lt; 0.01), age of patients (p &lt; 0.001), size of primary tumor (p &lt; 0.001), invasion of adipose tissue (p &lt; 0.01) can serve as predictors of the increased LRMPTC risk. The presence of invasion of adipose tissue (diagnostic efficacy 64.8 %), tumor size more than 1.3 cm (66.7 % DE) and age &lt; 47 (60.0 % DE) increased the risk of LRMPTC. The presence of thyroiditis (the frequency of thyroiditis exposure in control group was higher than in the main group (p &lt; 0.05)), contralateral lesions of the thyroid gland (p &gt; 0.05), multifocal lesions (p &gt; 0.05) cannot serve as reliable prognostic factors for the increased LRMrisk.